insulin-glargine and Diabetes-Mellitus

No insulin formulation should be considered best by default for management of feline diabetes. Rather, the choice of insulin formulation should be tailored to the specific clinical situation. In most cats that have some residual beta cell function, administering only a basal insulin might lead to complete normalization of blood glucose concentrations. Basal insulin requirements are constant throughout the day. Therefore, for an insulin formulation to be effective and safe as a basal insulin, its action should be roughly the same every hour of the day. At present, only insulin glargine U300 approaches this definition in cats.

Topics: Animals; Blood Glucose; Cat Diseases; Cats; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Insulin; Insulin Glargine

Understanding the pharmacology of insulin and how it relates to the pathophysiology of diabetes can lead to better clinical outcomes. No insulin formulation should be considered "best" by default. Insulin suspensions (NPH, NPH/regular mixes, lente, and PZI) as well as insulin glargine U100 and detemir are intermediate-acting formulations that are administered twice daily. For a formulation to be an effective and safe basal insulin, its action should be roughly the same every hour of the day. Currently, only insulin glargine U300 and insulin degludec meet this standard in dogs, whereas in cats, insulin glargine U300 is the closest option.

Topics: Animals; Cat Diseases; Cats; Diabetes Mellitus; Diabetes Mellitus, Type 2; Dog Diseases; Dogs; Hypoglycemic Agents; Insulin; Insulin Glargine

Smarter understanding of diabetes pathophysiology and pharmacology of insulin therapy can lead to better clinical outcomes. Rather than looking for an insulin formulation that is considered "best" for a general population, it could be appropriate to seek the "smart" insulin choice, tailored to the specific clinical situation. Different treatment goals should be considered, with pros and cons to each. Ideally, insulin therapy in most diabetic dogs should mimic a "basal-bolus" pattern. The "intermediate"-acting insulin formulations might provide better "bolus" treatment in dogs than the rapid-acting formulations used in people. In patients with some residual beta cell function such as many diabetic cats, administering only a "basal" insulin might lead to complete normalisation of blood glucose concentrations. Insulin suspensions (neutral protamine Hagedorn, neutral protamine Hagedorn/regular mixes, lente and protamine zinc insulin) as well as insulin glargine U100 and detemir are "intermediate"-acting formulations that are administered twice daily. For a formulation to be an effective and safe "basal" insulin, its action should be roughly the same every hour of the day. Currently, only insulin glargine U300 and insulin degludec meet this standard in dogs, whereas in cats, insulin glargine U300 is the closest option.

Topics: Animals; Blood Glucose; Cat Diseases; Cats; Diabetes Mellitus; Dog Diseases; Dogs; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Protamines

Although randomized, controlled trials (RCTs) are seen as the gold standard for evidence in clinical medicine, a number of considerations are increasing the use of real-world data (RWD) to generate evidence. A series of methodological challenges must be overcome in order for such real-world evidence (RWE) to gain acceptance. In diabetes, RWE faces some particular issues that have limited its development. As the natural history of diabetes progresses, patients' disease changes over time and treatments will be modified as a result. This evolving disease and treatment pattern requires application of methods that account for such changes over time. Research developing RWE in diabetes and other conditions has sometimes been subject to important biases, and researchers should be aware of, and take steps to mitigate potential for bias in order to enhance the evidence produced.. We review a RWE study that replicated and extended evidence provided by a RCT regarding the effects of weekly exenatide relative to basal insulin (glargine or detemir) to illustrate a potential application of RWE. This study observed a 0.7% decrease in HbA1C for weekly exenatide relative to a 0.5% decrease in HbA1C for the comparator along with a 2 kg weight loss for weekly exenatide relative to a 0.25 kg weight gain, effects that were close to those from the RCT. Further, the RWE study was able to extend results to patient populations that were not well represented in the RCT.. Despite numerous challenges, RWE can be used to complement evidence from RCTs.

Topics: Diabetes Mellitus; Exenatide; Humans; Insulin Glargine

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

Diabetes remains a global epidemic and a tremendous health challenge, especially in the Asian population. Dramatic increases in the prevalence of diabetes across different countries or areas in Asia have been reported in recent epidemiological studies. Although clinical guidelines have strengthened appropriate antihyperglycemic medications and lifestyle modifications for optimal diabetes management, inadequate glycemic control still occurs in many patients with an increased risk of developing microvascular and macrovascular complications. Insulin administration is the main therapy for diabetes in response to the inability to secrete insulin, and is recommended in current guidelines to treat patients with type 2 diabetes after failure of oral antidiabetic drugs. Clinical studies have shown that long-acting insulin analogs improve basal glycemic control with reduced risk of hypoglycemia. In the present review, we discuss previous challenges with basal insulin therapy in Asia, the pharmacological development of insulin analogs to overcome the unmet medical needs and recent clinical studies of the new ultra-long-acting insulin analog, insulin glargine U300. Furthermore, relevant findings of current real-world evidence are also included for the comparison of the efficacy and safety of different insulin formulations. Based on the accumulating evidence showing a low incidence of hypoglycemia and technical benefits of dose titration, treatment with glargine U300 can be a promising strategy for Asian diabetes patients to achieve glycemic targets with favorable safety.

Topics: Asia; Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin Glargine; Needs Assessment; Prognosis

Insulin remains a predominant life-saving medication for type 1 and type 2 Diabetes Mellites. Natural insulin secretion limits the fluctuation of the narrow and high surge of blood glucose levels. However, imitating the same by external insulin remains a challenge as a variety of insulin analogs (rapid acting, short acting, intermediate acting and long-acting) have different pharmacokinetic (PK) and pharmacodynamic (PD) properties. Inconsistent reduction in overall hyperglycemia level and nocturnal hypoglycemia due to variable absorption time and time action profile predominantly highlights the need of revisiting the PK/PD of insulin analogs as single analog is not yet sufficed to replace internal insulin exogenously. Combination therapy with basal and prandial insulins or intensification of hypoglycemic therapy with premixed insulins are of prime importance in managing diabetes effectively, imitating the natural insulin secretion. Therefore, the knowledge of PK/PD properties might help a practitioner to design, implement and manage insulin replacement therapy effectively and averting adverse events. Present study reports the comparative analysis of PK/PD profile of various insulin analogs based on the concurrent information about clinical aspects. Moreover, study interlinks the major concerns of therapeutic efficacy of insulin analogs with their respective onset of action and duration of effectiveness and reported adverse drug reaction which explore the scope of improvement.

Topics: Diabetes Mellitus; Forecasting; Humans; Insulin; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting

Diabetes mellitus is a disease that affects millions of Americans, and its prevalence is only anticipated to increase in coming years. It is estimated that diabetes-related visits account for 1% of all emergency department (ED) encounters. In recent years, there have been several new categories of medications approved for the treatment of diabetes, including new insulins, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, an amylin analogue, and sodium-glucose cotransporter-2 inhibitors.. This review presents recently approved agents to treat diabetes, with a focus on basic mechanism, place in therapy, and toxicities the ED provider may encounter.. Many of these new therapies have been incorporated as first- and second-line agents for the management of diabetes. Recently approved diabetes medications often have different mechanisms of action and adverse effect and overdose profiles compared to traditional agents, such as sulfonylureas and metformin.. Emergency providers will encounter patients taking these newly approved medications, as well as treat those presenting with adverse effects and overdoses from them. As such, emergency providers must have a basic understanding of these new therapies so that they can optimally care for diabetic patients.

Topics: Diabetes Mellitus; Dipeptidyl Peptidase 4; Drug Therapy; Emergency Medicine; Glucagon-Like Peptide-1 Receptor; Humans; Insulin Glargine; Insulin, Long-Acting; Islet Amyloid Polypeptide; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors

Topics: Biosimilar Pharmaceuticals; Blood Glucose; Diabetes Mellitus; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Antibodies; Insulin Glargine; Insulin Lispro

Hyperinsulinemia is a recognized risk factor for cancer and plays a major role for the increased cancer incidence in diabetic patients. Whether insulin analogs, and particularly long-acting analogs, worsen the pro-cancer effect of excess insulin is still controversial.. In this paper we summarize the biological bases for the potential detrimental effect of long-acting analogs on cancer cells and review the in vitro and in vivo evidence on this issue. Because of their different molecular structure relative to native insulin, insulin analogs may activate the insulin receptor (IR) and the post receptor pathways differently. Most, but not all, in vitro evidence indicate that long-acting analogs may have a stronger mitogenic potency than insulin on cancer cells. Notably insulin glargine, the most studied long-acting analog, also has a higher affinity for the insulin-like growth factor (IGF)-1 receptor, a potent growth mediator. In vitro observations, however, may not reflect what occurs in vivo when analogs are metabolized to derivatives with a different mitogenic activity. Clinical studies, mostly retrospective and predominantly concerning glargine, provide contrasting results. The only perspective trial found no cancer increase in patients treated with glargine. All these studies, however, have severe weaknesses because of the insufficient evaluation of important factors such as dose administered, length of exposure, patient follow-up duration and site-specific cancer investigation. Moreover, whether cancer promotion is a long-acting analog class characteristic or a specific effect of a single agent is not clear.. In conclusion the carcinogenic risk of long-acting analogs, and specifically glargine, can be neither confirmed nor excluded. A personalized and shared decision, considering all the individual risk factors (metabolic and non-metabolic), is the suggestion for the clinician.

Topics: Animals; Biomarkers; Blood Glucose; Clinical Decision-Making; Diabetes Mellitus; Humans; Hyperinsulinism; Hypoglycemic Agents; Incidence; Insulin Glargine; Neoplasms; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome

To achieve good metabolic control in diabetes and maintain it in the long term, a combination of changes in lifestyle and pharmacological treatment is necessary. The need for insulin depends upon the balance between insulin secretion and insulin resistance. Insulin is considered the most effective glucose-lowering therapy available and is required by people with type 1 diabetes mellitus to control their blood glucose levels; yet, many people with type 2 diabetes mellitus will also eventually require insulin therapy, due to the progressive nature of the disease. A variety of long-acting insulins is currently used for basal insulin therapy (such as insulin glargine, degludec, and detemir), each having sufficient pharmacodynamic and pharmacokinetic profiles to afford lower intrapatient variability and an extended duration of action. The new glargine-300 formulation was developed to have a flatter and more extended time-action profile than the original glargine-100, and these characteristics may translate into more stable and sustained glycemic control over a 24 h dosing interval. The objective of this comprehensive review was to summarize the available evidence on the clinical efficacy and safety of glargine-300 versus glargine-100 from the EDITION clinical trial program, in patients with type 1 and type 2 diabetes mellitus.

Topics: Blood Glucose; Diabetes Mellitus; Dose-Response Relationship, Drug; Humans; Hypoglycemic Agents; Insulin Glargine; Treatment Outcome

Diabetes, particularly type 2 diabetes (T2D), has become an epidemic in the United States, with a significant portion of patients unable to meet recommended glycemic targets. All individuals with type 1 diabetes (T1D) and a significant majority of those with T2D will ultimately require insulin therapy. However, there are several barriers to its use. The introduction of the new, ultra-long-acting basal insulins degludec and glargine U-300, and the single-injection combinations of insulin degludec/liraglutide and insulin glargine U-100/lixisenatide, offer options that may overcome several of those barriers, including the high risk of hypoglycemia, glycemic variability, and relatively short duration of action. This article spotlights the outcomes of the phase 3 clinical trials for these newer formulations, as well as more recent meta-analyses and real-world studies. It also highlights the implications for managed care plans as they move to add these insulins to their formularies.

Topics: Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Insulin; Insulin Glargine; Insulin, Long-Acting; Managed Care Programs; Randomized Controlled Trials as Topic; Treatment Outcome

In the past decade, there has been much advancement in oral antidiabetic agents, but few changes in insulin therapy. With the addition of the ultra-long-acting insulins, insulin glargine U300 (IGlar 300) and insulin degludec (IDeg 100 and IDeg 200), it is important to understand key aspects in the agents' clinical properties, efficacy, safety, dosing, packaging, and place in therapy.. A literature review was conducted using PubMed database and was limited to English, full-text articles published from January 2000 to January 2018. The following search terms were used: insulin glargine 300, insulin degludec, Toujeo, Tresiba, and ultra-long-acting insulin.. These agents are longer acting with sustained insulin coverage as compared with other basal insulins while having a low potential for hypoglycemia. Efficacy and safety profiles are quite good, and potential for weight gain was similar to IGlar 100.. Depending on the patient's needs, these newer agents may offer some advantages. Insulin glargine U300 and IDeg 200 are concentrated, allowing for administration of large doses by less volume, thereby theoretically improving absorption. For patients needing flexible dosing, IDeg may be beneficial. The ultra-long-acting agents may also be useful if it is suspected that the basal insulin is not lasting the entire day.

Topics: Blood Glucose; Diabetes Mellitus; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Patient Safety; Prevalence; Weight Gain

Manufacturers of insulin products for diabetes therapy have long sought ways to modify the absorption rate of exogenously administered insulins in an effort to better reproduce the naturally occurring pharmacokinetics of endogenous insulin secretion. Several mechanisms of protraction have been used in pursuit of a basal insulin, for which a low injection frequency would provide tolerable and reproducible glucose control; these mechanisms have met with varying degrees of success. Before the advent of recombinant DNA technology, development focused on modifications to the formulation that increased insulin self-association, such as supplementation with zinc or the development of preformed precipitates using protamine. Indeed, NPH insulin remains widely used today despite a frequent need for a twice-daily dosing and a relatively high incidence of hypoglycaemia. The early insulin analogues used post-injection precipitation (insulin glargine U100) or dimerization and albumin binding (insulin detemir) as methods of increasing therapeutic duration. These products approached a 24-hour glucose-lowering effect with decreased variability in insulin action. Newer basal insulin analogues have used up-concentration in addition to precipitation (insulin glargine U300), and multihexamer formation in addition to albumin binding (insulin degludec), to further increase duration of action and/or decrease the day-to-day variability of the glucose-lowering profile. Clinically, the major advantage of these recent analogues has been a reduction in hypoglycaemia with similar glycated haemoglobin control when compared with earlier products. Future therapies may bring clinical benefits through hepato-preferential insulin receptor binding or very long durations of action, perhaps enabling once-weekly administration and the potential for further clinical benefits.

Topics: Chemistry, Pharmaceutical; Diabetes Mellitus; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Lente; Insulin, Long-Acting; Recombinant Proteins

Topics: Animals; Diabetes Mellitus; Drug Delivery Systems; Humans; Hypoglycemic Agents; Insulin Glargine

Insulin glargine 300 units/mL: Insulin glargine 300 units/mL (Gla-300) is a formulation of insulin glargine that delivers the same number of insulin units in one-third of the injectable volume of insulin glargine 100 units/mL (Gla-100). Glucose control: Recently approved in the United States and in Europe for use in type 1 and type 2 diabetes, Gla-300 has a more constant and evenly distributed glucose-lowering effect compared with Gla-100, with a duration of action beyond 24 hours and lower within-day and between-day intra-individual variability in blood glucose levels. These benefits translate into predictable and sustained glucose control from a once-daily injection, with potential for fewer hypoglycemia episodes and less weight gain.. Case studies are presented to highlight the potential clinical benefits and considerations associated with initiating treatment with Gla-300 in people with type 1 and type 2 diabetes.

Topics: Diabetes Mellitus; Drug Monitoring; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Treatment Outcome

Insulin glargine 300 U/mL (Toujeo(®)) is a long-acting basal insulin analogue approved for the treatment of diabetes mellitus. Insulin glargine 300 U/mL has a more stable and prolonged pharmacokinetic/pharmacodynamic profile than insulin glargine 100 U/mL (Lantus(®)), with a duration of glucose-lowering activity exceeding 24 h. In several 6-month phase III trials, insulin glargine 300 U/mL achieved comparable glycaemic control to that seen with insulin glargine 100 U/mL in patients with type 1 or type 2 diabetes, albeit with consistently higher daily basal insulin requirements. These improvements in glycaemic control were maintained during longer-term (12 months) treatment. Insulin glargine 300 U/mL was generally associated with a lower risk of nocturnal hypoglycaemia than insulin glargine 100 U/mL in insulin-experienced patients with type 2 diabetes, while the risk of nocturnal hypoglycaemia did not significantly differ between treatment groups in insulin-naïve patients with type 2 diabetes or in patients with type 1 diabetes. To conclude, once-daily subcutaneous insulin glargine 300 U/mL is an effective and generally well tolerated basal insulin therapy option for patients with type 1 or type 2 diabetes.

Topics: Blood Glucose; Clinical Trials, Phase III as Topic; Diabetes Mellitus; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Hypoglycemic Agents; Infant, Newborn, Diseases; Injections, Subcutaneous; Insulin Glargine; Time Factors; Treatment Outcome

The pharmacokinetics, efficacy, and safety of U-300 insulin glargine for the management of diabetes are reviewed.. U-300 (300 units/mL) insulin glargine is a long-acting basal insulin with low within-day variability, high day-to-day reproducibility, longer duration, and constant pharmacokinetic profile compared with U-100 (100 units/mL) insulin glargine. U-300 was evaluated in six randomized, active-comparator, open-label, Phase III clinical studies (EDITION trials) among patients with type 1 or 2 diabetes. The primary endpoint for all EDITION studies was the reduction in glycosylated hemoglobin from baseline to six months. Safety endpoints included confirmed or nocturnal hypoglycemia between week 9 and month 6 and the change in weight from baseline. For hypoglycemic episodes, U-300 insulin glargine was superior to U-100 insulin glargine when comparing the risk of hypoglycemia. U-300 insulin glargine is supplied in a prefilled device (for safety purposes) and packaged in boxes of three or five pens. It is still early to determine the role of U-300 insulin glargine in diabetes management. When compared with U-100 insulin glargine, U-300 insulin glargine appeared to be associated with a lower risk of hypoglycemia and nocturnal hypoglycemia, most likely due to its pharmacokinetics. The wholesale average cost of U-300 insulin glargine is $335.48 per box of three pens.. The efficacy outcomes of U-300 insulin glargine were similar to those of U-100 insulin glargine, but the constant pharmacokinetic profile and longer duration of action of U-300 insulin glargine may help certain patients with type 1 or type 2 diabetes achieve better glycemic control.

Topics: Clinical Trials, Phase III as Topic; Diabetes Mellitus; Dosage Forms; Humans; Hypoglycemic Agents; Insulin Glargine; Randomized Controlled Trials as Topic

The purpose of this article is to educate nurse practitioners about the role of Toujeo®, insulin glargine U-300 (Gla-300), which is a new option for the treatment of diabetes mellitus.. A comprehensive literature search was conducted using MEDLINE with the key terms: insulin glargine 300, Toujeo, Gla-300, and EDITION for clinical trial data. Other resources included package inserts, drug information websites, and the World Health Organization (WHO).. Gla-300 appears to be a safe and effective option for basal insulin therapy. In clinical trials, it was shown to be equally efficacious as Gla-100 with fewer episodes of hypoglycemia and slightly less weight gain, and subjects receiving Gla-300 required approximately 10 units more basal insulin to obtain the same hemoglobin A1c (HbA1c) as subjects receiving Gla-100.. This new basal therapy option represents a potential advantage for patients who require higher doses of insulin because of the higher concentration of Gla-300. The lower incidence of hypoglycemia and more predictable pharmacokinetics could offer a significant therapeutic benefit in difficult-to-control patients with diabetes mellitus. The biggest disadvantage of this product is the slightly higher insulin dosage that is required to improve and/or maintain patients' HbA1c.

Topics: Diabetes Mellitus; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Weight Gain

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

A more concentrated insulin glargine formulation, containing 300 U/mL (Gla-300) was approved in 2015 in the US and Europe for the treatment of diabetes mellitus in adults.. This drug evaluation focuses on the pharmacokinetics (PK) and pharmacodynamics (PD) of Gla-300 from studies published up to May 2016. The clinical relevance of this new formulation will be addressed.. Gla-300 was developed to produce a flatter and more prolonged PK/PD profile compared with insulin glargine 100 U/mL (Gla-100) in order to maintain effective glycemic control and reduce the risk of hypoglycemia. Compared to Gla-100, Gla-300 achieves lower and delayed peak concentrations with a PK exposure that is more stable and evenly distributed across a 24-h dosing interval. As a consequence, Gla-300 results in a consistent glucose-lowering effect with less variability over a 24-h dosing interval, which translates to a reduction in the rate of hypoglycemia (particularly nocturnal events).

Topics: Adult; Blood Glucose; Diabetes Mellitus; Drug Administration Schedule; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine

To systematically evaluate the efficacy and safety of insulin degludec for diabetes mellitus (DM).. Databases including Cochrane Library, PubMed, Embase, Wanfang Data, China Biology Medicine disc (CBM) and China National Knowledge Infrastructure (CNKI) were searched electronically for randomized controlled trials (RCTs) meeting including criteria and the methodological quality of studies was assessed. Then meta-analysis was performed using RevMan 5.0 software.. Twelve RCTs with 6 527 patients were included into our study: 4 358 patients in degludec group and 2 169 patients in control group. Compared with insulin glargine, insulin degludec was more effective in reducing fasting blood glucose (MD=-0.40, 95%CI: -0.65--0.16, P=0.001), but less effective in improving levels of glycated hemoglobin (MD=0.13, 95%CI: 0.08-0.17, P<0.001). There was no significant difference in the incidence rate of adverse events in two groups (OR=0.98, 95%CI: 0.87-1.10, P=0.700), but incidence rate of nocturnal hypoglycaemia was significantly lower in insulin degludec group (OR=0.82, 95%CI: 0.72-0.94, P=0.004).. Insulin degludec is non-inferior to other basal insulin in reducing levels of blood glucose, but insulin degludec can obviously reduce the incidence rate of nocturnal hypoglycaemia, so it is safer than other basal insulin. The long-term efficacy and safety should be further studied .

Topics: Blood Glucose; Diabetes Mellitus; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Randomized Controlled Trials as Topic; Safety

Meta-analysis to compare hypoglycemia rates of basal insulin degludec (IDeg) with insulin glargine (IGlar) in patients with diabetes achieving good glycemic control (hemoglobin A1c [HbA1c] <7% at end of trial).. In a preplanned meta-analysis, patient data from 7 randomized, treat-to-target, 26- or 52-week trials in patients with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) who administered IDeg (n = 2,899) or IGlar (n = 1,431) once daily were analyzed. Using a negative binomial regression model, this meta-analysis compared hypoglycemia rates in patients achieving HbA1c <7% at end of trial with IDeg (n = 1,347) and IGlar (n = 697).. In all trials, IDeg was noninferior to IGlar in HbA1c reduction from baseline. At end of trial, 2,044 patients (T2DM, n = 1,661; T1DM, n = 383) achieved HbA1c <7%. The overall confirmed hypoglycemia rate, defined as plasma glucose <56 mg/dL or severe hypoglycemia if requiring assistance, was significantly lower with IDeg versus IGlar (estimated rate ratio [ERR] IDeg:IGlar, 0.86; 95% confidence interval [CI], 0.76 to 0.98). The nocturnal confirmed hypoglycemia rate, defined as occurring between midnight and 6:00 am, was significantly lower with IDeg (ERR, 0.63; 95% CI, 0.52 to 0.77). In the maintenance period (16 weeks onward when average insulin dose and glycemic levels stabilized), the overall confirmed hypoglycemia rate was significantly lower (ERR, 0.79; 95% CI, 0.68 to 0.92) and the nocturnal confirmed hypoglycemia rate was significantly lower (ERR, 0.57; 95% CI, 0.45 to 0.72) with IDeg versus IGlar.. Patients with T1DM and T2DM achieved HbA1c <7% with significantly lower rates of overall and nocturnal confirmed hypoglycemia with IDeg versus IGlar. The lower hypoglycemia rate with IDeg was more pronounced in the maintenance period.

Topics: Clinical Trials, Phase III as Topic; Diabetes Mellitus; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting

The epoch-making discovery of insulin heralded a new dawn in the management of diabetes. However, the earliest, unmodified soluble insulin preparations were limited by their short duration of action, necessitating multiple daily injections. Initial attempts to protract the duration of action of insulin involved the use of various additives, including vasoconstrictor substances, which met with limited success. The subsequent elucidation of the chemical and three-dimensional structure of insulin and its chemical synthesis and biosynthesis allowed modification of the insulin molecule itself, resulting in insulin analogs that are designed to mimic normal endogenous insulin secretion during both fasting and prandial conditions. Insulin glargine was the first once-daily, long-acting insulin analog to be introduced into clinical practice more than 10 years ago and is specifically designed to provide basal insulin requirements. It has a prolonged duration of action and no distinct insulin peak, making it suitable for once-daily administration and reducing the risk of nocturnal hypoglycemia that is seen with intermediate-acting insulins. Insulin glargine can be used in combination with prandial insulin preparations and non-insulin anti-diabetic agents according to individual requirements.

Topics: Animals; Delayed-Action Preparations; Diabetes Mellitus; Drug Administration Schedule; Drug Therapy, Combination; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Time Factors

Appropriate management of diabetes mellitus before a procedure or operation is important for the prevention of hypo- and hyperglycemia in the periprocedural/perioperative period. This can significantly influence glucose levels after a procedure, which in turn affects outcomes. There is a paucity of prospective trials addressing algorithms to guide adjustment of oral diabetes medications and insulin prior to a procedure. Our institution has developed guidelines that allowed us to standardize the periprocedural process for glucose management across departments. This article describes our experience with guidelines, discusses salient features of medication management, and summarizes prospective trials and expert opinion to provide recommendations for clinicians to effectively manage glucose preprocedurally for their patients with diabetes.

Topics: Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Practice Guidelines as Topic; Preoperative Care

The central role of insulin in the management of patients with type 1 diabetes mellitus (T1DM) remains, nearly a century after its first use in humans. In patients with type 2 diabetes mellitus (T2DM), the role of insulin has evolved as other therapies have been introduced, with insulin now used across the spectrum of the disease. This article discusses the use of insulin in patients with T1DM or T2DM, including combined use with other agents in T2DM, with an emphasis on incretin-based therapies. In addition, new insulin products and concentrations are discussed along with their varied routes of administration.

Topics: Chemistry, Pharmaceutical; Diabetes Mellitus; Drug Combinations; Humans; Hypoglycemic Agents; Incretins; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Insulins; Treatment Outcome

An association of insulin use and risk of cancer has been reported but evidence is conflicting and methodological issues have been identified.. To summarize results regarding insulin use and cancer risk by a systematic review and meta-analysis of cohort and case-control studies examining risk of cancer associated with insulin use in patients with diabetes.. Systematic literature search in 5 databases: PubMed, Embase, Web of Science, Scopus and Cochrane Library. STUDY ELIGIBILITY CRITERIA (PICOS):. diabetes patients.. Users of any exogenous insulin. Comparison: Diabetes patients with or without use of antidiabetic drugs.. Any incident cancer.. Cohort and case-control studies.. 42 eligible studies examined risk of any cancer and 27 site-specific cancers. Results of individual studies were heterogeneous. Meta-analyses were significant for: Insulin vs No Insulin: Increased risk for pancreas, liver, kidney, stomach and respiratory cancer, decreased risk for prostate cancer. Insulin vs Non-Insulin Antidiabetics: Increased risk for any, pancreatic and colorectal cancer. Glargine vs Non-Glargine Insulin: Increased risk for breast cancer, decreased risk for colon cancer.. Few studies available for most cancer sites and exposure contrasts, and few assess effect of dose and duration of exposure. Methodological issues in several studies. Availability of confounders.. Insulin use was associated with risk of cancer at several sites. Cautious interpretation of results is warranted as methodological issues and limitations in several of the included studies have been identified. Choice of study design may have a profound effect on estimated cancer risk.

Topics: Breast Neoplasms; Case-Control Studies; Cohort Studies; Colorectal Neoplasms; Diabetes Mellitus; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Neoplasms; Observational Studies as Topic; Publication Bias; Registries; Research Design

Topics: Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting

The aim of the present paper is to provide some further data on the relationship between β-blocker treatment and the incidence of cancer, using two different approaches (epidemiological study and meta-analysis of clinical trials).. In a consecutive series of 1340 diabetic patients starting insulin therapy, 112 cases of cancer during a mean follow-up of 75.9 months were identified as first hospital admission or death. For each case, the controls were chosen randomly from those members of the cohort matched for age, sex and BMI. The main predefined analysis was the comparison of cases and controls for length of exposure to β-blockers and proportion of patients exposed using a conditional logistic regression which takes into account the matching structure. For the meta-analytic sub-study, an extensive search of Medline and the Cochrane Library (any date up to December 31st, 2011) was performed for all trials in which a β-blocker was used. Mantel-Haenszel Odds Ratios (MH-OR) with 95% confidence intervals for incident malignancies were calculated using a random effect model.. After adjusting for mean daily dose of glargine and metformin, and ischemic heart disease, exposure to β-blockers was associated with a reduced overall risk of cancer (HR 0.33 [0.13; 0.83], p = 0.019; HR for each month of exposure 0.87 [0.77; 0.98], p = 0.025). In the meta-analysis sub-study, performed on nine trials, β-blockers were associated with a non-significant trend toward lower risk of cancer (MH-OR 0.93 [0.86; 1.01], p = 0.070).. Limitations of the observational study are the small sample size that limits the statistical power of analyses, that it was performed on diabetic patients only, and that diagnoses of malignancies were derived from administrative data.. In conclusion, this research seem to confirm a possible beneficial effect of β-blockers against the risk of cancer development.

Topics: Adrenergic beta-Antagonists; Aged; Atenolol; Benzopyrans; Bisoprolol; Carbazoles; Carvedilol; Diabetes Mellitus; Ethanolamines; Female; Humans; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Metformin; Myocardial Ischemia; Nebivolol; Neoplasms; Propanolamines; Risk

Retrospective, observational studies have reported an association between diabetes treatment with insulin and a higher incidence of cancer.. Overview the literature for in vitro and in vivo studies of the metabolic and mitogenic properties of basal insulin analogues and assess the implications for clinical use.. Relevant studies were identified through PubMed and congress abstract database searches; data on metabolic and mitogenic signalling in relation to insulin treatment of diabetes are included in this review.. The balance of evidence shows that although some analogues have demonstrated mitogenic potency in some in vitro studies in cancer cell lines, these findings do not translate to the in vivo setting in animals or to the clinical setting in humans.. The current consensus is that there is no clinical or in vivo evidence to indicate that any commercially available insulin analogue has carcinogenic effects. Large-scale, prospective clinical and observational studies will further establish any potential link.

Topics: Cell Proliferation; Databases, Factual; Diabetes Complications; Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Mitogens; Neoplasms; Phosphorylation; Protein Binding; Receptor, IGF Type 1; Receptor, Insulin; Signal Transduction

Insulin analogues provide clinically important benefits for people with diabetes, including more predictable action profiles and lower risk of hypoglycemia compared with human insulin. However, it has been suggested that certain insulin analogues may lead to greater activation of insulin-like growth factor-1 (IGF-1) signaling, with risk for adverse mitogenic effects. This article aims to critically review studies on the mitogenic effects of the insulin analogue insulin glargine (glargine) and its metabolites. A review of in vitro studies suggests that glargine may stimulate mitogenic activity in some cell lines at supraphysiological concentrations (nanomolar/micromolar concentrations). Mitogenicity appeared to be related to the expression of the IGF-1 receptor, being present in cells expressing high levels of the receptor and absent in cells with limited or no IGF-1 receptor expression. In animal studies, glargine did not promote tumor growth, despite administration at supraphysiological concentrations (nanomolar/micromolar), which are unlikely to be observed in clinical practice because the doses needed to produce these concentrations are liable to lead to hypoglycemia. Furthermore, glargine in vivo is rapidly transformed into its metabolites, the metabolic and mitogenic characteristics of which have been shown to be broadly equal to those of human insulin. Thus, the suggestion of increased relative mitogenic potency of insulin glargine seen in some cell lines does not appear to carry over to the in vivo situation in animals and humans.

Topics: Animals; Diabetes Mellitus; Humans; Insulin; Insulin Glargine; Insulin-Like Growth Factor I; Insulin, Long-Acting; Mitogens; Protein Binding; Receptor, IGF Type 1; Signal Transduction

Since their introduction, insulin analogues are the preferred choice for short-acting insulin due to their superior pharmacologic profiles, leading to greater flexibility and convenience of dosing and, thus, greater patient satisfaction and improved quality of life. Over the past few years, clinical experience with insulin analogues in pregnancy has increased. The most studied, insulin lispro, has been shown to be a safe and clinically effective option in the treatment of the diabetic gravida. Studies of the other insulin analogues are limited, but promising. Further research is warranted to evaluate safety and efficacy of these analogues.

Topics: Diabetes Mellitus; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Pregnancy

Inadequately controlled diabetes accounts for chronic complications and increases mortality. Its therapeutic management aims in normal HbA1C, prandial and postprandial glucose levels. This review discusses diabetes management focusing on the latest insulin analogues, alternative insulin delivery systems and the artificial pancreas.. Intensive insulin therapy with multiple daily injections (MDI) allows better imitation of the physiological rhythm of insulin secretion. Longer-acting, basal insulin analogues provide concomitant improvements in safety, efficacy and variability of glycaemic control, followed by low risks of hypoglycaemia. Continuous subcutaneous insulin infusion (CSII) provides long-term glycaemic control especially in type 1 diabetic patients, while reducing hypoglycaemic episodes and glycaemic variability. Continuous subcutaneous glucose monitoring (CGM) systems provide information on postprandial glucose excursions and nocturnal hypo- and/or hyperglycemias. This information enhances treatment options, provides a useful tool for self-monitoring and allows safer achievement of treatment targets. In the absence of a cure-like pancreas or islets transplants, artificial "closed-loop" systems mimicking the pancreatic activity have been also developed.. Individualized treatment plans for insulin initiation and administration mode are critical in achieving target glycaemic levels. Progress in these fields is expected to facilitate and improve the quality of life of diabetic patients.

Topics: Amino Acid Sequence; Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin Infusion Systems; Insulin, Long-Acting; Models, Biological; Molecular Sequence Data

The widespread use of insulin analogues is based not only on the pharmacokinetics of these preparations, which is much closer to the physiology of insulin secretion under normal conditions, but also on their safety and effectiveness. The publication of a possible association between the use of a long-acting insulin analogue (glargine) and breast cancer has caused uneasiness among the medical community regarding the safety of these analogues. The mechanism of increased tumor activity of insulin analogues is explained by the fact that they act through insulin receptors (IR) and insulin-like growth factor-1 (IGF-1R), stimulating cell growth and inhibiting apoptosis. There are two major mechanisms: an increase in the binding time of insulin to IR and increased activation of IGF-1R. Therefore, to evaluate the safety of an analogue, the slower dissociation rate from its insulin receptor must be excluded, as well as the increased affinity for the IGF-1 receptor. This is equivalent to an index of mitogenic/metabolic activity of less than 1. These aspects can only be evaluated through study of cell lines and animal testing, which are reductionist models that cannot always be extrapolated to humans. To date, there are no data to question the safety of insulin analogues in general. However, the results of observational studies and some in vitro studies, suggesting a potential risk of mitogenicity with the administration of glargine, have caused some alarm among the medical community. Until now, there are no data to refute or confirm this risk and, therefore, evaluation of the existing data is crucial to obtain objective information.

Topics: Amino Acid Sequence; Animals; Apoptosis; Cell Line, Tumor; Cell Transformation, Neoplastic; Diabetes Mellitus; Drug Evaluation, Preclinical; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin-Like Growth Factor I; Insulin, Long-Acting; Male; Mammary Neoplasms, Experimental; Mitosis; Molecular Sequence Data; Neoplasms; Rats; Rats, Sprague-Dawley; Receptor, IGF Type 1; Receptor, Insulin

The risk of malignancy in patients using insulin glargine was evaluated.. Patients with diabetes mellitus have increased rates of cancers including breast, colon, and pancreatic cancers. Since nondiabetic patients with increased levels of insulin have similar rates of the same cancers, hyperinsulinemia could be key. Normally, insulin produces metabolic effects and insulin-like growth factor-I (IGF-I) produces mitogenic effects. Since the molecules are structurally similar, it is possible for insulin to act like IGF-I, promoting mitogenicity. Concern that insulin may promote the growth of some cancers is heightened with insulin analogues, since changing the structure of human insulin could produce molecules with increased mitogenic potential. In vivo, insulin glargine has been shown to have greater mitogenic potential than human insulin. It is unknown whether this occurs in vitro, because the insulin glargine molecule is transformed once injected. Studies published in 2009 suggest that patients on insulin glargine could be at greater risk for cancer than patients on other antidiabetes therapies, but the trial results are conflicting. In response, the Food and Drug Administration, American Diabetes Association, American Association of Clinical Endocrinologists, and European Association for the Study of Diabetes have formally stated that patients should continue to use insulin glargine until more information is available.. Studies on the relationship between insulin glargine and cancer have been inconclusive.

Topics: Animals; Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin-Like Growth Factor I; Insulin, Long-Acting; Mitogens; Neoplasms; Risk

Analogues of human insulin have been developed to more closely replicate the physiology of meal-related and basal insulin secretion. Three rapid-acting analogues and two basal analogues are available for clinical use. Insulin aspart and insulin lispro have nearly identical pharmacokinetic and pharmacodynamic profiles and provide better postprandial glucose control and less hypoglycaemia (primarily nocturnal and severe hypoglycaemia in type 1 diabetes mellitus) than regular insulin. Insulin glulisine is a new rapid-acting analogue and has characteristics nearly identical to those of its predecessors. Insulin glargine was the first basal analogue approved for clinical use and has shown better fasting glucose control and less risk of hypoglycaemia than conventional human neutral protamine Hagedorn (NPH) insulin. More recent studies have indicated that insulin glargine may not be truly 'peakless' at higher doses and that the adjustment of dose timing and frequency may have favourable effects on the risk of hypoglycaemia and the duration of the effect. Insulin detemir is a new basal insulin analogue with superiority to NPH insulin similar to that demonstrated by insulin glargine, though its duration of action appears to be shorter. The intraindividual variability in the response to a given dose is lower for insulin detemir than for both NPH insulin and insulin glargine. The clinical significance of this finding is not clear, though it may contribute to the lower rate of hypoglycaemia seen with insulin detemir. A number of 'alternative routes' of insulin administration have been studied, the most promising of which has been the pulmonary route. The time-action profile of inhaled insulins is generally characterized by a rapid onset of action similar to those of rapid-acting analogues and a slightly protracted duration of action similar to that of regular insulin. Inhaled insulin is similar to regular insulin with respect to efficacy and safety, though small reversible changes in pulmonary function have been noted. For technical and practical reasons, other alternative routes have generally not met with clinical success.

Topics: Blood Glucose; Clinical Trials as Topic; Diabetes Mellitus; Drug Administration Routes; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting

The new rDNA and DNA-derived "basal" insulin analogs, glargine and detemir, represent significant advancement in the treatment of diabetes compared with conventional NPH insulin. This review describes blood glucose homeostasis by insulin in people without diabetes and outlines the physiological application of exogenous insulin in patients with type 1 and type 2 diabetes. The requirements for optimal basal insulin treatment are discussed and the methods used in the evaluation of basal insulins are presented. An essential criterion in the development of an "ideal" basal insulin preparation is that the molecular modifications made to the human insulin molecule do not compromise safety. It is also necessary to obtain a clear understanding of the pharmacokinetic and pharmacodynamic characteristics of the two currently available basal insulin analogs. When comparing glargine and detemir, the different molar concentration ratios of the two insulin formulations should be considered along with the nonspecificity of assay systems used to determine insulin concentrations. However, euglycemic clamp studies in crossover study design provide a good basis for comparing the pharmacodynamic responses. When the latter is analyzed by results of intervention clinical trials, it is concluded that both glargine and detemir are superior to NPH in type 1 and type 2 diabetes. However, there is sufficient evidence to demonstrate that these two long-acting insulin analogs are different in both their pharmacokinetic and pharmacodynamic profiles. These differences should be taken into consideration when the individual analogs are introduced to provide basal insulin supplementation to optimize blood glucose control in patients with type 1 and type 2 diabetes as well. PubMed-Medline was searched for articles relating to pharmacokinetics and pharmacodynamics of glargine and detemir. Articles retrieved were reviewed and selected for inclusion if (1) the euglycemic clamp method was used with a duration >or=24 h, (2) a single subcutaneous dose of glargine/detemir was used, and (3) area under the curve for insulin concentrations or glucose infusion rates were calculated.

Topics: Amino Acid Sequence; Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Molecular Sequence Data

While the advantages of the two basal insulin analogues, glargine and detemir, over neutral protamine Hagedorn are well established, the relative merit of the two compared with each other has been a matter of some controversy. The two analogues are popularly perceived to differ from each other in their pharmacodynamic (PD) profiles, in particular with regard to 'flatness' and duration of action. The aim of this review, therefore, is to give a complete overview on the available PD data of both analogues as derived with the glucose clamp technique. In order to improve parity across studies, a common definition for duration of action (time from injection to plasma glucose >8.3 mmol/l) was applied and study data were recalculated when necessary. Despite differences in methodological details, the results of most clamp studies were very consistent. Glargine and detemir both typically show a gentle rise and fall in glucose-lowering action over time. Duration of action with both analogues is dose dependent, but in the clinically relevant range of 0.35-0.8 U/kg it is close to 24 h in people with type 1 diabetes and in excess of this in people with type 2 diabetes. While both analogues seem to be very similar with regard to the mean shape of their PD profile and duration of action, detemir shows less within-subject variability in its metabolic effect. These findings in experimental glucose clamp studies are consistent with observations in clinical trials and support routine once daily use with either analogue, in particular in people with type 2 diabetes.

Topics: Blood Glucose; Clinical Trials as Topic; Diabetes Mellitus; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin Secretion; Insulin, Long-Acting; Male; Treatment Outcome

For both type 1 and type 2 diabetes, tight glycaemic control is vital to reduce the risk of long-term complications. However, this must be achieved with minimal risk of hypoglycaemia. Glargine is a new long-acting insulin analogue with an action profile designed to overcome this and has now been in clinical use for a number of years. In many countries glargine is widely used. Here we present an update on the clinical information available on glargine with respect to glycaemic control, the risk of hypoglycaemia and quality of life in both type 1 and type 2 diabetes.

Topics: Blood Glucose; Child; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Quality of Life; Randomized Controlled Trials as Topic

To review intermediate- and long-acting insulins with specific emphasis on the newer insulin analogs.. A MEDLINE search, in English, was conducted with a cut-off of June 30, 2006, using the terms 'NPH insulin', 'insulin analogs', 'insulin glargine', 'insulin detemir' and 'long-acting insulins'. All clinical trials from within the search period were included.. The insulin analogs, insulin glargine and insulin detemir, were introduced in an attempt to improve glycemic control among patients with diabetes, without increasing the risk of hypoglycemia. This review indicates that both insulin analogs demonstrate better glycemic control than NPH insulin, based on measurements of HbA1c, fasting glucose and intra-subject variability in blood glucose. This was accomplished with similar or reduced risk of hypoglycemia. Also, insulin detemir appears to be associated with less body weight increase than NPH insulin or insulin glargine.. The newer long-acting insulin analogs, insulin detemir and glargine, appear to provide better glycemic control than NPH insulin without increasing the risk of hypoglycemia.

Topics: Diabetes Mellitus; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Hypoglycemic Agents; Injections; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Treatment Outcome

The primary aim of insulin therapy is to replace endogenous insulin secretion in patients with type 1 or type 2 diabetes between meals and overnight as well as postprandially. The most frequently used insulin for basal therapy is the intermediate-acting neutral protamin Hagedorn (NPH) insulin, although it does not correspond to a physiological profile. Insulin glargine is a new extended-action recombinant insulin analog, which is absorbed slowly into the bloodstream, reaching peak action in about 4 h and maintaining this concentration profil for 24-30 h. Some studies demonstrated that insulin glargine reduces the incidence of hypoglycemia and is at least as effective as NPH insulin given once or twice daily. It is equally effective administered before breakfast, dinner or at bedtime. Similar absorption rates were recorded after subcutaneous injection in differents part of body. The continuous subcutaneous insulin infusion utilizing an external insulin infusion pump (CSII) is one approach to intensive insulin therapy. Some studies indicate that pump therapy is associated with improved glycemic control compared with traditional insulin therapies and with significant decreases in frequency of both mild and severe hypoglycemic episodes. The author summarizes the indication, the effect and side effects of pump therapy.

Topics: Blood Glucose; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Administration Schedule; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Infusion Systems; Insulin, Isophane; Insulin, Long-Acting

Abstract Recent years have seen the development of alternatives to human insulin for the treatment of diabetes. Both rapid-acting and long-acting analogues are available. Alternative routes of insulin administration are emerging. The present review briefly summarizes the present knowledge on insulin analogues and alternative administration routes.

Topics: Administration, Inhalation; Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting

Neonatal diabetes mellitus (NDM) is a rare disease reported to have an incidence of one in 400,000 to 500,000 live births. The disorder may be more common as it is not routinely considered a diagnostic possibility by many neonatologists who may routinely use insulin to treat neonatal hyperglycemia. NDM can be grouped into two distinct clinical entities--transient and permanent--based on certain features detailed herein; however, distinction between the two categories can only be definitely made in hindsight. Treatment is with insulin; however, determining the correct dose and method of delivery is often challenging, given the sensitivity of neonates to insulin and the risk of hypoglycemia. We report the successful use of Glargine insulin in the treatment of three infants with NDM, review the recent discoveries, and discuss guidelines for the care of newborns with NDM.

Topics: Diabetes Mellitus; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Practice Guidelines as Topic

The primary aim of insulin therapy is to replace endogenous insulin secretion in patients with type 1 or type 2 diabetes in a physiologically sound manner, mimicking normal secretion patterns to adequately regulate glucose metabolism. The currently available human insulins for basal therapy--neutral protamine Hagedorn (NPH), Lente and Ultralente--and analogs such as insulin glargine, differ in pharmacokinetic properties. Clinical trial data indicate that insulin glargine may satisfy basal insulin requirements, with an improved safety profile relative to other available insulins used for basal supplementation. This review describes the unique pharmacokinetic properties and clinical efficacy of insulin glargine.

Topics: Clinical Trials as Topic; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Insulin; Insulin Glargine; Insulin, Long-Acting

The initial injection in 1922 of a pancreatic extract, or insulin as it came to be known, into a patient with diabetes mellitus has since been followed by the successive introduction of longer-acting insulins, more highly purified insulins, and insulins that have been modified to more closely match insulin activity to patients' physiologic requirements. The recently introduced rapid-acting insulin analogues lispro and aspart and the long-acting analogue glargine are further refinements of insulin therapy. Current treatment strategies for severe insulin deficiency are based on the need to provide 2 components of insulin replacement: basal and postprandial. Rapid-acting insulin has been shown to provide superior postprandial glucose control compared with regular insulin. Truly effective control of basal insulin has been achieved by the introduction of the insulin pump in the 1980s and insulin glargine in 2001. Insulin glargine is the first insulin analogue to provide, in a majority of patients, a continuous level of insulin without a pronounced peak after a single daily injection, closely mimicking the normal pancreatic release of basal insulin in healthy individuals. Clinical experience is providing many insights into how basal and prandial components of insulin therapy can be best combined, although evidence from controlled trials will take some years to accumulate. Experience and observations since 2001 indicate that insulin therapy should be introduced earlier in patients with type 2 diabetes to control blood glucose levels. More importantly, the greatest benefit of insulin glargine has been to change positively the way physicians and patients think about insulin therapy. Newer insulin analogues, improved devices for home glucose monitoring, and pulmonary inhaled insulin are other innovations that promise improvement of hemoglobin A(1c) levels.

Topics: Diabetes Mellitus; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Postprandial Period

Insulin glargine (Lantus) is a human insulin analogue produced by recombinant DNA technology and recently launched by Aventis. Modification of the human insulin molecule at position A21 and at the C-terminus of the B-chain results in the formation of a stable compound that is soluble at pH 4.0, but forms amorphous microprecipitates in subcutaneous tissue (pH > 7,4) from which small amounts of insulin glargine are gradually released. The plasma concentration versus time profile of insulin glargine is therefore relatively constant over 24 hours as compared to conventional human insulins, especially NPH. This allows once-daily injection as basal insulin therapy, at any moment of the clock time (but if possible at the same time from day to day). Reproducibility of plasma insulin levels is also improved with insulin glargine as compared to human NPH insulin. Insulin glargine administration should be combined to rapid insulin injections, before each meal in order to control postprandial hyperglycaemia, or with oral antidiabetic agents in type 2 diabetes. The pharmacokinetic properties of insulin glargine allow an easier titration of basal insulin dose, which should facilitate adequate blood glucose control while decreasing the risk of hypoglycaemia, especially during night time. Insulin glargine use is safe with no increased antigenicity, immunogenicity or mitogenicity reactions as compared to human insulin. Optimal use of this new insulin analogue should be integrated in a global management of the diabetic patient as well as in a new culture of insulin therapy.

Topics: Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting

To evaluate the use of insulin glargine in its licensed basal-bolus indication in terms of both clinical and cost-effectiveness.. Electronic databases.. A systematic review of the literature, involving a range of databases, was performed to identify all papers relating to insulin glargine.. Nineteen studies met the inclusion criteria but full reports were available for only six. For type 1 diabetes patients, insulin glargine appears to be more effective than neutral protamine Hagedorn (NPH) in reducing fasting blood glucose (FBG) but not in reducing glycosylated haemoglobin (HbA1c) and there is some evidence that both insulins are as effective as each other in both FBG and HbA1c control. For type 2 patients for whom oral antidiabetic agents provide inadequate glycaemic control, there is no evidence that insulin glargine is more effective than NPH in reducing either FBG or HbA1c and some evidence that both insulins are as effective as each other in both FBG and HbA1c control. Evidence for control of hypoglycaemia is equivocal. In studies where insulin glargine is demonstrated to be superior to NPH in controlling nocturnal hypoglycaemia, this may be only apparent when compared with once-daily NPH and not twice-daily NPH. Further, this superiority of glargine over NPH in the control of nocturnal hypoglycaemia may relate to one formulation of insulin glargine (HOE901[80]) and not another (HOE901[30]). There is no conclusive evidence that insulin glargine is superior to NPH in controlling symptomatic hypoglycaemia and severe hypoglycaemia. Insufficient data are available to conclude whether insulin glargine is different from each of the commonly used NPH dosing regimens: once daily and more than once daily. Given the lack of a published evidence base for the cost-effectiveness of insulin glargine, the economic review concentrates on a review of the industry submission and an amended model. Three economic models are provided in the submission, two relating to type 1 diabetes and one relating to type 2 diabetes. All three models compare the cost--utility of insulin glargine against NPH insulin. In general, the structures of the models are poor and in all three models, mistakes relating to assumptions and calculations have been made. The assessment team believe that the cost per QALY estimates generated by the Aventis model may be an underestimate for several reasons. The cost-effectiveness of insulin glargine in both type 1 and type 2 diabetes is highly sensitive to the amount of utility associated with reducing the fear of hypoglycaemia.. The evidence suggests that, compared with NPH insulin, insulin glargine is effective in reducing the number of nocturnal hypoglycaemic episodes, especially when compared with once-daily NPH. There appears to be no improvement in long-term glycaemic control and therefore insulin glargine is unlikely to reduce the incidence of the long-term microvascular and cardiovascular complications of diabetes. Further research into insulin glargine is needed that addresses the quality of life issues associated with fear of hypoglycaemia and also the economic impact of balance of HbA1c control and incidence of hypoglycaemia achieved in practice. Studies examining the economic evidence on insulin glargine should be published.

Topics: Adult; Aged; Cost-Benefit Analysis; Diabetes Mellitus; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Models, Economic; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Treatment Outcome

Insulin glargine is a human insulin analogue prepared by recombinant DNA technology. Modification of the human insulin molecule at position A21 and at the C-terminus of the B-chain results in the formation of a stable compound that is soluble at pH 4.0, but forms amorphous microprecipitates in subcutaneous tissue from which small amounts of insulin glargine are gradually released. The plasma concentration versus time profile of insulin glargine is therefore relatively constant in relation to conventional human insulins, with no pronounced peak over 24 hours. This allows once-daily administration as basal therapy. Early randomised trials with insulin glargine generally showed greater reductions in fasting blood or plasma glucose levels and a reduced frequency of nocturnal hypoglycaemia relative to neutral protamine Hagedorn (NPH) insulin in patients with type 1 diabetes mellitus. In addition to this basal therapy, patients continued to use the regular mealtime insulin regimen to which they were accustomed. More recent data with insulin glargine have included evidence of improved glycaemic control, with improvements in satisfaction with treatment over NPH insulin. Furthermore, the time of day at which insulin glargine is injected has no clinically relevant effect on glycaemic control in these patients. There are also data from small, nonblind studies to suggest comparable glycaemic control with insulin glargine and continuous subcutaneous insulin infusion. Results from comparative studies and meta-analyses in individuals with type 2 diabetes show lower incidences of nocturnal hypoglycaemia with insulin glargine than with NPH insulin, with two studies showing a significantly greater improvement in glycosylated haemoglobin levels with insulin glargine than with NPH. Insulin glargine is well tolerated, and is not associated with greater immunogenicity or increases in bodyweight than NPH insulin. Long-term data show maintenance of glycaemic control with insulin glargine for up to 39 months in adults and children with type 1 and adults with type 2 diabetes. In conclusion, insulin glargine is an effective and well tolerated basal insulin therapy when given as a single daily subcutaneous injection to patients with diabetes, with benefits in terms of glycaemic control and reduced frequency of hypoglycaemia over regimens based on conventional basal insulins. Accumulating data and official recommendations show the suitability of insulin glargine for first-line use in

Topics: Adolescent; Adult; Aged; Diabetes Mellitus; Drug Administration Schedule; Humans; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin, Long-Acting; Middle Aged; Time Factors; Treatment Outcome; United Kingdom

Tight glycaemic control (ideally, HbA1c<7%) is central to reducing the risk of long-term complications of diabetes. This approach, for both Type 1 and Type 2 diabetes, commonly involves the use of basal insulin, and must be achieved with minimal risk of hypoglycaemia (particularly nocturnal episodes). Indeed, concern around hypoglycaemia is a major barrier to achieving tight glycaemic control, and is a common problem with those protracted-acting insulins most frequently used in clinical practice for basal insulin supply. Other drawbacks include inter- and intra-patient variability that compromises dosing reproducibility and unsuitability for single daily dosing. New long-acting human insulin analogues with action profiles designed to overcome these problems are now available in clinical practice or are under evaluation in clinical trials. Clinical evidence suggests efficacy and safety advantages for these analogues over NPH insulin (the most commonly used basal insulin), and may bring closer the goal of tight glycaemic control in patients with diabetes.

Topics: Carrier Proteins; Delayed-Action Preparations; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Administration Schedule; Humans; Hypoglycemia; Hypoglycemic Agents; Infusions, Parenteral; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting

The rising incidence of diabetes means that it is no longer viable for patients to be treated solely within the secondary care setting and primary health-care professionals, including community nurses working within community-based diabetes clinics, are likely to continue to take on greater responsibility for the assessment and management of patients with diabetes. This article discusses recent advances in insulin therapy--namely the advent of the new insulin analogues--and examines their likely impact on community nurses in terms of improved time management and quality of care for patients with diabetes on patients in terms of improved quality of care.

Topics: Community Health Nursing; Critical Care; Diabetes Mellitus; Drug Administration Schedule; Humans; Insulin; Insulin Glargine; Insulin, Long-Acting; Patient Satisfaction; Treatment Outcome; Workload

Topics: Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting

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: Amino Acid Sequence; Animals; Blood Glucose; Clinical Trials as Topic; Delayed-Action Preparations; Diabetes Mellitus; Humans; Hydrogen-Ion Concentration; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Molecular Sequence Data; Solubility; Treatment Outcome

The pharmacodynamics, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of insulin glargine are reviewed. Current treatment regimens for patients with type 1 diabetes mellitus and some with type 2 are designed to provide a basal insulin level with intermittent preprandial insulin coverage. Insulin glargine precipitates after subcutaneous injection, slowing absorption. Insulin glargine is used as a basal insulin and exhibits a flat pharmacokinetic profile, with a duration of action of at least 24 hours. Hypoglycemia is the most commonly reported adverse effect, especially within the first four weeks after a switch to insulin glargine. Insulin glargine should not be mixed with any other insulin product and should be administered with a syringe that has not been used for other insulin products or other medications. Insulin glargine is administered once daily at bedtime. Patients previously receiving twice-daily isophane insulin (NPH) should receive an insulin glargine dosage 20% less than the total daily dose of NPH insulin. Clinical trials did not consistently show improvements in hemoglobin A1c levels when patients with type 1 diabetes mellitus were switched from NPH insulin once or twice daily to insulin glargine. Insulin glargine should be considered for patients who continue to have elevated morning blood glucose levels and problems with nocturnal hypoglycemia despite receiving NPH insulin at bedtime. In patients with type 2 diabetes mellitus, insulin glargine significantly improved glycemic control compared with once-daily NPH insulin, but not when it was compared with combined treatment with once- or twice-daily NPH insulin. Clinical trials assessing progression of retinopathy and nephropathy and comparing insulin glargine therapy with continuous subcutaneous insulin infusion therapy are needed to more clearly determine insulin glargine's role. Insulin glargine is a new long-acting formulation that can provide prolonged basal glucose control in patients with diabetes mellitus.

Topics: Area Under Curve; Diabetes Mellitus; Drug Costs; Humans; Hypoglycemia; Insulin; Insulin Glargine; Insulin, Long-Acting; Randomized Controlled Trials as Topic

To review the pharmacology, pharmacokinetics, dosing guidelines, adverse effects, drug interactions, and clinical efficacy of insulin glargine.. Primary and review articles regarding insulin glargine were identified by MEDLINE search (1966-July 2001); abstracts were identified through Institute for Scientific Information Web of Science (1995-July 2001) and the American Diabetes Association. Additional information was obtained from the insulin glargine product information.. All of the articles and meeting abstracts identified from the data sources were evaluated, and all information deemed relevant was included in this review. Priority was placed on data from the primary medical literature.. Insulin glargine is a long-acting, recombinant human insulin analog that is given once daily as a basal source of insulin in patients with type 1 or type 2 diabetes mellitus. Modification of the basic insulin structure has produced a new insulin that is soluble at an acidic pH, but precipitates in the subcutaneous tissue and is slowly released from a depot. Insulin glargine has a slower onset of action than NPH insulin and a longer duration of action with no peak activity. Once-daily administration of insulin glargine has comparable efficacy to that of NPH insulin administered once or twice daily in basal-bolus regimens when used in combination with intermittent doses of regular insulin or insulin lispro in patients with type 1 and type 2 diabetes, and in conjunction with oral antidiabetic agents in patients with type 2 diabetes. Overall, insulin glargine has an incidence of hypoglycemia comparable to or less than that of NPH insulin, with a reduced incidence of nocturnal hypoglycemia compared with NPH insulin seen in some studies.. Insulin glargine is a long-acting insulin analog capable of providing 24-hour basal insulin coverage when administered once daily at bedtime. Its activity profile, which lacks a pronounced peak, more closely resembles that of endogenous basal insulin than that of other intermediate- or long-acting insulins and appears more likely to be associated with a reduced incidence of hypoglycemia, particularly nocturnal hypoglycemia. Insulin glargine physiologically provides basal insulin but, for most patients, the addition of a rapid-acting insulin, like insulin lispro, before or with meals will need to be included in the treatment regimen to achieve optimal management of blood glucose concentrations.

Topics: Amino Acid Sequence; Clinical Trials as Topic; Diabetes Mellitus; Drug Administration Schedule; Drug Interactions; Economics, Pharmaceutical; Humans; Insulin; Insulin Glargine; Insulin, Long-Acting

Landmark studies have confirmed the importance of intensified insulin treatment for minimizing long-term diabetic complications. Human insulin is still first-line treatment. However, even the most intensive of human insulin-based regimens can only poorly reproduce physiologically desirable insulin release, which includes rapid outbursts of insulin at mealtimes coupled with relatively low and stable basal levels between meals. Encouragingly, there are now four available or soon-to-be-available insulin analogues that offer the potential for more physiological insulin profiles. Insulin lispro and insulin aspart are rapid-acting insulin analogues intended for immediate pre-meal administration in type 1 or type 2 diabetes. Compared with injected human insulin, they improve post-prandial glucose control and reduce late post-meal and night-time hypoglycaemic episodes. Two basal insulin analogues, insulin glargine and insulin detemir, have also shown beneficial profiles with regard to night-time hypoglycaemia.Some, but not all, studies with the two rapid-acting insulins have shown improvement in overall glucose control, as assessed by HbA(1c), in comparison to human insulin. These results are encouraging and provide hope that entirely analogue-based regimens may improve overall glycaemic control and ease of use of insulin.

Topics: Carrier Proteins; Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting

Topics: Amino Acid Sequence; Blood Glucose; Clinical Trials as Topic; Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Molecular Sequence Data

Topics: Carrier Proteins; Diabetes Mellitus; Dose-Response Relationship, Drug; Drug Approval; Drug Therapy, Combination; Europe; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Randomized Controlled Trials as Topic; United States

In diabetes mellitus, the clinical goal of intensive glycemic control (lowering blood glucose concentrations to normal or near-normal levels) has been hindered by the lack of insulin regimens that duplicate the basal-bolus secretion of insulin by the healthy pancreas. In particular, intensive therapy has been associated with a risk of hypoglycemia.. This article reviews the pharmacology, pharmacokinetics, dosing guidelines, adverse effects, and potential drug interactions of insulin glargine, a new long-acting recombinant human insulin analogue. Results of clinical trials of its efficacy and tolerability as a basal insulin in the treatment of type 1 and type 2 diabetes are summarized.. Primary research and review articles on insulin glargine were identified through a search of MEDLINE from 1966 to July 2001. Abstracts were identified through a search of the Institute for Scientific Information Web of Science from 1995 to July 2001 and proceedings of American Diabetes Association scientific meetings. Additional information was obtained from the product information for insulin glargine. All identified articles and abstracts were evaluated for relevance, and all relevant information was included in the review. Priority was given to data from the primary medical literature.. Insulin glargine has a slower onset of action than human neutral protamine Hagedorn (NPH) insulin, a longer duration of action (up to 24 hours), and no pronounced peak. It has similar tolerability and produces similar glycemic control to once- or twice-daily human NPH insulin, with a similar glucose-lowering effect on a molar basis. A decreased incidence of hypoglycemia, particularly at night, has been reported with insulin glargine compared with human NPH insulin. Insulin glargine appears to be comparable to human NPH insulin in terms of toxicity, adverse effects, immunogenicity, and potential for drug interactions. Results of clinical trials of insulin glargine in both type 1 and type 2 diabetes support its use in combination with a short-acting insulin, insulin lispro, or oral antidiabetic medications. Although insulin glargine cannot be mixed with other insulin preparations, it has the potential convenience of providing basal insulin with once-daily bedtime dosing.. Based on the as yet small amount of data from full clinical study reports in peer-reviewed publications, insulin glargine appears to be a well-tolerated and effective basal insulin preparation for patients with type 1 or type 2 diabetes (including pediatric patients). Its delayed onset of action and prolonged, flat time-action profile mimic the action of endogenous basal insulin (or an insulin pump), decreasing the risk of hypoglycemic episodes. Insulin glargine may be a useful new option for meeting overnight insulin requirements, although most patients will require a rapid-acting insulin such as insulin lispro with or before meals for optimal management of blood glucose levels.

Topics: Adult; Child; Diabetes Mellitus; Drug Interactions; Humans; Hypoglycemia; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Randomized Controlled Trials as Topic

Insulin glargine is a new extended-action insulin analogue, created by recombinant DNA modification of human insulin. Extension of the C-terminal of the B-chain with two arginine residues and the substitution of glycine for asparagine at position A-21 increases the isoelectric point, resulting in precipitation of the insulin at the injection site and a protracted absorption. Pharmacodynamic studies have demonstrated a prolonged metabolic profile without a pronounced peak and with a duration of action of 20 - 30 h. In clinical studies in people with Type 1 and Type 2 diabetes, insulin glargine has demonstrated improved pre-breakfast blood glucose control and a reduction in the frequency of hypoglycaemia, especially nocturnal hypoglycaemia, in comparison with neutral protamine hagedorn (NPH) insulin. In addition, 24h glycaemic control in Type 2 diabetes and treatment satisfaction may also be improved. However, whilst appearing achievable, insulin glargine has not yet demonstrated the ability to improve HbA(1c), though this may relate to inexperience in the use of the new compound. In order to fully exploit its metabolic advantages, it appears vital that the dose of insulin glargine should be titrated to achieve aggressive pre-breakfast blood glucose targets beyond those achievable with NPH in the absence of nocturnal hypoglycaemia. Insulin glargine appears to be a promising new addition to the insulin family and with increased experience in its use, especially in combination with rapid-acting insulin analogues, its full benefits may be realised. The use of insulin glargine with a rapid-acting insulin analogue brings us the closest we have ever been to providing the physiological insulin replacement that has long been awaited.

Topics: Animals; Diabetes Complications; Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting

Topics: Administration, Inhalation; Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting

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

Topics: Amino Acid Sequence; Blood Glucose; Diabetes Mellitus; Humans; Insulin; Insulin Glargine; Insulin-Like Growth Factor I; Insulin, Long-Acting; Molecular Sequence Data

For the treatment of diabetes mellitus (DM) in dogs, novel insulins with decreased injection frequency while maintaining safety and efficacy are desirable. Insulin fused with immunoglobulin-fragment-crystallizable (Fc) has an ultra-long plasma half-life because it recycles through cells, protected from proteolysis.. Glycemic control can be achieved in diabetic dogs with a recombinant fusion protein of a synthetic insulin and canine Fc (AKS-218d) administered subcutaneously once-weekly.. Five client-owned dogs with naturally occurring DM.. Prospective clinical trial in dogs with DM that were recruited from the UC Davis Veterinary Teaching Hospital and local veterinary clinics. Dogs previously controlled using intermediate-acting insulin q12h were transitioned to once-weekly injections of a preliminary construct identified as AKS-218d. The dose of AKS-218d was titrated weekly for 8 weeks based on clinical response and continuous interstitial glucose monitoring. Clinical signs, body weight, serum fructosamine concentrations, and mean interstitial glucose concentrations (IG) over the preceding week were compared between baseline (before AKS-218d) and during the last week of treatment. Data were compared using nonparametric paired tests.. Once-weekly AKS-218d, compared to baseline twice-daily insulin therapy, resulted in no significant changes in clinical signs, median (range) body weight (+0.4 kg [-0.5-1.1]; P = .6), fructosamine concentration (-75 mmol/L [-215 to +126]; P = .4), or mean IG (+81 mg/dL [-282 to +144]; P = .8). No adverse reactions were reported.. Control of clinical signs, body weight, and maintenance of glycemia was achieved with this once-weekly novel insulin construct in 4 of 5 dogs.

Topics: Animals; Blood Glucose; Blood Glucose Self-Monitoring; Body Weight; Diabetes Mellitus; Diabetes Mellitus, Type 2; Dog Diseases; Dogs; Fructosamine; Hospitals, Animal; Hospitals, Teaching; Hypoglycemic Agents; Insulin; Insulin Glargine; Prospective Studies

Topics: Diabetes Mellitus; Female; Heart Failure; Hospitalization; Humans; Hypoglycemic Agents; Incidence; Insulin Glargine; Male; Middle Aged; Prospective Studies; Recurrence; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome

A commonly used therapeutic strategy for type 2 diabetes mellitus (DM) in humans involves the use of synthetic incretin hormone-based therapies including exenatide, a glucagon-like pepetide-1 hormone agonist. Glucagon-like pepetide-1 agonists can be used alone or as an ancillary therapy with other agents, including insulin and oral antihyperglycemics. Little is known about the role of these therapies for DM in cats. Therefore, the primary objective of this study was to evaluate the safety and efficacy of short-acting exenatide combined with insulin, as compared to placebo and insulin for the treatment of DM in cats. Treatment with exenatide was well tolerated; only 2 cats developed side effects requiring dose reduction. Two cats (25%) went into diabetic remission while receiving exenatide and insulin, whereas remission was not reported during placebo treatment. The average change in the daily exogenous insulin dose was significant (β = -0.56 U/kg, 95% confidence interval, -0.96 to -0.15, P = 0.007), and the dose of insulin administered was lower during exenatide treatment. The average weight loss experienced on exenatide was significantly higher than on placebo (β = 0.65 kg, 95% confidence interval, 0.09-1.21, P = 0.02). There was no significant difference in any of the hormone concentrations evaluated for cats on exenatide vs placebo treatments. Overall, the treatment of diabetic cats with insulin and a fixed dose of exenatide was found to be safe. The weight loss and decreased exogenous insulin requirement experienced with exenatide treatment could be a significant benefit for overweight diabetic cats and warrants further evaluation.

Topics: Animals; Blood Glucose; Cat Diseases; Cats; Cross-Over Studies; Diabetes Mellitus; Double-Blind Method; Drug Therapy, Combination; Exenatide; Female; Glucagon-Like Peptide 1; Hypoglycemic Agents; Insulin Glargine; Male; Placebos; Random Allocation; Weight Loss

To ensure patient safety when replacing insulin glargine (IG) with neutral protamine Hagedorn (NPH) insulin and to determine differences in blood glucose control, frequency of hypoglycemia, insulin dosing, health resource utilization and quality of life between users of IG and NPH insulin.. A single-site, open-label, randomized, 6-month comparative study of 66 patients from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Randomization was 1:1 to receive IG or NPH insulin. Data regarding blood glucose control, insulin dosage adjustment and recording of hypoglycemia episodes were obtained through telephone calls; office visits were conducted to measure weight, glycated hemoglobin, fasting plasma glucose and blood glucose profile. The Diabetes Treatment Satisfaction Questionnaire (DTSQ) was used to measure patients' satisfaction with their diabetes treatment.. Rates of symptomatic hypoglycemia did not differ significantly between groups: 37.5±2.2 for the IG group and 31.1±2.1 for the NPH group. However, patients treated with NPH insulin had higher frequencies of severe hypoglycemia (6.1±0.9) compared with 2.7±0.6 for the IG group. A significant difference in changes in glycated hemoglobin (A1C) was observed between the groups: the mean ± standard error A1C decreases from baseline were -0.34%±0.11 for the IG group, vs -0.01%±0.10 for the NPH insulin group. The data obtained from the DTSQ showed greater treatment satisfaction in the IG group compared with the NPH insulin group.. Switching from IG to NPH insulin resulted in more than double the rate of severe hypoglycemias and led to decreased metabolic control. Greater treatment satisfaction was observed with IG, compared with NPH insulin, as measured by change from baseline in the DTSQ scores.

Topics: Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus; Drug Substitution; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Male; Patient Satisfaction; Risk Factors; Treatment Outcome

Diabetes patients are usually started on a low dose of insulin and their dose is adjusted or "titrated" according to their blood glucose levels. Insulin titration administered through face-to-face visits with a clinician can be time consuming and logistically burdensome for patients, especially those of low socioeconomic status (SES). Given the wide use of mobile phones among this population, there is the potential to use short message service (SMS) text messaging and phone calls to perform insulin titration remotely.. The goals of this pilot study were to (1) evaluate if our Mobile Insulin Titration Intervention (MITI) intervention using text messaging and phone calls was effective in helping patients reach their optimal insulin glargine dose within 12 weeks, (2) assess the feasibility of the intervention within our clinic setting and patient population, (3) collect data on the cost savings associated with the intervention, and (4) measure patient satisfaction with the intervention.. This was a pilot study evaluating an intervention for patients requiring insulin glargine titration in the outpatient medical clinic of Bellevue Hospital Center in New York City. Patients in the intervention arm received weekday SMS text messages from a health management platform requesting their fasting blood glucose values. The clinic's diabetes nurse educator monitored the texted responses on the platform website each weekday for alarm values. Once a week, the nurse reviewed the glucose values, consulted the MITI titration algorithm, and called patients to adjust their insulin dose. Patients in the usual care arm continued to receive their standard clinic care for insulin titration. The primary outcome was whether a patient reached his/her optimal insulin glargine dose within 12 weeks.. A total of 61 patients consented and were randomized into the study. A significantly greater proportion of patients in the intervention arm reached their optimal insulin glargine dose than patients in the usual care arm (88%, 29/33 vs 37%, 10/27; P<.001). Patients responded to 84.3% (420/498) of the SMS text messages requesting their blood glucose values. The nurse reached patients within 2 attempts or by voicemail 91% of the time (90/99 assigned calls). When patients traveled to the clinic, they spent a median of 45 minutes (IQR 30-60) on travel and 39 minutes (IQR 30-64) waiting prior to appointments. A total of 61% (37/61) of patients had appointment copays. After participating in the study, patients in the intervention arm reported higher treatment satisfaction than those in the usual care arm.. MITI is an effective way to help low-SES patients reach their optimal insulin glargine dose using basic SMS text messaging and phone calls. The intervention was feasible and patients were highly satisfied with their treatment. The intervention was cost saving in terms of time for patients, who were able to have their insulin titrated without multiple clinic appointments. Similar interventions should be explored to improve care for low-SES patients managing chronic disease.. Clinicaltrials.gov NCT01879579; https://clinicaltrials.gov/ct2/show/NCT01879579 (Archived by WebCite at http://www.webcitation.org/6YZik33L3).

Topics: Blood Glucose; Cell Phone; Chronic Disease; Diabetes Mellitus; Female; Healthcare Disparities; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Male; Middle Aged; Patient Satisfaction; Pilot Projects; Telemedicine; Text Messaging

To evaluate the effects of twice-daily glargine insulin administration in dogs with diabetes mellitus.. Open-label, prospective clinical trial.. 10 dogs with naturally occurring diabetes mellitus.. Dogs with poorly regulated or newly diagnosed diabetes mellitus were enrolled if their owners agreed to return them to the hospital at 1- to 3-week intervals for 4 follow-up visits. During each follow-up visit, blood glucose concentrations were measured every 2 hours for at least 10 hours after feeding a diet high in insoluble fiber and after administration of glargine insulin (time 0). The initial glargine insulin dosage was 0.5 U/kg (0.23 U/lb) SC twice daily.. All dogs had well-regulated diabetes mellitus at a mean ± SD of 38 ± 14 days (median, 43 days; range, 7 to 55 days) following study enrollment. At the time diabetes mellitus was well regulated, mean glargine insulin dosage was 0.5 ± 0.15 U/kg (0.23 ± 0.068 U/lb; median, 0.5 U/kg; range, 0.32 to 0.67 U/kg [0.15 to 0.30 U/lb]) twice daily, and 3 dogs were receiving a dosage < 0.4 U/kg (0.18 U/lb). In dogs with well-regulated diabetes mellitus, the mean minimum blood glucose concentration (163 ± 89 mg/dL; 95% confidence interval, 100 to 227 mg/dL) was detected 2 hours after administration of glargine insulin and the mean maximum blood glucose concentration (230 ± 95 mg/dL; 95% confidence interval, 64 to 323 mg/dL) was detected 12 hours after administration of glargine insulin. There was no significant difference between mean minimum and mean maximum blood glucose concentrations nor were there significant differences between blood glucose concentrations measured at other time points. Blood glucose concentration < 80 mg/dL was measured at least once in 7 of 10 dogs.. Results of the present study suggested that, in diabetic dogs fed a diet high in insoluble fiber, glargine insulin is a peakless insulin that does not induce a distinct blood glucose concentration nadir. For glargine insulin, 0.3 U/kg (0.136 U/lb) SC twice daily is recommended as an initial dosage.

Topics: Animals; Diabetes Mellitus; Dog Diseases; Dogs; Female; Insulin Glargine; Insulin, Long-Acting; Male

The aim of this study was to evaluate the effectiveness of sitagliptin, alone or in combination with metformin, in kidney transplant patients with newly diagnosed new-onset diabetes mellitus after transplant who had inadequate glycemic control, compared with a group of patients receiving insulin glargine with special emphasis on weight gain.. Newly diagnosed renal transplant patients with new-onset diabetes mellitus after a transplant was defined by a blood glucose ≥ 11.1 mmol/L after an oral glucose tolerance test were examined. They were treated with standard immunosuppression composed of triple therapy with tacrolimus or cyclosporine, mycophenolate mofetil or azathioprine, and prednisone. They had stable graft function for more than 6 months after the transplant.. Patients with new-onset diabetes mellitus after transplant (n=28) whose glycemia was not controlled adequately with oral hypoglycemic agents (either alone or in combination) received oral sitagliptin 100 mg once daily in addition to existing therapy for 12 weeks. Patients who received insulin glargine as add-on therapy (n=17) served as the control group. Data analyses included glycated hemoglobin, fasting plasma glucose, lipid profile, body weight, and the occurrence of hypoglycemia. We found significant reductions in glycated hemoglobin and fasting plasma glucose values after 12 weeks of additional sitagliptin therapy that were comparable to those with insulin glargine. While the addition of stagliptin resulted in a small weight loss (0.4 kg), the addition of insulin glargine resulted in a weight gain (0.8 kg). The overall incidence of adverse experiences was low and generally mild in both groups.. In a group of renal transplant recipients with new-onset diabetes mellitus after a transplant in whom glycemia was not controlled adequately by oral hypoglycemic agents, the addition of sitagliptin helped to achieve glycemic control similar to insulin glargine but with a marginal weight advantage.

Topics: Adult; Anti-Obesity Agents; Blood Glucose; Diabetes Mellitus; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Female; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Kidney Transplantation; Male; Metformin; Middle Aged; Pyrazines; Sitagliptin Phosphate; Treatment Outcome; Triazoles; Weight Gain; Weight Loss

The aim of the present paper is to provide some further data on the relationship between β-blocker treatment and the incidence of cancer, using two different approaches (epidemiological study and meta-analysis of clinical trials).. In a consecutive series of 1340 diabetic patients starting insulin therapy, 112 cases of cancer during a mean follow-up of 75.9 months were identified as first hospital admission or death. For each case, the controls were chosen randomly from those members of the cohort matched for age, sex and BMI. The main predefined analysis was the comparison of cases and controls for length of exposure to β-blockers and proportion of patients exposed using a conditional logistic regression which takes into account the matching structure. For the meta-analytic sub-study, an extensive search of Medline and the Cochrane Library (any date up to December 31st, 2011) was performed for all trials in which a β-blocker was used. Mantel-Haenszel Odds Ratios (MH-OR) with 95% confidence intervals for incident malignancies were calculated using a random effect model.. After adjusting for mean daily dose of glargine and metformin, and ischemic heart disease, exposure to β-blockers was associated with a reduced overall risk of cancer (HR 0.33 [0.13; 0.83], p = 0.019; HR for each month of exposure 0.87 [0.77; 0.98], p = 0.025). In the meta-analysis sub-study, performed on nine trials, β-blockers were associated with a non-significant trend toward lower risk of cancer (MH-OR 0.93 [0.86; 1.01], p = 0.070).. Limitations of the observational study are the small sample size that limits the statistical power of analyses, that it was performed on diabetic patients only, and that diagnoses of malignancies were derived from administrative data.. In conclusion, this research seem to confirm a possible beneficial effect of β-blockers against the risk of cancer development.

Topics: Adrenergic beta-Antagonists; Aged; Atenolol; Benzopyrans; Bisoprolol; Carbazoles; Carvedilol; Diabetes Mellitus; Ethanolamines; Female; Humans; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Metformin; Myocardial Ischemia; Nebivolol; Neoplasms; Propanolamines; Risk

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

The purpose of this study was to evaluate the effects of dietary modification in addition to twice daily insulin glargine. Cats were treated with insulin glargine twice daily and randomized to receive either a low carbohydrate, high protein (LCHP) diet (n=6) or a control diet (n=6) for 10 weeks. Re-evaluations of clinical signs, blood glucose curves, and serum fructosamine concentrations were performed at weeks 1, 2, 4, 6, and 10. Two of 12 cats achieved complete remission by the end of the study but remission rate was not different between diet groups. Using twice daily insulin glargine and frequent monitoring, all cats in both diet groups achieved successful glycemic control. Frequent monitoring is key to achieving glycemic control in diabetic cats; potential benefits of dietary modification require further evaluation.

Topics: Animals; Blood Glucose; Cat Diseases; Cats; Diabetes Mellitus; Diet, Carbohydrate-Restricted; Diet, Diabetic; Dietary Carbohydrates; Dietary Proteins; Female; Fructosamine; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Treatment Outcome

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

The aim of the PREDICTIVE study, a large, multinational observational trial, was to evaluate the efficacy and safety of insulin detemir (IDet) in routine clinical practice.. Twelve-week follow-up data from patients with type 1 (T1D) or type 2 (T2D) diabetes in the European cohort switched from once (qd) or twice (bid) daily insulin glargine (IGlarg) (+/-oral antidiabetic therapy) to qd IDet in a basal-bolus regimen. End-points, assessed from patient recall/diaries, included incidence of serious adverse drug reactions, glycaemic parameters, hypoglycaemia and weight change.. The analysis included 1285 patients with T1D (n = 508) or T2D (n = 777). At 12 weeks, glycosylated haemoglobin (HbA1c) was significantly reduced (qd IGlarg to qd IDet: T1D, -0.47%; T2D, -0.51%; p < 0.0001 for both; bid IGlarg to qd IDet: T1D, -0.31%; T2D, -0.89%, p < 0.05 for both). Fasting blood glucose (FBG) and FBG variability were also reduced. Reductions in overall, major and nocturnal hypoglycaemic events were observed after switching from qd IGlarg to qd IDet (overall, T1D, 39.7-18.85 episodes/patient-year; overall, T2D, 11.57-2.99 episodes/patient-year, p < 0.0001 for both). Similar reductions were observed in bid IGlarg to qd IDet patients. Mean weight change was -0.3 to -0.4 kg across patient groups.. Switching from IGlarg to qd IDet was associated with improvements in glycaemic parameters with no associated increase in hypoglycaemic episodes or weight gain.. Patients with T1D and T2D may be switched from IGlarg to qd IDet as part of a basal-bolus regimen.

Topics: Adult; Aged; Cohort Studies; Diabetes Mellitus; Drug Administration Schedule; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Treatment Outcome; Weight Gain

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

Glycaemic control and remission probabilities were compared in 24 newly diagnosed diabetic cats treated twice daily with either glargine, protamine zinc (PZI) or lente insulin and fed a low carbohydrate diet. After day 17, the probability of remission was substantially higher for cats with lower mean 12h blood glucose concentrations on day 17, irrespective of insulin type. Glargine-treated cats had lower mean 12h blood glucose concentrations on day 17 than PZI- or lente-treated cats, and all eight glargine-treated cats achieved remission compared to three PZI- and two lente-treated cats. The probability of remission was greater for cats treated with glargine than cats treated with PZI or lente insulin. In newly diagnosed diabetic cats, twice daily treatment with glargine provides better glycaemic control and higher probability of remission compared to twice daily treatment with PZI or lente insulin. Good glycaemic control soon after diagnosis is associated with increased probability of remission and should be the goal of insulin therapy.

Topics: Analysis of Variance; Animals; Blood Glucose; Cat Diseases; Cats; Diabetes Mellitus; Dietary Carbohydrates; Female; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Protamines; Remission Induction; Treatment Outcome

Pen devices can help to overcome some of the barriers associated with insulin therapy. The present study evaluated the accuracy of dose delivery by people with diabetes using the novel prefilled, disposable SoloSTAR device with insulin glargine (Lantus) and insulin glulisine (Apidra) (all from sanofi-aventis, Paris, France).. People with type 1 or type 2 diabetes (insulin users or insulin naive) were eligible to participate in this randomized, single-center, open-label study. Each participant delivered six separate insulin doses into a sponge using SoloSTAR (three with glargine [10, 40, and 80 units] and three with glulisine [5, 15, and 30 units]). Pens were weighed before and after each test dose to determine the dose delivered. Thresholds for dosing accuracy were calculated according to the 2000 International Organization for Standardization (ISO) recommendations (Guideline 11608-1).. All doses of glargine and glulisine delivered (60 participants; 360 individual doses) were within the ISO limits. Mean (standard deviation) glargine doses delivered were 9.87 (0.24), 39.63 (0.36), and 79.02 (0.62) units for 10, 40, and 80 units, respectively. Insulin glulisine doses delivered were 4.98 (0.20), 14.87 (0.29), and 29.67 (0.34) units for 5, 15, and 30 units, respectively.. The SoloSTAR pen allows people with diabetes to achieve a dosing accuracy with glargine and glulisine similar to that achieved in laboratory conditions. The dosing accuracy and ease of use of SoloSTAR may provide greater confidence in the precision and accuracy of the device while titrating glargine and/or glulisine to goal.

Topics: Adolescent; Adult; Aged; Diabetes Mellitus; Drug Delivery Systems; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Prospective Studies; Reproducibility of Results

Cystic fibrosis related diabetes (CFRD) with fasting hyperglycemia is found in 15% of adult and 11% of adolescent CF patients. Because of concerns about hypoglycemia, it is not common practice to treat CFRD with 24-hour basal insulin therapy, despite evidence that insulin deficiency may contribute to protein catabolism and have an adverse effect on weight, muscle mass, pulmonary function, and, ultimately, survival. We hypothesized that insulin glargine would improve blood glucose control and weight in patients with CFRD without causing hypoglycemia.. A randomized cross-over study compared 12 weeks each of bedtime NPH or glargine in 19 CFRD patients.. There was significantly greater reduction in fasting plasma glucose with glargine (P=0.03), and participants showed a non-significant trend towards weight gain with this insulin (P=0.07). No serious hypoglycemia occurred. At study end, all patients chose to continue glargine.. A study of longer duration is needed to determine whether insulin glargine impacts protein catabolism and overall clinical status in CF patients, but these initial data suggest that this is a promising therapy in CFRD.

Topics: Adult; Blood Glucose; Cross-Over Studies; Cystic Fibrosis; Diabetes Mellitus; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Treatment Outcome

Determine if pre-emptive daily insulin glargine surpasses regular insulin when needed for glycaemic control after cardiac surgery.. Prospective, randomized study of 43 patients (scheduled for coronary artery bypass grafting) with preoperatively diagnosed diabetes (DM) or pre-DM. Lantus group received insulin glargine daily from start of surgery while Actrapid group received regular insulin (sliding scale) when needed (plasma glucose (P-glu)>10 mmol/l). Primary endpoint was percent of pre- and post-prandial P-glu values within Target Intervals: Pre-prandial P-glu: 4.5-7 mmol/l; post-prandial P-glu: 4.5-9 mmol/l. Study period 1-4 days after surgery. Tissue glucose was also measured continuously.. More than twice as many P-glu values were within Target Interval for Lantus patients as compared with Actrapid patients (p<0.001). One of 504 timed measurements was <4 mmol/l. Area under the curve for glucose>7 mmol/l was reduced by 61% by Lantus (p<0.001).. The routine protocol with pre-emptive glargine insulin studied here provides a major improvement in glycaemic control with a minimal incidence of hypoglycaemia and without an excessive increase in nursing burden.

Topics: Aged; Blood Glucose; Coronary Artery Bypass; Coronary Artery Disease; Diabetes Mellitus; Drug Administration Schedule; Female; Glucose Intolerance; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Pilot Projects; Prediabetic State; Prospective Studies; Time Factors; Treatment Outcome

LEAP is multicentric study in phase IV. The first aim was to affirm Lantus efficacy and safety in every day practice, in local conditions. The second aims were to verify therapy successful by measuring fast blood glucose (FBG) and HbA1c and to estimate patients' pleasure. Duration of study was 2 months. Lantus was administrated subcutaneously daily. Doses were individual. HbA1c was measured at the begining of therapy and at the last control. Blood glucose was measured every day. The study included patients who did not reach the control of glycemy, or patients with frequent hypoglycemic crysis, older then 6 year. LEAP study in Sarajevo included 114 patients. Fifty four patients (47%) were men, and 60 (53%) were women. 46% diabetics have type 1 of diabetes mellitus and 54% have type 2 diabetes mellitus. The results of study demonstrated statistically significant decreasing of FBG and HbA1c in both groups (I group--patients younger than 18 years and II group--patients older than 18 years), p<0.05. FBG in I group on the start of Lantus therapy was 9.9+/-3.9 mmol/l but on ending control was 8.7+/-4.4 mmol/l (p<0.05). HbA1c on start of therapy was 9.4+/-1.9%, but on end control was 8.0+/-1.8% (p<0.05). FBG in II group on start was 13.6+/-4.7 mmol/l but on finish was 7.3+/-2.9 mmol/l (p<0.01). HbA1c on start was 9.3+/-1.8% and on end was 7.2+/-1.2% (p<0.01). These results showed that the Lantus is very efficacious for good glycoregulation. Just for two months, HbA1c decreased for 2%. Undesirable effects were not registered. We concluded that Lantus is very safe. Most patients (89%) were satisfied with therapy.

Topics: Adolescent; Adult; Blood Glucose; Child; Diabetes Mellitus; Female; Glycated Hemoglobin; Humans; Insulin; Insulin Glargine; Insulin, Long-Acting; Male

Insulin glargine is a human insulin analogue prepared by recombinant DNA technology. Modification of the human insulin molecule at position A21 and at the C-terminus of the B-chain results in the formation of a stable compound that is soluble at pH 4.0, but forms amorphous microprecipitates in subcutaneous tissue from which small amounts of insulin glargine are gradually released. The plasma concentration versus time profile of insulin glargine is therefore relatively constant in relation to conventional human insulins, with no pronounced peak over 24 hours. This allows once-daily administration as basal therapy. Early randomised trials with insulin glargine generally showed greater reductions in fasting blood or plasma glucose levels and a reduced frequency of nocturnal hypoglycaemia relative to neutral protamine Hagedorn (NPH) insulin in patients with type 1 diabetes mellitus. In addition to this basal therapy, patients continued to use the regular mealtime insulin regimen to which they were accustomed. More recent data with insulin glargine have included evidence of improved glycaemic control, with improvements in satisfaction with treatment over NPH insulin. Furthermore, the time of day at which insulin glargine is injected has no clinically relevant effect on glycaemic control in these patients. There are also data from small, nonblind studies to suggest comparable glycaemic control with insulin glargine and continuous subcutaneous insulin infusion. Results from comparative studies and meta-analyses in individuals with type 2 diabetes show lower incidences of nocturnal hypoglycaemia with insulin glargine than with NPH insulin, with two studies showing a significantly greater improvement in glycosylated haemoglobin levels with insulin glargine than with NPH. Insulin glargine is well tolerated, and is not associated with greater immunogenicity or increases in bodyweight than NPH insulin. Long-term data show maintenance of glycaemic control with insulin glargine for up to 39 months in adults and children with type 1 and adults with type 2 diabetes. In conclusion, insulin glargine is an effective and well tolerated basal insulin therapy when given as a single daily subcutaneous injection to patients with diabetes, with benefits in terms of glycaemic control and reduced frequency of hypoglycaemia over regimens based on conventional basal insulins. Accumulating data and official recommendations show the suitability of insulin glargine for first-line use in

Topics: Adolescent; Adult; Aged; Diabetes Mellitus; Drug Administration Schedule; Humans; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin, Long-Acting; Middle Aged; Time Factors; Treatment Outcome; United Kingdom

Insulin preparations, which are drug treatments for diabetes, cause fatal hypoglycemia when an overdose is administered. Cases of homicide and suicide using these preparations have been reported and are of great forensic interest. However, there are few reports assessing the postmortem concentration of insulin preparations, and it is often difficult to determine the cause of death. In the present study, we report a case of a suspected insulin glargine and insulin lispro overdose for suicide. A woman in her 30s had a history of mental illness and diabetes. The day before her death, she reported to her boyfriend that she had taken large doses of insulin preparations and prescription drugs. An autopsy revealed no fatal injuries or lesions. Drug screening tests revealed several prescription drugs, none of which showed toxic concentrations. Analysis using LC-MS/MS detected insulin glargine in the peripheral and cardiac blood at 429 μU/mL and 1362 μU/mL, respectively, whereas insulin lispro was detected in both the peripheral and cardiac blood at levels below the lower limit of quantification (LLOQ; <50 μU/mL). The cause of death was considered likely to be hypoglycemia caused by an overdose of insulin glargine. Insulin glargine is rapidly metabolized after subcutaneous administration and is rarely detected in the blood when used at therapeutic doses. There are no other reports on the quantification of insulin glargine parent compounds in postmortem samples, and this case provides important data on postmortem blood concentrations of insulin glargine intoxication.

Topics: Blood Glucose; Chromatography, Liquid; Diabetes Mellitus; Drug Overdose; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Tandem Mass Spectrometry

Diabetes mellitus rates and associated costs continue to rise across Europe enhancing health authority focus on its management. The risk of complications is enhanced by poor glycaemic control, with long-acting insulin analogues developed to reduce hypoglycaemia and improve patient convenience. There are concerns though with their considerably higher costs, but moderated by reductions in complications and associated costs. Biosimilars can help further reduce costs. However, to date, price reductions for biosimilar insulin glargine appear limited. In addition, the originator company has switched promotional efforts to more concentrated patented formulations to reduce the impact of biosimilars. There are also concerns with different devices between the manufacturers. As a result, there is a need to assess current utilisation rates for insulins, especially long-acting insulin analogues and biosimilars, and the rationale for patterns seen, among multiple European countries to provide future direction.. Typically increasing use of long-acting insulin analogues across Europe including both Western and Central and Eastern European countries reflects perceived patient benefits despite higher prices. However, activities by the originator company to switch patients to more concentrated insulin glargine coupled with lowering prices towards biosimilars have limited biosimilar uptake, with biosimilars not currently launched in a minority of European countries. A number of activities were identified to address this. Enhancing the attractiveness of the biosimilar insulin market is essential to encourage other biosimilar manufacturers to enter the market as more long-acting insulin analogues lose their patents to benefit all key stakeholder groups.. There are concerns with the availability and use of insulin glargine biosimilars among European countries despite lower costs. This can be addressed.

Topics: Biosimilar Pharmaceuticals; Cost-Benefit Analysis; Diabetes Mellitus; Europe; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Patient Education as Topic

Topics: Adrenergic beta-Antagonists; Aminobutyrates; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Biphenyl Compounds; Blood Pressure; Calcium Channel Blockers; Cats; COVID-19; COVID-19 Serotherapy; Diabetes Mellitus; Diabetes Mellitus, Type 2; Dogs; Drug Combinations; Gastric Inhibitory Polypeptide; Heart Sounds; History, 20th Century; Humans; Hypertension; Immunization, Passive; Incretins; Insulin Glargine; Meta-Analysis as Topic; Randomized Controlled Trials as Topic; SARS-CoV-2; Thiazides; Valsartan

Topics: Diabetes Mellitus; Humans; Hypoglycemic Agents; Inpatients; Insulin; Insulin Glargine; Parenteral Nutrition, Total

Topics: Biosimilar Pharmaceuticals; Diabetes Mellitus; Drug Approval; Drug Costs; Health Care Sector; Humans; Hypoglycemic Agents; Insulin Glargine; Interrupted Time Series Analysis; Marketing; United States

Day-to-day variability impacts safety of insulin therapy and the choice of monitoring strategies. Side-by-side comparisons of insulin formulations in diabetic dogs are scarce.. Insulin glargine 300 U/mL (IGla300) and insulin degludec (IDeg) are associated with less day-to-day glucose variability compared to porcine lente (PL) in diabetic dogs.. Seven intact male purpose-bred beagles with toxin-induced diabetes.. In this repeated measured study, PL, IGla300 and IDeg were compared in 2 phases: once-daily (q24h) and twice-daily (q12h) administration. Interstitial glucose concentrations (IG) were measured continuously throughout the study. For each formulation, maximal q24h dose was determined using the same algorithm (while avoiding hypoglycemia) and then maintained for 72 hours. In phase 2, 70% of the maximal q24h dose was administered q12h and maintained for 5 days regardless of hypoglycemia. Coefficient of variation (CV) and glycemic variability percentage (GVP) were calculated to determine day-to-day and intraday variability, respectively.. There was no difference in day-to-day variability between PL, IGla300, and IDeg in the q24h phase. In the q12h phase, day-to-day variability was higher (P = .01) for PL (CV = 42.6 ± 6.8%) compared to IGla300 and IDeg (CV = 30.1 ± 7.7%, 25.2 ± 7.0%, respectively). The GVP of PL was lower (P = .02) compared to IGla300. There was no difference between PL, IGla300 and IDeg in %time IG < 70 mg/dL.. Insulin degludec and IGla300 administered q12h were associated with lower day-to-day variability, which might be advantageous in minimizing monitoring requirements without increasing the risk of hypoglycemia.

Topics: Animals; Blood Glucose; Diabetes Mellitus; Diabetes Mellitus, Type 2; Dog Diseases; Dogs; Glycated Hemoglobin; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Swine; Swine Diseases

The aim is to devise a new short-term intensive insulin therapy (N-SIIT) based on the concept of "treat to target" to avoid hypoglycaemia and was applied it to various diabetic state. We determined dosage of 1 basal and 3 bolus "treat" insulin based on "target" blood glucose level and changed each insulin dose by small units (2 units) every day for 2 weeks. We evaluated the effects of N-SIIT in 74 subjects with type 2 diabetes (male 45, female 29, 64.9 ± 16.6 years old, HbA1c 10.4 ± 2.6%). Glargine U300 ("treat") and morning blood glucose level ("target") was significantly correlated with increasing insulin dose and decreasing blood glucose level in day 1-7, indicating that insulin amount was determined by target blood glucose level and lowered next target blood glucose level. Remission rates were 67.3% (Hypoglycaemia rate 5.6 %) in N-SIIT and 47.3% (Hypoglycaemia rate 38.1%) in conventional SIIT. Required amount of insulin would be automatically determined, depending on each patient pathophysiology and life style. This method is pretty simple, flexible and cheap, and provides information about the dynamic pathophysiological alteration of insulin resistance and glucotoxicity from the profile of blood glucose levels and insulin shot.

Topics: Aged; Aged, 80 and over; Blood Glucose; Diabetes Mellitus; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin Resistance; Life Style; Male; Middle Aged; Practice Guidelines as Topic

Lantus, the reference insulin glargine used for the treatment of diabetes, lost its patent protection in 2014, opening the market to biosimilar competitors.. First, to analyze the adoption rates of insulin glargine biosimilars in primary care in England and estimate the savings realized and missed, since an insulin glargine biosimilar was first used, and second, to assess potential variations in adoption rates across Clinical Commissioning Groups (CCGs).. Data sets capturing information on all insulin glargine items prescribed by all general practitioners up to December 2018 were used. Total costs of insulin glargine and uptake rates of biosimilars were calculated. The real-world budget impact was estimated assuming the cost of reference insulin glargine for all items and comparing the total costs in this scenario with the total costs in the real world. The missed savings were estimated assuming the cost of biosimilars for all insulin glargine items. Choropleth maps were generated to assess potential variations in uptake across CCGs.. Insulin glargine biosimilars generated savings of £900,000 between October 2015 (time of first prescription) and December 2018. The missed savings amounted to £25.6 million in this period, indicating that only 3.42% of the potential savings were achieved. The analyses demonstrated a large level of variation in the uptake of insulin glargine biosimilars across CCGs, with market shares ranging from 0 to 53.3% (December 2018).. These results may encourage decision makers in England to promote the use of best-value treatments in primary care and to reevaluate variation across CCGs.

Topics: Biosimilar Pharmaceuticals; Cost Savings; Diabetes Mellitus; Drug Costs; England; Health Care Costs; Humans; Hypoglycemic Agents; Implementation Science; Insulin Glargine; Practice Patterns, Physicians'; Primary Health Care; Therapeutic Equivalency

To evaluate the effectiveness of the different insulin therapies on obstetrics-fetal outcomes in women with pregestational diabetes mellitus. We enrolled 147 pregnant women with pre-existing type 1 or 2 diabetes mellitus. Clinical and biochemical parameters were analysed in relation to obstetric and fetal outcomes. 14.2% received treatment with Neutral Protamine Hagedorn insulin and short-acting insulin analogues; 19% with premixed human insulin; 40.1% with insulin glargine and lispro, 6.2% with detemir and aspart and 20% with continuous subcutaneous insulin infusion. All 5 types of treatment achieved a reduction of the mean HbA1c during pregnancy (p = 0.01). Pre-pregnancy care was carried out for 48% of patients. We found no statistically significant differences between the different insulin therapies and the obstetric-fetal outcomes. In conclusión, the different insulin therapies used in patients with pregestational diabetes mellitus does not seem to affect obstetric-fetal outcomes.

Topics: Adult; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetes, Gestational; Drug Combinations; Female; Glycated Hemoglobin; Humans; Insulin; Insulin Detemir; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Pregnancy; Pregnancy Outcome

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

Hypoglycemia is a key barrier to optimum glycemic control in insulin treated diabetes patients. A national level expert group meeting was held at the 11th national insulin summit to analyze published data from clinical studies and guidelines to evolve consensus recommendations on identification and management of hypoglycemia in insulin-treated diabetes patients. This consensus statement emphasizes consideration of suggestive symptoms or blood glucose levels ≤70 mg/dl and ability to self-treat in identification and classification of hypoglycemia. Patient questionnaire administration at each patient visit will enable accurate reporting of hypoglycemia. Patients with strict glycemic control, high glycemic variability, history of severe hypoglycemia, impaired hypoglycemia awareness, long duration of disease or insulin therapy could be at an increased risk of hypoglycemia. Prevention of hypoglycemia should include monitoring and goal setting, patient education, dietary intervention, exercise counseling and medication adjustment. Basal insulin analogues (vs. NPH), rapid-acting insulin analogues (vs. RHI) and premix insulin analogues (vs. BHI) are more appropriate options with superiority of insulin degludec to insulin glargine U100 and IDegAsp to BIAsp 30 to reduce the risk of hypoglycemia. This consensus statement provides practical guidance for physicians in effectively managing and minimizing the risk of hypoglycemia in insulin treated diabetes patients.

Topics: Blood Glucose; Diabetes Mellitus; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine

Topics: Diabetes Mellitus; Drug Administration Schedule; Drug Compounding; Excipients; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Insulin, Regular, Human; Osmolar Concentration; Recombinant Proteins

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

Topics: Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus; Drug Combinations; Glucose; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Infusion Systems; Insulin, Long-Acting; Inventions; Liraglutide; Mobile Applications; Peptides; Self Care; Self-Management; Sweetening Agents; Transdermal Patch

The longer acting basal insulin analogs glargine and detemir have shown a lower incidence of hypoglycemia compared to insulin NPH in clinical studies. We evaluated the real-life risk of severe hypoglycemia among new users of insulins in the working-age population in Finland.. All persons aged 18-65 years with diabetes mellitus who were newly prescribed with insulins NPH, glargine, or detemir during 2006-2009, were identified from national registers. Risk of severe hypoglycemia requiring hospital care was compared between insulin types.. A total of 16,985 persons initiated basal insulin treatment (5586, 7499, and 3900 patients started NPH, glargine, and detemir, respectively) during follow-up. Five hundred and thirty-six persons were hospitalized because of severe hypoglycemia. Absolute rate (per 1000 patient-years) was 20.6 (95% CI 17.9, 23.8), 17.8 (15.6, 20.3), and 12.4 (9.9, 15.5) for NPH, glargine, and detemir initiators, respectively. With NPH as reference, the adjusted hazard ratio (HR) was 0.92 (95% CI 0.74, 1.15, p = 0.47) for glargine, and 0.70 (0.51, 0.94, p= 0.018) for detemir. The HR for detemir compared to glargine was 0.76 (0.58, 0.99, p = 0.040).. Initiating insulin treatment with detemir, but not with glargine, was associated with a significantly lower risk of severe hypoglycemia compared to NPH, among working-age adults. KEY MESSAGES The comparative safety of modern basal insulins regarding hypoglycemia among the working-age population is unclear. Large reductions in the incidence of severe hypoglycemia were seen among real-life patients who started insulin detemir, as compared to patients who initiated glargine or especially NPH insulin. Given the large amount of patients using insulin, these findings may have considerable clinical consequences at the population level.

Topics: Adult; Diabetes Mellitus; Female; Hospitalization; Humans; Hypoglycemia; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Longitudinal Studies; Male; Middle Aged; Young Adult

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: Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin Glargine

Topics: Administration, Oral; Computer-Assisted Instruction; Diabetes Mellitus; Germany; Humans; Hypoglycemic Agents; Insulin Glargine; Internet; Patient Education as Topic; Software

This article presents a new formulation of insulin glargine concentrated at 300 U/mL (Gla-300). It is commercialized under the trade name of Toujeo® in an optimized pre-filled SoloStar™ pen for the treatment of type 1 and type 2 diabetes in adults. Besides a threefold higher concentration compared to the classical insulin Lantus® (100 U/mL or Gla-100), both pharmacokinetic and pharmacodynamic profiles of Gla-300 are flatter and longer (more than 24 hours) and have a lesser intra-/inter-variability, which makes them more reproducible. Overall, Toujeo® offers the same hypoglycaemic efficacy and the same safety profile when compared with Lantus®. However, a lower risk of hypoglycaemia, especially at night, a slightly smaller weight gain and a better flexibility in the time of injection have been reported. The two insulin formulations are not bioequivalent and the daily insulin requirement is slightly higher with insulin Gla-300 than with insulin Gla-100. The shift from an already available basal insulin towards Toujeo® may require a dose adjustment and a reinforcement of blood glucose monitoring.

Topics: Clinical Trials as Topic; Diabetes Mellitus; Humans; Hypoglycemic Agents; Injections; Insulin Glargine

It is known that after pancreatectomy, patients experience hyposecretion of endogenous insulin and frequently develop diabetes. However, it has been unclear whether combination therapy with glucagon-like peptide-1 receptor agonists and basal insulin is effective for such patients. In the present study, we evaluated the efficacy and safety of combination therapy with long-acting insulin glargine and the glucagon-like peptide-1 receptor agonist lixisenatide in patients who developed diabetes after pancreatectomy.. Japanese patients who developed diabetes after pancreatectomy were eligible for this study. Participants were treated with combination therapy of glargine and lixisenatide for 12 weeks. Fasting and postprandial plasma glucose, C-peptide immunoreactivity, glycated hemoglobin, bodyweight, visceral fat and subcutaneous fat were measured.. At 12 weeks after initiation of lixisenatide, glycated hemoglobin levels decreased from 8.46 ± 1.64% to 6.81 ± 1.15%. In addition, 1-h postprandial plasma glucose and 2-h postprandial plasma glucose levels significantly decreased from 222.9 ± 56.2 mg/dL to 125.1 ± 37.5 mg/dL (P < 0.001) and from 247.5 ± 56.8 mg/dL to 115.1 ± 29.0 mg/dL (P < 0.001), respectively. Neither hypoglycemia nor clinically relevant adverse events occurred during this study.. The present study shows that combination therapy with basal insulin and glucagon-like peptide-1 receptor agonists after partial pancreatectomy can be a useful therapeutic option for providing effective glycemic control with a reduced risk of hypoglycemia.

Topics: Adipose Tissue; Aged; Aged, 80 and over; Blood Glucose; Body Weight; Diabetes Mellitus; Drug Therapy, Combination; Female; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Japan; Male; Pancreatectomy; Peptides; Postoperative Complications; Postprandial Period; Risk; Treatment Outcome

Hypoglycemia remains one of the main challenges of insulin therapy. To reduce insulin-related hypoglycemia at our institution, we restricted inpatient ordering of high glargine doses (≥0.5 U/kg/day) to endocrine staff in May 2013. This retrospective cohort study assesses its effect on hypoglycemia and glycemic control within 48 hours of admission (ADM).. We identified 692 adult patients hospitalized at Boston Medical Center who received glargine upon ADM from November 1, 2012 through April 30, 2013 as the pre-intervention group, and 651 adult patients admitted between November 1, 2013 and April 30, 2014 as the postintervention group. Demographics, medical history, home insulin regimen, concurrent oral diabetes medications or glucocorticoid administration, ADM serum creatinine, all blood glucose levels (BG) ≤48 hours of ADM, and hemoglobin A1c values ≤3 months were assessed. Hypoglycemia was defined as BG ≤70 mg/dL, and hyperglycemia as BG ≥200 mg/dL. Multivariable regression models assessed potential associations between covariates and incidence of hypoglycemia and average BG ≤48 hours of ADM.. Demographics were similar between groups. Significantly less patients received high-dose glargine in the post-intervention group (5.2% vs. 0.3%, P<.001). Incidences of hypoglycemia were significantly lower in the postintervention group (20.9% vs. 17.8%, P<.001 per ADM; 3.4% vs. 2.3%, P = .001 per BG measurements [BGM]). Mean BG levels ≤48 hours of ADM and incidence of hyperglycemia were not significantly different. The adjusted incident rate ratio of hypoglycemia was 0.63 per ADM and 0.74 per BGM in the postintervention group compared to the pre-intervention group (P = .001 and P = .063, respectively).. We found that implementation of a restriction on high doses of glargine resulted in lower rates of hypoglycemia without worsening glycemic control.. ADM = admission BG = blood glucose BGM = blood glucose measurements BMC = Boston Medical Center BMI = body mass index EMR = electronic medical record HgbA1c = hemoglobin A1c IRR = incidence rate ratio NPH = neutral protamine Hagedorn TDD = total daily dose T2D = type 2 diabetes.

Topics: Adult; Aged; Diabetes Mellitus; Female; Hospitalization; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Male; Middle Aged; Retrospective Studies

Topics: Diabetes Mellitus; Humans; Insulin Glargine; Internet; Mobile Applications; Randomized Controlled Trials as Topic; Self Care; United Kingdom

Hypoglycemia has long been recognized as a major barrier to achieving normoglycemia with intensive diabetic therapies. It is a common safety concern for the diabetes patients. Therefore, it is important to apply appropriate statistical methods when analyzing hypoglycemia data. Here, we carried out bootstrap simulations to investigate the performance of the four commonly used statistical models (Poisson, negative binomial, analysis of covariance [ANCOVA], and rank ANCOVA) based on the data from a diabetes clinical trial. Zero-inflated Poisson (ZIP) model and zero-inflated negative binomial (ZINB) model were also evaluated. Simulation results showed that Poisson model inflated type I error, while negative binomial model was overly conservative. However, after adjusting for dispersion, both Poisson and negative binomial models yielded slightly inflated type I errors, which were close to the nominal level and reasonable power. Reasonable control of type I error was associated with ANCOVA model. Rank ANCOVA model was associated with the greatest power and with reasonable control of type I error. Inflated type I error was observed with ZIP and ZINB models.

Topics: Analysis of Variance; Binomial Distribution; Biomarkers; Blood Glucose; Computer Simulation; Diabetes Mellitus; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Models, Statistical; Poisson Distribution; Randomized Controlled Trials as Topic; Reproducibility of Results; Risk Assessment; Time Factors; Treatment Outcome

This report describes the performance of a wireless electronic diary (e-diary) system for data collection and enhanced patient-investigator interactions during intensive insulin management in diabetes clinical trials.. We implemented a customized electronic communication system featuring an e-diary and a Web portal in three global, randomized, controlled Phase 3 clinical trials testing basal insulin peglispro compared with insulin glargine, both combined with prandial insulin lispro, in patients with type 1 or type 2 diabetes mellitus (T1DM and T2DM, respectively). We collected data during 28 weeks of study e-diary use for the report.. Patients (n=2,938) in 31 countries used e-diaries to transmit 2,439,087 blood glucose (BG) values, 96% of which were associated by the patient with a protocol time point during the 72-h response window. Of 208,192 hypoglycemia events captured, 96% had a BG value, and 95% had treatments and outcomes entered by patients within the 72-h window. Patients recorded administration of 1,964,477 insulin doses; 93% of basal insulin doses were adherent with the investigator prescription. Investigators adjusted 13 basal and 92 bolus insulin prescriptions per patient-year using the e-diary system. After 26 weeks of treatment and e-diary use in the combined study arms, hemoglobin A1c values decreased by 0.6% or 1.6% and fasting BG decreased by 7.8 or 28 mg/dL in patients with T1DM or T2DM, respectively.. The e-diary system enabled comprehensive data collection and facilitated communication between investigators and patients for intensive insulin management in three global clinical trials testing basal insulins.

Topics: Adult; Aged; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus; Electronic Prescribing; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Male; Middle Aged; Randomized Controlled Trials as Topic; Telemetry; Time Factors

Recent studies suggested that insulin glargine use could be associated with increased risk of cancer. We compared the incidence of cancer in new users of glargine versus new users of NPH in a longitudinal clinical cohort with diabetes for up to 6 years.. From all patients who had been regularly followed at Massachusetts General Hospital from 1/01/2005 to 12/31/2010, 3,680 patients who had a medication record for glargine or NPH usage were obtained from the electronic medical record (EMR). From those we selected 539 new glargine users (age: 60.1±13.6 years, BMI: 32.7±7.5 kg/m2) and 343 new NPH users (61.5±14.1 years, 32.7±8.3 kg/m2) who had no prevalent cancer during 19 months prior to glargine or NPH initiation. All incident cancer cases were ascertained from the EMR requiring at least 2 ICD-9 codes within a 2 month period. Insulin exposure time and cumulative dose were validated. The statistical analysis compared the rates of cancer in new glargine vs. new NPH users while on treatment, adjusted for the propensity to receive one or the other insulin. There were 26 and 28 new cancer cases in new glargine and new NPH users for 1559 and 1126 person-years follow-up, respectively. There were no differences in the propensity-adjusted clinical characteristics between groups. The adjusted hazard ratio for the cancer incidence comparing glargine vs. NPH use was 0.65 (95% CI: 0.36-1.19).. Insulin glargine is not associated with development of cancers when compared with NPH in this longitudinal and carefully retrieved EMR data.

Topics: Diabetes Mellitus; Disease-Free Survival; Electronic Health Records; Female; Humans; Incidence; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Neoplasms; Time Factors

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

Topics: Animals; Biosimilar Pharmaceuticals; Chemistry, Pharmaceutical; Delayed-Action Preparations; Diabetes Mellitus; Dogs; History, 20th Century; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin Infusion Systems; Insulin, Isophane; Insulin, Long-Acting; Swine

The aim of the paper is to determine the dose accuracy and injection force of FlexTouch (FT) filled with insulin degludec 100 U/ml, insulin degludec 200 U/ml and insulin degludec/insulin aspart 100 U/ml, SoloStar (SS) filled with insulin glargine 100 U/ml and KwikPen (KP) filled with insulin lispro mix 75/25 100 U/ml.. Dose accuracy was measured at minimum, midpoint and maximum doses (FT 1, 2, 40, 80 and 160 U; SS 1, 40 and 80 U; KP 1, 30 and 60 U). Injection force was measured during the injection of the maximum dose.. All doses delivered from FT were within ISO limits (ISO 11608-1:2012) for degludec 100 U/ml, degludec 200 U/ml and degludec/aspart 100 U/ml, and the pens delivered insulin accurately and consistently at all doses tested. Similarly, all tested doses from KP filled with insulin lispro mix 75/25 100 U/ml were within ISO limits, while some doses from SS filled with insulin glargine 100 U/ml were outside ISO limits. FT had a significantly lower injection force than SS and KP (p < 0.05).. FT filled with insulin degludec and insulin degludec/insulin aspart, delivered insulin accurately and consistently within ISO limitations at all doses tested; similarly, KP delivered insulin within ISO limitations at all doses tested and SS delivered most doses within ISO limitations. The significantly lower injection force of FT compared to SS and KP is an important feature that has the potential to make the injection process easier for people with diabetes.

Topics: Diabetes Mellitus; Drug Combinations; Drug Delivery Systems; Humans; Hypoglycemic Agents; Injections; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting

To evaluate the dose and frequency of insulin detemir for patients with diabetes mellitus undergoing conversion from insulin glargine to insulin detemir, and to assess glycemic control, weight gain, and risk of hypoglycemia after converting to insulin detemir.. Retrospective medical record review.. Large academic medical center.. Thirty-one patients with type 1 (10 patients) or type 2 (21 patients) diabetes who were converted from insulin glargine to insulin detemir by usual practice between January 1, 2006, and March 3, 2007, after an Iowa Medicaid formulary switch.. Data were collected for 12 months after conversion from insulin glargine to insulin detemir. No significant change in mean basal insulin dose was noted in patients with type 1 diabetes at the end of 12 months (insulin detemir 31.1 units/day vs baseline insulin glargine 32.0 units/day, p=0.89; insulin detemir 0.41 unit/kg/day vs baseline insulin glargine 0.42 unit/kg/day, p=0.91). In patients with type 2 diabetes, however, the mean basal insulin dose was significantly higher with insulin detemir compared with baseline insulin glargine (74.2 vs 55.8 units/day, p=0.002; 0.68 vs 0.48 unit/kg/day, p=0.001) at the end of 12 months. Twice-daily administration was required in a higher proportion of patients receiving insulin detemir (15 patients [48%]) at 12 months compared with insulin glargine (4 patients [13%]) at baseline (p=0.043). A significant change in hemoglobin A(1c) was not observed in patients with type 1 diabetes (9.7% with insulin detemir vs 9.3% with insulin glargine, p=0.41) or type 2 diabetes (9.4% with insulin detemir vs 9.7% with insulin glargine at baseline, p=0.57) despite the use of higher insulin detemir doses in patients with type 2 diabetes. No significant differences in weight or frequency of hypoglycemia were noted.. Treatment with insulin detemir appears to require more frequent administration and higher insulin doses compared with insulin glargine in patients with type 2 diabetes, with 33% higher doses, on average, observed in this study. These findings suggest that a unit-for-unit conversion from insulin glargine to insulin detemir, as suggested by the manufacturer of insulin detemir, may not be adequate in patients with type 2 diabetes.

Topics: Adult; Diabetes Mellitus; Dose-Response Relationship, Drug; Drug Substitution; Female; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Treatment Outcome; Young Adult

The objective of this study was to evaluate the safety and efficacy of insulin glargine in dogs with diabetes mellitus (DM). Twelve client-owned dogs with DM were included. All dogs received insulin glargine every 12 hours for at least six months, re-evaluations were performed after one, two, four, eight, 12 and 24 weeks and included clinical signs, blood glucose curves (BGCs) and measurement of serum fructosamine concentrations. Mean blood glucose concentrations were significantly lower after two weeks of treatment and remained significantly lower for the duration of the study. By week 24, polyuria/polydipsia had improved in 91 per cent of the dogs. No clinical signs that could have been caused by hypoglycaemia were observed. Based on BGCs and remission of the clinical signs for judging the success of the treatment, 58, 33 and 8 per cent of the dogs attained good, moderate and poor glycaemic control by week 24 of the study, respectively. Insulin glargine administered subcutaneously twice daily is a possible and safe method of treatment for dogs with naturally occurring DM. Although only a few studies are available on the use of other types of insulin in dogs, their success rate is somewhat greater than that with insulin glargine.

Topics: Animals; Blood Glucose; Diabetes Mellitus; Dog Diseases; Dogs; Female; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Prospective Studies; Treatment Outcome

A 7.5-year-old spayed female ferret was evaluated because of weight loss despite a good appetite. Pancreatic insulinoma had been diagnosed at another animal hospital on the basis of detection of low blood glucose concentration on 1 occasion; however, concurrent determination of blood insulin concentration was not performed. The ferret had been treated SC with methylprednisolone acetate (unknown dosage) every 30 days for 2 years. No follow-up data regarding blood glucose concentration were available.. On physical examination, the ferret was thin (weight, 0.619 kg [1.36 lb]) and bruised easily. Serum biochemical analysis revealed hyperglycemia (blood glucose concentration, 855 mg/dL; reference range, 63 to 134 mg/dL).. Glucocorticoid injections were discontinued, and the ferret was administered prednisolone (1.13 mg/kg [0.51 mg/lb], q 12 h for 14 days, then 0.56 mg/kg [0.25 mg/lb], q 12 h for 7 days) orally. After prednisolone administration was discontinued, hyperglycemia and weight loss persisted. The ferret was administered insulin glargine (0.5 U) SC; blood glucose concentration was monitored every 2 hours for 24 hours, at which time the value had decreased to nearly within reference range. The owner continued insulin glargine administration at that dose every 12 hours; after 77 days of treatment, the ferret's weight was 0.731 kg (1.61 lb), which was considered normal, and blood glucose concentration was within reference range.. Regular SC administration of insulin glargine was successful in the treatment of diabetes mellitus in the ferret of this report and may be effective for other diabetic ferrets.

Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus; Female; Ferrets; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting

Insulin glargine is a relatively new medication in the treatment of diabetes mellitus, and there have only been six case reports of overdoses in the literature with this specific insulin.. We present a unique case of insulin glargine overdose that presented with persistent hypoglycemia and required prolonged in-hospital treatment.. A 51-year-old woman with insulin-dependent diabetes and a history of suicide attempts by medication overdose presented to the Emergency Department the morning after she had self-administered 2700 units of her insulin glargine in an attempted suicide. She was treated with continuous intravenous dextrose infusion with liberal oral intake, and continued to have recurrent hypoglycemic episodes 96 h into her hospital stay. She was discharged on hospital day 5 after psychiatric clearance without any permanent complications.. A single massive overdose of insulin glargine can present with prolonged hypoglycemia. Emergency physicians should have a low threshold for initiating continuous dextrose infusions and admitting these patients for frequent blood glucose and serum electrolyte monitoring, preferably in an intensive care setting.

Topics: Diabetes Mellitus; Drug Overdose; Female; Glucose; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Middle Aged; Suicide, Attempted

Insulin detemir is the first member of a new class of long-acting soluble insulin analogues capable of maintaining the basal level of insulin in humans. In this preliminary study, we investigated the time-action profiles of insulin detemir in normal and diabetic dogs since the use of insulin detemir in canines has yet to be determined. Eight animals were used in our study (three normal and five insulin dependent diabetic dogs). Time-action profiles of insulin detemir were monitored in normal dogs using an artificial pancreas apparatus under euglycemic condition. Blood sampling was performed at 2h intervals post feeding, with insulin administration, in insulin dependent diabetic dogs. Time-action profiles of insulin detemir, in normal dogs, demonstrated that insulin detemir is a long-lasting preparation similar to what has been observed in humans. A pronounced peak was detected at 8-10h while the glucose-lowering effect lasted for over 24h after insulin injection, thus illustrating its longer prolonged peak activity time. Furthermore, intensive glycemic control was achieved with insulin detemir in insulin dependent diabetic dogs, using a lower dosage than NPH insulin and insulin glargine therapeutic doses. Our results indicate that insulin detemir has a greater effect than either NPH insulin or insulin glargine in canines, requiring a lower dose than either insulin preparation. However, using insulin detemir also carries a higher risk of inducing hypoglycemia as compared to either NPH insulin or insulin glargine.

Topics: Animals; Blood Glucose; Diabetes Mellitus; Dog Diseases; Dogs; Female; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male

Clinical evaluation of insulin assay system reacting with only human insulin molecule (kit B) was performed by comparing it with conventional insulin assay system (kit A) cross-reacting with insulin analogue as well as human insulin preparation. In vitro, the kit B was confirmed to cross-react with only human insulin, not with insulin analogue preparations such as insulin aspart, lyspro and glargine. In non-insulin treated diabetic patients, postprandial and post-insulin injected serum immunoreactive insulin (IRI) concentrations measured by kit B were almost the same as those measured by the kit A. On the other hand, in diabetic patients treated with insulin analogue preparations, postprandial and post-insulin injected serum IRI levels measured by kit B were obviously low compared with those by kit A. After intravenous injection of insulin analogue preparations (0.1 unit/kg), insulin lyspro or insulin aspart, serum IRI levels measured by the kit B were not increased but gradually decreased in contrast to the obviously increased serum IRI level measured by the kit A. From these results, the kit B was confirmed not to measure the insulin analogue preparations in vitro and in vivo.

Topics: Cross Reactions; Diabetes Mellitus; Humans; Injections, Intravenous; Insulin; Insulin Aspart; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Reagent Kits, Diagnostic

Despite significant advances in inpatient diabetes management, it is still a challenge to choose the safest and most efficacious subcutaneous insulin regimen for diabetic patients on continuous enteral nutrition (EN) therapy. The authors conducted a retrospective analysis of glycemic control in 22 non-critically ill diabetic patients, receiving at least 3 days of continuous EN. Patients received different insulin regimens while on continuous EN, including a basal/bolus glargine/lispro regimen (group 1, n = 8), 70/30 biphasic insulin twice daily (group 2, n = 8), and 70/30 biphasic insulin 3 times a day (group 3, n = 6). The glucose data from 72 hours from the initiation of EN were analyzed (12 point-of-contact glucose measurements per patient). Overall, the degree of control was comparable in all groups, with target range maintained more consistently in group 3 (70/30 insulin administered 3 times daily). In this group, 69% of values were in the target range (140-180 mg/dL) as compared with 24% in glargine/lispro group and 22% in the 70/30 insulin bid group. Eight hypoglycemic episodes occurred among the 3 groups: 5 episodes in group 1 (5.4%), 2 episodes in group 2 (2.1%), and 1 episode in group 3 (1.4%) (P = .05, groups 2 and 3 vs group 1). Administration of 70/30 biphasic insulin 3 times daily is a safe therapeutic regimen in diabetic patients on continuous EN as it maintains glycemia in the target range and might produce fewer episodes of hypoglycemia.

Topics: Adult; Aged; Biphasic Insulins; Blood Glucose; Diabetes Mellitus; Dose-Response Relationship, Drug; Enteral Nutrition; Hospitalization; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Middle Aged; Retrospective Studies; Young Adult

Neonatal diabetes mellitus (NDM) is a rare condition that can be either transient or permanent. K(ATP) channel (Kir6.2 or SUR1) mutation, chromosome 6 abnormalities, insulin, or glucokinase gene mutations can lead to isolated NDM. Cases caused by Kir6.2 mutation usually result in permanent NDM (PNDM) rather than transient NDM (TNDM). The majority of patients with the Kir6.2 or SUR1 mutation can be successfully managed with a sulfonylurea agent, without the need for insulin. We report a preterm male with NDM having two novel missense mutations, E322A and D352H, in the KCNJ11 gene. At 2 months of age, successful transition from insulin to glibenclamide (glyburide) therapy of the patient was managed. At 5 months of age, his diabetes went in to remission.

Topics: Diabetes Mellitus; Glyburide; Humans; Hypoglycemic Agents; Infant; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature; Insulin Glargine; Insulin, Long-Acting; Male; Point Mutation; Potassium Channels, Inwardly Rectifying; Remission Induction

Either endogenous or exogenous hyperinsulinaemia in the setting of insulin resistance promotes phosphorylation and activation of farnesyltransferase, a ubiquitous enzyme that farnesylates Ras proteins. Increased availability of farnesylated Ras at the plasma membrane enhances mitogenic responsiveness of cells to various growth factors, thus contributing to progression of cancer and atherosclerosis. This effect is specific to insulin, but is not related to the type of insulin used. The stimulatory effect of hyperinsulinaemia on farnesyltransferase in the presence of insulin resistance represents one potential mechanism responsible for mitogenicity and atherogenicity of insulin.

Topics: Atherosclerosis; Cell Division; Diabetes Mellitus; Farnesyltranstransferase; Humans; Hyperinsulinism; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Resistance; Insulin, Long-Acting; Neoplasms; ras Proteins

Topics: Diabetes Mellitus; Dose-Response Relationship, Drug; Ethics, Medical; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Neoplasms; Risk Factors; Safety

Insulin glargine (Lantus) stimulates growth of MCF-7 cells stronger than human insulin. We investigated if serum from diabetic patients treated with glargine versus human insulin may display a similar effect.. Pairs of serum samples from 31 C-peptide negative type-1 diabetic patients were investigated. In cross-over fashion, 23 patients were treated with glargine plus rapid-acting insulin analogues, and similar doses of human NPH and rapid-acting insulin. For comparison, eight patients were treated with insulin detemir (Levemir) and human NPH. MCF-7 cells were incubated with 10% serum and proliferation was assessed after 72 hours.. Serum containing insulin glargine was 1.11(95% CI 1.05-1.18) fold more mitogenic than human insulin-containing serum (p < 0.005); mitogenicity of serum containing detemir was 0.99(95% CI 0.98-1.02) fold that of human insulin-containing serum.. The serum of diabetic patients was slightly stronger mitogenic when using glargine as compared to human insulin or detemir for treatment.

Topics: Breast Neoplasms; C-Peptide; Cell Line, Tumor; Cells; Chemotactic Factors; Diabetes Mellitus; Diabetes Mellitus, Type 1; Female; Humans; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Pilot Projects; Risk Factors

Topics: Diabetes Mellitus; Dose-Response Relationship, Drug; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Neoplasms; Registries; Reproducibility of Results; Risk Factors

Topics: Child; Diabetes Mellitus; Diabetes Mellitus, Type 1; Eating; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin Infusion Systems; Insulin, Isophane; Insulin, Long-Acting; Patient Education as Topic

Several insulin analogues have been developed in recent years and are increasingly being used in the treatment of diabetes. However, modifying the insulin molecule not only changes its metabolic effects, but can also alter its mitogenic potency. In vitro experiments had previously suggested a potential association between insulin analogues and cancer. In 2009 several articles were published in Diabetologia describing an association between administration of glargine (Lantus) and higher incidence of cancer rates. The present article aims at briefly presenting the state of the art based upon currently available data on insulin and cancer. We will summarize the mechanisms by which insulin can increase cell proliferation, the observations reported in recent publications and finally conclude with some practical recommendations.

Topics: Diabetes Mellitus; Evidence-Based Medicine; Humans; Hypoglycemic Agents; Incidence; Insulin; Insulin Glargine; Insulin, Long-Acting; Neoplasms; Risk

Diabetes mellitus has reached epidemic proportions worldwide, eliciting extensive research on both the disease process and its treatment. Regardless of diabetes type, the progressive nature of the disease makes insulin the long-term mainstay of diabetes management. Recently, the insulin analog glargine was reported in several epidemiologic studies to be associated with an increased risk of cancer. Inconsistent study results and media attention have caused much angst and concern to health care professionals and the general population. A clear understanding of the current evidence is needed to adequately develop a patient-oriented risk:benefit assessment. Members of the Endocrine and Metabolism Practice and Research Network of the American College of Clinical Pharmacy evaluated available evidence to provide guidance and discussion on the risk of cancer with insulin glargine use. We believe the current link between insulin glargine and cancer is tenuous but merits further evaluation. An independent analysis of all available glargine clinical trial data should be performed, and a vigorous postmarketing safety study of glargine should be conducted. Until more substantial data are available, however, neither the choice of initial insulin therapy nor insulin maintenance regimens should be influenced by the current information linking insulin glargine to cancer.

Topics: Clinical Trials as Topic; Diabetes Mellitus; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Meta-Analysis as Topic; Neoplasms; Risk Factors; Societies, Pharmaceutical; United States

Topics: Breast Neoplasms; Canada; Case-Control Studies; Confounding Factors, Epidemiologic; Diabetes Mellitus; Female; France; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; International Cooperation; Multicenter Studies as Topic; Risk Factors; United Kingdom

The first Injection Technique workshop brought together endocrinologists and injection experts from around the world in Strasbourg in 1997. From its work came groundbreaking recommendations which advanced best practices in areas such as the use of a skin fold when injecting. The second Injection Technique workshop, with an expanded format including nurses and diabetes educators, took place in Barcelona in 2000. The initial stimulus to use shorter injecting needles can be said to date from this meeting. The third Injection Technique workshop was held in Athens in September 2009 and involved 127 experts from across the globe. After a comprehensive review of all publications since 2000 as well as several unpublished studies, the attendees divided into smaller groups to debate and draft new injecting recommendations based on the new data and their collective experience. This paper summarizes all the formal presentations given at this practical consensus workshop.

Topics: Blood Glucose; Diabetes Mellitus; Diabetes Mellitus, Type 1; Drug Storage; Equipment Design; Europe; Evidence-Based Medicine; Expert Testimony; Female; Humans; Hypertrophy; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin Infusion Systems; Insulin, Long-Acting; Male; Needles; Needlestick Injuries; Patient Education as Topic; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications; Subcutaneous Fat, Abdominal; Syringes; United Kingdom; United States

The aim of this cohort study was to investigate the risk of malignant neoplasms and mortality in patients with diabetes treated either with human insulin or with one of three insulin analogues.. Data were provided by the largest German statutory health insurance fund (time-frame: January 1998 to June 2005 inclusive), on patients without known malignant disease who had received first-time therapy for diabetes mellitus exclusively with human insulin, aspart, lispro or glargine. The primary outcome was the diagnosis of a malignant neoplasm. Data were analysed by multiple Cox regression models adjusting for potential confounders.. A total of 127,031 patients were included, with a mean follow-up time of 1.63 (median 1.41, maximum 4.41) years. A positive association between cancer incidence and insulin dose was found for all insulin types. Because patients receiving combined therapy with insulin analogues and human insulin were excluded, the mean daily dose was much lower for glargine than for human insulin, and a slightly lower cancer incidence in the glargine group was found. After adjusting for dose, a dose-dependent increase in cancer risk was found for treatment with glargine compared with human insulin (p < 0.0001): the adjusted HR was 1.09 (95% CI 1.00 to 1.19) for a daily dose of 10 IU, 1.19 (95% CI 1.10 to 1.30) for a daily dose of 30 IU, and 1.31 (95% CI 1.20 to 1.42) for a daily dose of 50 IU. No increased risk was found for aspart (p = 0.30) or lispro (p = 0.96) compared with human insulin.. Considering the overall relationship between insulin dose and cancer, and the lower dose with glargine, the cancer incidence with glargine was higher than expected compared with human insulin. Our results based on observational data support safety concerns surrounding the mitogenic properties of glargine in diabetic patients. Prospective long-term studies are needed to further evaluate the safety of insulin analogues, especially glargine.

Topics: Aged; Aged, 80 and over; Analysis of Variance; Cohort Studies; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Germany; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Infusion Systems; Insulin, Long-Acting; Male; Middle Aged; Neoplasms; Patient Selection; Proportional Hazards Models; Regression Analysis; Reproducibility of Results

Topics: Diabetes Mellitus; Drug Industry; Insulin; Insulin Glargine; Insulin, Long-Acting; Interdisciplinary Communication; Professional Corporations; Public Health Practice

Topics: Bias; Breast Neoplasms; Clinical Trials as Topic; Delayed-Action Preparations; Diabetes Mellitus; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Neoplasms; Risk

Topics: Bias; Clinical Trials as Topic; Delayed-Action Preparations; Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Neoplasms; Patient Education as Topic; Retrospective Studies; Risk

Topics: Bias; Clinical Trials as Topic; Conflict of Interest; Delayed-Action Preparations; Diabetes Mellitus; Germany; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Neoplasms; Patient Education as Topic; Risk

This study aimed to compare the accuracy of SoloSTAR(sanofi-aventis, Paris, France) and FlexPen (Novo Nordisk, Bagsvaerd, Denmark) to deliver doses of insulin when used by insulin/device-naive people attending a local healthcare practice.. For the determination of dose accuracy, SoloSTAR containing insulin glargine (lot 672) and FlexPen containing insulin aspart (lot SH70557) were used for all tests. The participants were given instruction by an independent monitor on how to use the pens. To be consistent, users were trained to hold the pens in situ for 10 s at the end of injection to ensure that the full dose was injected. Forty-eight subjects performed three dose deliveries of 20 units (into a sponge) with each pen type. The method of injecting into a sponge aimed to mimic real-life practice; this approach is commonly used to ensure the patient has a correct injection technique before the patient self-administers the injection.. The delivery (n = 144) of individual doses of 20 units was not statistically different (P = 0.187) between SoloSTAR (mean +/- SD, 19.75 +/- 0.30 units) and FlexPen (19.80 +/- 0.33 units). In total, 2% of doses from both devices were <19 units; 98% were within 19-21 units.. Both SoloSTAR and FlexPen were similarly accurate when used by device-naive subjects to deliver 20-unit doses of insulin. This is likely to have beneficial clinical effects in terms of glycemic control, as well as improved patient confidence that insulin pens accurately deliver doses of insulin.

Topics: Ambulatory Care; Analysis of Variance; Diabetes Mellitus; Drug Delivery Systems; Female; Germany; Humans; Hypoglycemic Agents; Injections; Insulin; Insulin Aspart; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Patient Education as Topic

Topics: Diabetes Mellitus; Editorial Policies; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Neoplasms; Periodicals as Topic; Risk Factors

Topics: Diabetes Mellitus; Humans; Insulin; Insulin Glargine; Insulin Resistance; Insulin, Long-Acting; Neoplasms; Obesity

Topics: Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Mass Media; Neoplasms; Risk Assessment

Insulin glargine is widely used as basal insulin in the treatment of type 1 and type 2 diabetes mellitus. However, this insulin analogue has been recently suspected to be associated with an increased risk of cancer, especially breast cancer, in patients with type 2 diabetes. The present article aims at briefly presenting the state of the art based upon currently available data. We will first summarize the observations reported in recent publications, then we will present a critical analysis of these in fact non-conclusive findings, and finally we will conclude with some practical recommendations.

Topics: Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Neoplasms; Risk

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Animals; Breast Neoplasms; Diabetes Complications; Diabetes Mellitus; Dose-Response Relationship, Drug; Europe; Female; Humans; Insulin; Insulin Glargine; Insulin, Long-Acting; Mammary Neoplasms, Experimental; Metformin; Middle Aged; Randomized Controlled Trials as Topic; Rats; Young Adult

Topics: Blood Glucose Self-Monitoring; Diabetes Mellitus; Drug Overdose; Female; Humans; Hypoglycemia; Insulin; Insulin Glargine; Insulin, Long-Acting; Middle Aged; Self Administration

A study group gathered by the Pharmacy & Therapeutics Society reviewed data on the Department of Veterans Affairs (VA) health care system's implementation of a new technology (insulin glargine) for patients with diabetes. It examined local implementation of VA criteria for nonformulary use of insulin glargine in 21 VA treatment facilities that were surveyed about the issue. The examination found differences in the use of insulin glargine across the 21 treatment facilities and in the approach to implementing the criteria for nonformulary use of insulin glargine used at the individual VA treatment facility level. Differences were identified regarding the respective roles of endocrinologists and PCPs in prescribing insulins, including insulin glargine. The study group urges further short- and long-term research to better understand the utilization, cost, and health outcome implications of the implementation process for the nonformulary criteria. Lessons learned from such research could benefit other health care systems and formulary committees.

Topics: Ambulatory Care Facilities; Attitude to Computers; Delivery of Health Care, Integrated; Diabetes Mellitus; Diffusion of Innovation; Formularies as Topic; Health Services Research; Hospitals, Veterans; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Interviews as Topic; Organizational Innovation; Pharmacy and Therapeutics Committee; United States; United States Department of Veterans Affairs

New classes of antidiabetic medications have been introduced, but details of their use are not well known. The aim was to assess prescription patterns and dosing for insulin glargine (market launch: 6/2000) in primary care patients.. Computerized data on prescriptions (Disease Analyzer, 6/1999 to 8/2003) from 277 general and internal medicine practices throughout Germany were analysed (67,402 diabetic patients; 340 incident glargine (age: 67+/-12 years) and 378 incident NPH users (66+/-11 years).. Diabetes prevalence in the practices increased over the three-year period (5.1% to 6.2%). The highest increase was observed for insulin treated patients (+29%), followed by diet (+21%) and oral antidiabetics (+19%). Premixed insulin (short-acting insulin and NPH) remained constant as largest insulin group. A continuous increase of short-acting insulin analogues was found (+70%). Long-acting insulin analogues (glargine) increased threefold. Glargine was more often prescribed in combination with oral antidiabetics than NPH (76% vs 49%; p<0.05). Only about a quarter received short-acting insulin (NPH: 61%; p<0.05). The cumulative annual dose was higher among NPH users (geometric mean; NPH: 7971 IU; glargine: 5719 IU) (p<0.01), which persisted after adjusting for age, sex, and morbidity (p<0.01).. Diabetes prevalence continuously increased in German primary care practices from 1999 to 2003. The largest increase was found for insulin treatment, in particular, for short and long-acting insulin analogues. Insulin glargine was more often prescribed in combination with oral agents, whereas NPH insulin was more frequently prescribed with short-acting insulin, indicating different prescription patterns in primary care.

Topics: Administration, Oral; Aged; Databases, Factual; Diabetes Mellitus; Drug Prescriptions; Female; Germany; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Primary Health Care; Treatment Outcome

Newer insulins, such as long-acting analogues, offer promise of better glycemic control, reduced risk for diabetes complications, and moderation of health care use and costs.. We studied initiation of insulin glargine to evaluate its association with subsequent health service utilization and estimated expenditures.. Patients of the Veterans Health Administration, US Department of Veterans Affairs (VA) who initiated insulin glargine (n=5064) in 2001-2002 were compared with patients receiving other insulin (n=69,944), matched on prescription month (index date). Inpatient and outpatient VA care in the 12 months after a patient's index date was evaluated using Tobit regression, controlling for prior utilization, demographic characteristics, comorbidities, glycosylated hemoglobin (HbA(1c)) levels, and diabetes severity. National average utilization costs and medication acquisition costs were used to estimate the value of VA expenditures.. Compared with other insulin users, insulin glargine initiators had higher HbA(1c) values (8.72% vs 8.16%) prior to the index date, but greater subsequent HbA(1c) reduction (-0.50% vs -0.22%). After adjustment for age, prior utilization, HbA(1c) levels, and other factors, insulin glargine initiation was associated with 2.4 (95% CI, 1.1-3.7) fewer inpatient days for patients with any hospital admission (US $820 lower costs per initiator), 1.6 (1.2-1.9) more outpatient encounters ($279 higher costs per initiator), and $374 ($362-$387) higher costs for diabetes medications. The net difference was an average lower VA cost of $166 (-$290 to $622) per patient.. Insulin glargine use was associated with decreased inpatient days but increased outpatient care, and the value of the net change in utilization to VA offset the additional medication expenditures. Initiation of insulin glargine improves glycemic control and may reduce time in hospital without additional use of health resources.

Topics: Adult; Aged; Aged, 80 and over; Databases as Topic; Diabetes Mellitus; Female; Glycated Hemoglobin; Health Care Costs; Health Resources; Hospitals, Veterans; Humans; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; United States; Veterans

Topics: Cost of Illness; Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Treatment Outcome

Patients with diabetes have been found to have a preference for insulin pens over a vial and syringe since these devices offer improvements in compliance, freedom, and flexibility.. This study assessed the usability, specific pen features, and patient preference for 4 prefilled, disposable, insulin pens: Solostar, Humulin/Humalog pen (Lilly pen), FlexPen, and a fourth, prototype pen, Pen X, in patients with type 1 or 2 diabetes. In 1-hour interviews, patients carried out simulated use (preparing the pens, setting a dose, and injecting into a receptacle, not the body) under observation, and answered qualitative and quantitative questions. Patients were supplied with the relevant user manual. The usability (ability and time taken to carry out handling tasks) and preference (based on 14 key pen features and overall preference) of each pen were assessed without blinding for pen make/manufacturer. During the interviews, the patients prepared each pen and performed injections into a receptacle. Comparisons were made between the pens at every step. Subgroup analyses of the usability exercises were carried out based on age (11-15 years; >/=60 years), previous pen experience, and disability (visual and dexterity).. In total, 510 diabetes patients (65% type 2 diabetes; 51% female; mean age, 43 years [range, 11-82 years]) from 4 countries (United States, Germany, France, and Japan) completed the study. Overall, a greater proportion of patients correctly prepared the pen and performed an injection into a receptacle with Solostar versus all comparator pens (P < 0.05). Similar findings were observed in the usability subgroup analyses based on age, previous pen experience, and visual/dexterity disabilities. A significantly (P < 0.05) higher proportion of patients expressed overall preference for Solostar (53%) versus FlexPen (31%) or Lilly pen (15%).. Of the 4 pens compared, both the Solostar pen and FlexPen were found to have high patient usability, and the new Solostar pen was found to have high patient preference in these patients with diabetes.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Diabetes Mellitus; Disposable Equipment; Female; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Patient Satisfaction; Syringes

Topics: Diabetes Mellitus; Drug Approval; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; National Health Programs; New Zealand

The purpose of this observational study was to determine if switching from isophane insulin human (NPH) to insulin glargine would improve glycemic control in a medically vulnerable population with uncontrolled diabetes.. A retrospective cohort review of patients' medical records was performed that recorded events occurring between January 1, 2001, and December 31, 2003. The cohort consisted of patients with diabetes in an adult medicine clinic at a county hospital. Patients were included if they were receiving NPH insulin for a minimum of six months and subsequently switched to insulin glargine for a minimum of six months.. The study included 43 patients. There was no significant difference in mean glycosylated hemoglobin (HbA(1c)) between NPH insulin (9.6%) and insulin glargine (9.7%) regimens (p = 0.78, 95% confidence interval, -0.62%, 0.82%). Neither was there a significant difference in the frequency or severity of hypoglycemic episodes between the two treatments. Patients experienced significantly fewer diabetes-associated visits over six months while on insulin glargine. Refill frequency did not differ significantly when patients were receiving NPH insulin versus insulin glargine. When analyzing patient characteristics, those of Hispanic ethnicity experienced HbA(1c) values significantly higher than white patients. Several characteristics were associated with refill frequency.. The results of our study indicate that both NPH- and glargine-based basal insulin regimens result in similar levels of glycemic control in a medically vulnerable population with diabetes, without significant differences in the number or severity of hypoglycemic episodes or in refill frequency.

Topics: Adult; Aged; Blood Glucose; Cohort Studies; Diabetes Mellitus; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Retrospective Studies

Topics: Algorithms; Blood Glucose Self-Monitoring; Diabetes Mellitus; Diet, Diabetic; Dose-Response Relationship, Drug; Drug Administration Schedule; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Metformin; Postprandial Period; Randomized Controlled Trials as Topic

Topics: Child; Diabetes Mellitus; Humans; Insulin; Insulin Glargine; Insulin, Long-Acting; Mitosis; Receptors, Somatomedin

Insulin glargine is a long-acting insulin analogue providing a more predictable and reproducible circulating insulin profile than other available basal insulin products. Hypoglycaemia is one of the main limiting factors to patients with diabetes requiring insulin, in achieving tight glycaemic control and reduced rates of complications. Evidence from randomised controlled clinical trials demonstrates reduced rates of hypoglycaemia in patients with type 1 and type 2 diabetes using insulin glargine compared with other basal insulin. Insulin glargine has been registered for use in New Zealand since June 2001, but currently remains unsubsidised by PHARMAC. Reducing the incidence and impact of diabetes is one of the stated aims in the New Zealand Health Strategy and the complete lack of funding for pharmaceutical agents such as insulin glargine severely limits its accessibility to patients with diabetes and would seem in contradiction to this aim.

Topics: Diabetes Mellitus; Drug Costs; Drug Industry; Financing, Government; Humans; Insulin; Insulin Glargine; Insulin, Long-Acting; Insurance, Pharmaceutical Services; New Zealand

Topics: Adult; Blood Glucose; Body Mass Index; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Obesity

Topics: Administration, Inhalation; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Diabetes Mellitus; Diabetes Mellitus, Type 1; Double-Blind Method; Heat-Shock Proteins; Humans; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin, Long-Acting; Islets of Langerhans; Randomized Controlled Trials as Topic; Time Factors; Vaccination

Topics: Adult; Blood Glucose; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Insulin; Insulin Glargine; Insulin, Long-Acting; Middle Aged; Time Factors

Topics: Diabetes Mellitus; Drug Prescriptions; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Medication Errors; Nursing Assessment; United States; United States Food and Drug Administration

Topics: Administration, Oral; Adult; Age Factors; Child; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Insulin; Insulin Glargine; Insulin, Long-Acting; Time Factors

Development of the insulin analogues has made it possible to reproduce much more accurately the physiologic insulin profiles seen in people who do not have diabetes. The rapidacting analogues, such as insulin aspart and insulin lispro, offer improved postprandial glycemic control and reduced risk of hypoglycemia. The long-acting analogues, such as insulin glargine and insulin detemir, mimic the insulin secretory profile of basal insulin. Together, they approximate physiologic insulin secretion.

Topics: Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin Lispro; Insulin Secretion; Insulin, Long-Acting

In recent years, the approach to the insulin treatment of type 2 diabetics has undergone a change. Age and clinical status of the patient are decisive determinants for the selection of the appropriate form of treatment. The therapeutic strategy aims to achieve insulin substitution matched to the therapeutic objective, that is, continuous monitoring should be carried out to enable adaptation of the form and intensity of treatment to meet the target end point HbA1c < 6.5%. This necessity results in the earlier use of insulin in all, not only obese, type 2 diabetics. As a compromise solution, a certain percentage of these diabetics will have to be satisfied with simpler forms of insulin substitution and a higher HbA1c value. Attention is drawn to the other parameters of the metabolic syndrome, such as blood pressure, weight, and lipid metabolism. Particular importance attaches to non-pharmacological measures, in particular with the aim of avoiding a further increase in weight due to the treatment with insulin.

Topics: Combined Modality Therapy; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet, Diabetic; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Obesity; Patient Education as Topic

Topics: Diabetes Mellitus; Drug Delivery Systems; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Liver

The U.S. Food and Drug Administration approved more than 100 drugs and devices in 2001. This article discusses several of the new approvals, including ophthalmic drugs, contraceptive therapies, mental health medications, and medical devices.

Topics: Amides; Antihypertensive Agents; Bimatoprost; Cloprostenol; Contraception; Device Approval; Diabetes Mellitus; Drug Approval; Humans; Insulin; Insulin Glargine; Insulin, Long-Acting; Intraocular Pressure; Lipids; Macular Degeneration; Ocular Hypertension; Pacemaker, Artificial; Porphyrins; Travoprost; United States; United States Food and Drug Administration; Verteporfin

Topics: Diabetes Mellitus; Humans; Insulin; Insulin Glargine; Insulin, Long-Acting; Patient Education as Topic

Topics: Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Medication Errors

Topics: Delayed-Action Preparations; Diabetes Mellitus; Humans; Injections; Insulin; Insulin Glargine; Insulin, Long-Acting

Topics: Blood Glucose; Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting

Topics: Clinical Trials as Topic; Diabetes Mellitus; Humans; Insulin; Insulin Glargine; Insulin, Long-Acting