Efficacy and safety of insulin in type 2 diabetes: meta-analysis of randomised controlled trials

BMC Endocrine Disorders

Research Article

Michaela B. Rehman¹  Christophe Berkhout²  Rémy Boussageon³  Catherine Cornu⁴  Behrouz Kassaï⁴  François Gueyffier⁵  Francis Regnault⁶  Emilie Guérin⁶  Irène Supper⁶  Christophe Pigache⁶  Sylvie Erpeldinger⁶  Yves Zerbib⁷ 

[1] Department of Cardiology, CHU de Poitiers, 86000, Poitiers, France;Department of General Medicine, University Lille-Nord de France, Lille 2, Lille, France;Department of General Medicine, Université de Poitiers, Poitiers, France;UMR 5558, CNRS, Université Claude Bernard Lyon 1, Lyon, France;Clinical Investigation Centre, INSERM CIC1407, Lyon, France;Clinical Pharmacology and Clinical Trials Department, Hospices Civils de Lyon, Lyon, France;UMR 5558, CNRS, Université Claude Bernard Lyon 1, Lyon, France;Clinical Pharmacology and Clinical Trials Department, Hospices Civils de Lyon, Lyon, France;University college of General Medicine, University Claude Bernard Lyon 1, Lyon, France;University college of General Medicine, University Claude Bernard Lyon 1, Lyon, France;SCF SHS/S2HEP (EA 4148), University Claude Bernard Lyon 1, Lyon, France;

关键词: Meta-analysis;    Type 2 Diabetes Mellitus;    Hypoglycaemic drugs;    Insulin;    Mortality;    Morbidity;    Randomised Controlled Trials;   

DOI  :  10.1186/s12902-016-0120-z

 received in 2016-03-09, accepted in 2016-06-28,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundIt is essential to anticipate and limit the social, economic and sanitary cost of type 2 diabetes (T2D), which is in constant progression worldwide.When blood glucose targets are not achieved with diet and lifestyle intervention, insulin is recommended whether or not the patient is already taking hypoglycaemic drugs. However, the benefit/risk balance of insulin remains controversial. Our aim was to determine the efficacy and safety of insulin vs. hypoglycaemic drugs or diet/placebo on clinically relevant endpoints.MethodsA systematic literature review (Pubmed, Embase, Cochrane Library) including all randomised clinical trials (RCT) analysing insulin vs. hypoglycaemic drugs or diet/placebo, published between 1950 and 2013, was performed. We included all RCTs reporting effects on all-cause mortality, cardiovascular mortality, death by cancer, cardiovascular morbidity, microvascular complications and hypoglycaemia in adults ≥ 18 years with T2D. Two authors independently assessed trial eligibility and extracted the data. Internal validity of studies was analyzed according to the Cochrane Risk of Bias tool. Risk ratios (RR) with 95 % confidence intervals (95 % CI) were calculated, using the fixed effect model in first approach. The I2 statistic assessed heterogeneity. In case of statistical heterogeneity, subgroup and sensitivity analyses then a random effect model were performed. The alpha threshold was 0.05. Primary outcomes were all-cause mortality and cardiovascular mortality. Secondary outcomes were non-fatal cardiovascular events, hypoglycaemic events, death from cancer, and macro- or microvascular complications.ResultsTwenty RCTs were included out of the 1632 initially identified studies. 18 599 patients were analysed: Insulin had no effect vs. hypoglycaemic drugs on all-cause mortality RR = 0.99 (95 % CI =0.92–1.06) and cardiovascular mortality RR = 0.99 (95 % CI =0.90–1.09), nor vs. diet/placebo RR = 0.92 (95 % CI = 0.80–1.07) and RR = 0.95 (95 % CI 0.77–1.18) respectively. No effect was found on secondary outcomes either. However, severe hypoglycaemia was more frequent with insulin compared to hypoglycaemic drugs RR = 1.70 (95 % CI = 1.51–1.91).ConclusionsThere is no significant evidence of long term efficacy of insulin on any clinical outcome in T2D. However, there is a trend to clinically harmful adverse effects such as hypoglycaemia and weight gain. The only benefit could be limited to reducing short term hyperglycemia. This needs to be confirmed with further studies.

【 授权许可】

CC BY   
© The Author(s). 2016