insulin--isophane and Myocardial-Infarction

People with type 1 diabetes mellitus (T1DM) need treatment with insulin for survival. Whether any particular type of (ultra-)long-acting insulin provides benefit especially regarding risk of diabetes complications and hypoglycaemia is unknown.. To compare the effects of long-term treatment with (ultra-)long-acting insulin analogues to NPH insulin (neutral protamine Hagedorn) or another (ultra-)long-acting insulin analogue in people with type 1 diabetes mellitus.. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Scopus, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform and the reference lists of systematic reviews, articles and health technology assessment reports. We explored the US Food and Drug Administration (FDA) and European Medical Agency (EMA) web pages. We asked pharmaceutical companies, EMA and investigators for additional data and clinical study reports (CSRs). The date of the last search of all databases was 24 August 2020.. We included randomised controlled trials (RCTs) with a duration of 24 weeks or more comparing one (ultra-)long-acting insulin to NPH insulin or another (ultra-)long-acting insulin in people with T1DM.. Two review authors assessed risk of bias using the new Cochrane 'Risk of bias' 2 (RoB 2) tool and extracted data. Our main outcomes were all-cause mortality, health-related quality of life (QoL), severe hypoglycaemia, non-fatal myocardial infarction/stroke (NFMI/NFS), severe nocturnal hypoglycaemia, serious adverse events (SAEs) and glycosylated haemoglobin A1c (HbA1c). We used a random-effects model to perform meta-analyses and calculated risk ratios (RRs) and odds ratios (ORs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, using 95% confidence intervals (CIs) and 95% prediction intervals for effect estimates. We evaluated the certainty of the evidence applying the GRADE instrument.. We included 26 RCTs. Two studies were unpublished. We obtained CSRs, clinical study synopses or both as well as medical reviews from regulatory agencies on 23 studies which contributed to better analysis of risk of bias and improved data extraction. A total of 8784 participants were randomised: 2428 participants were allocated to NPH insulin, 2889 participants to insulin detemir, 2095 participants to insulin glargine and 1372 participants to insulin degludec. Eight studies contributing 21% of all participants comprised children. The duration of the intervention varied from 24 weeks to 104 weeks. Insulin degludec versus NPH insulin: we identified no studies comparing insulin degludec with NPH insulin. Insulin detemir versus NPH insulin (9 RCTs): five deaths reported in two studies including adults occurred in the insulin detemir group (Peto OR 4.97, 95% CI 0.79 to 31.38; 9 studies, 3334 participants; moderate-certainty evidence). Three studies with 870 participants reported QoL showing no true beneficial or harmful effect for either intervention (low-certainty evidence). There was a reduction in severe hypoglycaemia in favour of insulin detemir: 171/2019 participants (8.5%) in the insulin detemir group compared with 138/1200 participants (11.5%) in the NPH insulin group experienced severe hypoglycaemia (RR 0.69, 95% CI 0.52 to 0.92; 8 studies, 3219 participants; moderate-certainty evidence). The 95% prediction interval ranged between 0.34 and 1.39. Only 1/331 participants in the insulin detemir group compared with 0/164 participants in the NPH insulin group experienced a NFMI (1 study, 495 participants; low-certainty evidence). No study reported NFS. A total of 165/2094 participants (7.9%) in the insulin detemir group compared with 102/1238 participants (8.2%) in the NPH insulin group experienced SAEs (RR 0.95, 95% CI 0.75 to 1.21; 9 studies, 3332 participants; moderate-certainty evidence). Severe nocturnal hypoglycaemia was observed in 70/1823 participants (3.8%) in the insulin detemir group compared with 60/1102 participants (5.4%) in the NPH insulin group (RR 0.67, 95% CI 0.39 to 1.17; 7 studies, 2925 participants; moderate-certainty evidence). The MD in HbA1c comparing insulin detemir with NPH insulin was 0.01%, 95% CI -0.1 to 0.1; 8 studies, 3122 participants; moderate-certainty evidence. Insulin glargine versus NPH insulin (9 RCTs): one adult died in the NPH insulin group (Peto OR 0.14, 95% CI 0.00 to 6.98; 8 studies, 2175 participants; moderate-cert. Comparing insulin detemir with NPH insulin for T1DM showed lower risk of severe hypoglycaemia in favour of insulin detemir (moderate-certainty evidence). However, the 95% prediction interval indicated inconsistency in this finding. Both insulin detemir and insulin glargine compared with NPH insulin did not show benefits or harms for severe nocturnal hypoglycaemia. For all other main outcomes with overall low risk of bias and comparing insulin analogues with each other, there was no true beneficial or harmful effect for any intervention. Data on patient-important outcomes such as QoL, macrovascular and microvascular diabetic complications were sparse or missing. No clinically relevant differences were found between children and adults.

Topics: Adolescent; Adult; Bias; Child; Child, Preschool; Confidence Intervals; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Myocardial Infarction; Quality of Life; Randomized Controlled Trials as Topic; Stroke; Young Adult

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

Recent reports have described different risks of acute myocardial infarction (AMI) in association with specific oral antidiabetic medications. The present study compared the AMI incidence rates in new users of traditional neutral protamine Hagedorn (NPH) insulin and a long-acting synthetic insulin analog for basal insulin therapy. We retrospectively examined in-patient medical claims for AMI in a cohort of oral agent-treated patients with type 2 diabetes mellitus after the initiation of basal insulin therapy with either NPH (n = 5,461) or insulin glargine (n = 14,730) in a national administrative claims database comprising >30 managed healthcare plans in the United States. Poisson regression and Cox proportional hazards regression models, as well as the propensity score methods, were used to compare the subsequent AMI incidence rates after the initiation of NPH or glargine. At a mean follow-up of 2 years, the unadjusted AMI incidence was 17.6/1,000 person-years after the initiation of NPH versus 11.5/1,000 person-years after initiation of glargine (rate ratio 1.53, 95% confidence interval 1.29 to 1.81). The Cox regression model (hazard ratio 1.39, 95% confidence interval 1.14 to 1.69) and sensitivity analyses (hazard ratio range 1.30 to 1.56) showed a greater risk of AMI in the NPH group than in the glargine group. Propensity matched (1:1) analysis yielded similar results (odds ratio 1.55, 95% confidence interval 1.23 to 1.96 for NPH vs glargine). In conclusion, these results suggest that the initiation of basal insulin therapy with NPH rather than glargine in patients with type 2 diabetes mellitus is associated with a greater risk of AMI.

Topics: Age Distribution; Confidence Intervals; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Hypoglycemic Agents; Incidence; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Poisson Distribution; Probability; Prognosis; Proportional Hazards Models; Registries; Retrospective Studies; Risk Assessment; Severity of Illness Index; Sex Distribution; Statistics, Nonparametric; United States

Topics: Diabetes Mellitus, Type 2; Drug Administration Schedule; Heart Rate; Humans; Insulin, Isophane; Myocardial Infarction; Survival Rate