insulin-glargine and Cardiovascular-Diseases

Cardiovascular disease is the leading cause of mortality in type 2 diabetes mellitus. Hyperinsulinemia is associated with increased cardiovascular risk, but the effects of exogenous insulin on cardiovascular disease progression have been less well studied. Insulin has been shown to have both cardioprotective and atherosclerosis-promoting effects in laboratory animal studies. Long-term clinical trials using insulin to attain improved diabetes control in younger type 1 and type 2 diabetes patients have shown improved cardiovascular outcomes. Shorter trials of intensive diabetes control with high insulin use in higher risk patients with type 2 diabetes have shown either no cardiovascular benefit or increased all cause and cardiovascular mortality. Glargine insulin is a basal insulin analog widely used to treat patients with type 1 and type 2 diabetes. This review focuses on the effects of glargine on cardiovascular outcomes. Glargine lowers triglycerides, leads to a modest weight gain, causes less hypoglycemia when compared with intermediate-acting insulin, and has a neutral effect on blood pressure. The Outcome Reduction With Initial Glargine Intervention (ORIGIN trial), a 6.2 year dedicated cardiovascular outcomes trial of glargine demonstrated no increased cardiovascular risk.

Topics: Biomarkers; Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Drug Administration Schedule; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome

The main objective of the ORIGIN study was an observation of the effects of treatment with insulin analogue, insulin glargine on cardiovascular complications in patients with severe atherosclerosis and early stages of well-compensated diabetes and prediabetes. The authors expected that a long-term reduction of glycaemia on an empty stomach will reduce the number of occurrences of cardiovascular complications. The study, which was conducted over a period of more than six years, showed neither a positive nor a negative effect of insulin treatment on cardiovascular complications. The second main objective of the study was the following: to compare the effect of the omega-3 fatty acid treatment versus placebo on the development of cardiovascular complications. However, no influence of n-3 fatty acids on the development of cardiovascular complications was found. The study investigated whether the insulin glargine treatment leads to an increased number of cancer occurrences. No correlation between cancer and the insulin glargine treatment was proven in this study. Long-term insulin treatment in the early stages of diabetes led to a minimal increase in weight through the course of six years (1.5 kg) and to three times more hypoglycaemia occurrences compared to placebo. However, the number of hypoglycaemia occurrences was very small.. The study has confirmed the safety of the insulin glargine treatment combined with metformin in the early stages of diabetes, without an increased number of atherosclerosis or cancer occurrences, and with minimal weight gain.

Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Fatty Acids, Omega-3; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Neoplasms; Randomized Controlled Trials as Topic

Patients with type 2 diabetes mellitus (T2DM) have an increased risk of cardiovascular disease (CVD). Unfortunately, several potential barriers exist for CVD risk management in diabetes, including the need for significant lifestyle changes, potential problems with hypoglycemia, weight gain, injection tolerability, treatment complexity with current diabetes therapies and other, unmodifiable factors. Improving glycemic control may impact CVD risk. Treatment of T2DM usually starts with lifestyle changes such as diet and exercise. When these become insufficient, pharmacotherapy is required. Various oral antidiabetic drugs (OADs) are available that reduce hyperglycemia. The first line of therapy is usually metformin, since it does not increase weight and seems to have a beneficial effect on CVD mortality and risk factors. As T2DM progresses, insulin treatment becomes necessary for the majority of patients. The last few years have seen the development of long-acting, rapid-acting, and premixed insulin analog formulations. The treat-to-target algorithms of recent studies combining OADs plus insulin analogs have demonstrated that patients can reach glycemic treatment targets with low risk of hypoglycemia, greater convenience, and--with some analogs--limited weight gain vs conventional insulins. These factors may possibly have a positive influence on CVD risk. Future studies will hopefully elucidate the benefits of this approach.

Topics: C-Reactive Protein; Cardiovascular Diseases; Diabetic Angiopathies; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Metformin; Postprandial Period; Risk Assessment; Risk Factors; Thiazolidinediones

Insulin glargine is an analogue of human insulin that is modified to provide a consistent level of plasma insulin over a long duration. Pharmacokinetic and pharmacodynamic studies show that a single injection of insulin glargine leads to a smooth 24-hour time-action profile with no undesirable pronounced peaks of activity. In clinical trials, this profile has been associated with at least equivalent, if not better, glycemic control than other traditional basal insulins and a significantly lower rate of overall and nocturnal hypoglycemia. The convenience of a once-daily injection, a lack of need for resuspension (insulin glargine is a clear solution when injected), and lower rates of hypoglycemia should translate into improvements in patient treatment satisfaction. This review appraises the evidence for the view that insulin glargine represents an advance in basal insulin therapy for both type 1 and type 2 diabetes patients.

Topics: Blood Glucose; Cardiovascular Diseases; Delayed-Action Preparations; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Drug Administration Schedule; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin, Long-Acting; Patient Compliance; Patient Satisfaction; Practice Guidelines as Topic; Risk Factors; Treatment Outcome

Data are lacking on the comparative effectiveness of commonly used glucose-lowering medications, when added to metformin, with respect to microvascular and cardiovascular disease outcomes in persons with type 2 diabetes.. We assessed the comparative effectiveness of four commonly used glucose-lowering medications, added to metformin, in achieving and maintaining a glycated hemoglobin level of less than 7.0% in participants with type 2 diabetes. The randomly assigned therapies were insulin glargine U-100 (hereafter, glargine), glimepiride, liraglutide, and sitagliptin. Prespecified secondary outcomes with respect to microvascular and cardiovascular disease included hypertension and dyslipidemia, confirmed moderately or severely increased albuminuria or an estimated glomerular filtration rate of less than 60 ml per minute per 1.73 m. During a mean 5.0 years of follow-up in 5047 participants, there were no material differences among the interventions with respect to the development of hypertension or dyslipidemia or with respect to microvascular outcomes; the mean overall rate (i.e., events per 100 participant-years) of moderately increased albuminuria levels was 2.6, of severely increased albuminuria levels 1.1, of renal impairment 2.9, and of diabetic peripheral neuropathy 16.7. The treatment groups did not differ with respect to MACE (overall rate, 1.0), hospitalization for heart failure (0.4), death from cardiovascular causes (0.3), or all deaths (0.6). There were small differences with respect to rates of any cardiovascular disease, with 1.9, 1.9, 1.4, and 2.0 in the glargine, glimepiride, liraglutide, and sitagliptin groups, respectively. When one treatment was compared with the combined results of the other three treatments, the hazard ratios for any cardiovascular disease were 1.1 (95% confidence interval [CI], 0.9 to 1.3) in the glargine group, 1.1 (95% CI, 0.9 to 1.4) in the glimepiride group, 0.7 (95% CI, 0.6 to 0.9) in the liraglutide group, and 1.2 (95% CI, 1.0 to 1.5) in the sitagliptin group.. In participants with type 2 diabetes, the incidences of microvascular complications and death were not materially different among the four treatment groups. The findings indicated possible differences among the groups in the incidence of any cardiovascular disease. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; GRADE ClinicalTrials.gov number, NCT01794143.).

Topics: Albuminuria; Blood Glucose; Cardiovascular Diseases; Comparative Effectiveness Research; Diabetes Complications; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Drug Therapy, Combination; Dyslipidemias; Glomerular Filtration Rate; Glycated Hemoglobin; Heart Failure; Humans; Hypertension; Hypoglycemic Agents; Insulin Glargine; Liraglutide; Metformin; Microvessels; Sitagliptin Phosphate; Sulfonylurea Compounds

Epidemiological studies have reported a relationship between severe hypoglycemia, cognitive dysfunction, and dementia in middle-aged and older people with type 2 diabetes. However, whether severe or nonsevere hypoglycemia precedes cognitive dysfunction is unclear. Thus, the aim of this study was to analyze the relationship between hypoglycemia and incident cognitive dysfunction in a group of carefully followed patients using prospectively collected data in the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial.. This prospective cohort analysis of data from a randomized controlled trial included individuals with dysglycemia who had additional cardiovascular risk factors and a Mini-Mental State Examination (MMSE) score ≥24 (. This analysis did not demonstrate an association between severe hypoglycemia and incident cognitive impairment either before (hazard ratio [HR] 1.16; 95% CI 0.89, 1.52) or after (HR 1.00; 95% CI 0.76, 1.31) adjusting for the severe hypoglycemia propensities. Conversely, nonsevere hypoglycemia was inversely related to incident cognitive impairment both before (HR 0.59; 95% CI 0.52, 0.68) and after (HR 0.58; 95% CI 0.51, 0.67) adjustment.. Hypoglycemia did not increase the risk of incident cognitive dysfunction in 11,495 middle-aged individuals with dysglycemia.

Topics: Aged; Cardiovascular Diseases; Cognitive Dysfunction; Educational Status; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin Glargine; Male; Metformin; Middle Aged; Proportional Hazards Models; Prospective Studies; Risk Factors

Testosterone and its binding protein sex hormone-binding globulin have been associated with cardiovascular disease and dysglycaemia. However, information on the prognostic implication in patients at high cardiovascular risk with dysglycaemia is inconsistent. The study objective was to determine whether testosterone and/or sex hormone-binding globulin predict cardiovascular events or death in dysglycaemic patients.. Dysglycaemic males at high cardiovascular risk ( n = 5553) who participated in the Outcome Reduction with an Initial Glargine Intervention (ORIGIN) trial and provided baseline blood samples were studied. Testosterone and sex hormone-binding globulin were measured at baseline and used to estimate free testosterone. Low levels of total and free testosterone were defined as ≤300 ng/dl and ≤7 ng/dl, respectively. Patients were followed for six years for cardiovascular events (defined as the composite of cardiovascular death, non-fatal myocardial infarction or stroke) and all-cause mortality.. The mean total and free testosterone levels were 416.6 ng/dl and 8.4 ng/dl, and low levels were present in 13% and 37% of the patients. The median sex hormone-binding globulin level was 35 nmol/l. In Cox regression models adjusted for age, previous diseases and pharmacological treatment, neither total nor free testosterone predicted cardiovascular events. However, a one-standard-deviation increase in sex hormone-binding globulin predicted both cardiovascular events (hazard ratio 1.07; 95% confidence interval 1.00-1.14; p = 0.03) and all-cause mortality (hazard ratio 1.13; 95% confidence interval 1.06-1.21; p < 0.01).. Sex hormone-binding globulin, but not total testosterone, predicts cardiovascular disease and all-cause mortality in dysglycaemic males at high cardiovascular risk.

Topics: Aged; Biomarkers; Blood Glucose; Cardiovascular Diseases; Cause of Death; Glucose Metabolism Disorders; Humans; Hypoglycemic Agents; Insulin Glargine; Male; Middle Aged; Risk Assessment; Risk Factors; Sex Hormone-Binding Globulin; Testosterone; Time Factors; Treatment Outcome

The aim of this study was to describe the risks of cardiovascular (CV) events and severe hypoglycaemia with insulin degludec (degludec) vs insulin glargine 100 units/mL (glargine U100) in patients with type 2 diabetes (T2D) aged 65 years or older.. A total of 7637 patients in the DEVOTE trial, a treat-to-target, randomized, double-blind trial evaluating the CV safety of degludec vs glargine U100, were divided into three age groups (50-64 years, n = 3682; 65-74 years, n = 3136; ≥75 years, n = 819). Outcomes by overall age group and randomized treatment differences were analysed for major adverse cardiovascular events (MACE), all-cause mortality, severe hypoglycaemia and serious adverse events (SAEs).. Patients with increasing age had higher risks of CV death, all-cause mortality and SAEs, and there were non-significant trends towards higher risks of MACE and severe hypoglycaemia. Treatment effects on the risk of MACE, all-cause mortality, severe hypoglycaemia and SAEs were consistent across age groups, based on the non-significant interactions between treatment and age with regard to these outcomes.. There were higher risks of CV death, all-cause mortality and SAEs, and trends towards higher risks of MACE and severe hypoglycaemia with increasing age after adjusting for baseline differences. The effects across age groups of degludec vs glargine U100 on MACE, all-cause mortality and severe hypoglycaemia were comparable, suggesting that the risk of MACE, as well as all-cause mortality, is similar and the risk of severe hypoglycaemia is lower with degludec regardless of age. Evidence is conclusive only until 74 years of age.

Topics: Aged; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged

To evaluate an additional rapid-acting insulin bolus on postprandial lipaemia, inflammation and pro-coagulation following high-carbohydrate high-fat feeding in people with type 1 diabetes.. Triglyceride concentrations following LF remained similar to baseline, whereas triglyceride levels following HF were significantly greater throughout the 6-h observation period. The additional insulin bolus (HFA) normalised triglyceride similarly to low fat 3-6 h following the meal. HF was associated with late postprandial elevations in tumour necrosis factor alpha, whereas LF and HFA was not. Fibrinogen, plasminogen activator inhibitor-1 and tissue factor pathway levels were similar between conditions.. Additional bolus insulin 3 h following a high-carbohydrate high-fat meal prevents late rises in postprandial triglycerides and tumour necrosis factor alpha, thus improving cardiovascular risk profile.

Topics: Adult; Biomarkers; Blood Coagulation; Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus, Type 1; Diet, High-Fat; Dietary Carbohydrates; Dietary Fats; England; Humans; Hypoglycemic Agents; Inflammation Mediators; Insulin Detemir; Insulin Glargine; Male; Meals; Postprandial Period; Risk Factors; Time Factors; Treatment Outcome; Triglycerides; Tumor Necrosis Factor-alpha; Young Adult

Fibrinolytic factors, plasminogen activator inhibitor-1, tissue plasminogen activator, tissue plasminogen activator/plasminogen activator-complex and the haemostatic factor von Willebrand factor are known markers of cardiovascular disease. Their plasma levels are adversely affected in patients with dysglycaemia, and glucose normalization with insulin glargine might improve the levels of these factors.. Prespecified Swedish substudy of the Outcome Reduction with an Initial Glargine Intervention trial (ClinicalTrials.gov number, NCT00069784). Tissue plasminogen activator activity, tissue plasminogen activator antigen, plasminogen activator inhibitor-1 antigen, tissue plasminogen activator/plasminogen activator inhibitor-1 complex and von Willebrand factor were analysed at study start, after 2 years and at the end of the study (median follow-up of 6.2 years).. Of 129 patients (mean age of 64 ± 7 years, females: 19%), 68 (53%) and 61 (47%) were randomized to the insulin glargine and standard care group, respectively. Allocation to insulin glargine did not significantly affect the studied fibrinolytic markers or von Willebrand factor compared to standard care. Likewise, there were no significant differences in plasminogen activator inhibitor-1, tissue plasminogen activator antigen and von Willebrand factor. During the whole study period, the within-group analysis revealed a curvilinear pattern and significant changes for tissue plasminogen activator/plasminogen activator inhibitor-1 complex, tissue plasminogen activator antigen and von Willebrand factor in the insulin glargine but not in the standard care group.. In people with dysglycaemia and other cardiovascular risk factors, basal insulin does not improve the levels of markers of fibrinolysis or von Willebrand factor compared to standard glucose-lowering treatments.

Topics: Aged; Biomarkers; Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; Fibrinolysis; Glucose Intolerance; Humans; Hypoglycemic Agents; Insulin Glargine; Male; Middle Aged; Plasminogen Activator Inhibitor 1; Risk Factors; Sweden; Time Factors; Tissue Plasminogen Activator; Treatment Outcome; von Willebrand Factor

Degludec is an ultralong-acting, once-daily basal insulin that is approved for use in adults, adolescents, and children with diabetes. Previous open-label studies have shown lower day-to-day variability in the glucose-lowering effect and lower rates of hypoglycemia among patients who received degludec than among those who received basal insulin glargine. However, data are lacking on the cardiovascular safety of degludec.. We randomly assigned 7637 patients with type 2 diabetes to receive either insulin degludec (3818 patients) or insulin glargine U100 (3819 patients) once daily between dinner and bedtime in a double-blind, treat-to-target, event-driven cardiovascular outcomes trial. The primary composite outcome in the time-to-event analysis was the first occurrence of an adjudicated major cardiovascular event (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) with a prespecified noninferiority margin of 1.3. Adjudicated severe hypoglycemia, as defined by the American Diabetes Association, was the prespecified, multiplicity-adjusted secondary outcome.. Of the patients who underwent randomization, 6509 (85.2%) had established cardiovascular disease, chronic kidney disease, or both. At baseline, the mean age was 65.0 years, the mean duration of diabetes was 16.4 years, and the mean (±SD) glycated hemoglobin level was 8.4±1.7%; 83.9% of the patients were receiving insulin. The primary outcome occurred in 325 patients (8.5%) in the degludec group and in 356 (9.3%) in the glargine group (hazard ratio, 0.91; 95% confidence interval, 0.78 to 1.06; P<0.001 for noninferiority). At 24 months, the mean glycated hemoglobin level was 7.5±1.2% in each group, whereas the mean fasting plasma glucose level was significantly lower in the degludec group than in the glargine group (128±56 vs. 136±57 mg per deciliter, P<0.001). Prespecified adjudicated severe hypoglycemia occurred in 187 patients (4.9%) in the degludec group and in 252 (6.6%) in the glargine group, for an absolute difference of 1.7 percentage points (rate ratio, 0.60; P<0.001 for superiority; odds ratio, 0.73; P<0.001 for superiority). Rates of adverse events did not differ between the two groups.. Among patients with type 2 diabetes at high risk for cardiovascular events, degludec was noninferior to glargine with respect to the incidence of major cardiovascular events. (Funded by Novo Nordisk and others; DEVOTE ClinicalTrials.gov number, NCT01959529 .).

Topics: Aged; Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin Glargine; Insulin, Long-Acting; Kaplan-Meier Estimate; Male; Middle Aged

Subclinical myocardial injury, as measured by high-sensitivity cardiac troponin T (hsTnT), and myocardial stress, as measured by N-terminal pro-B-type natriuretic peptide (NT-proBNP), are related to glycemic control in patients with type 2 diabetes mellitus, and are strong predictors of adverse cardiovascular outcomes. We sought to determine whether antihyperglycemic therapy improves measures of myocardial injury and myocardial stress in patients with type 2 diabetes mellitus.. We randomized, in a 2×2 factorial fashion, 438 patients with type 2 diabetes mellitus to insulin glargine, metformin, the combination, or placebo and measured changes in NT-proBNP and hsTnT after 12 weeks of therapy. At baseline, the median (Q1-Q3) plasma concentration was 35.4 (15.7-86.3) ng/L for NT-proBNP and 6.7 (4.6-10.1) ng/L for hsTnT. The adjusted (95% confidence interval) change in NT-proBNP concentration was 20.7% (7.9-35.0) in the insulin arm compared with 0.13% (-10.8 to 12.5) in the no-insulin arm (. Insulin glargine was associated with a significant 20.7% increase in NT-proBNP, a marker of myocardial stress, after 12 weeks of therapy. No change in hsTnT, a marker of myocardial injury, was observed. The changes were independent of substantial improvements in glucose control.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00366301.

Topics: Biomarkers; Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Male; Metformin; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Risk Factors; Troponin T

The Outcome Reduction With Initial Glargine Intervention (ORIGIN) trial reported neutral effects of insulin glargine on cardiovascular outcomes and cancers and reduced incident diabetes in high-cardiovascular risk adults with dysglycemia after 6.2 years of active treatment. Omega-3 fatty acids had neutral effects on cardiovascular outcomes. The ORIGIN and Legacy Effects (ORIGINALE) study measured posttrial effects of these interventions during an additional 2.7 years.. Surviving ORIGIN participants attended up to two additional visits. The hazard of clinical outcomes during the entire follow-up period from randomization was calculated.. Of 12,537 participants randomized, posttrial data were analyzed for 4,718 originally allocated to insulin glargine (2,351) versus standard care (2,367), and 4,771 originally allocated to omega-3 fatty acid supplements (2,368) versus placebo (2,403). Posttrial, small differences in median HbA1c persisted (glargine 6.6% [49 mmol/mol], standard care 6.7% [50 mmol/mol], P = 0.025). From randomization to the end of posttrial follow-up, no differences were found between the glargine and standard care groups in myocardial infarction, stroke, or cardiovascular death (1,185 vs. 1,165 events; hazard ratio 1.01 [95% CI 0.94-1.10]; P = 0.72); myocardial infarction, stroke, cardiovascular death, revascularization, or hospitalization for heart failure (1,958 vs. 1,910 events; 1.03 [0.97-1.10]; P = 0.38); or any cancer (524 vs. 529 events; 0.99 [0.88-1.12]; P = 0.91) or between omega-3 and placebo groups in cardiovascular death (688 vs. 700; 0.98 [0.88-1.09]; P = 0.68) or other outcomes.. During >6 years of treatment followed by >2.5 years of observation, insulin glargine had neutral effects on health outcomes and salutary effects on metabolic control, whereas omega-3 fatty acid supplementation had no effect.

Topics: Aged; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dietary Supplements; Fatty Acids, Omega-3; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Male; Metformin; Middle Aged; Proportional Hazards Models; Risk Factors; Sulfonylurea Compounds; Treatment Outcome

DEVOTE was designed to evaluate the cardiovascular safety of insulin degludec (IDeg) vs insulin glargine U100 (IGlar) in patients with T2D at high risk of cardiovascular events. DEVOTE is a phase 3b, multicenter, international, randomized, double-blind, active comparator-controlled trial, designed as an event-driven trial that would continue until 633 positively adjudicated primary events were accrued. The primary end point was the time from randomization to a composite outcome consisting of the first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Patients with T2D at high risk of cardiovascular complications were randomized 1:1 to receive either IDeg or IGlar, each added to background therapies. This trial was designed to demonstrate statistical noninferiority of IDeg vs IGlar for the primary end point. DEVOTE enrolled 7,637 patients between October 2013 and November 2014 at 436 sites in 20 countries. Of these, 6,506 patients had prior cardiovascular disease or chronic kidney disease, and the remainder had multiple cardiovascular risk factors. DEVOTE was designed to provide conclusive evidence regarding the cardiovascular safety of IDeg relative to IGlar in a high-risk population of patients with T2D.

Topics: Aged; Angina, Unstable; Cardiovascular Diseases; Comorbidity; Coronary Disease; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glycated Hemoglobin; Heart Failure; Hospitalization; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Myocardial Infarction; Proportional Hazards Models; Renal Insufficiency, Chronic; Risk Factors; Stroke

Hypoglycemia is a leading risk of glucose-lowering therapy. Treatment with insulin glargine compared with standard care early in the course of dysglycemia in the Outcome Reduction with an Initial Glargine Intervention (ORIGIN) trial provides information on the frequency and predictors of hypoglycemia in this setting.. A total of 12,537 people with high cardiovascular risk and dysglycemia treated with one or no oral glucose-lowering agents were randomized to add glargine titrated to a fasting glucose level of ≤5.3 mmol/L (≤95 mg/dL) or to use standard therapies. Independent associations of both nonsevere hypoglycemia (symptomatic and confirmed with a glucose level of ≤3 mmol/L [≤54 mg/dL]) and severe hypoglycemia with characteristics at baseline, treatment allocation, and average HbA1c were assessed by Cox proportional hazards models.. During a median follow-up period of 6.2 years, 28% of participants reported nonsevere hypoglycemia, and 3.8% reported severe hypoglycemia. Prior use of a sulfonylurea and allocation to glargine independently predicted a higher risk for both categories of participants. Nonsevere events were independently associated with younger age, lower BMI, the presence of diabetes, and higher baseline HbA1c level. Severe events were associated with older age, hypertension, higher serum creatinine level, and lower cognitive function, but not baseline glycemic status. Progressively higher on-treatment HbA1c level was associated with a lower risk of nonsevere events in both treatment groups; a lower risk of severe events in the glargine group, and a higher risk of severe events with standard care.. Hypoglycemia was relatively uncommon in the ORIGIN trial, but was more frequent with sulfonylurea use at baseline and allocation to glargine. Nonsevere and severe events were associated with different clinical characteristics, awareness of which may guide individualized therapy.

Topics: Aged; Blood Glucose; Body Mass Index; Cardiovascular Diseases; Creatinine; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Proportional Hazards Models; Risk Factors; Sulfonylurea Compounds

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

To demonstrate the efficacy of exenatide versus insulin glargine on endothelial functions and cardiovascular risk markers.. Thirty-four insulin and incretin-naive patients with type 2 diabetes mellitus (body mass index 25-45 kg/m(2)) who received metformin for at least two months were randomized to exenatide or insulin glargine treatment arms and followed-up for 26 weeks. Measurements of endothelial functions were done by ultrasonography, cardiovascular risk markers by serum enzyme-linked immunosorbent assay, and total body fat mass by bioimpedance.. Levels of high sensitivity-C-reactive protein and endothelin-1 decreased (27.5% and 18.75%, respectively) in the exenatide arm. However, in the insulin glargine arm, fibrinogen, monocyte chemoattractant protein-1, leptin and endothelin-1 levels (13.4, 30.2, 47.5, and 80%, respectively) increased. Post-treatment flow mediated dilatation and endothelium independent vascular responses were significantly higher in both arms (p=0.0001, p=0.0001). Positive correlation was observed between the changes in body weight and endothelium-independent vasodilatation, leptin, plasminogen activator inhibitor type 1 and endothelin-1 in both arms (r=0.376, r=0.507, r=0.490, r=0.362, respectively).. Insulin glargine improved endothelial functions, without leading to positive changes in cardiovascular risk markers. Exenatide treatment of 26 weeks resulted in reduced body weight and improvement in certain cardiovascular risk markers and endothelial functions.

Topics: Biomarkers; Blood Glucose; Brachial Artery; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Endothelin-1; Endothelium, Vascular; Enzyme-Linked Immunosorbent Assay; Exenatide; Female; Follow-Up Studies; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Peptides; Prognosis; Risk Factors; Ultrasonography; Vasodilation; Venoms

Diabetes is associated with a higher risk for adverse cardiovascular outcomes. To improve the health outcomes of patients with type 2 diabetes (T2DM), the American Diabetes Association (ADA) recommended target goals for the improvement of glycemic control and the reduction of cardiovascular risk factors associated with the disease. This retrospective analysis calculated the absolute benefit increase (ABI) of using exenatide once weekly (QW), a glucagon-like peptide-1 (GLP-1) receptor agonist, vs an oral glucose-lowering medication or insulin glargine to achieve ADA-recommended goals. The number needed to treat (NNT) to achieve these goals was also calculated and provides a useful clinical metric for comparing potential therapies from different drug classes.. Patient data from three double-blind or open label, 26-week, randomized, controlled trials were retrospectively analyzed separately. ABI and NNT were calculated by comparing the percentage of patients treated with exenatide QW (N = 641) vs metformin (N = 246), sitagliptin (N = 329), pioglitazone (N = 328), or insulin glargine (N = 223), who achieved a single glycemic, weight, blood pressure, or lipid goal or a composite of these recommended goals, during the DURATION-2, -3, and -4 clinical trials.. Significant ABIs favoring exenatide QW over all four glucose-lowering medications were observed for at least one HbA1c glycemic goal. NNTs of 4 and 5 were calculated when exenatide QW was compared to sitagliptin for attaining HbA1c goals of <7.0% and ≤6.5%, respectively. Additionally, significantly more patients using exenatide QW compared to sitagliptin, pioglitazone, or insulin glargine attained the composite goal of HbA1c <7% or ≤6.5%, without weight gain or hypoglycemia. Exenatide QW was also favored over sitagliptin and insulin glargine for the achievement of the composite goals of HbA1c <7% (or ≤6.5%), systolic blood pressure <130 mm Hg, and low-density lipoprotein <2.59 mmol/L. For most goals, exenatide QW and metformin had similar effects in treatment naïve patients.. This analysis assessed the between-therapy differences in achieving therapeutic goals with therapies commonly used for glycemic control in patients with T2DM. In clinical trials, exenatide QW assisted more patients in reaching the majority of ADA-recommended therapeutic goals than treatment with sitagliptin, pioglitazone, or insulin glargine.. NCT00637273, NCT00641056, NCT00676338.

Topics: Administration, Oral; Adult; Aged; Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Administration Schedule; Exenatide; Female; Glycemic Index; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Patient Care Planning; Peptides; Retrospective Studies; Treatment Outcome; Venoms

The use of n-3 fatty acids may prevent cardiovascular events in patients with recent myocardial infarction or heart failure. Their effects in patients with (or at risk for) type 2 diabetes mellitus are unknown.. In this double-blind study with a 2-by-2 factorial design, we randomly assigned 12,536 patients who were at high risk for cardiovascular events and had impaired fasting glucose, impaired glucose tolerance, or diabetes to receive a 1-g capsule containing at least 900 mg (90% or more) of ethyl esters of n-3 fatty acids or placebo daily and to receive either insulin glargine or standard care. The primary outcome was death from cardiovascular causes. The results of the comparison between n-3 fatty acids and placebo are reported here.. During a median follow up of 6.2 years, the incidence of the primary outcome was not significantly decreased among patients receiving n-3 fatty acids, as compared with those receiving placebo (574 patients [9.1%] vs. 581 patients [9.3%]; hazard ratio, 0.98; 95% confidence interval [CI], 0.87 to 1.10; P=0.72). The use of n-3 fatty acids also had no significant effect on the rates of major vascular events (1034 patients [16.5%] vs. 1017 patients [16.3%]; hazard ratio, 1.01; 95% CI, 0.93 to 1.10; P=0.81), death from any cause (951 [15.1%] vs. 964 [15.4%]; hazard ratio, 0.98; 95% CI, 0.89 to 1.07; P=0.63), or death from arrhythmia (288 [4.6%] vs. 259 [4.1%]; hazard ratio, 1.10; 95% CI, 0.93 to 1.30; P=0.26). Triglyceride levels were reduced by 14.5 mg per deciliter (0.16 mmol per liter) more among patients receiving n-3 fatty acids than among those receiving placebo (P<0.001), without a significant effect on other lipids. Adverse effects were similar in the two groups.. Daily supplementation with 1 g of n-3 fatty acids did not reduce the rate of cardiovascular events in patients at high risk for cardiovascular events. (Funded by Sanofi; ORIGIN ClinicalTrials.gov number, NCT00069784.).

Topics: Aged; Cardiovascular Diseases; Cholesterol; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Fatty Acids, Omega-3; Female; Follow-Up Studies; Glucose Intolerance; Humans; Hypoglycemic Agents; Incidence; Insulin Glargine; Insulin, Long-Acting; Intention to Treat Analysis; Male; Middle Aged; Proportional Hazards Models; Treatment Failure; Triglycerides

The provision of sufficient basal insulin to normalize fasting plasma glucose levels may reduce cardiovascular events, but such a possibility has not been formally tested.. We randomly assigned 12,537 people (mean age, 63.5 years) with cardiovascular risk factors plus impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes to receive insulin glargine (with a target fasting blood glucose level of ≤95 mg per deciliter [5.3 mmol per liter]) or standard care and to receive n-3 fatty acids or placebo with the use of a 2-by-2 factorial design. The results of the comparison between insulin glargine and standard care are reported here. The coprimary outcomes were nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes and these events plus revascularization or hospitalization for heart failure. Microvascular outcomes, incident diabetes, hypoglycemia, weight, and cancers were also compared between groups.. The median follow-up was 6.2 years (interquartile range, 5.8 to 6.7). Rates of incident cardiovascular outcomes were similar in the insulin-glargine and standard-care groups: 2.94 and 2.85 per 100 person-years, respectively, for the first coprimary outcome (hazard ratio, 1.02; 95% confidence interval [CI], 0.94 to 1.11; P=0.63) and 5.52 and 5.28 per 100 person-years, respectively, for the second coprimary outcome (hazard ratio, 1.04; 95% CI, 0.97 to 1.11; P=0.27). New diabetes was diagnosed approximately 3 months after therapy was stopped among 30% versus 35% of 1456 participants without baseline diabetes (odds ratio, 0.80; 95% CI, 0.64 to 1.00; P=0.05). Rates of severe hypoglycemia were 1.00 versus 0.31 per 100 person-years. Median weight increased by 1.6 kg in the insulin-glargine group and fell by 0.5 kg in the standard-care group. There was no significant difference in cancers (hazard ratio, 1.00; 95% CI, 0.88 to 1.13; P=0.97).. When used to target normal fasting plasma glucose levels for more than 6 years, insulin glargine had a neutral effect on cardiovascular outcomes and cancers. Although it reduced new-onset diabetes, insulin glargine also increased hypoglycemia and modestly increased weight. (Funded by Sanofi; ORIGIN ClinicalTrials.gov number, NCT00069784.).

Topics: Aged; Blood Glucose; Cardiovascular Diseases; Cholesterol; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Fasting; Fatty Acids, Omega-3; Female; Follow-Up Studies; Glucose Intolerance; Hospitalization; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin Glargine; Insulin, Long-Acting; Intention to Treat Analysis; Male; Middle Aged; Proportional Hazards Models; Triglycerides

No study of transition from intravenous to subcutaneous insulin after cardiac surgery with dose based on percentage of intravenous total daily insulin (TDI) has reported a clearly superior regimen for achieving target blood glucose. We compared three first-dose transition strategies for insulin glargine: two based on TDI alone and one that also took body weight into account.. Mostly obese, type 1 and type 2 diabetes patients (n = 223) undergoing cardiac surgery were randomized to receive insulin glargine subcutaneously at 60% or 80% of TDI or in a dose based on TDI and body weight.. Transition to subcutaneous insulin occurred 27.4 ± 6.6 h after surgery. Over the study period, mean proportion of blood glucose values within target range (80-140 mg/dL) were 0.34 ± 0.24, 0.35 ± 0.24, and 0.36 ± 0.22 in the 60% TDI, 80% TDI, and weight-based groups, respectively. This difference was not significant. Significantly more insulin corrections were needed in the 60% TDI group than in the weight-based group. There was only one incidence of hypoglycemia (blood glucose < 40 mg/dL).. No subcutaneous insulin regimen implemented approximately 1 day after cardiac surgery showed significantly better control of blood glucose over the 3-day study period. Further studies are needed to determine optimal formulae for effecting an early transition to subcutaneous insulin after cardiac surgery or whether it is preferable and/or necessary to continue intravenous insulin therapy for an additional period of time.

Topics: Aged; Blood Glucose; Body Mass Index; Cardiovascular Diseases; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Dosage Calculations; Drug Monitoring; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Obesity; Postoperative Care

To study the effect of exenatide on body composition and circulating cardiovascular risk biomarkers.. Metformin-treated patients with type 2 diabetes (N = 69) were randomized to exenatide or insulin glargine and treated for 1 year. Body composition was evaluated by dual-energy X-ray absorptiometry. Additionally, body weight, waist circumference, and cardiovascular biomarkers were measured.. Treatment with exenatide for 1 year significantly reduced body weight, waist circumference, and total body and trunkal fat mass by 6, 5, 11, and 13%, respectively. In addition, exenatide increased total adiponectin by 12% and reduced high-sensitivity C-reactive protein by 61%. Insulin glargine significantly reduced endothelin-1 by 7%. These changes were statistically independent of the change in total body fat mass and body weight.. Exenatide treatment for 1 year reduced body fat mass and improved the profile of circulating biomarkers of cardiovascular risk. No significant changes were seen with insulin glargine except a trend for reduced endothelin-1 levels.

Topics: Absorptiometry, Photon; Adiponectin; Body Composition; Body Weight; C-Reactive Protein; Cardiovascular Diseases; Endothelin-1; Exenatide; Female; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Peptides; Risk Factors; Venoms; Waist Circumference

Intensification of insulin therapy in patients with type 2 diabetes, while improving glycemic control, often leads to an increase in body weight and other markers of cardiovascular risk. The effects of pramlintide as an adjunct to basal insulin titration (without mealtime insulin) on glycemia and cardiovascular risk markers were examined.. This was a post hoc analysis of a 16-week, double-blind, placebo-controlled study in patients with type 2 diabetes (N = 211) using insulin glargine (without mealtime insulin) +/- oral agents. Patients were randomized to treatment with placebo or pramlintide (60 or 120 mug with major meals), and insulin glargine was titrated to target a fasting plasma glucose concentration of > or = 70 to < 100 mg/dL.. Endpoints included the change from baseline to Week 16 in body weight, high sensitivity C-reactive protein (hsCRP), triglycerides, HDL, LDL, and blood pressure.. Pramlintide-treated patients lost weight and placebo-treated patients gained weight during 16 weeks of treatment (-1.6 +/- 0.3 kg vs. +0.7 +/- 0.3 kg, p < 0.001; mean +/- SE). hsCRP was reduced in pramlintide-treated versus placebo-treated patients (-0.8 +/- 0.2 mg/L vs. 0.1 +/- 0.2 mg/L, p < 0.01; mean +/- SE). Patients with baseline hsCRP > 3 mg/L (high cardiovascular risk) demonstrated greater hsCRP reductions with pramlintide versus placebo treatment at Week 16 (p < 0.05). Patients with baseline triglycerides > or = 150 mg/dL or > or = 200 mg/dL (high cardiovascular risk) showed significant reductions from baseline in triglyceride concentrations with pramlintide (-43 +/- 14 mg/dL or -59 +/- 19 mg/dL; p < 0.05; mean +/- SE) but not with placebo (1 +/- 29 mg/dL or -3 +/- 54 mg/dL; mean +/- SE). No significant differences between pramlintide and placebo were observed for changes in HDL, LDL, or blood pressure. Pramlintide treatment was generally well tolerated. The most frequent adverse event related to pramlintide was mild-to-moderate nausea (31% pramlintide vs. 10% placebo). Pramlintide added to basal insulin did not increase the incidence of hypoglycemia. A limitation of the study was its relatively short duration.. Pramlintide, as an adjunct to basal insulin, was associated with improvements in several cardiovascular risk markers, warranting long-term clinical studies to determine its potential effects on cardiovascular risk.

Topics: Aged; Amyloid; Biomarkers; Blood Glucose; Body Weight; C-Reactive Protein; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Islet Amyloid Polypeptide; Male; Middle Aged; Placebos; Risk Factors; Triglycerides

Impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and diabetes arise due to insufficient insulin secretion and are risk factors for cardiovascular (CV) events. Thus, targeting normal fasting glucose levels with insulin may reduce CV events. Previous studies suggest that omega-3 fatty acid supplements may reduce CV death; however, their effect in high-risk dysglycemic individuals is not known.. People aged > or = 50 years with evidence of CV disease and with IFG, IGT, newly detected or established diabetes (on 0 or 1 oral agent), and a local glycated hemoglobin < 150% of the upper limit of normal for that assay were recruited and allocated to (a) either 1 daily injection of insulin glargine with the dose titrated to achieve a fasting plasma glucose < or = 5.3 mmol/L (95 mg/dL), or standard glycemic care; and (b) either omega-3-acid ethyl esters 90 (1 g consisting of EPA 465 mg and DHA 375 mg) or identical placebo, according to a 2 x 2 factorial design. The 2 different primary outcomes for the insulin and omega-3 fatty acid arms are CV events and CV death, respectively.. A total of 12,612 (mean age 64, 35% women) people in 40 countries were randomized during a 2-year period ending December 2005. Eighty-two percent had established diabetes, 6% had new diabetes, and 12% had IGT or IFG; the mean fasting plasma glucose was 7.3 mmol/L (131 mg/dL).. The ORIGIN trial will determine whether or not either or both of these interventions can reduce CV events.

Topics: Aged; Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; International Cooperation; Male; Middle Aged; Patient Selection; Probability; Proportional Hazards Models; Reference Values; Research Design; Severity of Illness Index; Survival Analysis; Treatment Outcome

Real-world evidence of the safety of insulin degludec compared with insulin glargine U100 is sparse. This study sought to investigate the risk of major cardiovascular events, severe hypoglycaemia, and all-cause mortality after initiation of degludec or glargine U100 in the population of Denmark.. All Danish people with diabetes initiating treatment on degludec (n=5159) or glargine (n=4041) in 2016 to 2017 were included in the study. The effect of insulin treatment on the endpoints of major cardiovascular events, severe hypoglycaemia, and all-cause mortality was analysed with Cox proportional hazard models. The models were adjusted for age, sex, diabetes duration, diabetes type, highest completed education, and annual income. The model of severe hypoglycaemia was also adjusted for severe hypoglycaemia prior to baseline. The model of mortality was also adjusted for history of alcohol abuse, use of antidepressants, use of opioids, and use of anxiolytics. Lastly, the models of major cardiovascular events and mortality were also adjusted for Charlson comorbidity index.. Use of degludec resulted in an almost twofold decrease in risk of death (hazard rate [HR]: 0.54, 95% CI: 0.44-0.65) compared with use of glargine. No statistically significant risk changes were found for major cardiovascular events (HR: 0.86, 95% CI: 0.62-1.19) and severe hypoglycaemia (HR: 1.13, 95% CI: 0.66-1.93). The proportion of cause of death due to malignant neoplasm of pancreas was almost doubled for glargine compared with degludec.. These results indicate that insulin degludec has a safer profile with respect to all-cause mortality as compared with insulin glargine U100.

Topics: Aged; Biomarkers; Blood Glucose; Cardiovascular Diseases; Cohort Studies; Denmark; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin Glargine; Insulin, Long-Acting; Male; Prognosis; Risk Factors; Survival Rate

The cardiovascular outcomes of insulin detemir in patients with type 2 diabetes mellitus (T2DM) after acute coronary syndrome (ACS) or acute ischemic stroke (AIS) are unclear. The aim of our real-life cohort study was to evaluate the cardiovascular outcomes of insulin detemir (IDet) versus insulin glargine (IGlar) in T2DM patients after ACS or AIS.. A retrospective cohort study was conducted between June 1, 2005, and December 31, 2013, utilizing the Taiwan National Health Insurance Research Database. A total of 3,129 ACS or AIS patients were eligible for the analysis. Clinical outcomes were evaluated by comparing 1,043 subjects receiving IDet with 2,086 propensity score-matched subjects who received IGlar. The primary composite outcome included cardiovascular (CV) death, nonfatal myocardial infarction (MI) and nonfatal stroke.. The primary composite outcome occurred in 322 patients (30.9%) in the IDet group and 604 patients (29.0%) in the IGlar group (hazard ratio [HR], 1.12; 95% confidence interval [CI], 0.95 to 1.32) with a mean follow-up of 2.4 years. No significant differences were observed for CV death (HR, 1.09; 95% CI, 0.86 to 1.38), nonfatal MI (HR, 0.88; 95% CI, 0.66 to 1.19), and nonfatal stroke (HR, 1.15; 95% CI, 0.97 to 1.35). There were similar risks of all-cause mortality, hospitalization for heart failure and revascularization between the IDet group and the IGlar group (P = .647, .115, and .390 respectively).. Compared with IGlar, in T2DM patients after ACS or AIS, IDet was not associated with increased risks of CV death, nonfatal MI, or nonfatal stroke.. ACS = acute coronary syndrome; AIS = acute ischemic stroke; ASCVD = atherosclerotic cardiovascular disease; CI = confidence interval; CV = cardiovascular; DKA = diabetic ketoacidosis; HHF = hospitalization for heart failure; HHS = hyperosmolar hyperglycemic state; HR = hazard ratio; IDet = insulin detemir; IGlar = insulin glargine; MI = myocardial infarction; NHIRD = National Health Insurance Research Database; PCI = percutaneous coronary intervention; PSM = propensity score matching; T2DM = type 2 diabetes mellitus.

Topics: Brain Ischemia; Cardiovascular Diseases; Cohort Studies; Diabetes Mellitus, Type 2; Humans; Insulin Detemir; Insulin Glargine; Percutaneous Coronary Intervention; Retrospective Studies; Stroke; Taiwan; Treatment Outcome

To evaluate the short-term cost-effectiveness of insulin degludec (degludec) vs insulin glargine 100 units/mL (glargine U100) from a Canadian public healthcare payer perspective in patients with type 2 diabetes (T2D) who are at high risk of cardiovascular events and hypoglycaemia.. A decision analytic model was developed to estimate costs (2017 Canadian dollars [CAD]) and clinical outcomes (quality-adjusted life years [QALYs]) with degludec vs glargine U100 over a 2-year time horizon. The model captured first major adverse cardiovascular event, death, severe hypoglycaemia and insulin dosing. Clinical outcomes were informed by a post hoc subgroup analysis of the DEVOTE trial (NCT01959529), which compared the cardiovascular safety of degludec and glargine U100 in patients with T2D who are at high cardiovascular risk. High hypoglycaemia risk was defined as the top quartile of patients (n = 1887) based on an index of baseline hypoglycaemia risk factors.. In patients at high hypoglycaemia risk, degludec was associated with mean cost savings (CAD 129 per patient) relative to glargine U100, driven by a lower incidence of non-fatal myocardial infarction, non-fatal stroke and severe hypoglycaemia, which offset the slightly higher cost of treatment with degludec. A reduced risk of cardiovascular death and severe hypoglycaemia resulted in improved effectiveness (+0.0132 QALYs) with degludec relative to glargine U100. In sensitivity analyses, changes to the vast majority of model parameters did not materially affect model outcomes.. Over a 2-year period, degludec improved clinical outcomes at a lower cost as compared to glargine U100 in patients with T2D at high risk of cardiovascular events and hypoglycaemia.

Topics: Aged; Canada; Cardiovascular Diseases; Cost Savings; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Treatment Outcome

Topics: Aged; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Randomized Controlled Trials as Topic; Risk Factors; Treatment Outcome

Do novel therapies in type 2 diabetes have protective effects on cardiovascular and renal complications? A number of new antidiabetic drug classes have been introduced on the market in the last decade. Regulatory authorities have required that their safety in type 2 diabetes populations with high cardiovascular risk must be assessed. Consequently, a large number of outcome studies have been initiated, several of which have been published in recent years. Overall, this has so far shown that long-acting insulin analogues, DPP4-inhibitors, GLP1-receptor agonists and SGLT2-inhibitors are safe. In addition, a few select agents within the latter two classes have been shown to be superior to placebo with respect to cardiovascular as well as renal outcomes. This review summarizes these recent trials and discusses how the results can be interpreted. It is important to emphasize that the subjects included in these studies had/have high risk for or manifest cardiovascular disease. Therefore, the results cannot be extrapolated to all individuals with type 2 diabetes.

Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Insulin Glargine; Kidney Diseases; Sodium-Glucose Transporter 2 Inhibitors

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

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

Dyslipidaemia is a major contributor to the increased risk of cardiovascular disease (CVD) associated with type 2 diabetes (T2D). This study aimed to characterize the extent of lipid-lowering therapy use and its impact on lipid and glycaemic outcomes in people with T2D uncontrolled on oral agents who were enrolled in insulin glargine 100 units/mL (Gla-100) randomized controlled trials (RCTs).. A post hoc patient-level pooled analysis of eleven RCTs (≥24 weeks' duration) comparing Gla-100 (±oral antidiabetes drugs [OADs]) with OADs alone in people with T2D was performed. Baseline and Week 24 or study endpoint lipid status (low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], non-high-density lipoprotein cholesterol [non-HDL-C] and triglycerides) and indices of glycaemic control (glycosylated haemoglobin, fasting plasma glucose [FPG]) were examined in patient groups according to treatment received and CVD status. Lipid-lowering therapy was provided at the discretion of physicians at baseline and throughout the studies.. Of the 4768 participants included in the analysis, 41% (n = 1940) received lipid-lowering therapy. Only 51% of participants with CVD (1885/3672) were treated with lipid-lowering therapy; these participants had significantly lower levels of LDL-C, HDL-C and non-HDL-C, and higher levels of triglycerides versus patients not treated with lipid-lowering therapy at baseline and study endpoint (P < 0.001 for all). Antihyperglycaemia therapy resulted in decreases in glycosylated haemoglobin (-1.4 to -1.6%) and FPG (-68.9 to -75.3 mg/dL) at Week 24. Furthermore, slight improvements in non-HDL-C (-3.9 to -9.1 mg/dL) and triglyceride levels (-25.8 to -51.2 mg/dL) were observed. Similar changes were seen irrespective of lipid-lowering therapy or CVD status.. In a T2D cohort included in Gla-100 clinical studies, many participants with T2D and CVD did not receive lipid-lowering therapy, and for most categories of lipid the levels were outside the optimal range. Even in patients treated with antihyperglycaemic therapy but not lipid-lowering therapy, there were modest improvements in non-HDL-C and triglyceride levels in all participants with T2D and CVD. There is a need for increased implementation of guideline recommendations such as American College of Cardiology/American Heart Association for the management of dyslipidaemia in patients with T2D.

Topics: Aged; Biomarkers; Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hyperlipidemias; Hypoglycemic Agents; Hypolipidemic Agents; Insulin Glargine; Lipids; Male; Middle Aged; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome

Insulin therapy in type 2 diabetes may increase mortality and cancer incidence, but the impact of different types of basal insulins on these endpoints is unclear. Compared to the traditional NPH insulin, the newer, longer-acting insulin analogues detemir and glargine have shown benefits in randomized controlled trials. Whether these advantages translate into lower mortality among users in real life is unknown.. To estimate the differences in all-cause and cause-specific mortality rates between new users of basal insulins in a population-based study in Finland.. 23 751 individuals aged ≥40 with type 2 diabetes, who initiated basal insulin therapy in 2006-2009 were identified from national registers, with comprehensive data for mortality, causes of death, and background variables. Propensity score matching was performed on characteristics. Follow-up time was up to 4 years (median 1.7 years).. 2078 deaths incurred. With NPH as reference, the adjusted HRs for all-cause mortality were 0.39 (95% CI, 0.30-0.50) for detemir, and 0.55 (95% CI, 0.44-0.69) for glargine. As compared to glargine, the HR was 0.71 (95% CI, 0.54-0.93) among detemir users. Compared to NPH, the mortality risk for both cardiovascular causes as well as cancer were also significantly lower for glargine, and especially for detemir in adjusted analysis. Furthermore, the results were robust in various sensitivity analyses.. In real clinical practice, mortality was substantially higher among users of NPH insulin as compared to insulins detemir or glargine. Considering the large number of patients who require insulin therapy, this difference in risk may have major clinical and public health implications. Due to limitations of the observational study design, further investigation using an interventional study design is warranted.

Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Cause of Death; Cohort Studies; Databases, Factual; Diabetes Mellitus, Type 2; Female; Finland; Gastrointestinal Diseases; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Neoplasms; Risk

Topics: Benzhydryl Compounds; Biosimilar Pharmaceuticals; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus, Type 2; Glucosides; Humans; Hypoglycemic Agents; Insulin Glargine

The study investigated the impact of insulin glargine exposure on cardiovascular mortality in type 2 diabetes patients with incident insulin initiation. All consecutive diabetes patients aged >40 years were screened at their first diabetes outpatient visit between 01/01/2001 and 12/31/2008 (n = 79869). Exclusion criteria restricted the cohort to 4990 incident insulin users, aged 40-79 years, who were followed up for death until 12/31/2011. Baseline was defined 6 months after insulin initiation. Adjusted time-dependent competing risk regression analysis was performed. Mean baseline age was 62 ± 9 years, with mean follow-up of 4.7 ± 1.9 years. During 23179 person-years of exposure time, there were 887 deaths (521 cardiovascular). Glargine cumulative time exposure significantly lowered overall cardiovascular, subhazard ratio (SHR) 0.963 (CI 95% 0.944-0.981, p < 0.001), and myocardial infarction mortality, SHR 0.945 (CI 95% 0.899-0.994, p = 0.028), but not stroke mortality. Glargine cumulative dose exposure (10,000 IU increments) significantly lowered cardiovascular mortality, SHR 0.977 (CI 95% 0.960-0.993, p = 0.006), but not for myocardial infarction and stroke. Both cumulative dose and time exposure to insulin glargine were associated with lower cardiovascular mortality. The effect was mostly driven by myocardial infarction end point, supporting the concept of macrovascular benefit for basal analogue insulin use in type 2 diabetes.

Topics: Adult; Aged; Cardiovascular Diseases; Cohort Studies; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Incidence; Insulin Glargine; Male; Middle Aged; Myocardial Infarction; Proportional Hazards Models; Prospective Studies; Protective Factors; Stroke; Time Factors

Cardiovascular risk factors (CVRFs) may complicate optimization of therapy in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with oral antidiabetes drugs (OADs). We assessed the influence of patient baseline CVRFs on efficacy and rate of hypoglycemia with use of insulin glargine (glargine) added to ongoing OAD treatment compared with alternative therapeutic options; namely, intensification of lifestyle interventions or adding OADs, neutral protamine Hagedorn (NPH), lispro, or premixed insulin in patients failing OADs.. Patient-level data were pooled from 9 randomized controlled trials of glargine and comparators for 24 weeks in insulin-naive patients with T2DM inadequately controlled on OADs. Efficacy (goal attainment-glycated hemoglobin (HbA1c) level ≤ 7.0% or decrease ≥ 1.0% change from baseline) and hypoglycemia rates (symptomatic, confirmed, nocturnal, or severe) were compared for patients treated with glargine (n = 1462) and pooled (n = 1476) and individual comparators, overall; and in patients with hypertension (~69%), dyslipidemia (~58%), history of cardiovascular disease (~25%), or any CVRF (~83%) at baseline.. The patient groups were well-balanced at baseline (HbA1c level 8.7%; diabetes duration, 8.6 years). Use of glargine was associated with greater patient goal attainment (57.7% vs 51.4% for HbA1c level ≤ 7.0%; P < 0.001), modestly larger reductions in HbA1c level (-1.68% vs -1.51%; P < 0.001), and less symptomatic hypoglycemia than occurred with pooled comparators, regardless of patient CVRFs (5.04 vs 7.01 events/patient-year of exposure, respectively; P < 0.001). Reductions in HbA1c level and hypoglycemia rates were significantly greater with glargine use than with intensification of OADs or lifestyle modifications, overall, and in patients with any CVRF. Reductions in HbA1c level were greater and hypoglycemia rates lower with use of glargine compared with premixed insulin, overall, and in patients with any CVRF. Reductions in HbA1c level were similar and hypoglycemia rates lower with use of glargine, NPH, and lispro insulin, regardless of patient CVRFs.. The glycemic benefits of glargine use compared with alternative therapeutic options are maintained without excess hypoglycemia in patients with CVRFs.

Topics: Aged; Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Randomized Controlled Trials as Topic; Risk Factors

Topics: Aged; Blood Glucose; Cardiovascular Diseases; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Metformin; Practice Guidelines as Topic; Precision Medicine

Topics: Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; Glucose Intolerance; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Randomized Controlled Trials as Topic; Treatment Outcome

Topics: Blood Glucose; Cardiovascular Diseases; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Germany; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Randomized Controlled Trials as Topic; Risk Factors; Treatment Outcome

Topics: Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Fatty Acids, Omega-3; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Practice Guidelines as Topic

Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Glucose Intolerance; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Patient Safety; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome

Diabetes is ultimately the result of relative or absolute insulin deficiency; insulin should therefore represent its "natural" treatment, from the very moment of diagnosis, or even earlier, such as any other hormonal deficiency. Insulin treatment, however, has been accused of the worst crimes, including that of fostering obesity, insulin resistance, atherosclerosis, and, lately, cancer. Are these charges real? Does insulin treatment truly carry in its nature the original sin of causing such terrible consequences? This unresolvable, past and present dispute has had important effects on our clinical behavior in insulin initiation in the management of Type 2 diabetes, and we all hoped that a specifically designed trial could help us on this controversy. The ORIGIN (Outcome Reduction with an Initial Glargine Intervention) trial aimed to establish whether an initial insulin treatment with glargine, as compared with standard treatments, was able to delay the onset of cardiovascular disease. Although the trial appeared negative, several viewpoints came out, alimenting the debate on how to analyze results from the ORIGIN trial and, ultimately, on the role of early insulin treatment in type 2 diabetes. In these pages we invited two experienced scientists to freely argument their interpretation of the trial, aiming to help our understanding of the consequences of the ORIGIN trial on insulin therapy.

Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Randomized Controlled Trials as Topic; Risk Factors

To investigate whether the combination of HbA1c and fasting plasma glucose (FPG) can be used for the diagnosis of diabetes and impaired glucose tolerance (IGT) in people at high risk of cardiovascular disease (CVD).. A cross-sectional study was performed on 2907 people at high risk of cardiovascular events but without a previous diagnosis of diabetes. Optimal cut-off points and the diagnostic potential of FPG, HbA1c, and their combination were determined.. The sensitivity of the usually applied FPG cut-off point of 7.0 mmol/L to diagnose diabetes mellitus was low (59.0%). Receiver operating characteristic (ROC) curve analysis indicated that the optimal cut-off points for the diagnosis of diabetes using FPG and HbA1c were 6.4 mmol/L (sensitivity 75.7%; specificity 77.5%; likelihood ratio 3.37) and 5.9% (41 mmol/mol; sensitivity 68.7%; specificity 67.1%; likelihood ratio 2.09), respectively. To diagnose IGT, the optimal cut-off points for FPG and HbA1c were 6.1 mmol/L (sensitivity 57.1%; specificity 57.9%) and 5.7% (39 mmol/mol; sensitivity 63.8%; specificity 60.3%), respectively. For diabetes, combining cut-off points for FPG and HbA1c identified four categories with likelihood ratios ranging from 5.59 to 0.21, and post-test probabilities between 69.3% and 7.8%. For IGT, likelihood ratios varied between 2.05 and 0.56, whereas post-test probabilities ranged from 84.0% to 58.8%.. Using FPG alone results in the underdiagnosis of glucometabolic abnormalities in people at high risk of CVD. Using an algorithm with both HbA1c and FPG improves the detection of diabetes, but not IGT, and could be easily implemented in patient care.

Topics: Aged; Blood Glucose; Cardiovascular Diseases; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Fasting; Female; Glucose Intolerance; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Risk Factors; ROC Curve

Topics: Aspirin; Cardiovascular Diseases; Clopidogrel; Comparative Effectiveness Research; Germany; Government Agencies; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; National Health Programs; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Ticlopidine

The OnceMix and INITIATE studies have indicated that biphasic insulin aspart 30 (BIAsp 30) is more effective than insulin glargine (IGlarg), in terms of glycohemoglobin reductions, in patients with type 2 diabetes initiating insulin therapy. The cost-effectiveness of BIAsp 30 versus IGlarg in the Chinese setting is estimated here.. The validated and peer-reviewed CORE Diabetes Model was used. The nephropathy, retinopathy, and stroke submodels were modified to incorporate available Chinese clinical data. Diabetes complication costs were derived from hospital surveys in Beijing and Chengdu. Simulated cohorts and insulin treatment effects were based on the OnceMix study for once-daily BIAsp 30 versus IGlarg and on the INITIATE study for twice-daily BIAsp 30 versus IGlarg. Life expectancy and direct medical costs were calculated. Projections were made over 30-year time horizons, with costs and life years discounted at 3% annually. Extensive sensitivity analyses were performed, including adjustments to cardiovascular risk for Chinese ethnicity.. Once-daily BIAsp 30 increased life expectancy by 0.04 years (12.37 vs. 12.33 years) and reduced direct medical costs by Chinese Yuan (CNY) 59,710 per patient (CNY 229,911 vs. CNY 289,621 per patient) compared with IGlarg in the OnceMix-based analysis. Twice-daily BIAsp 30 increased life expectancy by 0.08 years (12.99 vs. 12.91 years) and reduced direct medical costs by CNY 107,349 per patient (CNY 303,142 vs. CNY 410,491 per patient) compared with IGlarg in the INITIATE-based analysis. Improvements in life expectancy were driven by reduced incidences of most diabetes-related complications. Cost savings were attributable to lower lifetime insulin costs for BIAsp 30 compared with IGlarg in China. Lowered cardiovascular risk for Chinese ethnicity reduced the projected clinical improvements for BIAsp 30 but increased treatment-related lifetime cost savings.. BIAsp 30, either once- or twice-daily, improved projected life expectancy and reduced projected costs compared with IGlarg in the Chinese setting.

Topics: Asian People; Biphasic Insulins; Cardiovascular Diseases; China; Computer Simulation; Cost-Benefit Analysis; Diabetes Complications; Diabetes Mellitus, Type 2; Drug Costs; Female; Health Care Costs; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Models, Econometric; Quality-Adjusted Life Years; Risk

The aim of this study was to compare incidence rates of heart failure, stroke, and acute myocardial infarction (AMI) in Type 2 diabetic patients using different types of insulin.. Included were patients with a diagnosis of Type 2 diabetes and at least one insulin prescription from May 2001 to July 2007. Incidence rate ratios (RRs) of heart failure, stroke, and AMI were estimated using Poisson regression with adjustment for age, gender, history of hypertension, dyslipidemia history, days supply, and duration of diabetes.. Incidence rates of heart failure, stroke, and AMI in the insulin glargine group were 306.9 (95%CI: [278.9, 334.8]), 174.8 (95%CI: [153.7, 195.8]), and 105.2 (95%CI: [88.9, 121.5]) cases per 10,000 person-years, respectively. After adjustment for covariates, the incidence rates of CVD events in the insulin glargine were comparable to those in the other long/intermediate acting insulin group (reference), except for AMI, which tended to be lower in the insulin glargine group (RR = 0.81, 95%CI: [0.65, 1.02]). Using the same reference, the incidence rate of stroke was higher in patients taking rapid/short acting insulin, premixed insulin, or mixed use of insulin except insulin glargine (RR = 1.20, 95%CI: [1.04, 1.40]).. This study suggested that insulin glargine use might be associated with a lower risk of AMI, compared to the other long/intermediate acting insulin use, and that insulin regimen of rapid/short acting insulin, premixed insulin, or mixed use of insulin except insulin glargine was associated with a higher risk of stroke using the same reference.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Cohort Studies; Diabetes Mellitus, Type 2; Female; Heart Failure; Humans; Hypoglycemic Agents; Incidence; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Myocardial Infarction; Retrospective Studies; Stroke

In the light of a report suggesting that insulin glargine may increase cancer occurrence, the EASD asked us to perform this study.. We followed 114,841 individuals who had a prescription dispensed for insulin between 1 July and 31 December 2005. From 1 January 2006 to 31 December 2007, we noted the occurrence of malignancies. Seven different nationwide registers were used to obtain information on insulin exposure, outcome and possible confounders; these were linked using the unique personal identity number assigned to every Swedish resident.. After adjustment for age and, when appropriate, sex, users of insulin glargine alone (no other types of insulin), compared with users of types of insulin other than insulin glargine, had an RR of 1.99 (95% CI 1.31-3.03) for breast cancer, 0.93 (95% CI 0.61-1.40) for gastrointestinal cancer, 1.27 (95% CI 0.89-1.82) for prostate cancer and 1.07 (95% CI 0.91-1.27) for any type of malignancy. Adjustment for age, smoking, BMI, age at onset of diabetes, age at birth of first child, cardiovascular disease and oestrogen use gave an RR for breast cancer of 1.97 (95% CI 1.29-3.00). The 95% CIs crossed 1.0 for the RR calculated in all analyses of users of insulin glargine in combination with other types of insulin.. In Sweden, during 2006 and 2007, women using insulin glargine alone (no other types of insulin) had an increased incidence rate of breast cancer as compared with women using types of insulin other than insulin glargine. This result may be due to a random fluctuation; the possibilities for examining validity are limited, and no statistically significant results were obtained for any other individual cancer site or for the outcome 'all malignancies'. No definitive conclusions regarding a possible causal relationship between insulin glargine use and the occurrence of malignancies can be drawn from the results of this study.

Topics: Adult; Aged; Aged, 80 and over; Body Mass Index; Breast Neoplasms; Cardiovascular Diseases; Diabetes Complications; Diabetic Angiopathies; Educational Status; Female; Follow-Up Studies; Gastrointestinal Neoplasms; Humans; Hypoglycemic Agents; Incidence; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Myocardial Infarction; Neoplasms; Prostatic Neoplasms; Registries; Smoking; Sweden

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

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

We wanted to assess the effectiveness and safety of glargine in the treatment of patients with type 2 diabetes mellitus in secondary failure and/or with severe comorbidities ("T2DM group"), and patients with secondary diabetes after corticosteroid and/or anticancer treatment ("secondary DM group"). We reviewed the records of patients on glargine from 1 August 2004 to 30 July 2005. The after-minus-before change in HbA1c was the main outcome measure. At baseline, the 18 "T2DM" patients had a mean (+/-SD) age of 66.7+/-9.5 years and a diabetes duration of 13.6+/-10.3 years; 52.9% were male. Their fasting plasma glucose (FPG) decreased from 228.6+/-76.6 to 134.6+/-37.5, two-hour post-prandial glycaemia (2hPPG) from 268.2+/-10.4 to 140.6+/-30.8 and HbA1c from 10.4+/-2.3 to 7.9+/-1.6%. Mean daily insulin dosage was 12.0+/-4.8 UI for glargine alone and 37.4+/-22.6 UI for basal-bolus scheme. The daily cost was Euro 0.75 (range Euro 0.31-1.15). The 24 "secondary DM" patients had a mean age of 67.0+/-11.0 years and a diabetes duration of 3.7+/-6.5 years; 54.2% were male and 91.7% had a metastatic cancer. Their FPG decreased from 222.3+/-108.6 to 121.5+/-28.7 mg/dl, 2hPPG from 259.4+/-108.6 to 133.0+/-35.0 mg/dl and HbA1c from 10.1+/-2.5 to 7.6+/-1.3%. Mean daily insulin dosage was 12.5+/-6.1 UI for glargine alone and 27.2+/-9.1 UI for basal-bolus scheme. Mean daily cost was Euro 0.70 (range Euro 0.31-1.38). One (4.2%) cancer patient withdrew from glargine because of nausea. Nine (37.5%) cancer patients had an increase in appetite after glargine therapy, including 3 end-of-life patients. No severe hypoglycaemia occurred. Insulin glargine was safe and effective in improving glycaemic control both in severe "T2DM" and in "secondary DM" patients.

Topics: Adrenal Cortex Hormones; Aged; Antineoplastic Agents; Blood Glucose; Body Mass Index; Body Weight; Cardiovascular Diseases; Comorbidity; Diabetes Complications; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Drug Administration Schedule; Fasting; Female; Glycated Hemoglobin; Humans; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Neoplasm Metastasis; Neoplasms; Renal Insufficiency; Retrospective Studies; Treatment Outcome

Topics: Administration, Oral; Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Middle Aged; Multicenter Studies as Topic; Patient Compliance; Randomized Controlled Trials as Topic; Time Factors

Type 2 diabetes mellitus is usually preceded by impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG), which are often referred to as pre-diabetes. Individuals with IGT demonstrate beta-cell dysfunction, insulin resistance, and increased hepatic glucose production; IGT and IFG are risk factors for both diabetes and cardiovascular disease. Type 2 diabetes is associated with micro- and macrovascular complications that lead to excessive mortality and morbidity and the risk of microvascular complications extends to people with pre-diabetes. Maintaining good glycemic control in type 2 diabetes can reduce the risk of developing chronic disease-associated complications. Most individuals who develop type 2 diabetes appear to pass through a stage of IFG or IGT; thus, early intervention (lifestyle and/or pharmacologic) in individuals with pre-diabetes may help prevent cardiovascular disease and the development of type 2 diabetes.The use of exogenous insulin treatment offers the potential to reduce the cardiovascular risk in individuals with type 2 diabetes or pre-diabetes through effective reductions in blood glucose and lipid levels, and in the associated tissue damage resulting from their chronic elevations. However, there are barriers associated with insulin initiation in both type 2 diabetes and pre-diabetes (e.g. hypoglycemia, weight gain, the possible unpredictable action of long-acting insulin, and the need for injections). Insulin glargine, with its flat time-action profile, near 24-hour duration of action, reduced risk of hypoglycemia, and improved glycemic control compared with insulin suspension isophane (neutral protamine hagedorn [NPH] insulin), may help to overcome some of these barriers.Initial results from a small study have indicated the feasibility of treating individuals with pre-diabetes to near-normoglycemia using a regimen of low-dose insulin glargine plus caloric restriction. This is being followed up in the ongoing ORIGIN (Outcomes Reduction with Initial Glargine INtervention) study, which will investigate whether treatment to near-normoglycemia with insulin glargine in individuals with IGT, IFG, or new-onset type 2 diabetes can reduce cardiovascular morbidity and mortality compared with conventional management of these conditions, and whether the rate of progression to type 2 diabetes can be similarly reduced.Further studies are needed to investigate the potential benefits of insulin therapy in individuals with pre-diabetes

Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Risk Factors