Efficacy and safety of DPP-4 inhibitors in patients with type 2 diabetes: Meta-analysis of placebo-controlled randomized clinical trials

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• 作者：M.B. Rehman^a ; ^{michaela.rehman@gmail.com} ; B.V. Tudrej^b ; J. Soustre^b ; M. Buisson^c ; P. Archambault^b ; D. Pouchain^d ; H. Vaillant-Roussel^e ; ^h ; F. Gueyffier^f ; J.-L. Faillie^c ; M.-C. Perault-Pochat^g ; C. Cornu^c ; R. Boussageon^b
• 关键词：DPP-4 inhibitors ; Meta-analysis ; Micro- and macrovascular complications ; Mortality ; Randomized clinical trials ; Type 2 diabetes
• 刊名：Diabetes & Metabolism
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：43
• 期：1
• 页码：48-58
• 全文大小：3177 K
• 卷排序：43

文摘

Guidelines for type 2 diabetes (T2D) recommend reducing HbA1c through lifestyle interventions and glucose-lowering drugs (metformin, then combination with dipeptidyl peptidase-4 inhibitors [DPP-4Is] among other glucose-lowering drugs). However, no double-blind randomized clinical trial (RCT) compared with placebo has so far demonstrated that DDP-4Is reduce micro- and macrovascular complications in T2D. Moreover, the safety of DPP-4Is (with increased heart failure and acute pancreatitis) remains controversial.MethodsA systematic review of the literature (PubMed, Cochrane Library Central Register of Controlled Trials [CENTRAL] and https://clinicaltrials.gov), including all RCTs vs placebo published up to May 2015 and the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS), published June 2015, was performed. Primary endpoints were all-cause mortality and death from cardiovascular causes; secondary endpoints were macrovascular and microvascular events. Safety endpoints were acute pancreatitis, pancreatic cancer, serious adverse events and severe hypoglycaemia.ResultsA total of 36 double-blind RCTs were included, allowing analyses of 54,664 patients. There were no significant differences in all-cause mortality (RR = 1.03, 95% confidence interval [CI] = 0.95–1.12), cardiovascular mortality (RR = 1.02, 95% CI = 0.92–1.12), myocardial infarction (RR = 0.98, 95% CI = 0.89–1.08), strokes (RR = 1.02, 95% CI = 0.88–1.17), renal failure (RR = 1.06, 95% CI = 0.88–1.27), severe hypoglycaemia (RR = 1.14, 95% CI = 0.95–1.36) and pancreatic cancer (RR = 0.54, 95% CI = 0.28–1.04) with the use of DPP-4Is. However, DDP-4Is were associated with an increased risk of heart failure (RR = 1.13, 95% CI = 1.01–1.26) and of acute pancreatitis (RR = 1.57, 95% CI = 1.03–2.39).ConclusionThere is no significant evidence of short-term efficacy of DPP-4Is on either morbidity/mortality or macro-/microvascular complications in T2D. However, there are warning signs concerning heart failure and acute pancreatitis. This suggests a great need for additional relevant studies in future.