insulin-glargine and Hyperglycemia

Severe hypoglycaemia (SH) remains a challenge to people with type 1 diabetes (T1DM), and new-generation basal insulins may improve patient outcomes. This post hoc meta-analysis explored the risk of SH with insulin glargine 300 U/mL (Gla-300) versus glargine 100 U/mL (Gla-100) in a pooled population with T1DM from three randomized, multicentre, 6-month similarly designed phase 3 trials: EDITION 4, EDITION JP 1 and EDITION JUNIOR. Endpoints included incidence and time to first occurrence of SH. Among 629 and 626 participants randomized to Gla-300 and Gla-100, respectively, glycated haemoglobin reductions were similar. Fewer participants experienced ≥1 SH event with Gla-300 (6.2%) than with Gla-100 (9.3%). From baseline to month 6, the risk of a first SH event was lower with Gla-300: hazard ratio 0.65 [95% confidence interval (CI) 0.44-0.98; stratified log-rank test P = 0.038]. SH event rates were numerically lower with Gla-300 versus Gla-100 from baseline to month 6 [relative risk (RR) 0.80 (95% CI 0.49-1.29); P = 0.356] and baseline to week 8 [RR 0.73 (95% CI 0.37-1.44); P = 0.369]. Thus, Gla-300 demonstrated similar glycaemic control with lower risk of SH versus Gla-100, particularly during the titration period.

Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Risk

Approximately 50% of patients with type 2 diabetes mellitus (T2DM) do not achieve glycemic targets and require treatment intensification. A fixed-ratio combination of a glucagon-like peptide-1 receptor agonist (GLP-1 RA) with basal insulin, such as lixisenatide with insulin glargine (iGlarLixi), exploits the complementary mechanisms of action of each component to address hyperglycemia while mitigating potential adverse events (AEs). The iGlarLixi dose is titrated considering the effect of basal insulin on fasting plasma glucose, and the fixed-ratio combination ensures that the lixisenatide dose never exceeds 20 μg/day. We describe the characteristics of iGlarLixi therapy, based on the LixiLan clinical program, and provide guidance on the characteristics of patients likely to benefit from such treatment in routine clinical practice. In the phase III LixiLan trials, iGlarLixi resulted in significantly greater reductions in glycated hemoglobin (HbA1c), better achievement of HbA1c targets, less glycemic variability versus insulin glargine, lixisenatide or GLP-1 RA alone, and was associated with weight control, less hypoglycemia versus insulin glargine, and fewer GI AEs versus lixisenatide. Findings were consistent regardless of age, diabetes duration, and baseline HbA1c. The efficacy, safety, and convenient once-daily administration schedule of iGlarLixi make it a valuable treatment option for patients with T2DM requiring treatment intensification.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Combinations; Female; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Glycemic Control; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Male; Peptides

The Cystic Fibrosis Foundation recommends both short-term and long-acting insulin therapy when cystic fibrosis-related diabetes (CFRD) has been diagnosed. Diagnosis is based on: an elevated fasting blood glucose level greater than 6.94 mmol/L (125 mg/dL); or oral glucose tolerance tests greater than 11.11 mmol/L (200 mg/dL) at two hours; or symptomatic diabetes for random glucose levels greater than 11.11 mmol/L (200 mg/dL); or glycated hemoglobin levels of at least 6.5%. This is an update of a previously published review.. To establish the effectiveness of insulin and oral agents for managing diabetes in people with cystic fibrosis in relation to blood sugar levels, lung function and weight management.. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also handsearched abstracts from pulmonary symposia and the North American Cystic Fibrosis Conferences. Date of most recent register search: 10 September 2020. We searched online trials registries; date of most recent searches: 21 March 2020.. Randomized controlled trials comparing all methods of pharmacological diabetes therapy in people with diagnosed CFRD.. Two authors independently extracted data and assessed the risk of bias in the included studies. Authors also used GRADE to assess the quality of the evidence.. The searches identified 29 trials (45 references). Four included trials provide results: one short-term single-center cross-over trial (seven adults) comparing insulin with oral repaglinide and no medication in adults with CFRD and normal fasting glucose; one long-term multicenter trial (61 adults with CFRD) comparing insulin with oral repaglinide and placebo; one long-term multicenter trial (67 adults) comparing insulin with oral repaglinide; and one 12-week single-center cross-over trial (20 adults) comparing the long-acting insulin glargine to short-term neutral protamine Hagedorn insulin. Two ongoing trials of newly approved incretin mimics have been noted for possible future inclusion. Downgrading of the quality of the evidence was mainly due to risks of bias across all domains, but particularly due to concerns surrounding allocation concealment and selective reporting. There were also some concerns due to imprecision from small sample sizes and low event rates. Finally, there may be some bias due to the amounts of insulin and repaglinide given not being comparable. Data from one trial comparing insulin to placebo (39 participants) did not show any difference between groups for the primary outcomes of blood glucose levels (very low-quality evidence), lung function (low-quality evidence) or nutritional status (low-quality evidence). Similarly, no differences between groups were seen for the secondary outcomes of number of hypoglycemic episodes (low-quality evidence), secondary infection complications or quality of life (QoL). These results were mirrored in the narrative reports for the second trial in this comparison (seven participants). Data from the one-year trial comparing repaglinide to placebo (38 participants), showed no differences between groups for the primary outcomes of blood glucose levels (very low-quality evidence), lung function (low-quality evidence) and nutritional status (low-quality evidence). Also, no differences were seen between groups for the secondary outcomes of number of hypoglycemic episodes (low-quality evidence), secondary infection complications or QoL. These findings were mirrored in the narrative reports for the second trial (n = 7) in this comparison. Three trials compared insulin to repaglinide (119 participants). Data from one trial (n = 67) showed no difference in blood glucose levels at either 12 months (high-quality evidence) or 24 months; narrative reports from one trial (45 participants) reported no difference. This review has not found any conclusive evidence that any agent has a distinct advantage over another in controlling hyperglycemia or the clinical outcomes associated with CFRD. Given the treatment burden already experienced by people with cystic fibrosis, oral therapy may be a viable treatment option. While some cystic fibrosis centers use oral medications to help control diabetes, the Cystic Fibrosis Foundation (USA) clinical practice guidelines support the use of insulin therapy and this remains the most widely-used treatment method. Randomized controlled trials specifically related to controlling diabetes and its impact on the course of pulmonary disease process in cystic fibrosis continue to be a high priority. Specifically, investigators should evaluate adherence to different therapies and also whether there is benefit in using additional hypoglycemic agents as well as the newly approved incretin mimics. Agents that potentiate insulin action, especially agents with additional anti-inflammatory potential should also be further investigated as adjuvant therapy to insulin.

Topics: Administration, Oral; Bias; Blood Glucose; Carbamates; Cystic Fibrosis; Diabetes Mellitus; Fasting; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Piperidines; Randomized Controlled Trials as Topic

As Type 2 diabetes progresses, treatment is intensified with additional therapies in an effort to manage hyperglycaemia effectively and therefore avoid complications. When greater efficacy is required, options for injectable treatments include glucagon-like peptide-1 receptor agonists and insulin, which may be added on to oral glucose-lowering treatments. Among individuals receiving long-acting basal insulin as their first injectable treatment, ~40-60% are unable to achieve or maintain their target HbA

Topics: Administration, Oral; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Glucagon; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incretins; Insulin Glargine; Insulin, Long-Acting; Peptides; Postprandial Period; Treatment Outcome

The best insulin regimen to treat hyperglycemia in hospitalized patients on nutritional support (NS) is unclear.. We searched electronic databases to identify cohort studies or randomized clinical trials in order to evaluate the efficacy of different insulin regimens used to treat hyperglycemia in hospitalized patients on NS on diverse outcomes: mean blood glucose (MBG), hypoglycemia, length of stay in hospital, and mortality.. Seventeen studies from a total of 5,030 were included. Enteral Group included 8 studies; 1,203 patients using rapid, glargine, NPH, or Premix insulin; MBG 108-225 mg/dL; hypoglycemia 0-13%. In indirect meta-analyses, NPH insulin ranked best for glucose control (MD 95% CI -2.50 mg/dL [2.65 to -2.35]). Parenteral Group included 4 studies; 228 patients using regular and glargine or NPH insulin; MBG 137-202 mg/dL; hypoglycemia 0-40%. In meta-analyses comparing regular insulin added to parenteral nutrition bag with glargine, MBG (MD 95% CI -3.78 mg/dL [-11.93 to 4.37]; I2 = 0%) or hypoglycemia frequency (RR 95% CI 1.37 [0.43-4.32]; I2 = 70.7%) did not differ. The description related to hospital length of stay and mortality was inconsistent between groups.. The best insulin regimen to treat hyperglycemia in hospitalized patients on NS has not been established; best results using insulin regimens with NPH in enteral nutrition do not seem to be clinically relevant.

Topics: Blood Glucose; Hospital Mortality; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Inpatients; Insulin; Insulin Glargine; Insulin, Isophane; Length of Stay; Nutritional Support; Parenteral Nutrition

The worrisome rise in pediatric type 2 diabetes (T2DM) is most prevalent among minority ethnic/racial populations. Typically, T2DM occurs during puberty in high risk obese adolescents with evidence of insulin resistance. Screening for T2DM in obese youth can be a daunting task for pediatricians and differentiating between pediatric T1DM and T2DM in obese youth can be challenging for pediatric endocrinologists. There is very limited data regarding the prevalence of T2DM among youth < 10 years of age. Here we present the case of a 5-year-old Hispanic male diagnosed with T2DM after referral by his pediatrician for abnormal weight gain, acanthosis nigricans and an elevated HbgA1c. He subsequently became symptomatic for diabetes with confirmed hyperglycemia and HbgA1c of 9.7% (83 mmol/mol) at the time of formal diagnosis. Type 1 diabetes autoantibodies (GAD65, Islet, and ZincT8) and monogenic diabetes genetic tests were negative. Due to elevated liver enzymes and baseline HbgA1c, he received basal insulin as his initial therapy. In this paper, we will discuss this case and present an IRB approved retrospective review of the characteristics of the 20 T2DM patients <10 years of age identified to date in our pediatric diabetes center. This review highlights that while uncommon, the diagnosis of T2DM merits consideration even in prepubertal children. This is especially true when working with a high risk population, such as our Hispanic South Texas youth.

Topics: Acanthosis Nigricans; Age of Onset; Body Mass Index; Child, Preschool; Combined Modality Therapy; Diabetes Mellitus, Type 2; Diet, Reducing; Family Health; Female; Glycated Hemoglobin; Healthy Lifestyle; Hispanic or Latino; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin Glargine; Male; Obesity, Morbid; Pediatric Obesity; Risk; Texas; Treatment Outcome

The Cystic Fibrosis Foundation recommends both short-term and long-acting insulin therapy when cystic fibrosis-related diabetes has been diagnosed. Diagnosis is based on: an elevated fasting blood glucose level greater than 6.94 mmol/liter (125 mg/deciliter); or oral glucose tolerance tests greater than 11.11 mmol/liter (200 mg/deciliter) at two hours; or symptomatic diabetes for random glucose levels greater than 11.11 mmol/liter (200 mg/deciliter); or glycated hemoglobin levels of at least 6.5%.. To establish the effectiveness of insulin and oral agents for managing diabetes in people with cystic fibrosis in relation to blood sugar levels, lung function and weight management.. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also handsearched abstracts from pulmonary symposia and the North American Cystic Fibrosis Conferences.Date of the most recent search of the Group's Cystic Fibrosis Trials Register: 18 February 2016.. Randomized controlled trials comparing all methods of diabetes therapy in people with diagnosed cystic fibrosis-related diabetes.. Two authors independently extracted data and assessed the risk of bias in the included studies.. The searches identified 22 trials (34 references). Four trials (200 participants) are included: one short-term single-center trial (n = 7) comparing insulin with oral repaglinide and no medication in people with cystic fibrosis-related diabetes and normal fasting glucose; one long-term multicenter trial (n = 100, 74 of whom had cystic fibrosis-related diabetes) comparing insulin with oral repaglinide and placebo; one long-term multicenter trial (n = 73) comparing insulin with oral repaglinide; and one 12-week single-center trial (n = 20) comparing the long-acting insulin glargine to short-term neutral protamine Hagedorn insulin.Two trials with data for the comparison of insulin to placebo did not report any significant differences between groups for the primary outcomes of blood glucose levels, lung function and nutritional status. This was also true for the single trial with data for the comparison of repaglinide to placebo. Two trials (one lasting one year and one lasting two years) contributed data for the comparison of insulin versus repaglinide. There were no significant differences for the primary outcomes at any time point, except at one year (in the two-year trial) when the insulin group had significant improvement in z score for body mass index compared to the repaglinide group. The single trial comparing glargine to neutral protamine Hagedorn insulin also did not report any significant differences in the review's primary outcomes. A few cases of hypoglycemia were seen in three out of the four trials (none in the longest trial), but these events resolved without further treatment.There was an unclear risk of bias from randomization and allocation concealment in two of the four included trials as the authors did not report any details; in the remaining two studies details for randomization led to a low risk of bias, but only one had sufficient details on allocation concealment to allow a low risk judgement, the second was unclear. There was a high risk from blinding for all trials (except for the comparison of oral repaglinide versus placebo) due to the nature of the interventions. Complete data for all outcomes were not available from any trial leading to a high risk of reporting bias. The amounts of insulin and repaglinide administered were not comparable and this may lead to bias in the results. None of the included trials were powered to show a significant improvement in lung function.. This review has not found any significant conclusive evidence that long-acting insulins, short-acting insulins or oral hypoglycemic agents have a distinct advantage over one another in controlling hyperglycemia or clinical outcomes associated with cystic fibrosis-related diabetes. While some cystic fibrosis centers use oral medications to help control diabetes, the Cystic Fibrosis Foundation (USA) clinical practice guidelines support the use of insulin therapy and this remains the most widely-used treatment method. Randomized controlled trials specifically related to controlling diabetes with this impact on the course of pulmonary disease process in cystic fibrosis continue to be a high priority.There is no demonstrated advantage yet established for using oral hypoglycemic agents over insulin, and further trials need to be evaluated to establish whether there is clear benefit for using hypoglycemic agents. Agents that potentiate insulin action, especially agents with additional anti-inflammatory potential should be further investigated to see if there may be a clinical advantage to adding these medications to insulin as adjuvant therapy.

Topics: Administration, Oral; Carbamates; Cystic Fibrosis; Diabetes Mellitus; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Piperidines; Randomized Controlled Trials as Topic

Insulin glargine 100 units/ml (Gla-100) has become a standard of care in diabetes treatment over the past decade, providing 24-h basal insulin coverage after once-daily subcutaneous injection for many people with diabetes, with a well-established efficacy and safety profile. New insulin glargine 300 units/ml (Gla-300) is a basal insulin that provides the same number of units as Gla-100 in a third of the volume. Compared with Gla-100, Gla-300 has shown more constant and prolonged pharmacokinetic (PK)/pharmacodynamic (PD) profiles. This review summarizes the findings from the EDITION series of clinical trials that investigated Gla-300 in individuals with type 1 and type 2 diabetes mellitus. Overall, Gla-300 has been shown to achieve similar glycaemic control with less, or similar, nocturnal hypoglycaemia compared with Gla-100, and a trend towards lower hypoglycaemia at any time of day. The EDITION series of clinical trials also provides some evidence for less weight gain with Gla-300 than with Gla-100. In addition, the PK/PD profiles of Gla-300 may allow more flexibility in the timing of doses, improving convenience; thus, Gla-300 could offer several positive features for individuals with diabetes requiring basal insulin therapy.

Topics: Administration, Oral; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Compounding; Drug Therapy, Combination; Evidence-Based Medicine; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin Glargine; Randomized Controlled Trials as Topic; Weight Gain

GLP-1 receptors agonists have been a substantial change in treatment of type 2 diabetes mellitus, and its weekly administration has broken pre-established schemes. Daily exenatide is administered every 12 hours (BID) subcutaneously, while weekly exenatide is administered once a week. Both molecules share a common mechanism of action but have differential effects on basal and postprandial glucose. We review the major clinical trials with both exenatide BID and weekly exenatide. It can be concluded that exenatide BID shows a hypoglycemic effect similar to other treatments for type 2 DM but adding significant weight loss with low incidence of hypoglycemia. Weekly exenatide decreases HbA1c similar to liraglutide but larger than exenatide BID, both glargine and biphasic insulin, sitagliptin, and pioglitazone, maintaining weight loss and adding to gastrointestinal intolerance the induration at the injection site as a side effect.

Topics: Delayed-Action Preparations; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Administration Schedule; Exenatide; Female; Gastrointestinal Diseases; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incretins; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin, Long-Acting; Liraglutide; Male; Metformin; Peptides; Pioglitazone; Receptors, Glucagon; Thiazolidinediones; Venoms; Weight Loss

Type 2 diabetes mellitus and malignant tumors are frequent diseases worldwide. The incidence of these two diseases is growing continuously and causes serious health care problem. Population based epidemiologic studies show that the coexistence of type 2 diabetes and malignant tumors is more frequent than expected by the age-corrected incidence and prevalence of each disease. Epidemiologic studies and meta-analyses show that type 2 diabetes increases the risk and tumor specific mortality of certain cancers. The overlapping risk factors of the diseases suggest a relationship between type 2 diabetes and malignant tumors, with a significant role of obesity as a major risk factor. In the pathophysiology of type 2 diabetes there are several biological processes, which may explain the higher cancer risk in type 2 diabetes. In vitro experiments, and in vivo animal studies show that the mitotic effect of hyperinsulinemia plays an important role in the relationship of cancer and type 2 diabetes mellitus. Recent studies show that the different treatment modalities, antidiabetic drugs and their combinations used for the treatment of type 2 diabetes can modify cancer risk. The majority of the data show that metformin therapy decreases, while insulin secretagog drugs slightly increase the risk of certain types of cancers in type 2 diabetes. Metformin can decrease cell proliferation and induce apoptosis in certain cancer cell lines. Endogenous and exogenous (therapy induced) hyperinsulinemia may be mitogenic and may increase the risk of cancer in type 2 diabetes. Human studies showed that the analogue insulin glargin increases the risk of certain cancers. As a result of conceptual weaknesses in study design, data collection, and statistical methods the results of these studies are questionable. According to present knowledge, obtaining and maintaining optimal metabolic target values with the appropriate choice of treatment modality is the aim of treatment in type 2 diabetes. Presently, study results showing elevated mitogenic potential with some antidiabetic treatment modalities are not taken into account, when considering the choice of antidiabetic treatment in type 2 diabetic patients. In the care of patients with increased cancer risk, oncologic considerations should be taken into account. Well designed, prospective, clinical studies would be necessary to demonstrate the possible correlation between treatment modalities of type 2 diabetes and change of cancer risk in

Topics: Adipokines; Age Factors; Animals; Cytokines; Diabetes Complications; Diabetes Mellitus, Type 2; Feeding Behavior; Humans; Hyperglycemia; Hyperinsulinism; Hypoglycemic Agents; Incidence; Insulin; Insulin Glargine; Insulin Resistance; Insulin, Long-Acting; Metformin; Motor Activity; Neoplasms; Obesity; Prevalence; Research Design; Risk Factors; Sex Factors; Smoking; Sulfonylurea Compounds; Thiazolidinediones

The treatment of type 2 diabetes mellitus (T2DM) has been revolutionized by the introduction of novel therapeutic regimens following the clinical approval of the long-acting basal insulin glargine 10 years ago, followed by insulin detemir and, more recently, agents that target the glucagon-like peptide (GLP)-1 system with dipeptidyl peptidase 4 (DPP-4)-resistant products, such as liraglutide and exenatide, and DPP-4 inhibitors, such as sitagliptin, saxagliptin, alogliptin, and vildagliptin. The position and clinical efficacy of the GLP-1 mimetics are less well understood, however, and how they should be best used in the context of the established clinical efficacy of long-acting insulin analogs is yet to be defined. The aim of this review is to provide a summary of the efficacy, safety, and weight changes associated with long-acting insulin analogs (insulin glargine and insulin detemir) and two GLP-1 mimetics (exenatide and liraglutide). MEDLINE, EMBASE, and BIOSIS databases were searched with a timeframe of January 1, 2003-January 12, 2009 using the following terms: "Insulin glargine," with the co-indexing terms "LANTUS" and "HOE901"; "Insulin detemir," with the co-indexing term "Levemir"; "Exenatide"; and "Liraglutide." This literature review demonstrates that GLP-1 and basal insulin therapies are effective treatment options for insulin-naïve patients with suboptimal glycemic control with oral hypoglycemic agents. There are potential advantages of basal insulin and GLP-1 therapies in particular populations of patients. Further comparative data are needed to fully investigate the relative positioning of these therapies within the T2DM treatment paradigm.

Topics: Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting

Topics: Algorithms; Blood Glucose; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Exenatide; Glucagon-Like Peptide 1; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Liraglutide; Peptides; Postprandial Period; Pyrazines; Risk Factors; Sitagliptin Phosphate; Triazoles; Venoms

The burden of type 2 diabetes mellitus will become even greater in coming decades as more young people present with the disease and patients live longer with the devastating complications of chronic hyperglycemia. Conventional and largely ineffectual treatment strategies consisting of lifestyle measures and long-term oral therapy are being challenged by studies showing that the early addition of insulin to oral agents can significantly improve glycemic control in patients with type 2 diabetes. Further, 2 recent randomized, controlled trials support the clinical utility of supplementing oral pharmacotherapy with once-daily insulin glargine to achieve and maintain target glycosylated hemoglobin levels < or =7%. This simple treat-to-target strategy may be readily adopted in general practice through a widely translatable algorithm moving from oral pharmacotherapy to early addition of basal insulin glargine if glycemic targets are not met. The once-daily flexible dosing of insulin glargine and its smooth, flat profile, associated with fewer episodes of nocturnal hypoglycemia, make it among the safest and most practical tools to date for transforming the paradigm of type 2 diabetes management.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting

Topics: Blood Glucose Self-Monitoring; Circadian Rhythm; Diabetes Complications; Dose-Response Relationship, Drug; Glucagon; Human Growth Hormone; Humans; Hydrocortisone; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Metformin; Somatomedins; Time Factors

The role of metabolic control following acute myocardial infarction, (AMI) is still subject of study to date. The only study performed in diabetic patients with an AMI is the DIGAMI which demonstrated that endovenous insulin therapy in the acute phase, followed by multiple subcutaneous administrations of insulin therapy in the follow-up, was able to obtain not only a better metabolic control in both the acute phase and in the follow-up, but also a better survival only in the follow-up. Even if this latter fact is disappointing, endovenous insulin infusion seems to be the best approach to effectively contrast the metabolic events secondary to hyperglycemia which accompany AMI. From the DIGAMI study derives the indication of multiple insulin injections in diabetic patients having survived an AMI, even if doubt still exists as to whether it is the insulin therapy in itself or rather the metabolic compensation obtained that is responsible for a better survival rate. There is no controversy regarding the use of multiple (3 but above all 4/day) subcutaneous rapid insulin administrations at meal time and retard insulin administrations at bed time. Over the last few years ultrarapid insulin has become available as well the newcomer glargine, a retard insulin, which presents a homogeneous 24 hour release pattern. These insulin forms, obtained by genetic engineering, allow for a 4 daily dose administration, ultrarapid at meal times and glargine once daily, which mimic a more physiological insulin secretion and as such probably render them more efficacious. When oral drugs are opted for, it is imperative to have acquaintance with their half-lives, bonding properties with K(+)(ATP) channels, the antioxidant and antithromobophylic properties. It is necessary to modulate their use considering the glycemic daily rhythm in diabetics (glycemia tending to be high in the early morning and low in the evening). In order to obtain an optimal metabolic control it is essential to have the patient perform a glycemia level self-assessment by means of portable measuring instruments which employ instantaneous reactive strips. Self-assessment is imperative for the prevention of hypoglycemic episodes considered particularly dangerous in diabetic patients with coronary heart disease, even if studies which have demonstrated and documented this danger do not exist.

Topics: Administration, Oral; Coronary Disease; Delayed-Action Preparations; Diabetes Complications; Diabetes Mellitus; Diabetic Angiopathies; Drug Administration Schedule; Glyburide; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Prognosis; Randomized Controlled Trials as Topic

Topics: Animals; Blood Glucose; Diabetes Mellitus; Dogs; Humans; Hyperglycemia; Hypoglycemia; Insulin; Insulin Aspart; Insulin Glargine; Insulin Lispro; Insulin, Isophane; Insulin, Long-Acting; Swine; Time Factors

To determine the effectiveness and safety of early combination of insulin glargine with intravenous (IV) insulin infusion compared with IV insulin infusion alone in the management of diabetic ketoacidosis (DKA).. This was a single-centre, open-label, randomized controlled trial of adults aged 18 years or older diagnosed with DKA. The 'early glargine' group was given subcutaneous insulin glargine 0.3 units/kg within the first 3 hours of DKA diagnosis, in addition to the standard IV insulin infusion. The control group received standard IV insulin treatment only. The primary outcome was the time to DKA resolution. The other outcomes included rebound hyperglycaemia, mortality, hypoglycaemia and hypokalaemia, as well as the length of hospital stay (LOS).. A total of 60 patients (30 patients per group) were enrolled. Most patients (76.7%) had type 2 diabetes. Both groups were similar in baseline characteristics, except for higher serum beta-hydroxybutyrate and lower pH levels in the early glargine group. The mean ± standard deviation time to DKA resolution in the early glargine group was significantly faster than the control group (9.89 ± 3.81 vs. 12.73 ± 5.37 hours; P = .022). The median (interquartile range) LOS was significantly shorter in the early glargine group than in the control group (4.75 [3.53-8.96] vs. 15.25 [5.71-26.38] days; P = .024). The incidence of rebound hyperglycaemia, all-cause mortality, hypoglycaemia and hypokalaemia was similar between the groups.. Early combination of insulin glargine with IV insulin infusion led to a faster DKA resolution and a shorter LOS, without increasing hypoglycaemia and hypokalaemia.

Topics: Adult; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Hypokalemia; Insulin; Insulin Glargine; Insulin, Regular, Human

We investigated the pathophysiology of the dawn phenomenon by examining the effects of changes in blood glucose levels from late night to early morning on various hormones in a group taking glargine BS and a group taking Lantus XR, with the goal of achieving better glycemic control. Patients with types 1 and 2 diabetes scheduled for inpatient education were divided into BS and XR groups. Blood glucose levels were tracked from 0:00 to 7:00, while blood samples were extracted at 3:00 and 7:00 to measure glucose levels and hormones related to the dawn phenomenon. Overall, we analyzed blood sample and intermittently scanned Continuous Glucose Monitoring data of 43 and 40 patients, respectively. From 0:00 to 7:00, the mean blood glucose was significantly lower in the BS group, although the fluctuation was similar (p < 0.0001). The BS group also exhibited significantly higher ∆ACTH (p = 0.0215) and ∆ cortisol (p = 0.0430) than the XR group. In the BS group, ∆Glu exhibited a significant negative correlation with ∆ACTH and ∆cortisol (p = 0.0491). Similar findings were not observed in the XR group. These results suggest that XR may be a better choice for long-acting insulin since it is less likely to induce cortisol secretion. Further, analysis of the dawn phenomenon and non-dawn phenomenon groups showed the mean CPR levels at 3:00 and 7:00 were significantly higher in the latter (p = 0.0135). This supports the conventional belief that appropriate basal insulin replacement therapy is a beneficial treatment for the dawn phenomenon.

Topics: Biosimilar Pharmaceuticals; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Humans; Hydrocortisone; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine

To aim of this analysis was to investigate the extent and evaluate risk factors of residual hyperglycaemia in Chinese individuals with type 2 diabetes (T2D) initiating basal insulin.. FPG GOAL was a 24-week, open-label, treat-to-target randomised controlled trial in Chinese individuals with T2D inadequately controlled with oral anti-hyperglycaemic drugs initiating treatment with basal insulin. This analysis categorised participants into the following glycaemic control categories: hyperglycaemia [glycated haemoglobin (HbA1c) ≥ 53 mmol/mol (≥ 7%), fasting plasma glucose (FPG) ≥ 7.0 mmol/L], residual hyperglycaemia [HbA1c ≥ 53 mmol/mol (≥ 7%), FPG < 7.0 mmol/L], discordant [HbA1c < 53 mmol/mol (< 7%), FPG ≥ 7.0 mmol/L] and at target [HbA1c < 53 mmol/mol (< 7%), FPG < 7.0 mmol/L]. The proportion of participants in each glycaemic control category was assessed at weeks 12 and 24. Multivariable regression analyses were conducted to evaluate risk factors for residual hyperglycaemia.. Of the 914 participants included, 22.1% had residual hyperglycaemia, 31.9% had hyperglycaemia, 11.1% were discordant and 29.3% were at target at week 24. More participants who were randomised to a fasting blood glucose (FBG) target of > 3.9 to ≤ 5.6 mmol/L had residual hyperglycaemia compared with participants randomised to a FBG target of > 3.9 to ≤ 6.1 mmol/L or > 3.9 to ≤ 7.0 mmol/L. Multivariable analysis indicated that higher HbA1c and lower FPG levels at baseline were associated with greater proportion of residual hyperglycaemia.. Some Chinese individuals with T2D may have residual hyperglycaemia 3-6 months after initiating basal insulin treatment and require further intensified treatment. Higher HbA1c and lower FPG levels could be risk factors for residual hyperglycaemia.. ClinicalTrials.gov identifier NCT02545842.

Topics: Blood Glucose; China; Diabetes Mellitus, Type 2; Disease Progression; Fasting; Glycated Hemoglobin; Glycemic Control; Goals; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin Glargine; Risk Factors

Administration of supplemental sliding scale insulin for correction of hyperglycemia in non-intensive care unit (ICU) patients with type 2 diabetes is frequently used with basal-bolus insulin regimens. In this noninferiority randomized controlled trial we tested whether glycemic control is similar with and without aggressive sliding scale insulin treatment before meals and bedtime in patients treated with basal-bolus insulin regimens.. Patients with type 2 diabetes with admission blood glucose (BG) 140-400 mg/dL treated with basal-bolus insulin were randomized to intensive (correction for BG >140 mg/dL, n = 108) or to nonintensive (correction for BG >260 mg/dL, n = 107) administration of rapid-acting sliding scale insulin before meals and bedtime. The groups received the same amount of sliding scale insulin for BG >260 mg/dL. Primary outcome was difference in mean daily BG levels between the groups during hospitalization.. Mean daily BG in the nonintensive group was noninferior to BG in the intensive group with equivalence margin of 18 mg/dL (intensive 172 ± 38 mg/dL vs. nonintensive 173 ± 43 mg/dL, P = 0.001 for noninferiority). There were no differences in the proportion of target BG readings of 70-180 mg/dL, <70 or <54 mg/dL (hypoglycemia), or >350 mg/dL (severe hyperglycemia) or total, basal, or prandial insulin doses. Significantly fewer subjects received sliding scale insulin in the nonintensive (n = 36 [34%]) compared with the intensive (n = 98 [91%] [P < 0.0001]) group with no differences in sliding scale insulin doses between the groups among those who received sliding scale insulin (intensive 7 ± 4 units/day vs. nonintensive 8 ± 4 units/day, P = 0.34).. Among non-ICU patients with type 2 diabetes on optimal basal-bolus insulin regimen with moderate hyperglycemia (BG <260 mg/dL), a less intensive sliding scale insulin treatment did not significantly affect glycemic control.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Regular, Human

To compare the benefits of iGlarLixi, a fixed-ratio combination of insulin glargine 100 U/mL and lixisenatide (iGlarLixi), with insulin glargine (iGlar) for reducing residual hyperglycaemia (defined as HbA1c ≥ 7% despite fasting plasma glucose [FPG] < 130 mg/dL) in Japanese people with type 2 diabetes (T2D) inadequately controlled on oral antidiabetic drugs.. The open-label LixiLan JP-O2 study compared iGlarLixi with iGlar over 26 weeks in 521 people with T2D. This post hoc analysis assessed the proportions of participants with residual hyperglycaemia in the overall population, and in subgroups defined by age and dipeptidyl peptidase-4 inhibitor (DPP4i) use at screening.. At 26 weeks, significantly fewer participants had residual hyperglycaemia in the iGlarLixi versus the iGlar arm (8.1% vs. 19.6%; P = .0002). There was also less residual hyperglycaemia with iGlarLixi than iGlar in all subgroup analyses: 9.0% versus 16.8% in participants aged younger than 65 years (P = .0369); 6.5% versus 24.2% in participants aged 65 years or older (P = .0008); 10.1% versus 20.5% (P = .0202) in participants with DPP4i use; and 6.2% versus 18.8% in those without DPP4i use (P = .0024). The proportion reaching both HbA1c less than 7% and FPG less than 130 mg/dL was higher with iGlarLixi versus iGlar in the overall population (50.8% vs. 31.5%; P < .0001), and in all studied subgroups.. iGlarLixi reduced the prevalence of residual hyperglycaemia in Japanese people with uncontrolled T2D compared with iGlar, both in the overall population and in subgroups defined by age and DPP4i use at screening.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Drug Combinations; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin Glargine; Japan; Peptides

To determine whether basal-bolus administration of glargine insulin is a safe and effective alternative treatment compared to the standard continuous rate infusion (CRI) protocol.. Prospective randomized clinical trial.. University teaching hospital.. Twenty cats diagnosed with diabetic ketoacidosis (DKA).. The cats were block-randomized to either a CRI protocol using regular insulin (CRI-group; n = 10) or a basal-bolus SC and IM glargine protocol (glargine-group, n = 10). Baseline blood gases, electrolytes, glucose, and β-hydroxybutyrate (β-OHB) concentrations were measured at the time of admission and later at predefined intervals until reaching the primary endpoint of the study, defined as a β-hydroxybutyrate concentration < 2.55 mmol/L.. The main outcome measure was time (h) to resolution of ketonemia. Secondary outcome measures were time until first improvement of hyperglycemia and ketonemia, decrease of glucose to ≤13.9 mmol/L (250 mg/dL), resolution of acidosis, consumption of first meal, and discharge from hospital. Additionally, occurrence of treatment-associated adverse events and death were compared. Seventeen cats (85%) survived to discharge, with no difference in survival between groups (P = 1.0). Median times to β-OHB < 2.55 mmol/L were 42 (CRI-group) and 30 (glargine-group) hours, respectively (P = 0.114). Median times to first improvement of hyperglycemia (glargine-group: 2 h; CRI-group: 6 h; P = 0.018) and until discharge from hospital (glargine-group: 140 h; CRI-group: 174 h; P = 0.033) were significantly shorter in the glargine-group. No significant differences were observed in any other parameter under investigation (P > 0.05).. Basal-bolus administration of glargine insulin appears to be an effective and safe alternative to the current standard CRI-protocol for the management of DKA in cats. The positive outcomes and simplicity make it a viable option for the treatment of feline DKA.

Topics: Animals; Blood Glucose; Cat Diseases; Cats; Clinical Trials, Veterinary as Topic; Diabetic Ketoacidosis; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Prospective Studies

Treatments for type 2 diabetes targeting baseline glucose levels but not postprandial glucose can result in normalized fasting blood glucose but suboptimal overall glycemic control (high glycated hemoglobin): residual hyperglycemia. In Japanese patients with type 2 diabetes the predominant pathophysiology is a lower insulin secretory capacity, and residual hyperglycemia is common with basal insulin treatment. Single-injection, fixed-ratio combinations of glucagon-like peptide-1 receptor agonists and basal insulin have been developed. iGlarLixi (insulin glargine 100 units/mL [iGlar]: lixisenatide ratio of 1 unit:1 µg) is for specific use in Japan. Post-hoc analysis of the LixiLan JP-L trial (NCT02752412) compared the effect of iGlarLixi with iGlar on this specific subpopulation with residual hyperglycemia.. Outcomes at week 26 (based on the last observation carried forward) were assessed in patients in the modified intent-to-treat population with baseline residual hyperglycemia.. Overall, 83 (32.5%) patients in the iGlarLixi group and 79 (30.7%) patients in the iGlar group had baseline residual hyperglycemia. The proportion of patients with residual hyperglycemia at week 26 decreased to 15.7% in the iGlarLixi group, and increased to 36.9% in the iGlar group. Patients in the iGlarLixi group had significantly greater reductions in glycated hemoglobin compared with the iGlar group (-0.72% difference between groups; P < 0.0001).. New data from this post-hoc analysis of the JP-L trial show that treatment with the fixed-ratio combination iGlarLixi reduced the proportion of Japanese patients with residual hyperglycemia from baseline to week 26 and significantly reduced glycated hemoglobin vs similar doses of iGlar alone.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Drug Combinations; Female; Glycated Hemoglobin; Glycemic Control; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin Glargine; Insulins; Japan; Male; Middle Aged; Peptides; Treatment Outcome

Globally, nearly half of patients with type 2 diabetes (T2D) do not successfully achieve target HbA1c with basal insulin, despite meeting fasting plasma glucose (FPG) targets. In this post hoc analysis of the LixiLan-L study, we determined whether iGlarLixi, a fixed-ratio combination of insulin glargine Gla-100 (iGlar) and the glucagon-like peptide-1 receptor agonist lixisenatide (Lixi), addresses the challenge of reducing residual hyperglycaemia in patients with T2D. In LixiLan-L, a randomized, open-label study, 1018 patients with T2D on basal insulin for ≥6 months ± oral antidiabetes drugs entered a 6-week run-in period, during which they were switched to and/or optimized for a daily dose of iGlar while continuing only metformin. Following the run-in period, 736 patients were then randomized to receive iGlarLixi or were continued on iGlar for 30 weeks ± metformin. Residual hyperglycaemia was defined as HbA1c ≥ 7.0% despite FPG of <140 mg/dL. The proportion of patients with residual hyperglycaemia was similar in both treatment arms at screening (~~42%), and increased after the run-in period (~~62%). After 30 weeks, the proportion of patients with residual hyperglycaemia declined to 23.8% in the iGlarLixi versus 47.1% in the iGlar arm (P < .0001). The proportion of patients achieving both HbA1c (<7.0%) and FPG (<140 mg/dL) targets was higher in the iGlarLixi compared with the iGlar arm (50.3% vs. 27.4%, respectively; P < .0001). iGlarLixi effectively reduces residual hyperglycaemia in patients with T2D on basal insulin therapy.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Drug Combinations; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin Glargine

To compare efficacy and safety of insulin glargine 300 units/mL (Gla-300) and 100 units/mL (Gla-100) in children and adolescents (6-17 years old) with type 1 diabetes.. EDITION JUNIOR was a noninferiority, international, open-label, two-arm, parallel-group, phase 3b trial. Participants were randomized 1:1 to Gla-300 or Gla-100, titrated to achieve fasting self-monitored plasma glucose levels of 90-130 mg/dL (5.0-7.2 mmol/L), with continuation of prior prandial insulin. The primary end point was change in HbA. Gla-300 provided similar glycemic control and safety profiles to Gla-100 in children and adolescents with type 1 diabetes, indicating that Gla-300 is a suitable therapeutic option in this population.

Topics: Adolescent; Blood Glucose; Child; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Equivalence Trials as Topic; Fasting; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin Glargine; Male

Topics: Anti-Obesity Agents; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Drug Combinations; Drug Monitoring; Drug Resistance, Multiple; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incretins; Insulin Glargine; Insulin, Long-Acting; Liraglutide; Metformin; Obesity; Overweight; Weight Gain; Weight Loss

Insulin glargine 300 U/mL (Gla-300) offers a flatter pharmacodynamic profile than insulin glargine 100 U/mL (Gla-100). We have compared these insulins over 1 year in people with type 1 diabetes (T1DM).. EDITION 4 was a 6-month, multicentre, randomized, open-label phase 3 study. People with T1DM who completed the 6 months continued randomized Gla-300 or Gla-100 once daily, morning or evening, for a further 6 months.. Among 549 participants randomized, 444 completed the 12-month study period (Gla-300, 80%; Gla-100, 82%). Mean HbA1c decreased similarly from baseline to month 12 in the 2 treatment groups (difference, 0.02 [95% CI, -0.13 to 0.17]) %-units [0.2 (-1.5 to 1.9) mmol/mol]), to a mean of 7.86 %-units (62.4 mmol/mol) in both groups. For morning vs evening injection, there was no difference in HbA1c change over 12 months for Gla-100, but a significantly larger decrease in HbA1c was observed in the Gla-300 morning group than in the Gla-300 evening group (difference, -0.25 [-0.47 to -0.04] %-units [-2.7 (-5.2 to -0.4) mmol/mol]). Mean glucose from the 8-point SMPG profiles decreased from baseline, and was similar between the 2 treatment groups. Basal insulin dose was 20% higher with Gla-300 than with Gla-100, while hypoglycaemia event rates, analysed at night, over 24 hours, or according to different glycaemic thresholds, did not differ between treatment groups, regardless of injection time. Adverse event profiles did not differ between groups.. In T1DM, Gla-300 provides glucose control comparable to that of Gla-100, and can be given at any time of day.

Topics: Activities of Daily Living; Adult; Blood Glucose Self-Monitoring; Body Mass Index; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Compounding; Drug Monitoring; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Insulin Glargine; Intention to Treat Analysis; Male; Middle Aged; Osmolar Concentration; Overweight; Patient Dropouts; Quality of Life; Severity of Illness Index; Weight Gain

In this post hoc analysis we compared glycaemic control and hypoglycaemia between insulin glargine 300 U/mL (Gla-300) and glargine 100 U/mL (Gla-100) administered once daily in people with type 2 diabetes (T2DM) from the EDITION 1 (basal plus mealtime insulin) and EDITION 2 (basal insulin plus oral antihyperglycaemic drugs) trials who were previously receiving twice-daily insulin. At randomization, 16.9% and 20.0% of people in EDITION 1 and 2, respectively, were receiving twice-daily basal insulin. Glycated haemoglobin change from baseline to Month 6 was similar over 6 months with Gla-300 or Gla-100 (least squares mean difference -0.01%; 95% confidence interval [CI] -0.27 to 0.24] in EDITION 1 and 0.16%; 95% CI -0.25 to 0.57, in EDITION 2). Participants previously receiving twice-daily insulin in EDITION 1 had a lower risk of confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia with Gla-300 vs Gla-100 at night (00:00-05:59 hours), but not at any time (24 hours); in EDITION 2 the risk was reduced at night and any time (24 hours). In conclusion, Gla-300 provided similar glycaemic control with less hypoglycaemia compared with Gla-100 in people with T2DM switching from twice-daily to once-daily basal insulin.

Topics: Administration, Oral; Adult; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Compounding; Drug Monitoring; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin Glargine; Intention to Treat Analysis; Osmolar Concentration; Severity of Illness Index

MK-1293 is an insulin glargine that has an amino acid sequence identical to that of Lantus, the originator insulin glargine. Two euglycaemic clamp studies, 1 in subjects with type 1 diabetes (T1D) and 1 in healthy subjects, were conducted to demonstrate pharmacokinetic (PK) and pharmacodynamic (PD) similarity between MK-1293 and Lantus commercially procured in both the European Union (EU-Lantus) and the USA (US-Lantus).. Both studies were single-dose, randomized, double-blind, single-centre, crossover studies with ≥7 days between dosing periods. A 2-treatment, 4-period replicate crossover study in T1D subjects (N = 76) compared the PK and PD of MK-1293 to EU-Lantus for 30 hours after dosing. A 3-period crossover study in healthy subjects (N = 109) compared the PK and PD of MK-1293, EU-Lantus and US-Lantus for 24 hours after dosing. In both studies, all subjects received single 0.4 units/kg subcutaneous doses of MK-1293 or Lantus in all dosing periods. Pharmacokinetic assessment was based on LC-MS/MS-based measurement of the major insulin glargine metabolite (M1) and PD was characterized using the euglycaemic clamp platform.. In both studies, pre-specified similarity criteria were met between MK-1293 and Lantus for comparison of PK (AUC. Based on comparative assessment in both T1D and healthy subjects, it can be concluded that the PK and PD properties of MK-1293 are highly similar to those of Lantus. (ClinicalTrials.gov: NCT02059174).

Topics: Adult; Biosimilar Pharmaceuticals; Biotransformation; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Double-Blind Method; European Union; Female; Glucose Clamp Technique; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Male; Patient Dropouts; United States; Young Adult

To test the hypothesis that, as well as lowering weight and increasing plasma triglyceride (TG) levels and hepatic fat compared with insulin glargine (GL) in patients with type 1 diabetes, the attenuated peripheral effects of basal insulin peglispro (BIL) may include increased free fatty acid flux to the liver, causing increased very-low-density lipoprotein (VLDL)-TG secretion and lipid oxidation, and decreased TG adipose tissue deposition.. In this open-label, randomized, 2-period crossover study, 14 patients with type 1 diabetes received once-daily, individualized, stable BIL or GL doses for 3 weeks. Palmitate flux was assessed using [9,10-. The VLDL-TG concentration and secretion rate, and palmitate flux were statistically significantly higher during BIL than during GL treatment (58%, 51% and 35%, respectively). The ratios of least squares (LS) geometric means for VLDL-TG clearance and oxidation were 0.92 (95% confidence interval [CI] 0.72, 1.17) and 1.31 (95% CI 0.91, 1.90), respectively. The difference in LS means for VLDL-TG storage rate was -0.36 (95% CI -0.83, 0.12).. BIL-treated patients had higher effective lipolysis, VLDL-TG secretion and VLDL-TG concentration compared with GL-treated patients, explaining the increased plasma TG concentrations reported previously. Data support attenuated effects of BIL on lipolysis, in addition to the recently described hepato-preferential glucodynamic effects.

Topics: Adult; Cross-Over Studies; Diabetes Mellitus, Type 1; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Hyperglycemia; Hypertriglyceridemia; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin Lispro; Lipolysis; Lipoproteins, VLDL; Male; Middle Aged; Polyethylene Glycols; Triglycerides; Young Adult

To evaluate the glycaemic control achieved by prandial once-daily insulin glulisine injection timing adjustment, based on a continuous glucose monitoring sensor, in comparison to once-daily insulin glulisine injection before breakfast in patients with type 2 diabetes who are uncontrolled with once-daily basal insulin glargine.. This was a 24-week open-label, randomized, controlled, multicentre trial. At the end of an 8-week period of basal insulin optimization, patients with HbA1c ≥ 7.5% and FPG < 130 mg/dL were randomized (1:1) to either arm A (no sensor) or arm B (sensor) to receive 16-week intensified prandial glulisine treatment. Patients in arm A received pre-breakfast glulisine, and patients in arm B received glulisine before the meal with the highest glucose elevation based on sensor data. The primary outcome was mean HbA1c at week 24 and secondary outcomes included rates of hypoglycaemic events and insulin dosage.. A total of 121 patients were randomized to arm A (n = 61) or arm B (n = 60). There was no difference in mean HbA1c at week 24 between arms A and B (8.5% ± 1.2% vs 8.4% ± 1.0%; P = .66). The prandial insulin glulisine dosage for arm A and arm B was 9.3 and 10.1 units, respectively (P = .39). The frequency of hypoglycaemic events did not differ between study arms (36.1% vs 51.7%; P = .08).. Using a CGM sensor to identify the meal with the highest glucose excursion and adjusting the timing of prandial insulin treatment did not show any advantage in terms of glycaemic control or safety in our patients.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Monitoring; Drug Therapy, Combination; Female; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Resistance; Intention to Treat Analysis; Lost to Follow-Up; Male; Meals; Middle Aged; Monitoring, Ambulatory; Patient Dropouts; Pilot Projects

To compare the efficacy and safety of adding the glucagon-like peptide-1 receptor agonist exenatide once weekly (QW) 2 mg or placebo among patients with type 2 diabetes who were inadequately controlled despite titrated insulin glargine (IG) ± metformin.. This multicentre, double-blind study (ClinicalTrials.gov identifier: NCT02229383) randomized (1:1) patients with persistent hyperglycaemia after an 8-week titration phase (glycated haemoglobin [HbA1c] 7.0%-10.5% [53-91 mmol/mol]) to exenatide QW or placebo. The primary endpoint was HbA1c change from baseline to week 28. Secondary endpoints included body weight, 2-hour postprandial glucose, and mean daily IG dose.. Of 464 randomized patients (mean: age, 58 years; HbA1c, 8.5% [69 mmol/mol]; diabetes duration, 11.3 years), 91% completed 28 weeks. Exenatide QW + IG vs placebo + IG significantly reduced HbA1c (least-squares mean difference, -0.73% [-8.0 mmol/mol]; 95% confidence interval, -0.93%, -0.53% [-10.2, -5.8 mmol/mol]; P < .001; final HbA1c, 7.55% [59 mmol/mol] and 8.24% [67 mmol/mol], respectively); body weight (-1.50 kg; -2.17, -0.84; P < .001); and 2-hour postprandial glucose (-1.52 mmol/L [-27.5 mg/dL]; -2.15, -0.90 [-38.7, -16.2]; P < .001). Significantly more exenatide QW + IG-treated patients vs placebo + IG-treated patients reached HbA1c <7.0% (<53 mmol/mol) (32.5% vs 7.4%; P < .001); daily IG dose increased by 2 and 4 units, respectively. Gastrointestinal and injection-site adverse events were more frequent with exenatide QW + IG (15.1% and 7.8%, respectively) than with placebo + IG (10.8% and 3.0%, respectively); hypoglycaemia incidence was similar between the exenatide QW + IG (29.7%) and placebo + IG (29.0%) groups, with no major hypoglycaemic events.. Among patients with inadequate glycaemic control, exenatide QW significantly improved glucose control and decreased body weight, without increased hypoglycaemia or unexpected safety findings.

Topics: Aged; Body Mass Index; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Administration Schedule; Drug Monitoring; Drug Therapy, Combination; Exenatide; Female; Follow-Up Studies; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incretins; Insulin Glargine; Male; Middle Aged; Obesity; Weight Loss

To test the safety and efficacy of MYL-1501D, a proposed insulin glargine biosimilar, in patients with type 1 diabetes mellitus (T1DM).. The safety and efficacy of MYL-1501D and reference insulin glargine were evaluated in INSTRIDE 1, a 52-week, open-label, randomized, phase III study in patients with T1DM. The primary objective was to determine whether once-daily MYL-1501D was non-inferior to once-daily insulin glargine when administered in combination with mealtime insulin lispro based on change in glycated haemoglobin (HbA1c) from baseline to week 24. Secondary endpoints were changes in fasting plasma glucose, insulin dose, self-monitored blood glucose and immunogenicity from baseline, and occurrences of hypoglycaemic, nocturnal hypoglycaemic and adverse events up to week 52.. Overall, 558 patients were randomized 1:1 to MYL-1501D or reference insulin glargine in combination with thrice-daily mealtime insulin lispro for 52 weeks. The mean change in HbA1c from baseline to week 24 was 0.14% (standard error [SE] 0.054; 95% confidence interval [CI] 0.033, 0.244) for MYL-1501D and 0.11% (SE 0.054; 95% CI 0.007, 0.220) for reference insulin glargine. MYL-1501D had a safety profile similar to that of reference insulin glargine and was well tolerated in patients with T1DM up to week 52.. The upper 95% CI limit for mean change in HbA1c at week 24 indicated that MYL-1501D was non-inferior to reference insulin glargine. There were no clinically meaningful differences between groups in incidence of overall and nocturnal hypoglycaemia, local or systemic reactions, safety or immunogenicity.

Topics: Activities of Daily Living; Biosimilar Pharmaceuticals; Blood Glucose; Blood Glucose Self-Monitoring; Body Mass Index; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin Glargine; Insulin Lispro; Meals; Overweight; Severity of Illness Index

To evaluate the pharmacodynamics of lixisenatide once daily vs sitagliptin once daily in Japanese patients with type 2 diabetes receiving insulin glargine U100.. This multicentre, open-label, phase IV study (NEXTAGE Study; ClinicalTrials.gov number, NCT02200991) randomly assigned 136 patients to either lixisenatide once daily via subcutaneous injection (10 µg initially increased weekly by 5 up to 20 µg) or once-daily oral sitagliptin 50 mg. The primary endpoint was the change in postprandial glucose (PPG) exposure 4 hours after a standardized breakfast (PPG area under the plasma glucose concentration-time curve [AUC. Lixisenatide reduced PPG significantly more than sitagliptin, when these agents were added to basal insulin glargine U100, and was well tolerated.

Topics: Administration, Oral; Aged; Biomarkers; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Resistance; Drug Therapy, Combination; Female; Follow-Up Studies; Gastric Emptying; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin Glargine; Japan; Male; Middle Aged; Peptides; Postprandial Period; Sitagliptin Phosphate

Topics: Body Mass Index; Diabetes Mellitus, Type 2; Disease Progression; Drug Combinations; Drug Resistance; Drug Therapy, Combination; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Insulin Glargine; Middle Aged; Obesity; Peptides; Postprandial Period; Weight Gain

To compare insulin glargine 300 U/mL (Gla-300) with glargine 100 U/mL (Gla-100) in Japanese adults with uncontrolled type 2 diabetes on basal insulin and oral anti-hyperglycaemic drugs over 12 months.. EDITION JP 2 was a randomised, open-label, phase 3 study. Following a 6-month treatment period, participants continued receiving previously assigned once daily Gla-300 or Gla-100, plus oral anti-hyperglycaemic drugs, in a 6-month extension period. Glycaemic control, hypoglycaemia and adverse events were assessed.. Over 12 months, Gla-300-treated participants achieved sustained glycaemic control and experienced less hypoglycaemia, particularly at night, versus Gla-100, supporting 6-month results.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Japan; Male; Middle Aged; Treatment Outcome

To determine whether previously reported reductions in hypoglycemia associated with insulin glargine 300 U/mL (Gla-300) compared with insulin glargine 100 U/mL (Gla-100) are impacted by patient risk category in type 2 diabetes (T2D), clinical performance measures based on the Healthcare Effectiveness Data and Information Set (HEDIS) were applied to patient-level data from the EDITION 2 and EDITION 3 clinical trials that compared Gla-300 and Gla-100.. In this post hoc analysis, patients were stratified as low risk (LR) if patients were <65 years old with no comorbidities derived from HEDIS (HbA1c target <7.0% [53 mmol/mol]), or as high risk (HR) if patients were either ≥65 years old or had one or more HEDIS-defined comorbidities (HbA1c target <8.0% [64 mmol/mol]). Primary endpoint was a composite of patients achieving HbA1c target without confirmed or severe hypoglycemia over 6 months in the different treatment groups in each of the EDITION trials.. There was a statistically nonsignificant trend of more patients treated with Gla-300 achieving the composite endpoint compared with Gla-100 in both the LR and HR patient cohorts, regardless of prior insulin experience. A similar trend was observed for the composite endpoint of HbA1c target without nocturnal hypoglycemia.. There is a consistent, nonsignificant trend suggesting that Gla-300 might reduce the burden of hypoglycemia compared with Gla-100 in patients with T2D irrespective of whether they are classed as LR or HR based on age- and National Committee for Quality Assurance Healthcare Effectiveness Data and Information Set-derived comorbidities.

Topics: Activities of Daily Living; Aged; Cohort Studies; Delayed-Action Preparations; Diabetes Complications; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Monitoring; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin Glargine; Middle Aged; Osmolar Concentration; Reproducibility of Results; Retrospective Studies; Risk; Severity of Illness Index; United States

We have previously reported that once-weekly albiglutide was noninferior to thrice-daily lispro for glycemic lowering, with decreased weight and risk of hypoglycemia, in patients inadequately controlled on basal insulin over 26 weeks. Findings after 52 weeks reveal similar responses to albiglutide as an add-on to insulin glargine.

Topics: Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Monitoring; Drug Resistance; Drug Therapy, Combination; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incidence; Incretins; Insulin Glargine; Insulin Lispro; Meals; Risk; Weight Gain; Weight Loss

Diabetes therapies that provide durable glycaemic control for people with type 2 diabetes mellitus (T2DM) are needed. We present efficacy results of albiglutide, a glucagon-like peptide-1 receptor agonist, in people with T2DM over a 3-year period.. Five of the 8 HARMONY phase 3 trials, comparing albiglutide with other therapies or placebo across a spectrum of clinical care, lasted for a preplanned 3years. Participants with uncontrolled hyperglycaemia who met predetermined criteria could receive rescue medication. The ability to remain on study medication without needing additional rescue was an efficacy measure. Glycaemic measures and body weight were analysed in 2 populations: those who remained rescue-free and all participants.. Participants (n=3132) were randomised to albiglutide or comparator. A greater proportion of participants who received albiglutide remained rescue-free (55-71%) compared with placebo (35-51%; p<0.001 to p=0.002). The proportion of rescue-free participants with albiglutide did not differ from glimepiride or insulin glargine, was higher than with sitagliptin (p=0.013), and lower than with pioglitazone (p=0.045). At 3years, albiglutide was associated with clinically significant reductions in hyperglycaemia (eg, rescue-free participants: HbA1c -0.52% [SE0.11] to -0.98% [0.12]; -5.7mmol/mol [1.2] to -10.7mmol/mol [1.3] and all participants: HbA1c -0.29% [0.11] to-0.92% [0.13]; -3.2mmol/mol [1.2] to -10.1mmol/mol [1.4]). Albiglutide was also associated with modest reductions in body weight vs pioglitazone, glimepiride, and insulin glargine, which were associated with weight gain.. These 3-year efficacy data support long-term use of albiglutide in the management of people with T2DM. ClinicalTrials.gov NCT00849056, NCT00849017, NCT00838903, NCT00838916, NCT00839527.

Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin Glargine; Male; Pioglitazone; Sitagliptin Phosphate; Sulfonylurea Compounds; Thiazolidinediones; Treatment Outcome

SAR342434 is a biosimilar follow-on of insulin lispro-Humalog. SORELLA-1 was a randomized, open-label phase 3 study (NCT02273180). Patients completing the 6-month main study continued on SAR-Lis or Ly-Lis, as randomized, for a 6-month safety extension. Assessments included change in HbA. Five hundred seven patients were randomized (SAR-Lis n = 253; Ly-Lis n = 254). Least square (LS) mean (SEM) change in glycosylated hemoglobin (HbA1c) (baseline to week 26; primary endpoint) was similar in both treatment groups (SAR-Lis: -0.42% [0.051]; Ly-Lis: -0.47% [0.050]). Noninferiority at prespecified 0.3% noninferiority margin and inverse noninferiority were demonstrated (LS mean difference of SAR-Lis vs. Ly-Lis: 0.06% [95% confidence interval: -0.084 to 0.197]). At week 52 (end of extension period) versus week 26, a small HbA1c increase was observed in both groups. FPG and seven-point SMPG profile changes, including postprandial glucose excursions, were similar between groups. At week 52, similar changes in mean daily mealtime and basal insulin doses were observed. Hypoglycemia, TEAEs, and AIAs (incidence, prevalence) did not differ between groups.. Results from this controlled study in patients with T1DM also using GLA-100 support similar efficacy and long-term safety (including immunogenicity) of SAR-Lis and Ly-Lis.

Topics: Adult; Autoantibodies; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Drug Administration Schedule; Drug Hypersensitivity; Drug Therapy, Combination; Equivalence Trials as Topic; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incidence; Injections, Subcutaneous; Insulin Glargine; Insulin Lispro; Intention to Treat Analysis; Patient Dropouts; Prevalence

To investigate whether sodium glucose co-transporter 2 inhibitors (SGLT2i), tofogliflozin or ipragliflozin, achieve optimal glycemic variability, when used together with insulin glargine 300 U/mL (Glargine 300). Thirty patients with type 2 diabetes were randomly allocated to 2 groups. For the first group: After admission, tofogliflozin 20 mg was administered; Fasting plasma glucose (FPG) levels were titrated using an algorithm and stabilized at 80 mg/dL level with Glargine 300 for 5 days; Next, glucose levels were continuously monitored for 2 days using continuous glucose monitoring (CGM); Tofogliflozin was then washed out over 5 days; Subsequently, ipragliflozin 50 mg was administered; FPG levels were titrated using the same algorithm and stabilized at 80 mg/dL level with Glargine 300 for 5 days; Next, glucose levels were continuously monitored for 2 days using CGM. For the second group, ipragliflozin was administered prior to tofogliflozin, and the same regimen was maintained. Glargine 300 and SGLT2i were administered at 8:00 AM. Data collected on the second day of measurement (mean amplitude of glycemic excursion [MAGE], average daily risk range [ADRR]; on all days of measurement) were analyzed. Area over the glucose curve (<70 mg/dL; 0:00 to 6:00, 24-h), M value, standard deviation, MAGE, ADRR, and mean glucose levels (24-h, 8:00 to 24:00) were significantly lower in patients on tofogliflozin than in those on ipragliflozin. Tofogliflozin, which reduces glycemic variability by preventing nocturnal hypoglycemia and decreasing postprandial glucose levels, is an ideal SGLT2i when used together with Glargine 300 during basal insulin therapy.

Topics: Activities of Daily Living; Aged; Benzhydryl Compounds; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glucosides; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Japan; Male; Membrane Transport Modulators; Middle Aged; Monitoring, Ambulatory; Risk; ROC Curve; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors; Thiophenes

Hyperglycemia is a major complication of parenteral nutrition (PN). Guidelines for hyperglycemia management in noncritically ill patients cite basal insulin administration but do not recommend a regimen. The GLUCOSE-in-PN study aimed to compare the efficacy of glargine insulin versus continuously infused regular insulin in PN (RI-in-PN) to achieve glycemic control in noncritically ill surgical patients with diabetes who were receiving PN.. This prospective randomized open-label study was conducted at King Faisal Specialist Hospital and Research Centre. Noncritically ill surgical patients with diabetes who were receiving PN were randomized to receive basal glargine insulin or RI-in-PN on day 4 of PN support. Mean blood glucose levels were compared on study days 5-9. The percentages of blood glucose measurements at goal were compared between groups.. Sixty-seven PN treatment episodes were analyzed. There were no statistically significant differences in mean glucose levels between groups on any study day ( P > .1). Overall glycemic control rates were 52.24% (glargine insulin) and 47.76% (RI-in-PN; P = .06). A significantly higher percentage of hyperglycemia was observed on day 5 for glargine insulin versus RI-in-PN (22.39% vs 5.97%, P = .0059). Blood glucose measurements indicated 6 hypoglycemic events: 2 for glargine insulin (5.7%) and 4 for RI-in-PN (11.4%; P > .1).. Both glargine insulin and RI-in-PN are effective basal insulin modalities for blood glucose control in noncritically ill surgical patients with diabetes who are receiving PN. Uncontrolled hyperglycemic events occurred more frequently with glargine insulin, and the rate of hypoglycemia was acceptable for both regimens.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Female; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin; Insulin Glargine; Male; Middle Aged; Parenteral Nutrition; Postoperative Care; Prospective Studies

Prednisolone causes hyperglycaemia predominantly between midday and midnight. Consequently, glargine-based basal-bolus insulin regimens may under treat daytime hyperglycaemia and cause nocturnal hypoglycaemia. We investigated whether an isophane-based insulin regimen is safer and more effective than a glargine-based regimen in hospitalized patients.. Fifty inpatients prescribed ≥20 mg/day prednisolone acutely with (1) finger prick blood glucose level (BGL) ≥15 mmol/L or (2) BGLs ≥10 mmol/L within the previous 24 hours were randomized to either insulin isophane or glargine before breakfast and insulin aspart before meals. The initial daily insulin dose was 0.5 U/kg bodyweight or 130% of the current daily insulin dose. Glycaemic control was assessed using a continuous glucose monitoring system.. On Day 1, there were no significant differences in percentage of time outside a target glucose range of 4 to 10 mmol/L (41.3% ± 5.5% vs 50.0% ± 5.7%, P  = .28), mean daily glucose (10.2 ± 0.7 vs 10.8 ± 0.8 mmol/L, P  = .57) or glucose <4 mmol/L (2.2% ± 1.1% vs 2.0% ± 1.3%, P  = .92) in patients randomized to isophane and glargine. In patients treated for 3 days, the prednisolone dose was reduced ( P  = .02) and the insulin dose was increased over time ( P  = .02), but the percentage of time outside the 4 to 10 mmol/L glucose range did not differ over time ( P  = .45) or between groups ( P  = .24).. There were no differences in the efficacy or safety of the isophane and glargine-based insulin regimens. We recommend an initial daily insulin dose of 0.5 units/kg bodyweight if not on insulin, a greater than 30% increase in pre-prednisolone insulin dose and larger insulin dose adjustments in patients with prednisolone-induced hyperglycaemia.

Topics: Aged; Blood Glucose; Drug Administration Schedule; Female; Hospitalization; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Inpatients; Insulin; Insulin Aspart; Insulin Glargine; Insulin, Isophane; Male; Meals; Middle Aged; Prednisolone; Treatment Outcome

To compare the addition of weekly dulaglutide vs the addition of placebo to titrated glargine in patients with type 2 diabetes (T2D) with sub-optimum glycated haemoglobin (HbA1c) concentration.. Patients (N = 300) from this phase III, double-blind, parallel-arm, placebo-controlled study were randomized to weekly subcutaneous injections of dulaglutide 1.5 mg or placebo with titrated daily glargine (mean ± standard deviation baseline dose: 39 ± 22 U), with or without metformin (≥1500 mg/d). The primary endpoint was superiority of dulaglutide/glargine to placebo/glargine with regard to change from baseline in HbA1c level at 28 weeks.. Least squares (LS) mean ± standard error (s.e.) HbA1c changes from baseline were -1.44 ± 0.09% (-15.74 ± 0.98 mmol/mol) with dulaglutide/glargine and -0.67 ± 0.09% (-7.32 ± 0.98 mmol/mol) with placebo/glargine at 28 weeks (LS mean difference [95% confidence interval] -0.77% [-0.97, -0.56]; P < .001). Body weight decreased with dulaglutide/glargine and increased with placebo/glargine (LS mean difference: -2.41 ± 0.39 kg; P < .001). Increases from baseline in mean glargine dose were significantly smaller with dulaglutide/glargine vs placebo/glargine (13 ± 2 U [0.1 ± 0.02 U/kg] vs 26 ± 2 U [0.3 ± 0.02 U/kg], respectively; P < .001; LS mean ± s.e. final dose: dulaglutide/glargine, 51 ± 2 U; placebo/glargine, 65 ± 2 U). The hypoglycaemia rate (≤3.9 mmol/L threshold) was 7.69 ± 15.15 and 8.56 ± 16.13 events/patient/year, respectively (P = .488). One episode of severe hypoglycaemia occurred in the dulaglutide/glargine group. Common gastrointestinal adverse events with dulaglutide were nausea (12.0%), diarrhoea (11.3%) and vomiting (6.0%).. Weekly dulaglutide 1.5 mg added to basal insulin is an efficacious and well tolerated treatment option for patients with T2D.

Topics: Aged; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Administration Schedule; Drug Monitoring; Drug Resistance; Drug Therapy, Combination; Female; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptides; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Immunoglobulin Fc Fragments; Incretins; Injections, Subcutaneous; Insulin Glargine; Intention to Treat Analysis; Male; Middle Aged; Patient Dropouts; Recombinant Fusion Proteins

To compare day-to-day and within-day variability in glucose-lowering effect between insulin degludec (IDeg) and insulin glargine 300 U/mL (IGlar-U300) in type 1 diabetes.. In this double-blind, crossover study, patients were randomly assigned to 0.4 U/kg of IDeg or IGlar-U300 once daily for two treatment periods lasting 12 days each. Pharmacodynamic variables were assessed at steady-state from the glucose infusion rate profiles of three 24-hour euglycaemic glucose clamps (days 6, 9 and 12) during each treatment period.. Overall, 57 patients completed both treatment periods (342 clamps). The potency of IGlar-U300 was 30% lower than IDeg (estimated ratio 0.70, 95% confidence interval [CI] 0.61; 0.80; P  < .0001). The distribution of glucose-lowering effect was stable across 6-hour intervals (24%-26%) for IDeg, while IGlar-U300 had greater effects in the first (35%) and last (28%) intervals compared with 6 to 12 hours (20%) and 12 to 18 hours (17%). Within-day variability (relative fluctuation) was 37% lower with IDeg than with IGlar-U300 (estimated ratio IDeg/IGlar-U300: 0.63, 95% CI 0.54; 0.73; P  < .0001). The day-to-day variability in glucose-lowering effect with IDeg was approximately 4 times lower than IGlar-U300 (variance ratio IGlar-U300/IDeg: 3.70, 95% CI 2.42; 5.67; P  < .0001). The day-to-day variability in glucose-lowering effect assessed in 2-hour intervals was consistently low with IDeg over 24 hours, but steadily increased with IGlar-U300 to a maximum at 10 to 12 hours and 12 to 14 hours after dosing (variance ratios 12.4 and 11.4, respectively).. IDeg has lower day-to-day and within-day variability than IGlar-U300 and a more stable glucose-lowering effect, which might facilitate titration and enable tighter glycaemic control with a reduced risk of hypoglycaemia.

Topics: Adult; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Double-Blind Method; Female; Glucose Clamp Technique; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin Resistance; Insulin, Long-Acting; Male; Middle Aged; Reproducibility of Results

To develop an algorithm that delivers an individualized dose of rapid-acting insulin after morning resistance exercise to counter post-exercise hyperglycaemia in individuals with Type 1 diabetes.. Eight people with Type 1 diabetes, aged 34 ± 7 years with HbA1c concentrations 72 ± 12 mmol/mol (8.7 ± 1.1%), attended our laboratory on two separate mornings after fasting, having taken their usual basal insulin the previous evening. These people performed a resistance exercise session comprising six exercises for two sets of 10 repetitions at 60% of the maximum amount of force that was generated in one maximal contraction (60% 1RM). In a randomized and counterbalanced order, the participants were administered an individualized dose of rapid-acting insulin (2 ± 1 units, range 0-4 units) immediately after resistance exercise (insulin session) by means of an algorithm or were not administered this (no-insulin session). Venous blood glucose concentrations were measured for 125 min after resistance exercise. Data (mean ± sem values) were analysed using anova (P ≤ 0.05).. Participants had immediate post-resistance exercise hyperglycaemia (insulin session 13.0 ± 1.6 vs. no-insulin session 12.7 ± 1.5 mmol/l; P = 0.834). The decline in blood glucose concentration between peak and 125 min after exercise was greater in the insulin exercise session than in the no-insulin session (3.3 ± 1.0 vs. 1.3 ± 0.4 mmol/l: P = 0.015). There were no episodes of hypoglycaemia (blood glucose <3.9 mmol/l).. Administration of rapid-acting insulin according to an individualized algorithm reduced the hyperglycaemia associated with morning resistance exercise without causing hypoglycaemia in the 2 h post-exercise period in people with Type 1 diabetes.

Topics: Adult; Blood Glucose; Combined Modality Therapy; Diabetes Mellitus, Type 1; Drug Administration Schedule; Drug Dosage Calculations; Drug Monitoring; Drug Therapy, Combination; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin Detemir; Insulin Glargine; Pilot Projects; Precision Medicine; Resistance Training; Risk; United Kingdom

To compare the immunogenicity profiles and the potential effects on clinical outcomes of LY2963016 insulin glargine (LY IGlar) and Lantus® insulin glargine (IGlar), products with identical primary amino acid sequences, in patients with type 1 or type 2 diabetes mellitus (T1DM or T2DM).. To assess immunogenicity, anti-insulin glargine antibodies (measured as percent binding) were compared between treatments in 52-week (open-label) and 24-week (double-blind) randomized studies in total study populations of patients with T1DM (N = 535) and T2DM (N = 756), respectively, and two subgroups of patients with T2DM: insulin-naïve patients and those reporting prestudy IGlar treatment (prior IGlar). Relationships between insulin antibody levels and clinical outcomes were assessed using analysis of covariance and partial correlations. Insulin antibody levels were assessed using Wilcoxon rank sum. Treatment comparisons for treatment-emergent antibody response (TEAR) and incidence of detectable antibodies were analysed using Fisher's exact test.. No significant treatment differences were observed for insulin antibody levels, incidence of detectable anti-insulin glargine antibodies, or incidence of TEAR [overall and endpoint, by last-observation-carried-forward (LOCF)] in patients with T1DM or patients with T2DM, including the insulin-naïve subgroup. A statistically significant difference was noted in the overall incidence of detectable antibodies but not at endpoint (LOCF) nor in TEAR for the prior IGlar subgroup of patients with T2DM. Insulin antibody levels were low (<5%) in both treatment groups. Insulin antibody levels or developing TEAR was not associated with clinical outcomes.. LY IGlar and IGlar have similar immunogenicity profiles; anti-insulin glargine antibody levels were low for both treatments, with no observed effect on efficacy and safety outcomes.

Topics: Asymptomatic Diseases; Biosimilar Pharmaceuticals; Cross Reactions; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Hypersensitivity; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Immunogenetic Phenomena; Incidence; Insulin Antibodies; Insulin Glargine; Insulin, Regular, Human; Recombinant Proteins

To use continuous glucose monitoring to examine the effects of insulin initiation with glargine, with or without glulisine, on glycaemic variability and glycaemia in a cohort of people with Type 2 diabetes receiving maximum oral hypoglycaemic agents in primary healthcare.. We conducted a post hoc analysis of continuous glucose monitoring data from 89 participants at baseline and at 24 weeks after insulin commencement. Indicators of glycaemic variability (standard deviation, J-index and mean amplitude of glycaemic excursion) and glycaemia (HbA1c , mean glucose, area under the glucose-time curve) were assessed. Multi-level regression analysis was used to identify the predictors of change.. Complete glycaemic variability data were available for 78 participants. Of these participants, 41% were women, their mean (sd) age was 59.2 (10.4) years, the median (interquartile range) diabetes duration was 10.4 (6.5, 13.3) years and the median (interquartile range) baseline HbA1c was 82.5 (71.6, 96.7) mmol/mol [9.7 (8.7, 11.0)%]. At baseline, BMI correlated negatively with standard deviation (r = -0.30) and mean amplitude of glycaemic excursion (r = -0.26), but not with J-index; HbA1c correlated with J-index (r = 0.61) but not with mean amplitude of glycaemic excursion and standard deviation. After insulin initiation the mean (sd) glucose level decreased [from 12.0 (3.0) to 8.5 (1.6) mmol/l; P < 0.001], as did the median (interquartile range) J-index [from 66.9 (47.7, 95.1) to 36.9 (27.6, 49.8) mmol/l; P < 0.001]. Baseline HbA1c correlated with a greater J-index reduction (r = -0.45; P < 0.001). The mean amplitude of glycaemic excursion and standard deviation values were unchanged. The baseline temporal profile, showing elevated postprandial morning glucose levels, was unchanged after insulin initiation, despite an overall reduction in glycaemia.. Insulin initiation reduced hyperglycaemia but did not alter glycaemic variability in adults with Type 2 diabetes receiving maximum oral hypoglycaemic agents. The most significant postprandial excursions were seen in the morning, which identifies prebreakfast as the most effective target for short-acting insulin therapy.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Blood Glucose; Blood Glucose Self-Monitoring; Cohort Studies; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Male; Middle Aged; Treatment Outcome; Young Adult

We compared changes in blood glucose (BG) and risk of hypoglycaemia during and after exercise in 40 patients with type 1 diabetes (T1D) treated with insulin degludec (IDeg) or insulin glargine (IGlar) in a randomized, open-label, two-period, crossover trial. After individual titration and a steady-state period, patients performed 30 min of moderate-intensity cycle ergometer exercise (65% peak rate of oxygen uptake). BG, counter-regulatory hormones and hypoglycaemic episodes were measured frequently during and for 24 h after exercise. BG changes during exercise were similar with IDeg and IGlar [estimated treatment difference (ETD) for maximum BG decrease: 0.14 mmol/l; 95% confidence interval (CI) -0.15, 0.42; p = 0.34], as was mean BG (ETD -0.16 mmol/l; 95% CI -0.36, 0.05; p = 0.13). No hypoglycaemic episodes occurred during exercise. Post-exercise mean BG, counter-regulatory hormone response and number of hypoglycaemic episodes in 24 h after starting exercise were similar with IDeg (18 events in 13 patients) and IGlar (23 events in 15 patients). This clinical trial showed that, in patients with T1D treated with a basal-bolus regimen, the risk of hypoglycaemia induced by moderate-intensity exercise was low with IDeg and similar to that with IGlar.

Topics: Adolescent; Adult; Circadian Rhythm; Cross-Over Studies; Diabetes Mellitus, Type 1; Drug Therapy, Combination; Exercise Test; Female; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Motor Activity; Risk; Young Adult

To compare the efficacy and safety of insulin glargine 300 U/ml (Gla-300) with glargine 100 U/ml (Gla-100) in Japanese people with type 2 diabetes using basal insulin plus oral antihyperglycaemic drug(s) [OAD(s)].. The EDITION JP 2 study (NCT01689142) was a 6-month, multicentre, open-label, phase III study. Participants (n = 241, male 61%, mean diabetes duration 14 years, mean weight 67 kg, mean body mass index 25 kg/m(2), mean glycated haemoglobin (HbA1c) 8.02 %, mean basal insulin dose 0.24 U/kg/day) were randomized to Gla-300 or Gla-100, while continuing OAD(s). Basal insulin was titrated to target fasting self-monitored plasma glucose 4.4-5.6 mmol/l. The primary efficacy endpoint was HbA1c change over 6 months. Safety endpoints included hypoglycaemia and weight change.. Gla-300 was non-inferior to Gla-100 for HbA1c reduction [least squares (LS) mean difference 0.10 (95% confidence interval [CI] -0.08, 0.27) %]. The mean HbA1c at month 6 was 7.56 and 7.52 % with Gla-300 and Gla-100, respectively. Nocturnal confirmed (≤3.9 mmol/l) or severe hypoglycaemia risk was 38% lower with Gla-300 versus Gla-100 [relative risk 0.62 (95% CI 0.44, 0.88)]; annualized rates were 55% lower at night [rate ratio 0.45 (95% CI 0.21, 0.96)] and 36% lower at any time [24 h; rate ratio 0.64 (95% CI 0.43, 0.96)]. Severe hypoglycaemia was infrequent. A significant between-treatment difference in weight change favoured Gla-300 [LS mean difference -1.0 (95% CI -1.5, -0.5) kg; p = 0.0003]. Adverse event rates were comparable between groups.. Japanese people with type 2 diabetes using basal insulin plus OAD(s) experienced less hypoglycaemia with Gla-300 than with Gla-100, while glycaemic control did not differ.

Topics: Administration, Oral; Aged; Delayed-Action Preparations; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Resistance, Multiple; Drug Therapy, Combination; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Japan; Male; Middle Aged; Risk

To compare efficacy and safety of new insulin glargine 300 U/ml (Gla-300) with that of insulin glargine 100 U/ml (Gla-100) in Japanese adults with type 1 diabetes.. The EDITION JP 1 study (NCT01689129) was a 6-month, multicentre, open-label, phase III study. Participants (n = 243) were randomized to Gla-300 or Gla-100 while continuing mealtime insulin. Basal insulin was titrated with the aim of achieving a fasting self-monitored plasma glucose target of 4.4-7.2 mmol/l. The primary endpoint was change in glycated haemoglobin (HbA1c) over 6 months. Safety measures included hypoglycaemia and change in body weight.. Gla-300 was non-inferior to Gla-100 for the primary endpoint of HbA1c change over the 6-month period {least squares [LS] mean difference 0.13 % [95 % confidence interval (CI) -0.03 to 0.29]}. The annualized rate of confirmed (≤3.9 mmol/l) or severe hypoglycaemic events was 34 % lower with Gla-300 than with Gla-100 at night [rate ratio 0.66 (95 % CI 0.48-0.92)] and 20 % lower at any time of day [24 h; rate ratio 0.80 (95 % CI 0.65-0.98)]; this difference was most pronounced during the first 8 weeks of treatment. Severe hypoglycaemia was infrequent. The basal insulin dose increased in both groups (month 6 dose: Gla-300 0.35 U/kg/day, Gla-100 0.29 U/kg/day). A between-treatment difference in body weight change over 6 months favouring Gla-300 was observed [LS mean difference -0.6 kg (95 % CI -1.1 to -0.0); p = 0.035]. Adverse event rates were comparable between the groups.. In Japanese adults with type 1 diabetes using basal plus mealtime insulin, less hypoglycaemia was observed with Gla-300 than with Gla-100, particularly during the night, while glycaemic control did not differ.

Topics: Adult; Delayed-Action Preparations; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Resistance, Multiple; Drug Therapy, Combination; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Japan; Male; Middle Aged; Risk

The safety and efficacy of LY2963016 insulin glargine (LY IGlar) and Lantus insulin glargine (IGlar), products with identical primary amino acid sequences, were assessed in subgroups of patients with type 1 (T1D, n = 452) or type 2 diabetes (T2D, n = 299) reporting prestudy IGlar treatment in 52-week open-label (ELEMENT-1) and 24-week double-blind (ELEMENT-2) studies. At randomization, patients transitioned from their prestudy IGlar to equivalent doses of LY IGlar or IGlar. Primary efficacy (change in glycated haemoglobin from baseline to 24 weeks), other efficacy and select safety outcomes of LY IGlar were compared with those of IGlar. Continuous data were analysed using analysis of covariance, categorical data by Fisher's exact test, and treatment comparisons for hypoglycaemia by Wilcoxon test. No statistically significant treatment differences were identified for efficacy and safety outcomes except for weight change (T1D), overall incidence of detectable insulin antibodies (T2D), and serious adverse events (T2D). These differences were neither consistently observed across both studies nor observed in the total study populations, and their magnitude suggests they were not clinically meaningful. LY IGlar and IGlar show similar efficacy and safety profiles in patients reporting prestudy IGlar treatment.

Topics: Biosimilar Pharmaceuticals; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Double-Blind Method; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine

Previous studies comparing insulin detemir versus insulin glargine showed conflicting results, and included only outpatients. This study compared the two insulin analogs once daily in hospitalized patients with type 2 diabetes (T2D).. A total of 55 patients aged 18-80 years with hyperglycemia admitted to the endocrinology wards were screened between June 2014 and February 2015. Forty-two enrolled patients were randomly assigned to receive either insulin detemir followed by insulin glargine once daily (n = 21), or vice versa (n = 21). The two insulin analogs were titrated 0.1 U/kg once daily based on fasting blood glucose (FBG). After achieving FBG <7.8 mmol/L (the first period), subjects were switched from one analog to the other (the second period) with no change in the dose. The second period lasted for 3 days. When hypoglycemia occurred in the second period, the observation was discontinued. Six-point blood glucose including FBG, 2 h after breakfast, lunch, dinner, bedtime, and at 3:00 am was tested every day. The glucose profiles of the final days in the two periods were compared.. At the end of the first period, days for achieving FBG target (4.0 ± 0.5 days vs. 3.3 ± 0.4 days, t = 1.079, P = 0.286) and total daily dose (30.1 ± 2.4 U vs. 30.1 ± 2.9 U, t = 0.002, P = 0.999) between insulin detemir and insulin glargine were similar. There was no significant difference in the 24-h glucose control between the two analogs. No hypoglycemia occurred with both analogs in the first period. However, in the second period, when insulin glargine was switched to insulin detemir, two, three and, one patients had hypoglycemia events on day 1, day 2 and day 3 of the second period, respectively. One patient had severe hypoglycemia on day 1.. When both basal insulin analogs were given once daily in T2D, insulin detemir achieved similar efficacy to insulin glargine. On the other hand, there may be differences in action of the compared basal insulins. Further studies with larger patient samples are necessary to support evidence and reveal possible mechanisms.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 2; Female; Hospitalization; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Male; Middle Aged; Young Adult

Insulin glargine 300 U/mL (Gla-300) has a more constant and prolonged action profile than insulin glargine 100 U/mL and in clinical studies is associated with similar glycemic control but less hypoglycemia. Whether its effects are altered by variability of injection time was examined in two 3-month substudies.. Eligible participants completing 6 months of optimized treatment with Gla-300 in EDITION 1 (n = 109) and EDITION 2 (n = 89), having a mean hemoglobin A1c (HbA1c) level of 7.3 % (SD 1.0 %), were randomized (1:1) to groups advised to increase variability of between-injection intervals to 24 ± up to 3 h or to maintain fixed 24-h intervals for 3 months. Changes of HbA1c level and other efficacy and safety measures were assessed.. In the fixed-dosing group, 64% of participants reported all intervals within the 23-25-h range, compared with 15% of those advised flexible dosing. In the fixed- and flexible-dosing groups, 12% and 41%, respectively, of between-injection intervals were outside the 23-25-h range, and 2% and 16%, respectively, were outside the 21-27-h range. Least squares mean between-group difference in HbA1c change from baseline was 0.05 % (95% confidence interval [CI], -0.13 to 0.23); for fasting plasma glucose, 2.7 mg/dL (95% CI, -9.0 to 14.4); and for daily basal insulin dose, 0.00 U/kg (95% CI, -0.02 to 0.03). Frequencies of hypoglycemia and adverse events did not differ between groups.. The efficacy and safety of Gla-300 demonstrated in EDITION 1 and EDITION 2 are maintained in substudies when the insulin was injected up to 3 h before or after the usual time of administration.

Topics: Activities of Daily Living; Administration, Oral; Chemistry, Pharmaceutical; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Intention to Treat Analysis; Male; Meals; Medication Adherence

To compare glucose variability in patients with type 1 diabetes (T1D) treated with insulin glargine (IGla) versus insulin degludec (IDeg) using continuous glucose monitoring (CGM).. Thirteen patients with T1D were randomly assigned to receive IDeg once-daily followed by IGla twice-daily or vice versa. They were evaluated for glucose variability by CGM after >4weeks of treatment with either insulin, and then were crossed over to the other, and evaluated by CGM after >4weeks.. The total daily insulin dose (TDD) (U/kg/day) and the total daily basal insulin dose (U/kg/day) in the patients were significantly lower while taking IDeg than while taking IGla (mean [95% confidence interval] 0.72 [0.61-0.83] vs. 0.76 [0.64-0.88]; P=0.001, 0.29 [0.22-0.36] vs. 0.33 [0.26-0.40]; P=0.001), although no significant difference was noted in the patients while on IDeg versus while on IGla in 24-h mean glucose and SDs of 24-h glucose. Again, the range of postprandial glucose increase was not significantly different between the meals in the patients while taking IDeg (P=0.288) but significantly different in the patients while taking IGla (P=0.033).. The use of once-daily IDeg leads not only to similar glycemic control to that seen with twice-daily IGla even in those who received IGla prior to the study, but also to significant decreases in TDD and long-acting basal insulin dose.

Topics: Adult; Blood Glucose; Blood Glucose Self-Monitoring; Cross-Over Studies; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Pilot Projects; Prognosis

To examine whether insulin glargine can lead to better control of glycated haemoglobin (HbA1c) than that achieved by neutral protamine Hagedorn (NPH) insulin, using a protocol designed to limit nocturnal hypoglycaemia.. The present study, the Least One Oral Antidiabetic Drug Treatment (LANCELOT) Study, was a 36-week, randomized, open-label, parallel-arm study conducted in Europe, Asia, the Middle East and South America. Participants were randomized (1:1) to begin glargine or NPH, on background of metformin with glimepiride. Weekly insulin titration aimed to achieve median prebreakfast and nocturnal plasma glucose levels ≤5.5 mmol/l, while limiting values ≤4.4 mmol/l.. The efficacy population (n = 701) had a mean age of 57 years, a mean body mass index of 29.8 kg/m², a mean duration of diabetes of 9.2 years and a mean HbA1c level of 8.2% (66 mmol/mol). At treatment end, HbA1c values and the proportion of participants with HbA1c <7.0 % (<53 mmol/mol) were not significantly different for glargine [7.1 % (54 mmol/mol) and 50.3%] versus NPH [7.2 % (55 mmol/mol) and 44.3%]. The rate of symptomatic nocturnal hypoglycaemia, confirmed by plasma glucose ≤3.9 or ≤3.1 mmol/l, was 29 and 48% less with glargine than with NPH insulin. Other outcomes were similar between the groups.. Insulin glargine was not superior to NPH insulin in improving glycaemic control. The insulin dosing algorithm was not sufficient to equalize nocturnal hypoglycaemia between the two insulins. This study confirms, in a globally heterogeneous population, the reduction achieved in nocturnal hypoglycaemia while attaining good glycaemic control with insulin glargine compared with NPH, even when titrating basal insulin to prevent nocturnal hypoglycaemia rather than treating according to normal fasting glucose levels.

Topics: Aged; Asia; Blood Glucose Self-Monitoring; Circadian Rhythm; Diabetes Mellitus, Type 2; Drug Dosage Calculations; Drug Resistance; Drug Therapy, Combination; Europe; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Metformin; Middle Aged; Middle East; South Africa; Sulfonylurea Compounds

To compare the efficacy and safety of new insulin glargine 300 U/ml (Gla-300) with that of glargine 100 U/ml (Gla-100) in insulin-naïve people with type 2 diabetes using oral glucose-lowering drugs.. The EDITION 3 study was a multicentre, open-label, parallel-group study. Participants were randomized to Gla-300 or Gla-100 once daily for 6 months, discontinuing sulphonylureas and glinides, with a dose titration aimed at achieving pre-breakfast plasma glucose concentrations of 4.4-5.6 mmol/l (80-100 mg/dl). The primary endpoint was change in glycated haemoglobin (HbA1c) from baseline to month 6. The main secondary endpoint was percentage of participants with ≥1 nocturnal confirmed [≤3.9 mmol/l (≤70 mg/dl)] or severe hypoglycaemia from week 9 to month 6. Other measures of glycaemia and hypoglycaemia, weight change and insulin dose were assessed.. Randomized participants (n = 878) had a mean (standard deviation) age of 57.7 (10.1) years, diabetes duration 9.8 (6.4) years, body mass index 33.0 (6.7) kg/m(2) and HbA1c 8.54 (1.06) % [69.8 (11.6) mmol/mol]. HbA1c levels decreased by equivalent amounts with the two treatments; the least squares mean difference in change from baseline was 0.04 [95% confidence interval (CI) -0.09 to 0.17] % or 0.4 (-1.0 to 1.9) mmol/mol. Numerically fewer participants reported ≥1 nocturnal confirmed (≤3.9 mmol/l) or severe hypoglycaemia from week 9 to month 6 [relative risk (RR) 0.89 (95% CI 0.66 to 1.20)] with Gla-300 versus Gla-100; a significantly lower risk of hypoglycaemia with this definition was found over the 6-month treatment period [RR 0.76 (95% CI 0.59 to 0.99)]. No between-treatment differences in adverse events were identified.. Gla-300 is as effective as Gla-100 in reducing HbA1c in insulin-naïve people with type 2 diabetes, with lower hypoglycaemia risk.

Topics: Administration, Oral; Aged; Blood Glucose; Delayed-Action Preparations; Diabetes Mellitus, Type 2; Drug Monitoring; Drug Resistance; Europe; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin Glargine; Japan; Male; Middle Aged; North America; Risk; Weight Gain

To compare the effectiveness and safety of two glycemic control regimens in stable critical care patients receiving parenteral nutrition (PN).. Prospective, randomized open-label clinical trial.. Eligible postoperative critical care patients in the ICU began PN on the first to the seventh day of ICU admission. The PN admixture included regular insulin, in doses sufficient to maintain 3 or more goal blood glucose (BG) levels between 110 and 180 mg/dl. After 3 to 5 days of PN containing regular insulin, patients were randomized to 3 more days of regular insulin at the same dose or 80% of their total daily regular insulin dose provided in PN solution as glargine insulin. Capillary BG monitoring was performed every 6 hours.. Twenty one patients were randomized to each treatment group. Median APACHE II scores were not significantly different between the two groups within the first 24-hour of ICU admission. There were no significant differences between the two groups at day 3 for mean daily dextrose (306.9 ± 46.2 vs. 305.2 ± 52.2 g; p=0.913) or insulin (18.3 ± 8.8 vs. 19.5 ± 10.0 units; p=0.696) doses. The percentage of BG values in the goal (110-180 mg/dl), hyperglycemic (> 180 mg/dl), and hypoglycemic (< 70 mg/dl) BG levels were similar between the two groups (69.0% vs. 66.7%, p=0.567; 11.9% vs. 11.1%, p=0.780; 0% vs. 1.6%, p=0.124, respectively). Mean daily BG levels were not significantly different between the two groups on each of the 3 study days (day 1: 140 ± 20 vs. 131 ± 25 mg/dl, p=0.194; day 2: 136 ± 20 vs. 140 ± 18 mg/dl, p=0.498; day 3: 142 ± 15 vs. 140 ± 19 mg/dl; p=0.741).. These data suggest that, compared with regular insulin added to PN, glargine insulin results in similar glycemic control and rates of hyperglycemia and hypoglycemia in stable critical care patients.

Topics: Adult; Aged; Aged, 80 and over; Blood Glucose; Critical Care; Female; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Intensive Care Units; Male; Parenteral Nutrition; Prospective Studies

Patients with type 1 diabetes face heightened risk of hypoglycemia after exercise. Subsequent overfeeding, as a preventative measure against hypoglycemia, negates the energy deficit after exercise. Patients are also required to reduce the insulin dose administered with postexercise foods to further combat hypoglycemia. However, the insulin dose is dictated solely by the carbohydrate content, even though postprandial glycemia is vastly influenced by glycemic index (GI). With a need to control the postexercise energy balance, appetite responses after meals differing in GI are of particular interest.. We assessed the appetite response to low-glycemic index (LGI) and high-glycemic index (HGI) postexercise meals in type 1 diabetes patients. This assessment also offered us the opportunity to evaluate the influence of GI on appetite responses independently of insulinemia, which confounds findings in individuals without diabetes.. Ten physically active men with type 1 diabetes completed 2 trials in a randomized crossover design. After 45 min of treadmill exercise at 70% of the peak oxygen uptake, participants consumed an LGI (GI ∼37) or HGI (GI ∼92) meal with a matched macronutrient composition, negligible fiber content, and standardized insulin-dose administration. The postprandial appetite response was determined for 180 min postmeal. During this time, circulating glucose, insulin, glucagon, and glucagon-like peptide-1 (GLP-1) concentrations and subjective appetite ratings were determined.. The HGI meal produced an ∼60% greater postprandial glucose area under the curve (AUC) than did the LGI meal (P = 0.008). Insulin, glucagon, and GLP-1 did not significantly differ between trials (P > 0.05). The fullness AUC was ∼25% greater after the HGI meal than after the LGI meal (P < 0.001), whereas hunger sensations were ∼9% lower after the HGI meal than after the LGI meal (P = 0.001).. Under conditions of matched insulinemia and fiber, an HGI postexercise meal suppresses feelings of hunger and augments postprandial fullness sensations more so than an otherwise equivalent LGI meal in type 1 diabetes patients.

Topics: Adult; Appetite Regulation; Combined Modality Therapy; Cross-Over Studies; Diabetes Mellitus, Type 1; Diet, Diabetic; Dietary Fiber; Drug Therapy, Combination; Exercise; Glucagon; Glucagon-Like Peptide 1; Glycemic Index; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin Glargine; Insulin, Long-Acting; Jogging; Male; Meals; Postprandial Period

The combination of a dipeptidyl peptidase-4 (DPP-4) inhibitor and a long-acting insulin analogue is widely used in clinical practice. However, some patients fail to achieve lower postprandial hyperglycemia. Mitiglinide, a short-acting insulinotropic sulfonylurea receptor ligand, is effective for postprandial hyperglycemia. Recently, it has been reported that the combination therapy of mitiglinide with a DPP-4 inhibitor could improve glycemic control. However, the efficacy of those under long-acting insulin analogue therapy remains to be investigated. Thus, we conducted a prospective single-center study of eight Japanese patients with type 2 diabetes mellitus receiving mitiglinide added to the combination therapy of sitagliptin and insulin glargine, and evaluated its efficacy and safety by continuous glucose monitoring (CGM). Participants' (four men and four women) mean age was 70.3 ± 10.6 years. Their mean body mass index, HbA1c level, and urinary C-peptide level were 22.0 ± 2.8 kg/m(2), 9.2 ± 1.2%, and 50.0 ± 31.4 μg/day, respectively. CGM showed that as compared with the combination of only sitagliptin and insulin glargine, mitiglinide in combination with sitagliptin and insulin glargine significantly reduced glycemic fluctuation indices, total area for the range of 24-h glycemic fluctuations (p = 0.04), mean amplitude of glycemic excursions (p = 0.03), and the proportion of time in hyperglycemia (p = 0.02) without significant difference in the proportion of time in hypoglycemia (p = 0.18). Hence, we have demonstrated the efficacy and safety of the add-on treatment with mitiglinide in type 2 diabetic patients, receiving the combination therapy of sitagliptin and insulin glargine.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Fasting; Female; Humans; Hyperglycemia; Insulin Glargine; Isoindoles; Male; Monitoring, Physiologic; Sitagliptin Phosphate

To test the hypothesis that a 'basal plus' regimen--adding once-daily main-meal fast-acting insulin to basal insulin once daily--would be non-inferior to biphasic insulin twice daily as assessed by glycated haemoglobin (HbA1c) concentration (predefined as ≤0.4%), but would provide superior treatment satisfaction.. This open-label trial enrolled adults to an 8- or 12-week run-in period, during which oral therapies except metformin were stopped and insulin glargine dose was titrated. Those with fasting glucose <7 mmol/l but HbA1c >7% (53 mmol/mol) were randomized to insulin glargine/glulisine once daily (n = 170) or insulin aspart/aspart protamine 30/70 twice daily (n = 165) for 24 weeks, with dose titration to glucose targets using standardized algorithms.. For HbA1c, the basal plus regimen was non-inferior to biphasic insulin (least squares mean difference, 0.21%, upper 97.5% confidence limit 0.38%) meeting the predefined non-inferiority margin of 0.4%. Treatment satisfaction (Diabetes Treatment Satisfaction Questionnaire change version and Insulin Treatment Satisfaction Questionnaire total scores) significantly favoured basal plus. No difference was observed between the basal plus and the biphasic insulin groups in responders (HbA1c <7%, 20.6 vs 27.9%; p = 0.12), weight gain (2.06 vs 2.50 kg; p = 0.2), diabetes-specific quality of life (Audit of Diabetes-Dependent Quality of Life average weighted impact (AWI) score) and generic health status (five-dimension European Quality of Life questionnaire). Overall hypoglycaemia rates were similar between groups (15.3 vs 18.2 events/patient-year; p = 0.22); nocturnal hypoglycaemia was higher with the basal plus regimen (5.7 vs 3.6 events/patient-year; p = 0.02).. In long-standing type 2 diabetes with suboptimal glycaemia despite oral therapies and basal insulin, the basal plus regimen was non-inferior to biphasic insulin for biomedical outcomes, with a similar overall hypoglycaemia rate but more nocturnal events.

Topics: Aged; Australia; Biphasic Insulins; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin; Insulin Aspart; Insulin Glargine; Insulin, Isophane; Intention to Treat Analysis; Male; Middle Aged; Patient Dropouts; Quality of Life; United Kingdom

To compare the efficacy and safety of new insulin glargine 300 U/ml (Gla-300) with insulin glargine 100 U/ml (Gla-100) over 12 months of treatment in people with type 2 diabetes using basal insulin and oral antihyperglycaemic drugs (OADs).. EDITION 2 (NCT01499095) was a randomized, 6-month, multicentre, open-label, two-arm, phase IIIa study investigating once-daily Gla-300 versus Gla-100, plus OADs (excluding sulphonylureas), with a 6-month safety extension.. Similar numbers of participants in each group completed 12 months of treatment [Gla-300, 315 participants (78%); Gla-100, 314 participants (77%)]. The reduction in glycated haemoglobin was maintained for 12 months with both treatments: least squares (LS) mean (standard error) change from baseline -0.55 (0.06)% for Gla-300 and -0.50 (0.06)% for Gla-100; LS mean difference -0.06 [95% confidence interval (CI) -0.22 to 0.10)%]. A significant relative reduction of 37% in the annualized rate of nocturnal confirmed [≤3.9 mmol/l (≤70 mg/dl)] or severe hypoglycaemia was observed with Gla-300 compared with Gla-100: rate ratio 0.63 [(95% CI 0.42-0.96); p = 0.031], and fewer participants experienced ≥1 event [relative risk 0.84 (95% CI 0.71-0.99)]. Severe hypoglycaemia was infrequent. Weight gain was significantly lower with Gla-300 than Gla-100 [LS mean difference -0.7 (95% CI -1.3 to -0.2) kg; p = 0.009]. Both treatments were well tolerated with a similar pattern of adverse events (incidence of 69 and 60% in the Gla-300 and Gla-100 groups).. In people with type 2 diabetes treated with Gla-300 or Gla-100, and non-sulphonylurea OADs, glycaemic control was sustained over 12 months, with less nocturnal hypoglycaemia in the Gla-300 group.

Topics: Administration, Oral; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Drug Compounding; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incidence; Injections, Subcutaneous; Insulin Glargine; Intention to Treat Analysis; Isophane Insulin, Human; Middle Aged; Patient Dropouts; Patient Satisfaction; Risk; Weight Gain

To investigate the clinical efficacy and safety of insulin glargine compared with NPH insulin as basal insulin for the management of corticosteroid-induced hyperglycemia in hospitalized people with type 2 diabetes (T2DM) and respiratory disease.. Randomized, two-arm parallel group, clinical trial undertaken from February 2011 to November 2012 on the pneumology ward of the Hospital Regional Universitario de Málaga (Spain), involving 53 participants with T2DM treated with medium/high doses of intermediate-acting corticosteroids. Participants were randomly assigned to receive one single dose of insulin glargine or NPH insulin in three equally divided doses before each meal as basal insulin within a basal-bolus insulin protocol. The intervention lasted six days or until discharge if earlier.. No significant differences were seen between groups during the study in mean blood glucose (11.43±3.44 mmol/l in glargine vs. 11.88±2.94 mmol/l in NPH, p=0.624), and measures of glucose variability (standard deviation 3.27±1.16 mmol/l vs. 3.61±0.99 mmol/l, p=0.273; coefficient of variation 1.55±0.33 mmol/l vs. 1.72±0.39 mmol/l, p=0.200). Results from CGM were concordant with those obtained with capillary blood glucose reading. The length of hospital stay was also similar between groups (8.2±2.8 days vs. 9.8±3.4 days, p=0.166) There was a non significant trend for lower episodes of mild (4 vs. 8, p=0.351) and severe hypoglycemia (0 vs. 3, p=0.13) in the glargine group.. The results of this study showed that insulin glargine and NPH insulin are equally effective in a basal-bolus insulin protocol to treat glucocorticoid-induced hyperglycemia in people with T2DM on a pneumology ward.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Male; Middle Aged; Respiratory Tract Diseases; Safety; Young Adult

Our aim was to compare the effects of an intermediate acting human insulin (NPH) and a long-acting insulin analog, insulin glargine, in insulin naïve type 2 diabetes patients, stratified by the type of hyperglycemia (fasting or postprandial type). Based on different action profiles, we hypothesized that patients having different hyperglycemia types would react differently when treated with these insulins. This is a post hoc analysis of the Lanmet study data. The Lanmet study was a randomized, 36-week controlled insulin initiation study in type 2 diabetes patients. 109 subjects with baseline HbA1c >8.0% (64 mmol/mol) completed the study. The patients were divided into two groups according to fasting glucose (mmol/l)/HbA1c (%) ratio. Patients with a ratio ≥1.3 were defined as having fasting type and those with a ratio <1.3 as having postprandial type hyperglycemia. The main outcome measures were change in HbA1c and body weight, and final insulin dose. Independently of insulin type, compared to patients with postprandial type hyperglycemia, those with fasting type hyperglycemia had 2.1 kg/m(2) greater initial BMI (p = 0.044), gained 2.0 kg more weight (p = 0.020, adjusted for baseline BMI p = 0.035), and had 36% greater final insulin dose/kg (p = 0.001). With respect to hyperglycemia type, there was no difference between NPH and glargine in their effects on HbA1c. When starting bedtime insulin in type 2 diabetes patients, those with fasting type hyperglycemia are prone to greater weight gain. Hyperglycemia type does not help in identifying patients who would benefit specially from either NPH insulin or insulin glargine.

Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Fasting; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Insulin Glargine; Insulin, Isophane; Male; Middle Aged; Postprandial Period; Statistics, Nonparametric

To compare efficacy and safety of two, once-daily basal insulin formulations [insulin lispro protamine suspension (ILPS) vs. insulin glargine (glargine)] added to oral antihyperglycaemic medications (OAMs) and exenatide BID in suboptimally controlled type 2 diabetes (T2D) patients.. This 24-week, open-label, multicentre trial randomized patients to bedtime ILPS (n = 171) or glargine (n = 168). Non-inferiority of ILPS versus glargine was assessed by comparing the upper limit of 95% confidence intervals (CIs) for change in haemoglobin A1c (HbA1c) from baseline to week 24 (adjusted for baseline HbA1c) with non-inferiority margin 0.4%.. Non-inferiority of ILPS versus glargine was demonstrated: least-squares mean between-treatment difference (ILPS minus glargine) (95% CI) was 0.22% (0.06, 0.38). Mean HbA1c reduction was less for ILPS- versus glargine-treated patients (-1.16 ± 0.84 vs. -1.40 ± 0.97%, p = 0.008). Endpoint HbA1c < 7.0% was achieved by 53.7% (ILPS) and 61.7% (glargine) (p = NS). Overall hypoglycaemia rates (p = NS) and severe hypoglycaemia incidence (p = NS) were similar. Nocturnal hypoglycaemia rate was higher in patients treated with ILPS versus glargine (p = 0.004). Weight gain was similar between groups (ILPS: 0.27 ± 3.38 kg; glargine: 0.66 ± 3.93 kg, p = NS). Endpoint total insulin doses were lower in patients treated with ILPS versus glargine (0.30 ± 0.17 vs. 0.37 ± 0.17 IU/kg/day, p < 0.001).. ILPS was non-inferior to glargine for HbA1c change over 24 weeks, but was associated with less HbA1c reduction and more nocturnal hypoglycaemia. Treat-to-target basal insulin therapy improves glycaemic control and is associated with minimal weight gain when added to OAMs and exenatide BID for suboptimally controlled T2D.

Topics: Administration, Oral; Adolescent; Adult; Aged; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Male; Middle Aged; Protamines; Treatment Outcome; Weight Gain; Young Adult

Basal and bolus insulin therapy is required for strict blood control in diabetic patients, which could lead to prevention of vascular complications in diabetes. However, the optimal combination regimen is not well established.. Fifty-nine diabetic patients (49 type 1 and 10 type 2; 52.9 ± 13.3 years old) whose blood glucose levels were uncontrolled (HbA1c  > 6.2%) by combination treatment of basal insulin glargine with multiple daily pre-meal injections of bolus short-acting insulin [aspart (n = 19), lispro (n = 37) and regular human insulin (n = 3)] for at least 8 weeks were enrolled in this study. We examined whether glycaemic control and vascular injury were improved by replacement of short-acting insulin with glulisine. Patient satisfaction was assessed with Diabetes Treatment Satisfaction Questionnaire.. Although bolus and basal insulin doses were almost unchanged before and after replacement therapy, switching to glulisine insulin for 24 weeks significantly decreased level of HbA1c , advanced glycation end products (AGEs), soluble receptor for AGEs (sRAGE), monocyte chemoattractant protein-1 (MCP-1) and urinary albumin excretion. In multiple stepwise regression analysis, change in MCP-1 values from baseline (ΔMCP-1) was a sole determinant of log urinary albumin excretion. ΔAGEs and ΔsRAGE were independently correlated with each other. The relationship between ΔMCP-1 and ΔsRAGE was marginally significant (p = 0.05). Replacement of short-acting insulin by glulisine significantly increased Diabetes Treatment Satisfaction Questionnaire scores.. Our present study suggests that combination therapy of glargine with multiple daily pre-meal injections of glulisine might show superior efficacy in controlling blood glucose, preventing vascular damage and improving treatment satisfaction in diabetic patients.

Topics: Adult; Aged; Biomarkers; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Drug Administration Schedule; Drug Resistance; Drug Therapy, Combination; Female; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin, Long-Acting; Japan; Male; Middle Aged; Patient Satisfaction

To determine the influence of different volumes of resistance exercise on circulating interleukin-6 (IL-6) and to explore the relationships between IL-6 and glycaemia.. Eight participants with complication-free type 1 diabetes, whose mean ± SEM age was 38 (6) years, mean ± SEM HbA(1c) concentration was 71 ±11 mmol/mol (8.7 ±1.0%) and mean ± SEM type 1 diabetes duration was 15 ±13 years, attended the research facility after an overnight fast on four separate occasions, having administered their basal insulin the night before (glargine 27.5±3.1U, n=8), but omitted morning rapid-acting insulin. Participants completed either a one-set (14-min), two-set (28-min), or three-set (42-min) resistance exercise trial (eight exercises × 10 repetitions) at 67±3% one-repetition maximum followed by a 60-min recovery, or a resting control trial. Venous blood samples were taken before and after exercise. Data were analysed using repeated-measures ANOVA (P≤0.05).. Whereas IL-6 levels remained similar to baseline levels after one set of resistance exercises (30 min, P=0.287; 60 min, P=0.318), IL-6 levels were > baseline levels at 60 min post-exercise after a two-set exercise trial (2.94 ± 0.94 pg/ml, P=0.002) and doubled at both 30 min (4.01 ± 1.00 pg/ml, P=0.048) and 60 min (4.28 ± 1.25 pg/ml, P=0.084) post-exercise after the three-set resistance exercise trial. Post-exercise blood glucose area under the curve (mmol/l/60 min) was greater after both the one-set (P=0.025) and two-set trials (P=0.008), than after the control trial, but similar between the three-set trial and the control trial (P=0.240). The rise in IL-6 from baseline to peak concentration significantly correlated inversely with blood glucose area under the curve (r=-0.65, P=0.041).. Circulating IL-6 is increased by resistance exercise in a volume-dependent manner, and resistance exercise-induced increases in IL-6 correlated with reductions in post-exercise hyperglycaemia in type 1 diabetes, suggesting a role for IL-6 in improving post-resistance exercise glycaemic disturbances in type 1 diabetes.

Topics: Adult; Blood Glucose; Cohort Studies; Combined Modality Therapy; Diabetes Mellitus, Type 1; Diet, Diabetic; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Interleukin-6; Male; Muscle, Skeletal; Resistance Training; Retrospective Studies; Time Factors; Up-Regulation

The purpose of this study was to evaluate the advantages of exenatide treatment on obesity and non-alcoholic fatty liver disease (NAFLD) with elevated liver enzymes in patients with type 2 diabetes (T2D).. A total of 60 newly diagnosed patients with obesity, NAFLD with elevated liver enzymes and T2D were included in the study. The patients were randomly divided into two groups. The exenatide treatment group (n = 30) were treated with exenatide and insulin glargine, and the intensive insulin therapy group (n = 30) were treated with insulin aspart and insulin glargine for 12 weeks. Selected clinical characteristics were determined, and ultrasonography was performed at both baseline and 12 weeks following treatment.. At baseline, the clinical characteristics were matched between the two groups. After 12 weeks, fasting blood glucose (FBG), postprandial blood glucose (PBG), glycosylated haemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG) and total bilirubin levels were significantly decreased in the two groups (p < 0.001). Body weight and waist circumference were significantly decreased in the exenatide group but increased in the intensive insulin group (p < 0.001). The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyl transpeptidase (γGGT) in the exenatide group were significantly lower than in the intensive insulin group (p < 0.001). The mean body weight change correlated with the levels of ALT, AST and γGGT change (ALT, r = 0.761; AST, r = 0.733; γGGT, r = 0.752; p < 0.001). Moreover, the reversal rate of fatty liver was significantly higher in the exenatide group (93.3%) than the intensive insulin group (66.7%) (p < 0.01).. Exenatide has a better hepatic-protective effect than intensive insulin therapy and perhaps represents a unique option for adjunctive therapy for patients with obesity, non-alcoholic fatty liver disease with elevated liver enzymes and T2D.

Topics: Adult; Biomarkers; Body Mass Index; Combined Modality Therapy; Diabetes Mellitus, Type 2; Diet, Diabetic; Drug Therapy, Combination; Exenatide; Exercise; Female; Glycated Hemoglobin; Hepatic Insufficiency; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Liver; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Obesity; Peptides; Ultrasonography; Venoms; Waist Circumference; Weight Loss

Diabetes and non-diabetic dysglycaemia are risk factors for accelerated cognitive decline. In this planned substudy of the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial, we assessed whether normalising glucose with insulin glargine or administering omega-3 fatty acids in this population may slow this process or affect the development of cognitive impairment.. The ORIGIN trial recruited participants older than 50 years with dysglycaemia who were taking either no or one oral glucose-lowering drug, who had additional risk factors for cardiovascular events, whose HbA1c was less than 9%, and who were not taking insulin. Participants were recruited from 573 sites in 40 countries. Participants were randomly assigned to either titrated basal insulin glargine targeting a fasting plasma glucose concentration of 5.3 mmol/L or lower or standard care and to either omega-3 fatty acid (1 g) or placebo by a factorial design. Outcome adjudicators and data analysts were masked to treatment allocation. Cognitive function was assessed by the Mini-Mental State Examination (MMS) and Digit Symbol Substitution (DSS). The effect of insulin glargine or omega-3 fatty * acid on cognitive function over time, the annualised change in test scores, and the development of probable cognitive impairment were measured. All analyses were restricted to those participants who had a cognitive measurement at both baseline and at least one follow-up visit. The ORIGIN trial is registered with ClinicalTrials.gov, NCT00069784.. Participants were randomly assigned between Sept 1, 2003, and Dec 15, 2005. MMSE and DSS were assessed in 11,685 and 3392 ORIGIN participants (mean age 63.4 years [SD 7.7]), who were followed up for a median of 6.2 years (IQR 5.8-6.7). There was no difference in the rate of change of cognitive test scores between the insulin glargine and standard care groups (for the MMSE 0.0046, 95% CI -0.0132 to 0.0224, p=0.39; and for the DSS -0.0362, -0.2180 to 0.1455, p=0.34) or between the omega-3 fatty acid and placebo groups (for the MMSE 0.0013, 95% CI -0.0165 to 0.0191, p=0.21; and for the DSS -0.0605, -0.2422 to 0.1212, p=0.72). Similarly, the incidence of probable cognitive impairment did not differ between the insulin glargine and standard care groups (p=0.065) or the omega-3 fatty acid and placebo groups (p=0.070). In a subgroup analysis, allocation to insulin glargine versus standard care seemed to reduce the decline in the MMSE (but not the DSS) in participants with dysglycaemia but without evidence of diabetes (pinteraction=0.024).. In this relatively young cohort of people with dysglycaemia, insulin mediated normoglycaemia and omega-3 fatty acid for over 6 years had a neutral effect on the rate of cognitive decline and on incident cognitive impairment. Future studies should assess the effect of these interventions in an older cohort or the effect of other glucometabolic interventions on cognitive decline.. Sanofi.

Topics: Aged; Blood Glucose; Cognition Disorders; Diabetes Mellitus, Type 2; Fatty Acids, Omega-3; Female; Glucose Metabolism Disorders; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Neuropsychological Tests; Risk Factors

Mealtime insulin is commonly added to manage hyperglycemia in type 2 diabetes when basal insulin is insufficient. However, this complex regimen is associated with weight gain and hypoglycemia. This study compared the efficacy and safety of exenatide twice daily or mealtime insulin lispro in patients inadequately controlled by insulin glargine and metformin despite up-titration.. In this 30-week, open-label, multicenter, randomized, noninferiority trial with 12 weeks prior insulin optimization, 627 patients with insufficient postoptimization glycated hemoglobin A1c (HbA1c) were randomized to exenatide (10-20 µg/day) or thrice-daily mealtime lispro titrated to premeal glucose of 5.6-6.0 mmol/L, both added to insulin glargine (mean 61 units/day at randomization) and metformin (mean 2,000 mg/day).. Randomization HbA1c and fasting glucose (FG) were 8.3% (67 mmol/mol) and 7.1 mmol/L for exenatide and 8.2% (66 mmol/mol) and 7.1 mmol/L for lispro. At 30 weeks postrandomization, mean HbA1c changes were noninferior for exenatide compared with lispro (-1.13 and -1.10%, respectively); treatment differences were -0.04 (95% CI -0.18, 0.11) in per-protocol (n = 510) and -0.03 (95% CI -0.16, 0.11) in intent-to-treat (n = 627) populations. FG was lower with exenatide than lispro (6.5 vs. 7.2 mmol/L; P = 0.002). Weight decreased with exenatide and increased with lispro (-2.5 vs. +2.1 kg; P < 0.001). More patients reported treatment satisfaction and better quality of life with exenatide than lispro, although a larger proportion of patients with exenatide experienced treatment-emergent adverse events. Exenatide resulted in fewer nonnocturnal hypoglycemic episodes but more gastrointestinal adverse events than lispro.. Adding exenatide to titrated glargine with metformin resulted in similar glycemic control as adding lispro and was well tolerated. These findings support exenatide as a noninsulin addition for patients failing basal insulin.

Topics: Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Administration Schedule; Exenatide; Female; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Male; Meals; Metformin; Middle Aged; Peptides; Quality of Life; Receptors, Glucagon; Treatment Outcome; Venoms

Insulin glargine is widely used as basal insulin. However, published dose titration regimens for insulin glargine are complex. This study aimed to compare the efficacy and safety profile of a user-friendly, weight-based insulin glargine dose titration regimen with 2 published regimens.. A total of 160 hospitalized patients with hyperglycemia in 3 medical centers were screened. Our inclusion criteria included age 18 to 80 years and being conscious. Exclusion criteria included pregnancy or breast-feeding and hepatic or renal dysfunction. A total of 149 patients were randomly assigned to receive weight-based, glucose level-based, or dose-based insulin glargine dose titration regimen between January 2011 and February 2013. The initial dose of insulin glargine was 0.2 U/kg. In the weight-based regimen (n = 49), the dose was titrated by increments of 0.1 U/kg daily. In the glucose level-based regimen (n = 51), the dose was titrated by 2, 4, 6, or 8 U daily when fasting blood glucose (FBG) was, respectively, between 7.0 and 7.9, 8.0 and 8.9, 9.0 and 9.9, or ≥10 mmol/L. In the current dose-based regimen (n = 49), titration was by daily increments of 20% of the current dose. The target FBG in all groups was ≤7.0 mmol/L. The incidence of hypoglycemia was recorded. One-way ANOVA and χ(2) test were used to compare data between the 3 groups.. All but 1 patient who required additional oral antidiabetic medication completed the study. The mean (SD) time to achieve target FBG was 3.2 (1.2) days with the weight-based regimen and 3.7 (1.5) days with the glucose level-based regimen (P = 0.266). These times were both shorter than that achieved with the current dose-based regimen (4.8 [2.8] days; P = 0.0001 and P = 0.005, respectively). The daily doses of insulin glargine at the study end point were 0.43 (0.13) U/kg with the weight-based regimen, 0.50 (0.20) U/kg with the glucose level-based regimen, and 0.47 (0.23) U/kg with the current dose-based regimen (P = 0.184). The incidence of hypoglycemia was 4.1%, 2.0%, and 6.3%, respectively (P = 0.557).. The currently proposed weight-based insulin glargine dose titration regimen is effective, tolerable, and user-friendly at achieving FBG target levels in hospitalized patients with hyperglycemia.

Topics: Aged; Aged, 80 and over; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Fasting; Female; Glycated Hemoglobin; Hospitalization; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Middle Aged; Research Design

To evaluate basal and prandial insulin initiation and titration in people with type 2 diabetes mellitus (T2DM) in primary care and to explore the feasibility of retrospective-continuous glucose monitoring (r-CGM) in guiding insulin dosing. The new model of care features General Practitioners (GPs) and Practice Nurses (PNs) working in an expanded role, with Credentialed Diabetes Educator - Registered Nurse (CDE-RN) support.. Insulin-naïve T2DM patients (HbA1c >7.5% [>58 mmol/mol] despite maximal oral therapy) from 22 general practices in Victoria, Australia commenced insulin glargine, with glulisine added as required. Each was randomised to receive r-CGM or self-monitoring of blood glucose (SMBG). Glycaemic control (HbA1c) was benchmarked against specialist ambulatory patients referred for insulin initiation.. Ninety-two patients mean age (range) 59 (28-77) years; 40% female; mean (SD) diabetes duration 10.5 (6.1) years participated. HbA1c decreased from (median (IQR)) 9.9 (8.8, 11.2)%; 85 (73, 99) mmol/mol to 7.3 (6.9, 7.8)%; 56 (52, 62) mmol/mol at 24 weeks (p < 0.0001). Comparing r-CGM (n = 46) with SMBG (n = 42), there were no differences in major hypoglycaemia (p=0.17) or ΔHbA1c (p = 0.31). More r-CGM than SMBG participants commenced glulisine (26/48 vs. 7/44; p < 0.001). Results were comparable to 82 benchmark patients, with similar low rates of major hypoglycaemia (2/89 vs. 0/82; p = 0.17) and less loss to follow up in the INITIATION group (3/92 vs. 14/82; p = 0.002).. Insulin initiation and titration for T2DM patients in primary care was safe and improved HbA1c with low rates of major hypoglycaemia. CDE-RNs were effective in a new consultant role. r-CGM use in primary care was feasible and enhanced post-prandial hyperglycaemia recognition. Trial registration ACTRN12610000797077.

Topics: Adult; Aged; Australia; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Feasibility Studies; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Patient Acceptance of Health Care; Postprandial Period; Primary Health Care; Retrospective Studies

This study investigated the safety and efficacy of sitagliptin (Januvia) for the inpatient management of type 2 diabetes (T2D) in general medicine and surgery patients.. In this pilot, multicenter, open-label, randomized study, patients (n = 90) with a known history of T2D treated with diet, oral antidiabetic agents, or low total daily dose of insulin (≤0.4 units/kg/day) were randomized to receive sitagliptin alone or in combination with glargine insulin (glargine) or to a basal bolus insulin regimen (glargine and lispro) plus supplemental (correction) doses of lispro. Major study outcomes included differences in daily blood glucose (BG), frequency of treatment failures (defined as three or more consecutive BG >240 mg/dL or a mean daily BG >240 mg/dL), and hypoglycemia between groups.. Glycemic control improved similarly in all treatment groups. There were no differences in the mean daily BG after the 1st day of treatment (P = 0.23), number of readings within a BG target of 70 and 140 mg/dL (P = 0.53), number of BG readings >200 mg/dL (P = 0.23), and number of treatment failures (P > 0.99). The total daily insulin dose and number of insulin injections were significantly less in the sitagliptin groups compared with the basal bolus group (both P < 0.001). There were no differences in length of hospital stay (P = 0.78) or in the number of hypoglycemic events between groups (P = 0.86).. Results of this pilot indicate that treatment with sitagliptin alone or in combination with basal insulin is safe and effective for the management of hyperglycemia in general medicine and surgery patients with T2D.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Female; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Inpatients; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Male; Middle Aged; Pyrazines; Sitagliptin Phosphate; Triazoles

Insulin glulisine (Glu) is a rapidly-acting insulin analog with a faster onset of action than the other insulin analogs of its class, which are insulin aspart (Asp) and insulin lispro (Lisp). While insulin Glu is usually injected just before meals, postprandial injection may help to avoid unexpected postprandial hypoglycemia or hyperglycemia by adjusting the insulin dosage according to food intake. However, the effect of postprandial insulin Glu on the glucose profile has not been evaluated. The aim of this study was to compare daily glucose excursion by continuous glucose monitoring (CGM) between multiple daily doses of preprandial insulin Asp or postprandial insulin Glu. In a randomized cross-over trial, we performed CGM to evaluate the 48-hour glucose profile during treatment with the same dosage of insulin Asp just before each meal in 12 hospitalized patients with type 2 diabetes. Patients also received the same dosage of long-acting insulin glargine at bedtime. The average glucose level, standard deviation of the glucose level, mean amplitude of glucose excursion, and daily glucose profile did not differ between preprandial Asp and postprandial Glu. The incidence of hypoglycemic episodes (glucose level<70 mg/dL with or without symptoms) and the area under the curve of glucose<70 mg/dL also did not differ between the two insulin regimens. Multiple daily injections of preprandial Asp and postprandial Glu achieved the same daily glucose excursion profile. Postprandial injection of Glu may provide greater flexibility for patients who require insulin therapy.

Topics: Adult; Aged; Blood Glucose; Cross-Over Studies; Diabetes Complications; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Monitoring, Ambulatory

Most studies report using percentage of total daily insulin (TDI) for converting therapy from continuous insulin infusion to subcutaneous insulin in cardiac surgery patients. Few studies have evaluated the efficacy of using body weight to calculate the basal insulin dose.. To compare the efficacy and safety of dosing insulin glargine by weight versus percentage of TDI in cardiac surgery patients transitioning from continuous insulin infusion to subcutaneous insulin.. We conducted a prospective, randomized, open-label, pilot study. Study patients who had a preoperative weight less than 100 kg and were receiving at least 6 hours of a continuous insulin infusion were randomized to receive either 50% of their TDI requirement or 0.5 units/kg of glargine as a one-time dose 2 hours before stopping the continuous insulin infusion. All patients were administered subcutaneous corrective insulin. Blood glucose monitoring occurred before each meal, at bedtime, and with morning laboratory tests for 24 hours after administration of the glargine dose.. A total of 200 blood glucose measurements were performed in each group. The percentage of blood glucose measurements in target range (80-140 mg/dL) was similar between the weight-based group and the percentage-based group (66% vs 64%, p = 0.75). Median blood glucose after transition was 120 mg/dL (interquartile range [IQR] 99-147) in the weight-based group compared to 127 mg/dL (IQR 107-149; p = 0.03) in the percentage-based group. The median glargine dose was higher in the weight-based group (41 units; IQR 36-44) than in the weight-based group (24 units; IQR 14-30, p < 0.001). The rate of hypoglycemia (blood glucose <60 mg/dL) was 2.5% in each group.. In this small cohort, dosing insulin glargine by weight proved to be safe, but larger scale studies are needed before adopting weight-based dosing in this patient population.

Topics: Aged; Aged, 80 and over; Blood Glucose; Body Weight; Cardiac Surgical Procedures; Dose-Response Relationship, Drug; Drug Dosage Calculations; Female; Humans; Hyperglycemia; Hypoglycemic Agents; Infusions, Intravenous; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Pilot Projects; Prospective Studies

Addition and titration of basal insulin is usually effective in improving glycaemic control in type 2 diabetes, but fear of hypoglycaemia remains a barrier. Ability to predict which patients might be at greatest risk of hypoglycaemia might facilitate individualization of treatment and improve safety. The aim of this study was to obtain information about clinical characteristics which might predict risk of hypoglycaemia during initiation of basal insulin.. Patient-level data from 2251 participants in 11 studies in which insulin glargine was started and titrated using similar treat-to-target methods was pooled and analysed with logistic regression models.. Participants had mean age 58 years, diabetes duration 8.9 years, body mass index 31.0 and baseline A1c 8.8%. They attained mean A1c 7.1% during 6 months of treatment with final mean glargine dosage 0.44 units/kg. Symptomatic hypoglycaemia occurred in 52%, glucose-confirmed hypoglycaemia (blood glucose <50 mg/dl) in 17%, repeated glucose-confirmed events in 7% and severe hypoglycaemia in 1.5%. Independent predictors of glucose-confirmed hypoglycaemia were younger age, lower body mass index, use of a sulphonylurea in addition to metformin, lower attained A1c and lower dosage of glargine.. These findings confirm low rates of clinically important hypoglycaemia using this method, and suggest that higher risk of hypoglycaemia may be suspected when patients needing insulin are younger, less obese and taking metformin and a sulphonylurea, and especially when A1c levels ≤7.0% are attained with glargine dosage ≤0.4 units/kg.

Topics: Age Factors; Aged; Body Mass Index; Diabetes Mellitus, Type 2; Drug Monitoring; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin Glargine; Insulin, Long-Acting; Logistic Models; Male; Middle Aged; Overweight; Risk; Sulfonylurea Compounds

This pilot study aimed to verify if glycemic control can be achieved in type 2 diabetes patients after acute myocardial infarction (AMI), using insulin glargine (iGlar) associated with regular insulin (iReg), compared with the standard intensive care unit protocol, which uses continuous insulin intravenous delivery followed by NPH insulin and iReg (St. Care).. Patients (n=20) within 24 h of AMI were randomized to iGlar or St. Care. Therapy was guided exclusively by capillary blood glucose (CBG), but glucometric parameters were also analyzed by blinded continuous glucose monitoring system (CGMS).. Mean glycemia was 141±39 mg/dL for St. Care and 132±42 mg/dL for iGlar by CBG or 138±35 mg/dL for St. Care and 129±34 mg/dL for iGlar by CGMS. Percentage of time in range (80-180 mg/dL) by CGMS was 73±18% for iGlar and 77±11% for St. Care. No severe hypoglycemia (≤40 mg/dL) was detected by CBG, but CGMS indicated 11 (St. Care) and seven (iGlar) excursions in four subjects from each group, mostly in sulfonylurea users (six of eight patients).. This pilot study suggests that equivalent glycemic control without increase in severe hyperglycemia may be achieved using iGlar with background iReg. Data outputs were controlled by both CBG and CGMS measurements in a real-life setting to ensure reliability. Based on CGMS measurements, there were significant numbers of glycemic excursions outside of the target range. However, this was not detected by CBG. In addition, the data indicate that previous use of sulfonylurea may be a potential major risk factor for severe hypoglycemia irrespective of the type of insulin treatment.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Female; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Monitoring, Ambulatory; Myocardial Infarction; Pilot Projects; Standard of Care; Time Factors; United States

Hyperglycemia during hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and high-dose cytarabine, with methylprednisolone premedication) chemotherapy is associated with poor outcomes of acute lymphoblastic leukemia (ALL). To examine whether intensive insulin therapy could improve outcomes, a randomized trial was conducted that compared glargine plus aspart vs. conventional therapy. Intensive insulin did not improve ALL clinical outcomes despite improved glycemic control. Secondary analysis suggests that the choice of antidiabetic pharmacotherapy may influence ALL outcomes.. Hyperglycemia during hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and high-dose cytarabine, with methylprednisolone premedication) chemotherapy is associated with poor outcomes of acute lymphoblastic leukemia (ALL).. To examine whether an intensive insulin regimen could improve outcomes compared with conventional antidiabetic pharmacotherapy, a randomized trial was conducted that compared glargine plus aspart vs. conventional therapy (control). Between April 2004 and July 2008, 52 patients newly diagnosed with ALL, Burkitt lymphoma, or lymphoblastic lymphoma who were on hyper-CVAD in the inpatient setting and had a random serum glucose level >180 mg/dL on ≥2 occasions during chemotherapy were enrolled.. The trial was terminated early due to futility regarding ALL clinical outcomes despite improved glycemic control. Secondary analysis revealed that molar insulin-to-C-peptide ratio (I/C) > 0.175 (a surrogate measure of exogenous insulin usage) was associated with decreased overall survival, complete remission duration and progression-free survival (PFS), whereas metformin and/or thiazolidinedione usage were associated with increased PFS. In multivariate analyses, factors that significantly predicted short overall survival included age ≥ 60 years (P = .0002), I/C ≥ 0.175 (P = .0016), and average glucose level ≥ 180 mg/dL (P = .0236). Factors that significantly predicted short PFS included age ≥ 60 years (P = .0008), I/C ≥ 0.175 (P = .0002), high systemic risk (P = .0173) and average glucose level ≥ 180 mg/dL (P = .0249). I/C ≥ 0.175 was the only significant (P = .0042) factor that predicted short complete remission duration.. A glargine-plus-aspart intensive insulin regimen did not improve ALL outcomes in patients with hyperglycemia. Exogenous insulin may be associated with poor outcomes, whereas metformin and thiazolidinediones may be associated with improved outcomes. Analysis of these results suggests that the choice of antidiabetic pharmacotherapy may influence ALL outcomes.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Blood Glucose; Burkitt Lymphoma; C-Peptide; Cyclophosphamide; Dexamethasone; Disease-Free Survival; Doxorubicin; Female; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Metformin; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Prospective Studies; Thiazolidinediones; Treatment Outcome; Vincristine; Young Adult

Transition of diabetic patients from iv insulin infusion to s.c. insulin frequently results in rebound hyperglycemia.. We hypothesized that initiation of a long-acting insulin therapy concurrently with i.v. insulin infusion would decrease the rate of rebound hyperglycemia after discontinuation of the insulin infusion.. Sixty-one diabetic patients receiving i.v. insulin therapy participated in this prospective randomized study. Subjects in the intervention group received daily injections of glargine s.c. (0.25 U/kg body weight) starting within 12 h of initiation of i.v. insulin infusion. Capillary blood glucose measurements were obtained up to 12 h after discontinuation of insulin infusion. Rebound hyperglycemia was defined as a blood glucose level greater than 180 mg/dl.. The study was conducted at the University of Colorado Hospital.. Sixty-one hospitalized patients with known type 1 or type 2 diabetes receiving i.v. insulin infusion participated in the study.. The primary outcome of this study was to compare the rates of rebound hyperglycemia between the control and the intervention groups after i.v. insulin infusion is discontinued.. Overall, 29 subjects in the control group (93.5%) had at least one glucose value above 180 mg/dl during the 12-h follow-up period. This was significantly greater than the rate of rebound hyperglycemia in the intervention group (10 subjects or 33.3%, P < 0.001). The effect of the intervention was apparent in subjects who presented with diabetic ketoacidosis, after solid organ transplantation, and in patients with other surgical and medical diagnoses. There were three hypoglycemic measurements in two control subjects (68, 62, and 58 mg/dl) and none in the intervention group.. Once-daily s.c. insulin glargine administered during i.v. insulin infusion is a safe method for preventing future rebound hyperglycemia, without increased risk of hypoglycemia.

Topics: Adult; Blood Glucose; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Hyperglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin Glargine; Insulin Infusion Systems; Insulin, Long-Acting; Male; Middle Aged; Prospective Studies; Treatment Outcome

Renal insufficiency may increase the risk of hypoglycemia in hospitalized patients with diabetes who are treated with insulin. We randomized inpatients with type 2 diabetes and chronic renal failure to treatment with two different dose levels of insulin glargine and glulisine and studied control of hyperglycemia and the frequency of hypoglycemia.. We conducted a multicenter, prospective, randomized trial to compare the efficacy of once-daily glargine and three-times daily glulisine at 0.5 vs. 0.25 units/kg/day. A total of 107 subjects had type 2 diabetes for >1 year, had a glomerular filtration rate <45 mL/min but did not require dialysis, and had an initial blood glucose (BG) >180 mg/dL. Doses were adjusted based on four-times daily BG measurements for 6 days.. Mean BG on the first day was 196 ± 71 mg/dL in the group receiving 0.5 units/kg (0.5 group) and 197 ± 55 mg/dL in the group receiving 0.25 units/kg (0.25 group; P = 0.94). On days 2 to 6, mean BG was 174 ± 52 mg/dL in the 0.5 group and 174 ± 46 mg/dL in the 0.25 group (P = 0.96). There were no significant differences between groups in the percentage of BG values within the target range of 100 to 180 mg/dL on any of the 6 study days. In the 0.5 group, 30% experienced hypoglycemia (BG <70 mg/dL) compared with 15.8% of the 0.25 group (P = 0.08).. Reduction of initial glargine/glulisine insulin weight-based dosing in hospitalized patients with diabetes and renal insufficiency reduced the frequency of hypoglycemia by 50% without compromising the control of hyperglycemia.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Female; Hospitalization; Humans; Hyperglycemia; Hypoglycemia; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Renal Insufficiency; Treatment Outcome

To investigate an effective and safe protocol for enteral nutrition (EN) patients permitting successfully transmit insulin administration from venous pump-in to subcutaneous injection.. A prospective randomized control study was conducted. Critical patients admitted to intensive care unit (ICU) of Beijing Tongren Hospital from September 2008 to February 2009 were randomly divided into two groups when the energy provided by EN up to half of the total energy requirement. Experiment group (n=44): the protocol was applied for insulin glargine and regular insulin injection; control group (n=43): protocol was applied for subcutaneous regular insulin injection. Target glucose range was 4.4-7.8 mmol/L (80-140 mg/dl). If blood glucose ≥11.1 mmol/L was maintained twicely, the approach of insulin administration would convert from subcutaneous injection to venous pump-in using the computerized glucose control protocol. If the infusion rate of insulin was less than 3 U/h and lasted more than 6 hours, blood glucose ≤7.8 mmol/L, insulin administration was switched to subcutaneous injection again. The general information and all glucose regulation data were recorded for analysis.. The two groups did not differ at baseline for the general information, mean blood glucose and the glucose variation. A total of 1689 blood glucose records were analyzed. The mean blood glucose in experiment group, and was significantly lower than that in control group(7.58±1.17 mmol/L vs. 9.40±1.74 mmol/L, P<0.05). The rate of glucose values within target range in experiment group was significantly higher than that in control group [49.72% (534/1074) vs. 35.61% (219/615), P<0.01]. The glucose standard deviation (SD) in experiment group was significantly lower than that in control group (1.89±0.52 mmol/L vs. 2.17±0.94 mmol/L, P<0.05). The number of measurements needed per patient per day was significantly reduced in experiment group compared with control group (7.51±1.31 vs. 8.15±0.97, P<0.05). The ratio of patients converted to venous pump-in was significantly decreased in experiment group compared with control group (9.09% vs. 44.19%, P<0.01). Hypoglycemia (≤3.3 mmol/L) did not different between experiment group and control group [0.74% (8/1074) vs. 0.49% (3/615), P=0.75].. Compared with the conventional subcutaneous insulin injection protocol, this protocol with insulin glargine combined regular insulin subcutaneous injection can control the glucose level effectively during EN in critical patients. The glucose variation and the numbers of measurements were significantly reduced by this protocol. It is helpful for the insulin transmission from venous pump-in to subcutaneous injection.

Topics: Adult; Aged; Blood Glucose; Critical Illness; Enteral Nutrition; Female; Humans; Hyperglycemia; Hypoglycemia; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin, Long-Acting; Intensive Care Units; Male; Middle Aged; Prospective Studies

In this randomized, single blind, cross-over study 2.5 mg and 5 mg of the modified-release terbutaline formulation (SKP-1052) were compared with conventional immediate-release terbutaline (IRT, 5 mg) and placebo on overnight blood glucose (BG) and hypoglycaemia in 30 subjects with type 1 diabetes mellitus.. Subjects received subcutaneous injections of insulin glargine (individualized doses) before dinner. SKP-1052, IRT or placebo was administered around 21:00 hours. BG and terbutaline concentrations were monitored overnight for 10 h post-dosing. Endpoints comprised of the nadir BG (BGn 0-10 h, primary endpoint), mean overnight BG (BGmean), morning BG (BGmorning) and hypoglycaemia rates as well as pharmacokinetic (PK) endpoints.. SKP-1052 delayed release of terbutaline by 2 h [PK-tmax (mean ± SD) 5.0 ± 2.1 h (2.5 mg) and 4.7 ± 1.7 h (5 mg) vs. 2.6 ± 1.3 h with IRT, p < 0.01, respectively]. Compared with placebo, no significant differences were observed for BGn 0-10 h across treatments, but both 5 mg formulations showed less hypoglycaemic events [10 (IRT), 16 (SKP-1052) vs. 33], higher BGmean (120, 114 and 95 mg/dl) and BGmorning (126, 126 and 101 mg/dl, all comparisons p < 0.05 vs. placebo). Numerically higher BG-levels between 3 and 8 h post-dosing were observed with 2.5 mg SKP-1052 vs. placebo.. Compared with IRT SKP-1052 delays release of terbutaline. 2.5 mg SKP-1052 led to numerically higher BG 3 to 8 h post-dose without fasting hyperglycaemia while 5 mg SKP-1052 resulted in fasting hyperglycaemia vs. placebo. Future studies will investigate optimized doses of SKP-1052 for nocturnal hypoglycaemia prevention.

Topics: Adolescent; Adult; Blood Glucose; Cross-Over Studies; Delayed-Action Preparations; Diabetes Mellitus, Type 1; Drug Administration Schedule; Fasting; Female; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Single-Blind Method; Terbutaline

To evaluate three evening insulin glargine dosing strategies for achievement of target (100-179 mg/dL; 5.5 - 9.8 mmol/L) and widened (80-249 mg/dL; 4.4 - 13.7 mmol/L) preoperative fasting blood glucose (FBG) ranges on the day of surgery.. Prospective, randomized, open trial.. Preoperative units at two sites of a suburban hospital system.. 401 adult, ASA physical status 3 and 4 patients with type 1 and type 2 diabetes, undergoing elective noncardiac surgery.. Patients were divided into two groups according to absence of daily rapid-acting/short-acting insulin (insulin glargine-only group) or presence of daily rapid-acting/short-acting insulin (insulin glargine plus bolus group). Subjects were then randomized to three evening insulin glargine dosing strategies: (a) take 80% of usual dose, (b) call physician for dose, or (c) refer to dosing table, based on self-reported usual FBG and insulin regimen. In the prehospital setting, patients administered the instructed insulin glargine dose on the evening before surgery.. Venous blood glucose values were recorded in the preoperative holding area on the day of surgery.. No significant differences in target preoperative FBG achievement were detected among strategies in the insulin glargine-only group (n = 174) or the insulin glargine plus bolus group (n = 227). In widened preoperative FBG achievement, no significant difference was noted among strategies in the insulin glargine-only group. In the insulin glargine plus bolus group, fewer subjects following the dosing table had FBG > 249 mg/dL (> 13.7 mmol/L; P = 0.031).. Target preoperative FBG achievement was similar among strategies in both insulin glargine groups. An insulin glargine adjustment strategy based on usual glycemic control may better prevent severe preoperative hyperglycemia in patients receiving basal/bolus regimens.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Elective Surgical Procedures; Female; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Preoperative Care; Prospective Studies

The aim of this study was to compare coefficient of variation of fasting capillary blood glucose (FBG) between insulin glargine and NPH in T2DM with poorly controlled by oral antidiabetic drugs. The results demonstrated that insulin glargine was more potent in improving glycemic control than NPH with stable FBG.

Topics: Adult; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Homeostasis; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Resistance; Insulin-Secreting Cells; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged

To compare the efficacy and safety of an intensified insulin regimen, using insulin glargine (glargine) once daily and pre-meal insulin glulisine (glulisine) (basal-bolus), with a conventional therapy, using premixed insulin (premix) twice daily.. This 52-week, open-label, randomized, multinational, multicentre trial included 310 subjects with type 2 diabetes (T2D) on premix, with or without metformin, who were randomized to a basal-bolus regimen with glargine and glulisine (n = 153; mean +/- s.d. age 60.2 +/- 7.5 years; HbA1c 8.6 +/- 0.8%; weight 87.0 +/- 15.1 kg; T2D duration 12.8 +/- 5.8 years) or twice-daily premix (n = 157; age 60.9 +/- 7.8 years; HbA1c 8.5 +/- 0.9%; weight 84.3 +/- 15.0 kg; T2D duration 12.5 +/- 6.8 years). The primary endpoint was change in HbA1c from baseline to endpoint.. Mean decrease in baseline-to-endpoint HbA1c for basal-bolus vs. premix was -1.31 vs. -0.80% (difference: -0.476%; 95% Cl: -0.714, -0.238; p = 0.0001, ancova). More subjects reached HbA1c < or = 7.0% in the basal-bolus group than in the premix group [68 (46.6%) vs. 43 (27.9%); p = 0.0004], while they also experienced significantly lower mean +/- s.d. daytime (-2.7 +/- 2.3 vs. -2.3 +/- 2.5 mmol/l; p = 0.0033) and postprandial (-3.1 +/- 2.6 vs. -2.5 +/- 2.8 mmol/l; p < 0.0001) blood glucose. Endpoint daily insulin doses were 98.0 +/- 48.7 vs. 91.3 +/- 44.3 IU (p = 0.2104); mean weight gain was +3.6 +/- 4.0 vs. +2.2 +/- 4.5 kg (p = 0.0073). Mean number of overall hypoglycaemic events with basal-bolus and premix was 13.99 and 18.54 events/patient year, respectively (difference: -3.90; 95% CI: -10.40, 2.60; p = 0.2385).. An intensified basal-bolus regimen using glargine/glulisine results in a significantly superior glycaemic control vs. premix therapy in a population with long-standing insulin-treated T2D, with no increase in the rates of hypoglycaemia.

Topics: Adolescent; Adult; Aged; Analysis of Variance; Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Treatment Outcome; Young Adult

To assess the effect of a 4-week adjunctive therapy of exenatide (EXE) (5-10 microg b.i.d.) or sitagliptin (SITA) (100 mg once daily) in response to a standardized breakfast meal challenge in 48 men or women with type 2 diabetes receiving insulin glargine (GLAR) + metformin (MET).. This was a single-center, randomized, open-label, active comparator-controlled study with a three-arm parallel group design, consisting of: screening, 4- to 8-week run-in period, 4-week treatment period, and follow-up. In all three groups, the GLAR dose was titrated according to an algorithm (fasting blood glucose

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Exenatide; Female; Follow-Up Studies; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Metformin; Middle Aged; Peptides; Treatment Outcome; Venoms

Diabetes increases morbidity and mortality in cystic fibrosis (CF) patients, but several studies indicate that also prediabetic status may have a potential impact on both nutrition and lung function.. To evaluate the effect of glargine on the clinical course in CF patients with early glucose derangements.. CF population was screened for glucose tolerance. CF patients with age >10 yr were screened with fasting hyperglycemia (FH). CF patients with age >10 yr without FH and those with age <10 yr with occasional FH were evaluated for glucose abnormalities on the basis of oral glucose tolerance test and/or continuous glucose monitoring system. All CF patients with glucose derangements were enrolled in an open clinical trial with glargine. Body mass index (BMI) z-score, forced expiratory volume in the first second (FEV(1)), number of acute pulmonary exacerbations and hemoglobin A1c, were as outcome measures at baseline and after 1 yr of treatment.. After 12 months of therapy, BMI z-score improved only in patients with baseline BMI z-score less than -1 (p = 0.017). An 8.8% increase in FEV(1) (p = 0.01) and 42% decrease in the number of pulmonary exacerbations (p = 0.003) were found in the whole group compared with previous 12 months of therapy.. Glargine could represent an innovative strategy to prevent lung disease progression in CF patients with early glucose derangements. Larger controlled trials are needed to better clarify the effects of insulin on clinical status in CF patients with early glucose derangements.

Topics: Adolescent; Body Mass Index; Child; Cystic Fibrosis; Diabetes Mellitus; Forced Expiratory Volume; Glucose Intolerance; Glucose Tolerance Test; Glycated Hemoglobin; Growth; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Lung Diseases; Spirometry; Treatment Outcome

To compare two subcutaneous insulin strategies for glycemic management of hyperglycemia in non-critically ill hospitalized patients with diabetes during enteral nutrition therapy (ENT).. Fifty inpatients were prospectively randomized to receive sliding-scale regular insulin (SSRI) alone (n = 25) or in combination with insulin glargine (n = 25). NPH insulin was added for persistent hyperglycemia in the SSRI group (glucose >10 mmol/l).. Glycemic control was similar in the SSRI and glargine groups (mean +/- SD study glucose 8.9 +/- 1.6 vs. 9.2 +/- 1.6 mmol/l, respectively; P = 0.71). NPH insulin was added in 48% of the SSRI group subjects. There were no group differences in frequency of hypoglycemia (1.3 +/- 4.1 vs. 1.1 +/- 1.8%; P = 0.35), total adverse events, or length of stay.. Both insulin strategies (SSRI with the addition of NPH for persistent hyperglycemia and glargine) demonstrated similar efficacy and safety in non-critically ill hospitalized patients with type 2 diabetes during ENT.

Topics: Aged; Blood Glucose; Diabetes Complications; Diabetes Mellitus; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Inpatients; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Neoplasms; Severity of Illness Index

In this report, we quantify the effects of exenatide and glargine on the relative contributions of fasting and postprandial glucose (PPG) excursion to overall hyperglycemia based on self-monitored blood glucose. After 26 weeks of treatment, insulin glargine reduced fasting glucose to a greater extent than exenatide without significant effect on PPG excursion. The principal effect of exenatide on hyperglycemia was mitigating the rise in PPG with moderate improvement on fasting glucose. These findings may be limited by the fact that glucose measurements were collected through self-monitoring with six time points measured during the daytime, the meals were not standardized and the exact time for glucose measurements was unknown.

Topics: Aged; Area Under Curve; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Exenatide; Female; Humans; Hyperglycemia; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Peptides; Postprandial Period; Risk Assessment; Single-Blind Method; Treatment Outcome; Venoms

The objective was to compare the impact on treatment satisfaction (TS) and quality of life (QoL) of early insulinization with glargine versus adjusting oral antidiabetic drug (OAD) therapy in people with Type 2 diabetes with uncontrolled glycemia. TS and QoL were assessed at baseline, weeks 12 and 24 within the Canadian INSIGHT, a randomized 24-week trial of Type 2 patients. A total of 366 patients randomized to either the insulin glargine arm (n=182) or the adjusted OAD therapy arm (n=184) completed both questionnaires. At baseline, TS and QoL were similar in both groups. A1c reduction was greater in the insulin glargine arm. TS improved from baseline in both treatment arms; however, there was greater increase with insulin glargine+OAD. Perceived frequency of hypoglycemia and hypoglycemia were lower at week 24, with no differences between the two groups. Perceived frequency of hyperglycemia improved with glargine at week 12, and no difference was found at 24 weeks. Finally, QoL improved in both groups, but significantly more with glargine at both weeks 12 and 24. Improving glucose control by adding insulin glargine to OAD therapy had a positive impact on TS and general QoL without complaints related to hypoglycemia.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Patient Satisfaction; Quality of Life

We sought to study the optimal management of hyperglycemia in non-intensive care unit patients with type 2 diabetes, as few studies thus far have focused on the subject.. We conducted a prospective, multicenter, randomized trial to compare the efficacy and safety of a basal-bolus insulin regimen with that of sliding-scale regular insulin (SSI) in patients with type 2 diabetes. A total of 130 insulin-naive patients were randomized to receive glargine and glulisine (n = 65) or a standard SSI protocol (n = 65). Glargine was given once daily and glulisine before meals at a starting dose of 0.4 units x kg(-1) x day(-1) for blood glucose 140-200 mg/dl or 0.5 units x kg(-1) x day(-1) for blood glucose 201-400 mg/dl. SSI was given four times per day for blood glucose >140 mg/dl.. The mean admission blood glucose was 229 +/- 6 mg/dl and A1C 8.8 +/- 2%. A blood glucose target of <140 mg/dl was achieved in 66% of patients in the glargine and glulisine group and in 38% of those in the SSI group. The mean daily blood glucose between groups ranged from 23 to 58 mg/dl, with an overall blood glucose difference of 27 mg/dl (P < 0.01). Despite increasing insulin doses, 14% of patients treated with SSI remained with blood glucose >240 mg/dl. There were no differences in the rate of hypoglycemia or length of hospital stay.. Treatment with insulin glargine and glulisine resulted in significant improvement in glycemic control compared with that achieved with the use of SSI alone. Our study indicates that a basal-bolus insulin regimen is preferred over SSI in the management of non-critically ill, hospitalized patients with type 2 diabetes.

Topics: Adult; Aged; Diabetes Mellitus, Type 2; Female; Hospitalization; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Prospective Studies; Treatment Outcome

Mitiglinide is novel class of rapid-acting insulin secretagogues, which have been widely used alone or in combination with other oral hypoglycemic drugs to improve postprandial hyperglycemia in early type 2 diabetes. While mitiglinide enhances postprandial requirement of insulin, the efficacy of mitiglinide combined with insulin has yet to be established. We investigated the efficacy of mitiglinide combined with insulin glargine, the first soluble insulin analog that has a flat and prolonged effect. After control with the intensive regimen (daily aspart insulin and glargine), 30 inpatients with type 2 diabetes were switched to premeal mitiglinide combined with once daily insulin glargine (mitiglinide regimen), and daily profiles of blood glucose level were compared under each regimen. Fifteen patients showed similar control of hyperglycemia with mitiglinide regimen and intensive insulin regimen, assessed by M value (<32), while the remaining 15 showed worsening under the mitiglinide regimen. The patients who were well controlled with mitiglinide regimen were significantly younger (51.9 +/- 16.0 years, p<0.005) and heavier (body mass index: 25.7 +/- 3.3 kg/m(2), p<0.05) than those who were not (67.9 +/- 8.7 and 23.0 +/- 3.1, respectively). Moreover, insulin doses of aspart per body weight were significantly fewer in effective group than in ineffective group. Duration of diabetes was shorter in the effective group, albeit insignificantly. Previous treatment before starting intensive insulin regimen, such as insulin and sulfonylurea, was not different between the two groups. Our results suggest that mitiglinide plus insulin glargine combination therapy is useful for lowering both fasting and postprandial hyperglycemia in a subpopulation of type 2 diabetes. The long-term effects of such treatment need to be established in future studies.

Topics: Adult; Age Factors; Aged; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Hyperglycemia; Hypoglycemic Agents; Indoles; Insulin; Insulin Aspart; Insulin Glargine; Insulin, Long-Acting; Isoindoles; Male; Middle Aged; Postprandial Period; Time Factors

Traditionally hyperglycemia in surgical inpatients has been managed with six-hourly sliding-scale regular insulin. However, this approach is usually ineffective in preventing hyperglycemia since no basal insulin is provided. We compared glycemic control using NPH and regular insulin versus glargine insulin alone in patients after cardiovascular surgery on a general surgical ward.. Ninety-four hyperglycemic patients were randomized to subcutaneous insulin using twice-daily NPH/regular or once-daily glargine if they required at least 1 unit/h of intravenous insulin at the time of transfer from the ICU. NPH/regular was adjusted twice daily; glargine was adjusted once daily. Blood glucose was measured four times daily and targeted to 80-140 mg/dL.. The mean blood glucose after NPH/regular (124 mg/dL) and glargine (131 mg/dL) was similar (P = 0.065). In the subgroup of patients with a history of diabetes, mean blood glucose was significantly lower after NPH/regular (133 mg/dL) versus glargine (154 mg/dL) (P = 0.016). Blood glucose less than 60 mg/dL was significantly less common after glargine (0.5%) as compared with NPH/regular (2%) (P = 0.036).. Once-daily glargine insulin provides good glycemic control in hyperglycemic patients after cardiovascular surgery. Although twice-daily NPH/regular insulin provided better control than glargine insulin monotherapy, the simplicity and safety of glargine insulin make it an attractive option for the management of postoperative hyperglycemia. Patients with established diabetes will achieve better glucose control with NPH/regular insulin as compared with glargine but have a higher incidence of hypoglycemia.

Topics: Adult; Aged; Aged, 80 and over; Blood Glucose; Cardiovascular Surgical Procedures; Female; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Postoperative Complications

The purpose of this study was to verify whether it is possible to use insulin glargine (Lantus) subcutaneously in patients receiving artificial nutrition (AN) and if the analogue is capable of obtaining and maintaining good glycaemic control without inducing hypoglycaemia. The sample considers 25 patients receiving AN, diagnosed diabetics and non-diabetics, who had previously been prescribed traditional insulin therapy. All were to be given subcutaneous insulin glargine at a dosage equal to the average of insulin/day administered in the preceding days spent receiving AN. Twenty-five consecutive patients, not stratified in any way, were judged eligible in the last six months of 2004 and first two months of 2005. Four out of these 25 could not be evaluated, either because they did not begin or complete the treatment with Lantus (3/4) or because the proper number of glycaemic tests were not carried out (1/4); 21/25 patients, 84% of the sample with a mean age of 68.7 years (range 46-91 years), finished the study and could be evaluated. The mean glycaemic values after treatment with glargine were already better on the second day, and on the seventh day the difference was statistically significant. No hypoglycaemia requiring medical intervention occurred. This study confirms the possibility of using insulin glargine in patients receiving AN with hyperglycaemia regardless of the type of nutrition and whether or not the patient is diabetic.

Topics: Aged; Aged, 80 and over; Blood Glucose; Body Mass Index; Enteral Nutrition; Glycemic Index; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Middle Aged; Nutritional Support; Parenteral Nutrition, Total

The objective of this study was to compare the efficacy and safety of insulin glargine, a long-acting insulin analog, with NPH insulin in children and adolescents with type 1 diabetes mellitus (T1DM). In a multicenter, open-label, randomized, 6-month study, 349 patients with TIDM, aged 5-16 years, received insulin glargine once daily or NPH insulin either once or twice daily, based on their prior treatment regimen. Although there was no significant difference between the NPH insulin and insulin glargine treatment groups with respect to baseline to endpoint change in HbA1c levels, fasting blood glucose (FBG) levels decreased significantly more in the insulin glargine group (-1.29 mmol/l) than in the NPH insulin group (-0.68 mmol/L, p = 0.02). The percentage of symptomatic hypoglycemic events was similar between groups; however, fewer patients in the insulin glargine group reported severe hypoglycemia (23% vs 29%) and severe nocturnal hypoglycemia (13% vs 18%), although these differences were not statistically significant (p = 0.22 and p = 0.19, respectively). Fewer serious adverse events occurred in the insulin glargine group than in the NPH insulin group (p < 0.02). A once-daily subcutaneous dose of insulin glargine provides effective glycemic control and is well tolerated in children and adolescents with T1DM.

Topics: Adolescent; Age of Onset; Blood Glucose; Child; Child, Preschool; Diabetes Mellitus, Type 1; Double-Blind Method; Drug Hypersensitivity; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Multicenter Studies as Topic; Puberty

To assess satisfaction with treatment and psychological well-being associated with insulin glargine and Neutral Protamine Hagedorn (NPH). Insulin glargine, a new long-acting insulin analogue, provides constant, peakless insulin release following once-daily administration and is associated with fewer hypoglycaemic episodes, despite metabolic control equivalent to that achieved with NPH human basal insulin.. The Diabetes Treatment Satisfaction Questionnaire (DTSQ) and Well-being Questionnaire (W-BQ) were completed at baseline and at weeks 8, 20 or 28 by 517 patients with Type 1 diabetes participating in a randomized, controlled European trial comparing insulin glargine and NPH. Analysis of covariance was performed on change from baseline scores (main effects: treatment and pooled site; covariate: baseline scores).. Treatment satisfaction improved with insulin glargine at all time points, including endpoint, but deteriorated slightly with NPH. These differences were significant throughout the study (change from baseline to endpoint: +1.27 vs. -0.56; P = 0.0001). Outcomes were better with insulin glargine for the DTSQ items, Perceived Frequency of Hyperglycaemia and Hypoglycaemia, with statistically significant differences at week 28 and endpoint for hyperglycaemia (P = 0.0373 and 0.0379) and at week 20 for hypoglycaemia (P = 0.0024). There was no difference in psychological well-being between the treatment groups, with mean scores increasing in both.. Study participants had treatment-independent improvements in General Well-being. Advantages for insulin glargine were seen in significantly improved Treatment Satisfaction throughout the study, together with lower Perceived Frequency of Hyperglycaemia than for patients on NPH, without a significant increase in Perceived Frequency of Hypoglycaemia.

Topics: Adolescent; Adult; Aged; Attitude to Health; Diabetes Mellitus, Type 1; Female; Humans; Hyperglycemia; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Patient Satisfaction; Surveys and Questionnaires; Treatment Outcome

Steroid-induced hyperglycemia was diagnosed in an older hospitalized patient after he was treated with the intermediate-acting glucocorticoid methylprednisolone. Before hospital admission, the patient did not have a diagnosis of diabetes. His elevated admission glucose level of 167 mg/dL along with his significant hyperglycemia after glucocorticoid initiation prompted the medical team to obtain a hemoglobin A1c result, 8.4%, which confirmed the diagnosis of type 2 diabetes. The capillary blood glucose level was elevated into the 200 to 399 mg/dL range for most of the patient's hospital stay while he was receiving subcutaneous insulin therapy of glargine and aspart correction and prandial bolus dosing. When the patient's subcutaneous insulin therapy was changed from glargine to neutral protamine Hagedorn insulin, the target glucose level range of 140 to 180 mg/dL was attained. From this case report, we determined that it is important to consider modifying subcutaneous insulin therapy by using another type of insulin when target glucose values are not achieved during the treatment of steroid-induced hyperglycemia.

Topics: Diabetes Mellitus, Type 2; Glucocorticoids; Glucose; Humans; Hyperglycemia; Insulin; Insulin Glargine; Male; Steroids

Recent advances in Automated Insulin Delivery systems have been shown to dramatically improve glycaemic control and reduce the risk of hypoglycemia in people with type 1 diabetes. However, they are complex systems that require specific training and are not affordable for most. Attempts to reduce the gap with closed-loop therapies using advanced dosing advisors have so far failed, mainly because they require too much human intervention. With the advent of smart insulin pens, one of the main constraints (having reliable bolus and meal information) disappears and new strategies can be employed. This is our starting hypothesis, which we have validated in a very demanding simulator. In this paper, we propose an intermittent closed-loop control system specifically intended for multiple daily injection therapy to bring the benefits of artificial pancreas to the application of multiple daily injections.. The proposed control algorithm is based on model predictive control and integrates two patient-driven control actions. Correction insulin boluses are automatically computed and recommended to the patient to minimize the duration of hyperglycemia. Rescue carbohydrates are also triggered to avoid hypoglycemia episodes. The algorithm can adapt to different patient lifestyles with customizable triggering conditions, closing the gap between practicality and performance. The proposed algorithm is compared with conventional open-loop therapy, and its superiority is demonstrated through extensive in silico evaluations using realistic cohorts and scenarios. The evaluations were conducted in a cohort of 47 virtual patients. We also provide detailed explanations of the implementation, imposed constraints, triggering conditions, cost functions, and penalties for the algorithm.. The in-silico outcomes combining the proposed closed-loop strategy with slow-acting insulin analog injections at 09:00 h resulted in percentages of time in range (TIR) (70-180 mg/dL) of 69.5%, 70.6%, and 70.4% for glargine-100, glargine-300, and degludec-100, respectively, and injections at 20:00 h resulted in percentages of TIR of 70.5%, 70.3%, and 71.6%, respectively. In all the cases, the percentages of TIR were considerably higher than those obtained from the open-loop strategy, being only 50.7%, 53.9%, and 52.2% for daytime injection and 55.5%, 54.1%, and 56.9% for nighttime injection. Overall, the occurrence of hypoglycemia and hyperglycemia was notably reduced using our approach.. Event-triggering model predictive control in the proposed algorithm is feasible and may meet clinical targets for people with type 1 diabetes.

Topics: Algorithms; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Glycemic Control; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Infusion Systems; Pancreas, Artificial

Twice/day dosing of insulin glargine has been used to treat hyperglycemia in clinical practice; however, data supporting its use in the critically ill population are lacking. This study was designed to evaluate the safety and efficacy of twice/day insulin glargine in critically ill patients.. A retrospective study was conducted in adult patients admitted to the intensive care units between February 2013 and June 2017 who received insulin glargine twice/day or 40 units or more once/day for 48 hours or longer. Post cardiovascular surgery patients were excluded. Data were collected for up to 14 patient-days. The efficacy outcomes included the incidence of hyperglycemia (blood glucose [BG] above 180 mg/dl), predose hyperglycemia rate (BG above 180 mg/dl within 4 hrs before the dose), and BG variability (standard deviation). The safety outcome was assessed by the development of hypoglycemia (BG below 70 mg/dl).. This is the first study demonstrating that twice/day insulin glargine reduced the rate of predose hyperglycemia without increasing the risk of hypoglycemia in critically ill patients. A large randomized study is needed to confirm the safety and efficacy of twice/day glargine in the critically ill.

Topics: Aged; Blood Glucose; Critical Care; Critical Illness; Drug Administration Schedule; Female; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin Glargine; Male; Middle Aged; Retrospective Studies

We present a case of intoxication by synthetic cannabinoids (SC). SC are substances of abuse with effects similar to Marijuana but with a different chemical structure, which avoids its detectability by regular drug tests, making diagnosis difficult. Among the possible side effects of their use is hyperglycemia. Their presence should be suspected in cases of hyperglycemia that cannot be explained by any other cause, especially in young patients presenting another clinical picture suggestive of SC consumption such as agitation, confusional symptoms or psychosis; the patient should be questioned about their use. It is important that the diabetic population knows the side effects of synthetic cannabinoids to avoid their consumption, as it is a sector of the population especially vulnerable to the consequences of their use.

Topics: Cannabinoids; Diabetes Mellitus, Type 1; Dronabinol; Hallucinogens; Humans; Hyperglycemia; Hypoglycemic Agents; Illicit Drugs; Insulin Aspart; Insulin Glargine; Male; Synthetic Drugs; Young Adult

Both hyperglycemia and hypoglycemia in hospitalized patients represent a major concern as they are associated with adverse outcomes-including increased rates of infection, longer hospital stay, and even death. Insulin therapy is the mainstay in the management of inpatient hyperglycemia. The traditional approach of sliding scale insulin (SSI) therapy for the temporary management of blood glucose levels in hospitalized patients, has now given way to basal-bolus insulin (BBI) therapy. This is owing to the BBI affording a better glycemic control in non-critical hospital settings as observed in multiple clinical studies using insulin glargine 100 U/mL (Gla-100) as the basal component. Furthermore, a string of clinical studies has also attested to Gla-100 being used effectively even in patients on corticosteroids, enteral or parenteral nutrition, and in perioperative settings. Hence, overall, the existing evidence would point to the growing role of BBI regimens centering around basal insulin like Gla-100 as an effective option with low safety concerns for insulin therapy in both hospitalized and out-patient settings in the treatment of patients with type 2 diabetes mellitus (T2DM).

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine

Hyperglycemia is a frequent complication in patients receiving parenteral nutrition (PN) and has been associated with an increased risk of mortality. Treatment of hyperglycemia requires insulin therapy; however, the optimal dose and route have not been established. This study aimed to compare regular insulin added to PN (RI-in-PN) with subcutaneous insulin glargine for the management of hyperglycemia in patients receiving PN.. This retrospective study was conducted at a tertiary medical center and reviewed 113 adult, non-critically ill surgical patient admissions receiving PN over a 5-year period. The primary outcome was achievement of glycemic control. Secondary outcomes were time to glycemic control, hypoglycemic events, hospital length of stay, and 1-year mortality.. The RI-in-PN group had a significantly higher percentage of patient admissions who achieved glycemic control compared with the insulin glargine group (71.8% vs 48.6%, P = 0.017). There was no difference in time to glycemic control, hypoglycemic events, hospital length of stay, or 1-year mortality between groups. Among patients with diabetes mellitus (DM), however, the insulin glargine group had a significantly higher percentage of admissions with at least 1 hypoglycemic event (45.5% vs 20%, P = 0.035).. RI-in-PN is recommended over insulin glargine because of the higher likelihood of achieving glycemic control and, in patients with DM, lower risk of hypoglycemic events. Large, randomized controlled trials are needed to further guide prescribing practice.

Topics: Adult; Blood Glucose; Diabetes Mellitus; Female; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Male; Middle Aged; Parenteral Nutrition; Retrospective Studies; Treatment Outcome

Insulin receptor (IR) insufficiency in β-cells leads to impaired insulin secretion and reduced β-cell hyperplasia in response to hyperglycemia. Selective IR deficiency in β-cells in later embryological development may lead to compensatory β-cell hyperplasia. Although these findings suggest insulin signaling on the β-cell is important for β-cell function, they are confounded by loss of signaling by the insulinlike growth factors through the IR. To determine whether insulin itself is necessary for β-cell development and maturation, we performed a characterization of pancreatic islets in mice with deletions of both nonallelic insulin genes (Ins1-/-Ins2-/-). We immunostained neonatal Ins1-/-Ins2-/- and Ins1+/+Ins2+/+ pancreata and performed quantitative polymerase chain reaction on isolated neonatal islets. Insulin-deficient islets had reduced expression of factors normally expressed in maturing β-cells, including muscoloaponeurotic fibrosarcoma oncogene homolog A, homeodomain transcription factor 6.1, and glucose transporter 2. Ins1-/-Ins2-/-β-cells expressed progenitor factors associated with stem cells or dedifferentiated β-cells, including v-myc avian myolocytomatosis viral oncogene lung carcinoma derived and homeobox protein NANOG. We replaced insulin by injection or islet transplantation to keep mice alive into adulthood to determine whether insulin replacement was sufficient for the completed maturation of insulin-deficient β-cells. Short-term insulin glargine (Lantus®) injections partially rescued the β-cell phenotype, whereas long-term replacement of insulin by isogenic islet transplantation supported the formation of more mature β-cells. Our findings suggest that tightly regulated glycemia, insulin species, or other islet factors are necessary for β-cell maturation.

Topics: Animals; Animals, Newborn; Biomarkers; Cell Differentiation; Cell Size; Female; Fibrosis; Gene Expression Regulation, Developmental; Hormone Replacement Therapy; Hyperglycemia; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin Secretion; Insulin-Secreting Cells; Islets of Langerhans Transplantation; Male; Mice, Inbred C57BL; Mice, Knockout; Tissue Culture Techniques

We herein present a case of a 20-year-old woman who suffered from type I diabetes mellitus and died from a diabetic ketoacidosis in a context of addiction to hyperglycemia. Diabetic ketoacidosis is a lethal complication of insulin-dependent diabetes mellitus, which can result from insulin therapy stoppage. This can occur voluntarily with suicidal intent or involuntarily due to treatment inaccessibility, forgotten injections, or material deficiency. A new possibility is investigated in our case study: hyperglycemia addiction. The patient was treated by insulin glargine and insulin aspartate. She regularly stopped insulin glargine injections seeking the asthenia sensation produced by hyperglycemia, keeping the insulin aspartate injections to treat the disabling symptom related to hyperketonemia.

Topics: Asthenia; Behavior, Addictive; Depression; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin Glargine; Medication Adherence; Young Adult

This retrospective cohort study compared real-world clinical and healthcare-resource utilization (HCRU) data in patients with type 2 diabetes using basal insulin (BI) who switched to insulin glargine 300 units/mL (Gla-300) or another BI. Data from the Predictive Health Intelligence Environment database 12 months before (baseline) and 6 months after (follow-up) the switch date (index date, March 1, 2015 to May 31, 2016) included glycated haemoglobin A1c (HbA1c), hypoglycaemia, HCRU and associated costs. Baseline characteristics were balanced using propensity score matching. Change in HbA1c from baseline was similar in both matched cohorts (n = 1819 in each). Hypoglycaemia incidence and adjusted event rate were significantly lower with Gla-300. Patients switching to Gla-300 had a significantly lower incidence of HCRU related to hypoglycaemia. All-cause and diabetes-related hospitalization and emergency-department HCRU were also favourable for Gla-300. Lower HCRU translated to lower costs in patients using Gla-300. In this real-world study, switching to Gla-300 reduced the risk of hypoglycaemia in patients with type 2 diabetes when compared with those switching to another BI, resulting in less HCRU and potential savings of associated costs.

Topics: Cohort Studies; Cost Savings; Costs and Cost Analysis; Delivery of Health Care, Integrated; Diabetes Mellitus, Type 2; Drug Compounding; Drug Monitoring; Electronic Health Records; Female; Follow-Up Studies; Glycated Hemoglobin; Health Care Costs; Humans; Hyperglycemia; Hypoglycemia; Insulin; Insulin Glargine; Male; Middle Aged; Patient Acceptance of Health Care; Retrospective Studies; United States

This study examines the relationship between glycated haemoglobin (A1C) levels and treatment persistence with, or time to discontinuation of, basal insulin in patients with type 2 diabetes (T2D) newly initiating insulin. Claims data were extracted from the Optum Clinformatics database from January 2010 to June 2015. Adult patients with T2D initiating insulin glargine 100 U/mL (Gla-100) or insulin detemir (DET) with ≥1 A1C measurement during 12-month baseline and 18-month follow-up periods were included. Patients with a refill gap of >90 days were considered non-persistent; otherwise, patients were considered persistent with insulin. The main outcome was A1C, measured closest to the end of each quarter during the follow-up period. A total of 3993 of 109 934 patients met the inclusion criteria (43.0% persistent; 57.0% non-persistent). Persistent patients were older (54.7 vs 52.7 years; P < .001), were more likely to be male (59.4% vs 54.4%; P = .002), and had significantly lower mean unadjusted A1C values at 18 months (8.26% vs 8.60%; P < .001) and quarterly. Only 43.0% of adults initiating basal insulin persisted with treatment for 18 months, with earlier discontinuation associated with higher A1C.

Topics: Age Factors; Cohort Studies; Diabetes Mellitus, Type 2; Drug Monitoring; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin Detemir; Insulin Glargine; Insurance, Health; Male; Medicare; Medication Adherence; Middle Aged; Retrospective Studies; Sex Characteristics; United States

Neonatal hyperglycemia is common in extremely low birth weight (ELBW) infants because of physiologic stress, exogenous glucose infusion, and postnatal corticosteroid therapy for hypotension, adrenal insufficiency, and pulmonary immaturity. The use of long-acting insulin glargine has been described in the treatment of transient neonatal diabetes in the premature infant, but in these reports is a lack of regard to its use in the treatment of iatrogenic neonatal hyperglycemia. We present the case of an ELBW infant with significant hyperglycemia that was refractory to usual treatment but demonstrated a favorable response to long-acting subcutaneous insulin glargine. The pharmacokinetics on regular insulin and long-acting insulin are different. Regular insulin is broken down into biologically active monomers after subcutaneous injection, and long-acting insulin forms microprecipitates and is gradually released to the body at a neutral physiologic pH after subcutaneous injection. Pharmacokinetics of both regular insulin and long-acting insulin are not clear in ELBW infants. However, with further research on long-acting insulin, it can be used safely to achieve consistent euglycemia with once-daily administration in neonatal hyperglycemia.

Topics: Humans; Hydrocortisone; Hyperglycemia; Hypoglycemic Agents; Hypotension; Infant, Extremely Low Birth Weight; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Injections, Subcutaneous; Insulin Glargine

Hemoglobin A1C is universally used as a marker for glycemic control and to establish glycemic goals in patients with diabetes. In the older population, experts recommend liberating A1C goals to decrease the risk of hypoglycemia. However, it's not clear which A1C level is optimal for this purpose. This study's aim was to understand the relationship between A1C levels and risk of hypoglycemia.. In a prospective study, we performed continuous glucose monitoring (CGM) on older adults on insulin. Hypoglycemia duration and A1C were measured at baseline while patients were on multiple insulin injections, and again after de-intensification to once-a-day basal insulin with non-insulin agents.. We assessed 65 patients; mean age76±6years with on average 3.7±1.3 insulin injections/day. At baseline, 26% of the patients had A1C<7% (53mmol/mol), 42% between 7.1% and 8% (54-64mmol/mol), 21% between 8.1% and 9% (65-75mmol/mol), and 11% >9% (76mmol/mol). The duration of hypoglycemia (<70mg/dl, <60mg/dl, <50mg/dl) was not different between the A1c groups, regardless of treatment intensity (multiple insulin injections or once-a-day-basal insulin with non-insulin agents).. A1C levels are not associated with hypoglycemia risk in older population with type-2 diabetes on insulin therapy. Higher A1C goals do not protect against hypoglycemia.

Topics: Administration, Oral; Aged; Aged, 80 and over; Aging; Biomarkers; Blood Glucose; Boston; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Monitoring; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Monitoring, Ambulatory; Practice Guidelines as Topic; Prospective Studies; Risk; Sulfonylurea Compounds

To estimate the long-term cost-effectiveness of exenatide twice daily vs insulin glargine once daily as add-on therapy to oral antidiabetic agents (OADs) for Chinese patients with type 2 diabetes (T2DM).. The Cardiff Diabetes Model was used to simulate disease progression and estimate the long-term effects of exenatide twice daily vs insulin glargine once daily. Patient profiles and treatment effects required for the model were obtained from literature reviews (English and Chinese databases) and from a meta-analysis of 8 randomized controlled trials comparing exenatide twice daily with insulin glargine once daily add-on to OADs for T2DM in China. Medical expenditure data were collected from 639 patients with T2DM (aged ≥18 years) with and without complications incurred between January 1, 2014 and December 31, 2015 from claims databases in Shandong, China. Costs (2014 Chinese Yuan [¥]) and benefits were estimated, from the payers' perspective, over 40 years at a discount rate of 3%. A series of sensitivity analyses were performed.. Patients on exenatide twice daily + OAD had a lower predicted incidence of most cardiovascular and hypoglycaemic events and lower total costs compared with those on insulin glargine once daily + OAD. A greater number of quality-adjusted life years (QALYs; 1.94) at a cost saving of ¥117 706 gained was associated with exenatide twice daily vs insulin glargine once daily. (i.e. cost saving of ¥60 764/QALY) per patient.. In Chinese patients with T2DM inadequately controlled by OADs, exenatide twice daily is a cost-effective add-on therapy alternative to insulin glargine once daily, and may address the problem of an excess of medical needs resulting from weight gain and hypoglycaemia in T2DM treatment.

Topics: Administration, Oral; Cardiovascular Diseases; China; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Cardiomyopathies; Direct Service Costs; Drug Administration Schedule; Drug Therapy, Combination; Exenatide; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incidence; Incretins; Injections, Subcutaneous; Insulin Glargine; Middle Aged; Models, Economic; Peptides; Quality of Life; Randomized Controlled Trials as Topic; Venoms

Glargine and detemir insulin are the two most commonly prescribed basal insulin analogues for the ambulatory and inpatient management of diabetes. The efficacy and safety of basal insulin analogues in the hospital setting has not been established.. This observational study compared differences in glycemic control and outcomes in non-intensive care unit patients with blood glucose (BG) >140 mg/dL who were treated with glargine or detemir, between January 1, 2012, and September 30, 2015, in two academic centers.. Among 6,245 medical and surgical patients with hyperglycemia, 5,749 received one or more doses of glargine, and 496 patients received detemir during the hospital stay. There were no differences in the mean daily BG (glargine, 182 ± 46 mg/dL vs. detemir, 180 ± 44 mg/dL; P = .70). There were no differences in mortality, hospital complications, or re-admissions between groups (all, P>.05). After adjusting for potential confounders, there was no statistically significant difference in hypoglycemia rates between treatment groups. Patients treated with detemir required higher total daily basal insulin doses (0.27 ± 0.16 units/kg/day vs. 0.22 ± 0.15 units/kg/day; P<.001). Glargine-treated patients had statistically longer length of stay; however, this difference may not be clinically relevant (6.8 ± 7.4 days vs. 6.0 ± 6.3 days; P<.001).. Our study indicates that treatment with glargine and detemir results in similar inpatient glycemic control in general medicine and surgery patients. Detemir treatment was associated with higher daily basal insulin dose and number of injections. A prospective randomized study is needed to confirm these findings.. BG = blood glucose BMI = body mass index CI = confidence interval eGFR = estimated glomerular filtration rate HbA1c = glycated hemoglobin ICD-9 = International Classification of Diseases, ninth revision ICU = intensive care unit IQR = interquartile range LOS = length-of-stay OR = odd ratio.

Topics: Aged; Blood Glucose; Diabetes Mellitus; Female; Humans; Hyperglycemia; Hypoglycemic Agents; Inpatients; Insulin Detemir; Insulin Glargine; Length of Stay; Male; Middle Aged

The optimal initial dose of subcutaneous (SC) insulin after intravenous (IV) infusion is controversial, especially in patients receiving continuous enteral nutrition (EN) or total parenteral nutrition (TPN). The aim of this study was to evaluate the strategy used at our hospital intensive care unit (ICU) in patients switched from IV insulin to SC insulin glargine while receiving EN or TPN.. A retrospective analysis was made of 27 patients on EN and 14 on TPN switched from IV infusion insulin to SC insulin. The initial dose of SC insulin was estimated as 50% of the daily IV insulin requirements, extrapolated from the previous 12h. A corrective dose of short-acting insulin (lispro) was used when necessary.. Mean blood glucose (BG) level during SC insulin treatment was 136±35mg/dL in the EN group and 157±37mg/dL in the TPN group (p=0.01). In the TPN group, mean BG was >180mg/dL during the first three days after switching, and a 41% increase in the glargine dose was required to achieve the target BG. In the EN group, mean BG remained <180mg/dL throughout the days of transition and the dose of glargine remained unchanged.. In the transition from IV to SC insulin therapy, initial insulin glargine dose estimated as 50% of daily IV insulin requirements is adequate for patients on EN, but inadequate in those given TPN.

Topics: Aged; Aged, 80 and over; APACHE; Blood Glucose; Critical Care; Diabetes Mellitus; Drug Substitution; Enteral Nutrition; Female; Humans; Hyperglycemia; Infusions, Intravenous; Injections, Subcutaneous; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Male; Parenteral Nutrition; Retrospective Studies; Simplified Acute Physiology Score

In some circumstances, the premixed insulin should be switched to alternative therapy. The effectiveness and the safety of switching from premixed insulin to insulin glargine plus oral antidiabetic drugs (OADs) in Chinese patients with type 2 diabetes mellitus (T2DM) have not been clarified and, hence, will be assessed in this study. Chinese patients with T2DM (2013 men and women aged 18-75 years) who had received premixed insulin ± OADs for ≥3 months with glycated hemoglobin (HbA1c) ≤ 10% were enrolled in a prospective, observational study conducted at 53 hospitals across China. At baseline and at the discretion of the physician, patients switched from premixed insulin to insulin glargine plus OADs. Changes in HbA1c, fasting plasma glucose (FPG), 2-hour postprandial glucose (PPG), treatment satisfaction, and the incidence of hypoglycemia were assessed for 16 weeks. In total, 1850 patients completed the study. Mean HbA1c level for the group decreased significantly (from 7.8% ± 1.2% at week 1 to 7.0% ± 1.0% at week 16; P < .0001), and 55.2% of patients achieved HbA1c < 7% at week 16. Mean FPG and 2-hour PPG decreased significantly (-1.4 ± 2.2 and -2.1 ± 3.9 mmol/L, respectively; both P < .0001), whereas patient satisfaction improved significantly. Adverse events were reported in 18.7% of patients. Chinese patients with T2DM who switched from premixed insulin to insulin glargine plus OADs achieved significantly improved glycemic control and treatment satisfaction with a low incidence of hypoglycemia. Patients who are most likely to achieve the HbA1c target less than 7% are younger, have shorter disease duration, and have lower baseline HbA1c and FPG levels.

Topics: Administration, Oral; Biomarkers; Blood Glucose; China; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Postprandial Period; Prospective Studies; Treatment Outcome

Investigate contributors to treatment satisfaction in type 1 diabetes (T1D).. Post-hoc analysis using the Diabetes Treatment Satisfaction Questionnaire status version (DTSQs) in 771 T1D patients from two 28-week trials comparing once-daily insulin glargine 100U/mL (Gla-100) with once- or twice-daily NPH neutral protamine Hagedorn (NPH) insulin.. Gla-100 was associated with a significant improvement in treatment satisfaction versus NPH (overall population adjusted mean [standard error] DTSQs change from baseline: +1.13 [0.30] versus -0.04 [0.31]; p=0.006). In the overall population, treatment satisfaction improvement with all insulin regimens was related to less frequent severe hypoglycemia (coefficient-0.077; p=0.040) and HbA1c reduction (-0.066; p=0.082). By treatment regimen, relationships between treatment satisfaction and these outcomes approached or attained statistical significance for NPH insulin, but not Gla-100. In the overall population, predictors of treatment satisfaction improvement included: Gla-100 treatment (estimate 1.17, p=0.006), lower baseline DTSQs (-0.57, p<0.001), study (-1.01, p=0.019), lower severe hypoglycemia rate (0.17, p=0.012), and higher baseline HbA1c (0.44, p=0.014). By treatment regimen, these predictors remained significant for NPH insulin.. Gla-100 resulted in a significant improvement in treatment satisfaction versus NPH insulin, independent of baseline disease characteristics and clinical outcomes.

Topics: Adult; Clinical Trials, Phase III as Topic; Diabetes Mellitus, Type 1; Drug Administration Schedule; Drug Monitoring; Drug Resistance; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Male; Middle Aged; Patient Satisfaction; Randomized Controlled Trials as Topic; Retrospective Studies; Severity of Illness Index

Fibroblast growth factor 21 (FGF21) is a promising regulator of glucose and lipid metabolism with multiple beneficial effects including hypoglycemic and lipid-lowering. Previous studies have reported that FGF21 is expected to become a new drug for treatment of diabetes. Liraglutide and insulin glargine are the two representative anti-diabetic biological drugs. In the current study, we aim to compare the long-term pharmacological efficacy of mFGF21 (an FGF21 analogue), liraglutide and insulin glargine in type 2 diabetic db/db mice. Db/db mice were initially treated with three kinds of proteins (25nmol/kg/day) by subcutaneous injection once a day for 4weeks, then subsequently be treated with once every two days for next 4weeks. After 8weeks of treatments, the blood glucose levels, body weights, glycosylated hemoglobin levels, fasting insulin levels, serum lipid profiles, hepatic biochemical parameters, oral glucose tolerance tests and hepatic mRNA expression levels of several proteins (GK, G6P, GLUT-1 and GLUT-4) associated with glucose metabolism of the experimental mice were detected. Results demonstrated that three proteins could significantly decrease the fed blood glucose levels of db/db mice. After treatment for 1week, the fed blood glucose levels of db/db mice in liraglutide group were significantly lower than those in mFGF21 and insulin glargine groups. However, after 2weeks of administration, the long-lasting hypoglycemic effect of mFGF21 was superior to liraglutide and insulin glargine up to the end of the experiments. Compared with liraglutide and insulin glargine, mFGF21 significantly reduced the glycosylated hemoglobin levels and improved the ability on glycemic control, insulin resistance, serum lipid and liver function states in db/db mice after 8weeks treatments. In addition, mFGF21 regulated glucose metabolism through increasing the mRNA expression levels of GK and GLUT-1, and decreasing the mRNA expression level of G6P. But liraglutide and insulin glargine could only up-regulate the mRNA expression of GLUT-4. In summary, as a hypoglycemic drug for long-term treatment, mFGF21 has the potential to be an ideal drug candidate for the therapy of type 2 diabetes.

Topics: Animals; Biomarkers; Blood Glucose; Diabetes Mellitus, Type 2; Drugs, Investigational; Endopeptidases; Female; Fibroblast Growth Factors; Gene Expression Regulation; Hep G2 Cells; Hepatocytes; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin Resistance; Liraglutide; Mice, Inbred C57BL; Mice, Mutant Strains; Mutant Proteins; Random Allocation; Recombinant Proteins

Among patients with type 2 diabetes treated with insulin, perioperative hyperglycemia and hypoglycemia may cause undesirable symptoms, surgery delay or cancellation, or unexpected hospitalization. Our objective was to compare preoperative glargine dosing regimens on perioperative glycemic control in patients undergoing ambulatory surgery.. Observational study.. Pre- and postoperative holding areas.. One hundred fifty patients with type 2 diabetes using a once daily, evening insulin glargine regimen undergoing ambulatory surgery were included.. None.. To conduct the analysis, patients were divided into four groups based on the percentage of normal evening glargine dose taken. Group 1 took no glargine. Group 2 took 33%-57%. Group 3 took 60%-87% and Group 4 took 100% of their normal dose. The primary outcome was the proportion of patients in each group with blood glucose in the target range (100-180 mg/dL), and the incidence of hypoglycemia (defined as BG <70 mg/dL or symptomatic, requiring glucose).. Group 3 had the highest proportion (78%) of patients within target range (P<.001) and Group 4 had the highest proportion of patients with hypoglycemia (P=.01). Patients in Group 3 were significantly more likely to achieve target blood glucose than patients in either Group 1 (P=.001) or Group 4 (P=.002).. Our study shows that the percent of normal insulin dose given the evening before surgery directly impacts perioperative glucose levels in ambulatory surgery patients. Patients taking 60%-87% of their usual dose the evening before surgery were likely to arrive in target blood glucose range with decreased risk for hypoglycemia. The mean and mode dose taken in Group 3 were 73% and 75%, respectively, suggesting that the optimal dose may be 75% of normal dose.

Topics: Adult; Ambulatory Surgical Procedures; Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Male; Postoperative Complications; Preoperative Care

To compare glucose control and safety of different basal insulin therapies (BI, including Insulin NPH, glargine and detemir) in real-world clinical settings based on a large-scale registry study.. In this multi-center 6-month prospective observational study, patients with type 2 diabetes (HbA1c ≥ 7%) who were uncontrolled by oral anti-diabetic drugs (OADs) and were willing to initiate BI therapy were enrolled from 209 hospitals within 8 regions of China. Type and dose of BI were at the physician's discretion and the patients' willingness. Interviews were conducted at 0 months (visit 1), 3 months (visit 2) and 6 months (visit 3). Outcomes included change in HbA1c, hypoglycemia rate and body weight from baseline at 6 months.. A total of 16 341 and 9002 subjects were involved in Intention-To-Treat (ITT) and per-protocol (PP) analysis, respectively. After PS regression adjustment, ITT analysis showed that reduction in HbA1c in glargine (2.2% ± 2.1%) and detemir groups (2.2% ± 2.1%) was higher than that in the NPH group (2.0% ± 2.2%) (P < .01). The detemir group had the lowest weight gain (-0.1 ± 2.9 kg) compared with the glargine (+0.1 ± 3.0 kg) and NPH (+0.3 ± 3.1 kg) groups (P < .05). The glargine group had the lowest rate of minor hypoglycaemia, while there was no difference in severe hypoglycaemia among the 3 groups. The results observed in PP analyses were consistent with those in ITT analysis.. In a real-world clinical setting in China, treatment with long-acting insulin analogues was associated with better glycaemic control, as well as less hypoglycaemia and weight gain than treatment with NPH insulin in type 2 diabetes patients. However, the clinical relevance of these observations must be interpreted with caution.

Topics: China; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Monitoring; Drug Resistance; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Intention to Treat Analysis; Lost to Follow-Up; Prospective Studies; Registries; Severity of Illness Index; Weight Gain

In non-critical hospitalized patients with diabetes mellitus, guidelines suggest subcutaneous insulin therapy with basal-bolus regimen, even in old and vulnerable inpatients.. To evaluate safety, efficacy, and benefit on clinical management of the GesTIO protocol, a set of subcutaneous insulin administration rules, in old and vulnerable non-ICU inpatients.. Retrospective, observational study. Patients admitted to Geriatric Clinic of Padua were studied. 88 patients matched the inclusion criteria: type 2 diabetes or hospital-related hyperglycemia, ≥65 years, regular measurements of capillary glycemia, and basal-bolus subcutaneous insulin regimen managed by "GesTIO protocol" for five consecutive days.. ratio of patients with blood glucose (BG) <3.9 mmol/l; number of BG per patient in target range (5-11.1 mmol/l); daily mean BG; and calls to physicians for adjusting insulin therapy.. Mean age was 82 ± 7 years. 9.1% patients experienced mild hypoglycaemia, and no severe hypoglycaemia was reported. The median number of BG per patients in target range increased from 2.0 ± 2 to 3.0 ± 2 (p < 0.001). The daily mean BG decreased from 11.06 ± 3.03 to 9.64 ± 2.58 mmol/l (-12.8%, p < 0.005). The mean number of calls to physicians per patient decreased from 0.83 to 0.45 (p < 0.05).. Treatment with GesTIO protocol allows a safe and effective treatment even in very old and vulnerable inpatients with a faster management insulin therapy.

Topics: Aged; Aged, 80 and over; Blood Glucose; Clinical Protocols; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Geriatrics; Hospitalization; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Inpatients; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Retrospective Studies

Rebound hyperglycaemia (also termed Somogyi effect) is defined as hyperglycaemia caused by the release of counter-regulatory hormones in response to insulin-induced hypoglycaemia, and is widely believed to be common in diabetic cats. However, studies in human diabetic patients over the past quarter century have rejected the common occurrence of this phenomenon. Therefore, we evaluated the occurrence and prevalence of rebound hyperglycaemia in diabetic cats.. In a retrospective study, 10,767 blood glucose curves of 55 cats treated with glargine using an intensive blood glucose regulation protocol with a median of five blood glucose measurements per day were evaluated for evidence of rebound hyperglycaemic events, defined in two different ways (with and without an insulin resistance component).. While biochemical hypoglycaemia occurred frequently, blood glucose curves consistent with rebound hyperglycaemia with insulin resistance was confined to four single events in four different cats. In 14/55 cats (25%), a median of 1.5% (range 0.32-7.7%) of blood glucose curves were consistent with rebound hyperglycaemia without an insulin resistance component; this represented 0.42% of blood glucose curves in both affected and unaffected cats.. We conclude that despite the frequent occurrence of biochemical hypoglycaemia, rebound hyperglycaemia is rare in cats treated with glargine on a protocol aimed at tight glycaemic control. For glargine-treated cats, insulin dose should not be reduced when there is hyperglycaemia in the absence of biochemical or clinical evidence of hypoglycaemia.

Topics: Animals; Blood Glucose; Cat Diseases; Cats; Diabetes Mellitus; Hyperglycemia; Insulin Glargine; Retrospective Studies

Topics: Adolescent; Diabetes Insipidus, Neurogenic; Diabetes Mellitus, Type 2; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Magnetic Resonance Imaging; Male; Seizures

We evaluated the effect of sitagliptin on glycemic control, endogenous insulin secretion, and beta cell function in Japanese patients with type 2 diabetes mellitus (T2DM) receiving a combination of oral antidiabetics and basal insulin analog glargine (basal-supported oral therapy [BOT]). Twenty-one patients showing inadequate glycemic control with BOT were given dipeptidylpeptidase-4 inhibitor (DPP-4I) sitagliptin at 50 mg/day for 12 weeks. Clinical markers of glycemic control, HbA1c, glycated albumin (GA), and 1,5-anhydroglucitol (1,5-AG), were measured before and 4 and 12 weeks after the start of sitagliptin. A 2-hour morning meal test was performed upon enrollment and at 12 weeks, and plasma glucose (PG), serum C-peptide, and plasma intact proinsulin (PI) were measured. HbA1c, GA, and 1,5-AG at 4 and 12 weeks were significantly improved over enrollment levels. The area under the PG concentration curve (AUC-PG) during the meal test at 12 weeks was significantly reduced (from 350 ± 17 mg ･ hr/dL before sitagliptin treatment to 338 ± 21 mg ･ hr/dL [mean ± SE], P < 0.05,); the AUC-C-peptide was unchanged (from 3.4 ± 0.4 ng ･ hr/mL to 3.6 ± 0.5 ng ･ hr/mL). However, both fasting and 2-hour PI/C-peptide ratios at 12 weeks were significantly decreased (from 13.3 ± 2.3 to 11.1 ± 2.0 [P < 0 .05] and from 9.5 ± 1.6 to 5.3 ± 0.9 [P < 0.01], respectively). Adding sitagliptin to BOT in Japanese T2DM patients appears to improve glycemic control without increasing endogenous insulin secretion and to reduce fasting and 2-hour postprandial PI/C-peptide ratios.

Topics: Administration, Oral; Aged; Algorithms; Biomarkers; C-Peptide; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Monitoring; Drug Resistance; Drug Therapy, Combination; Fatty Acids, Nonesterified; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin-Secreting Cells; Insulin, Long-Acting; Japan; Male; Proinsulin; Pyrazines; Sitagliptin Phosphate; Triazoles

Neonatal diabetes mellitus (NDM) results from impaired insulin secretion, occurring within the first 6 months of life. NDM is classified as transient NDM (TNDM) or permanent NDM. To date there are no universal guidelines regarding its management. Intravenous insulin infusion represents the first and most adequate therapeutic approach for sustained hyperglycemia, but this can provide only a short-term solution. Several factors should be taken into account in the choice of the long-term treatment. We describe our experience with two infants affected by TNDM. The first child was treated with continuous subcutaneous insulin infusion, whereas the second infant was treated with subcutaneous insulin glargine injections. Our experience shows that the two different therapeutic approaches, if properly managed, are equally effective.

Topics: Diabetes Mellitus; Female; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Infant, Newborn; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin Infusion Systems; Insulin, Long-Acting; Italy; Precision Medicine; Treatment Outcome

The Somogyi effect postulates that nocturnal hypoglycaemia causes fasting hyperglycaemia attributable to counter-regulatory hormone release. Although most published evidence has failed to support this hypothesis, this concept remains firmly embedded in clinical practice and often prevents patients and professionals from optimizing overnight insulin. Previous observational data found lower fasting glucose was associated with nocturnal hypoglycaemia, but did not assess the probability of infrequent individual episodes of rebound hypoglycaemia. We analysed continuous glucose monitoring data to explore its prevalence.. We analysed data from 89 patients with Type 1 diabetes who participated in the UK Hypoglycaemia study. We compared fasting capillary glucose following nights with and without nocturnal hypoglycaemia (sensor glucose < 3.5 mmol/l).. Fasting capillary blood glucose was lower after nights with hypoglycaemia than without [5.5 (3.0) vs. 14.5 (4.5) mmol/l, P < 0.0001], and was lower on nights with more severe nocturnal hypoglycaemia [5.5 (3.0) vs. 8.2 (2.3) mmol/l; P = 0.018 on nights with nadir sensor glucose of < 2.2 mmol/l vs. 3.5 mmol/l]. There were only two instances of fasting capillary blood glucose > 10 mmol/l after nocturnal hypoglycaemia, both after likely treatment of the episode. When fasting capillary blood glucose is < 5 mmol/l, there was evidence of nocturnal hypoglycaemia on 94% of nights.. Our data indicate that, in clinical practice, the Somogyi effect is rare. Fasting capillary blood glucose ≤ 5 mmol/l appears an important indicator of preceding silent nocturnal hypoglycaemia.

Topics: Adult; Biphasic Insulins; Blood Glucose; Blood Glucose Self-Monitoring; Circadian Rhythm; Cohort Studies; Diabetes Mellitus, Type 1; Drug Monitoring; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Middle Aged; Monitoring, Ambulatory; Prevalence; Severity of Illness Index; United Kingdom

Impairment of the incretin effect is one of the hallmarks of type 2 diabetes mellitus (T2DM). However, it is unknown whether this abnormality is specific to incretin-stimulated insulin secretion or a manifestation of generalized β-cell dysfunction. The aim of this study was to determine whether improved glycemic control restores the incretin effect.. Fifteen T2DM subjects were studied before and after 8 weeks of intensified treatment with insulin. The incretin effect was determined by comparing plasma insulin and C-peptide levels at clamped hyperglycemia from iv glucose, and iv glucose plus glucose ingestion.. Long-acting insulin, titrated to reduce fasting glucose to 7 mM, lowered hemoglobin A1c from 8.6% ± 0.2% to 7.1% ± 0.2% over 8 weeks. The incremental C-peptide responses and insulin secretion rates to iv glucose did not differ before and after insulin treatment (5.6 ± 1.0 and 6.0 ± 0.9 nmol/L·min and 0.75 ± 0.10 and 0.76 ± 0.11 pmol/min), but the C-peptide response to glucose ingestion was greater after treatment than before (10.9 ± 2.2 and 7.1 ± 0.9 nmol/L·min; P = .03) as were the insulin secretion rates (1.11 ± 0.22 and 0.67 ± 0.07 pmol/min; P = .04). The incretin effect computed from plasma C-peptide was 21.8% ± 6.5% before insulin treatment and increased 40.9% ± 3.9% after insulin treatment (P < .02).. Intensified insulin treatment to improve glycemic control led to a disproportionate improvement of insulin secretion in response to oral compared with iv glucose stimulation in patients with type 2 diabetes. This suggests that in T2DM the impaired incretin effect is independent of abnormal glucose-stimulated insulin secretion.

Topics: Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Drug Monitoring; Female; Glucose Clamp Technique; Humans; Hyperglycemia; Hypoglycemic Agents; Incretins; Insulin; Insulin Glargine; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Insulin, Long-Acting; Male; Middle Aged; Overweight

Postprandial insulin pulsatility is impaired in patients with type 2 diabetes, but the effects of exogenous insulin therapy on pulsatile insulin secretion are not known. We addressed, whether pulsatile insulin secretion is related to glycaemic control, whether basal insulin supplementation increases postprandial insulin secretion, and if so, is this accomplished by a specific improvement in pulsatile insulin secretion?. Fourteen patients with type 2 diabetes underwent a mixed meal test before and after an 8-week treatment period with insulin glargine. Glucose, insulin and C-peptide levels were measured, and insulin pulsatility was determined by deconvolution analysis.. Insulin treatment lowered fasting glycaemia from 179.6 ± 7.5 mg/dl to 117.6 ± 6.5 mg/dl (p < 0.001). Postprandial insulin and C-peptide levels increased significantly after the treatment period (p < 0.0001). The total calculated insulin secretion rate increased with insulin treatment (p = 0.0039), with non-significant increases in both pulsatile and non-pulsatile insulin secretion. Insulin pulse frequency was unchanged by the intervention. There was an inverse relationship between fasting and postprandial glycaemia and insulin pulse mass (r(2) = 0.51 and 0.56, respectively), whereas non-pulsatile insulin secretion was unrelated to either fasting or postprandial glucose concentrations (r(2) = 0.0073 and 0.031).. Hyperglycaemia in type 2 diabetes is associated with a reduction in postprandial insulin secretion, specifically through a reduction in insulin pulsatility. Reducing chronic hyperglycaemia by basal insulin therapy enhances endogenous β-cell function in the postprandial state. These data support the use of basal insulin regimens in the pharmacotherapy of overtly hyperglycaemic patients with type 2 diabetes.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Female; Humans; Hyperglycemia; Insulin; Insulin Glargine; Insulin Secretion; Insulin, Long-Acting; Male; Middle Aged; Postprandial Period; Treatment Outcome

Topics: Communication; Diabetes Mellitus, Type 1; Drug Administration Schedule; Drug Delivery Systems; Humans; Hyperglycemia; Hypoglycemic Agents; Injections; Insulin; Insulin Glargine; Insulin, Long-Acting; Male

Early morning hyperglycemia is frequent among children and adolescents with type 1 diabetes. Reasons are a dawn phenomenon, a Somogyi phenomenon or a lack of insulin in the morning hours. Only few studies are published regarding incidence and relation to different modes of basal insulin treatment in this population.We analyzed all cases recorded in the DPV register from 1995 to 2010. 5 839 patients from 128 centers with at least 3 blood glucose measurements during the last night of a hospital stay were included.24.2% of patients showed a morning hyperglycemia above 200 mg/dl. 8.6% showed a dawn phenomenon, 7.0 % a lack of insulin and 2.0% a Somogyi phenomenon. A dawn phenomenon was significantly less frequent in patients treated with an insulin pump (1.1%) compared to long acting insulin analogs Glargin and Levemir (5.4%) or NPH insulin (8.2%). Lack of insulin was again less frequent during insulin pump treatment compared to other treatments (1.9% vs. 4.9% vs. 5.3%). Median rise of blood glucose levels was 33.4 mg/dl between midnight and 6 a.m. Mode of basal insulin treatment is an important factor: while treatment with an insulin pump led to a blood glucose fall of 28.5 mg/dl between 3 and 6 a.m., treatment with insulin analog or NPH insulin resulted in a rise of 28.5 or 35.9 mg/dl, respectively.This study shows that insulin pump treatment reduces the frequency of morning hyperglycemia caused by the dawn phenomenon or a lack of insulin.

Topics: Blood Glucose; Child; Circadian Rhythm; Diabetes Mellitus, Type 1; Humans; Hyperglycemia; Insulin; Insulin Detemir; Insulin Glargine; Insulin Infusion Systems; Insulin, Isophane; Insulin, Long-Acting; Quality Assurance, Health Care; Registries

To determine the relative contributions of basal hyperglycemia (BHG) versus postprandial hyperglycemia (PPHG) before and after treatment intensification in patients with glycated hemoglobin A(1c) (A1C) >7.0% while on prior oral therapy.. Self-measured, plasma-referenced glucose profiles and A1C values were evaluated from participants in six studies comparing systematically titrated insulin glargine with an alternative regimen (adding basal, premixed, or prandial insulin, or increasing oral agents). Hyperglycemic exposure (>100 mg/dL [5.6 mmol/L]) as a result of BHG versus PPHG was calculated.. On prior oral therapy, 1,699 participants (mean age 59 years, diabetes duration 9 years) had mean fasting plasma glucose (FPG) of 194 mg/dL (10.8 mmol/L), and mean A1C was 8.7%. BHG contributed an average of 76-80% to hyperglycemia over the observed range of baseline A1C levels. Adding basal insulin for 24 or 28 weeks lowered mean FPG to 117 mg/dL (6.5 mmol/L), A1C to 7.0%, and BHG contribution to 32-41%. Alternative regimens reduced FPG to 146 mg/dL (8.1 mmol/L), A1C to 7.1%, and the contribution of BHG to 64-71%. BHG contributions for patients with A1C averaging 7.6-7.7% were 76% at baseline and 34 and 68% after adding basal insulin or other therapies, respectively.. When A1C is >7.0% despite oral therapy, BHG routinely dominates exposure. Intensified therapy reduces A1C and changes this relationship, but BHG amenable to further intervention still accounts for one-third of total hyperglycemia after basal insulin treatment and two-thirds after alternative methods.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Insulin, Regular, Human; Isophane Insulin, Human; Male; Middle Aged; Randomized Controlled Trials as Topic; Treatment Outcome

Insulin pen devices have revolutionized the self-management of diabetes. Prefilled insulin pens are preferred by healthcare providers and patients because of ease-of-use, dosage flexibility, disposability, and widespread availability. However, like any mechanical device, these pens have the potential for mechanical malfunction. We are present a case in which glycemic control deteriorated because of a malfunction of an insulin pen. The possibility of insulin pen malfunction needs to be considered in addition to other factors in patients who present with acute deterioration of glycemic control.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Equipment Failure; Female; Humans; Hyperglycemia; Insulin; Insulin Aspart; Insulin Glargine; Insulin, Long-Acting; Middle Aged; Self Administration

The importance of near-normal blood glucose in the immediate postoperative period is generally accepted and is best achieved in the perioperative period with a constant intravenous (IV) infusion of insulin. This requires intensive nursing only achievable in an intensive care unit (ICU) setting. Glucose management after transfer to a regular nursing floor (RNF) has not been studied systematically. In August 2006, the Cleveland Clinic began using long-acting insulin glargine as the insulin infusion was terminated in the ICU.. This prospective analysis examined all patients receiving IV insulin infusion after cardiothoracic surgery in a 1 month period. The analyses evaluated the safety and efficacy of a protocol using a transition to subcutaneous insulin glargine of 50% of the calculated 24 h requirement at the end of the ICU insulin infusion protocol in preparation for transfer to the RNF.. Only 1 patient in 99 developed hypoglycemia, and no patient suffered severe hypoglycemia (glucose < 40 mg/dl), while the majority (70%) had euglycemia (glucose between 70 and 150 mg/dl).. This approach was both safe-as there was very little hypoglycemia (1 patient in 99)-and effective, as blood sugar was well controlled in most subjects. Efficacy for achieving euglycemia was 70%. Efficacy was likely reduced because of the upper limit of insulin glargine dosage imposed by some providers as a safety consideration. Although there was a physician option to override, the maximum protocol dose of 30 U was rarely exceeded, leading to inadequate dosing in some subjects who required high insulin infusion rates in the ICU.

Topics: Aged; Blood Glucose; Cardiovascular Diseases; Clinical Protocols; Dose-Response Relationship, Drug; Female; Humans; Hyperglycemia; Hypoglycemic Agents; Infusions, Intravenous; Insulin; Insulin Glargine; Insulin, Long-Acting; Intensive Care Units; Male; Middle Aged; Ohio; Postoperative Period; Prospective Studies; Retrospective Studies

Intensive insulin therapy improves glycosylated haemoglobin (Hb(A1C)) levels and delays the onset of long-term diabetes-related complications. Current treatment guidelines recommend maintaining a glycosylated haemoglobin (Hb(A1C)) of < or = 7% in patients with type 1 and 2 diabetes mellitus. However, the risk of hypoglycaemia increases with lower Hb(A1C) levels. As such, patients often choose to settle for suboptimal glucose control in order to prevent hypoglycaemic events. At a given Hb(A1C) level, treatment with insulin glargine results in a lower risk of hypoglycaemia in type 1 and 2 diabetes compared with NPH insulin. It has been proposed that the lower hypoglycaemic risk will allow more patients to achieve target Hb(A1C) levels with insulin glargine compared with NPH insulin. The objective of this study was to assess the cost effectiveness of insulin glargine compared with NPH insulin in patients with type 1 or 2 diabetes who had inadequate glycaemic control.. A long-term, state-transition model was developed to simulate the natural history of type 1 and 2 diabetes. Risks of diabetes-related macro- and microvascular complications and mortality by Hb(A1C) levels were estimated based on the UKPDS (United Kingdom Prospective Diabetes Study). Outcome measures included complication rates and associated costs, insulin costs, life years (LYs) and QALYs. The baseline analysis was conducted for patients with type 1 and 2 diabetes (aged 27 and 53 years, respectively) with Hb(A1C) levels >7%, using a 36-year time horizon and a Canadian public payer perspective. Costs and effects were discounted at 5% per annum. Univariate sensitivity analyses were performed on key model inputs. All costs were reported in $Can (2005 values).. The NPH insulin group had lower total costs than the insulin glargine group for patients with inadequately controlled diabetes (Hb(A1C) >7%; lifetime difference 1398 Can dollars and 1992 Can dollars, respectively, in type 1 and 2 diabetes). However, patients treated with insulin glargine had greater total and quality-adjusted life expectancy than those who received NPH insulin (incremental LY = 0.08 and QALYs = 0.07 in type 1 diabetes and incremental LY = 0.25 and QALYs = 0.23 in type 2 diabetes). The weighted incremental cost per LY gained and QALY gained were 18,661 Can dollars and 20,799 Can dollars, respectively, in type 1 diabetes and 8041 Can dollars and 8618 Can dollars, respectively, in type 2 diabetes (discounted results).. The cost-effectiveness ratios for insulin glargine use for type 1 and 2 diabetes provide evidence for its adoption from a Canadian healthcare payer perspective.

Topics: Analysis of Variance; Canada; Cost-Benefit Analysis; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Treatment Outcome

The purpose of this study was to evaluate the effectiveness of insulin lispro and insulin glargine at controlling blood glucose in patients with type 2 diabetes mellitus in a cardiovascular intensive care unit (CICU) and receiving enteral tube feedings.. This was a pilot study with a retrospective control designed to evaluate an insulin protocol in patients admitted to the CICU in a level 3 teaching institution. Patients were 18-99 years of age with type 2 diabetes mellitus, receiving bolus tube feeding. The control group included 24 patients who were retrospectively studied to determine mean blood glucose level. A glycemic management protocol was developed that included glargine and lispro insulins to maintain blood glucose levels between 80 and 140 mg/dL. The study group consisted of 28 patients who were treated according to the glycemic management protocol.. The mean blood glucose level of the retrospective control group was 225 mg/dL. The mean blood glucose level of the intervention group was 148 mg/dL. After protocol institution, 48.6% of blood glucose levels were within the goal blood glucose range of 80-140 mg/dL vs 8.26% (p = .01) before protocol institution. Hyperglycemia decreased from 90.0% to 47.2% (p < .0001) with institution of the protocol.. The average blood glucose of the intervention group was slightly above the goal blood glucose range of 80-140 mg/dL; however, the study protocol was superior to the previous CICU blood glucose management protocol.

Topics: Aged; Blood Glucose; Critical Care; Diabetes Mellitus, Type 2; Enteral Nutrition; Female; Hospitalization; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Male; Pilot Projects; Retrospective Studies; Treatment Outcome

Leprechaunism was first recognized in 1954 and is characterized by severe intrauterine and postnatal growth retardation, failure to thrive, lipoatrophy, dysmorphic features (globular eyes, large ears, and micrognathia), hirsutism and acanthosis nigricans. The presented infant, a 30 day-old boy, had multiple phenotypic anomalies, including low-set ears, prominent eyes, decreased subcutaneous fat, hirsutism, breast hyperplasia, and penile enlargement. We found persistent hyperglycemia with remarkably high immunoreactive insulin levels. His phenotypic and laboratory features were consistent with a diagnosis of leprechaunism. We observed some effect of treatment with metformin but not with insulin glargine.

Topics: Abnormalities, Multiple; Fatal Outcome; Humans; Hyperglycemia; Hypoglycemic Agents; Infant, Newborn; Insulin; Insulin Glargine; Insulin Resistance; Insulin, Long-Acting; Male; Metformin

The purpose of this study was to compare the effect of insulin glargine (glargine) and NPH insulin (NPH) on long-term outcomes in type 2 diabetes patients using the Diabetes Mellitus Model (DMM).. The DMM predicts short- and long-term complications over ten years using data in studies published previously. The main effect on outcome is the influence of the treatment on the HbA1c level which is simulated over time. The simulation was based on a cohort size of 10,000 type 2 diabetes patients taking either glargine or NPH. The best scenario, baseline scenario and worst case scenario were simulated based on differences of 0.13%, 0.44% and 0.85%, respectively, in HbA1c values and corresponding to potentially attainable improvements with comparable or lower hypoglycemia rates in glargine-treated patients and NPH-treated patients. Assumptions for scenarios 1, 2 and 3 were based on a regression analysis of clinical trial data (pooled data clinical trials comparing glargine and NPH) in which the effect of glargine on the HbA1c/hypoglycemia incidence ratio was superior to that of NPH.. The relative risks (RR, glargine/NPH) obtained for scenarios 1, 2 and 3 were 0.97, 0.89 and 0.81, respectively, for long-term microvascular complications and 0.99, 0.95 and 0.91, respectively, for long-term macrovascular complications. RR reductions ranged from 1% in the less optimistic scenario to > 20% in the "best case" scenario. Sensitivity analyses showed that variations in the mean baseline HbA1c values and duration of the diabetes were without effect on these outcomes.. Although there is a need to corroborate the results of these simulations with real, long-term clinical data, they have demonstrated that, assuming comparable or lower rates of hypoglycemia, a better glycemic control (HbA1c reduction) can be expected with glargine when compared to NPH together with a reduction in long-term complications, mortality and associated costs.

Topics: Computer Simulation; Diabetes Mellitus, Type 2; Epidemiologic Methods; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Sensitivity and Specificity

(Prepro)insulin is considered a central antigenic determinant in diabetic autoimmunity. Insulin has been used to modify diabetes development in NOD mice and prediabetic individuals. We have recently shown that (prepro)insulin can adversely promote diabetes development in murine type 1 diabetes. Based on these findings we have developed experimental autoimmune diabetes (EAD), a new mouse model characterized by (1) CD4(+)/CD8(+) insulitis, induced by (2) (prepro)insulin DNA vaccination, leading to (3) beta cell damage and insulin deficiency in (4) RIP-B7.1 transgenic mice (H-2(b)). EAD develops rapidly in 60-95% of mice after intramuscular, but not intradermal ("gene gun"), vaccination; and DNA plasmids expressing insulin or the insulin analogues glargine, aspart, and lispro are equally potent to induce EAD. Similar to NOD mice, diabetes is adoptively transferred into syngeneic recipients by spleen cell transplantation in a dose-dependent fashion. We have devised a two-stage concept of EAD in which T cell activation and expansion is driven by in vivo autoantigen expression, followed by islet damage that requires beta cell expression of costimulatory B7.1 for disease manifestation. Taken together, EAD is a novel, genetically defined animal model of type 1 diabetes suitable to analyze mechanisms and consequences of insulin-specific T cell autoimmunity.

Topics: Adoptive Transfer; Animals; Autoimmunity; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Disease Models, Animal; Hyperglycemia; Injections, Intramuscular; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Islets of Langerhans; Lymphocyte Subsets; Mice; Mice, Transgenic; Spleen; T-Lymphocytes; Time Factors; Transplantation, Isogeneic; Vaccination; Vaccines, DNA

To determine the effect of insulin glargine on glycemic control in pediatric type 1 and 2 diabetes, a retrospective repeated-measure analysis of variance was performed of hemoglobin A1C (HbA1C), frequency of hypoglycemia and hyperglycemia, mean blood glucose, body mass index (BMI), and daily weight-adjusted insulin dosage before and after institution of glargine therapy in 72 children and adolescents with diabetes. At glargine start, age range was 1.2-19.6 years, mean age was 12.5 +/- 4.6 years, BMI was 22.48 +/- 6.3 kg/m(2), and mean HbA1C was 9.7 +/- 1.9%. Mean duration of diabetes was 3.58 years, and mean baseline insulin dose was 0.93 U/kg/day. Gender breakdown was 60% female, and the majority (83%) had type 1 diabetes. Average HbA1C decreased from 9.5% pre-glargine to 8.6% post-glargine (p < 0.001). HbA1C decrease was significant in both types of diabetes without a concomitant increase in frequency of hypoglycemia, BMI, or weight-adjusted insulin dose. Hypoglycemia decreased significantly in type 1 diabetes. Thus, glargine therapy may decrease HbA1C and frequency of hypoglycemia in toddlers, children, and adolescents with diabetes, without an increase in BMI or insulin requirements.

Topics: Adolescent; Adult; Blood Glucose; Body Mass Index; Child; Child, Preschool; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Patient Compliance; Retrospective Studies; Sex Factors; Time Factors