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

• Published in: Diabetes & metabolism 2017-02, Vol.43 (1), p.48-58
• Main Authors: Rehman, M.B, Tudrej, B.V, Soustre, J, Buisson, M, Archambault, P, Pouchain, D, Vaillant-Roussel, H, Gueyffier, F, Faillie, J.-L, Perault-Pochat, M.-C, Cornu, C, Boussageon, R
• Format: Article
• Language: English
• Subjects: Diabetes Mellitus, Type 2 - drug therapy; Dipeptidyl-Peptidase IV Inhibitors - adverse effects; Dipeptidyl-Peptidase IV Inhibitors - therapeutic use; DPP-4 inhibitors; Endocrinology & Metabolism; Endocrinology and metabolism; Human health and pathology; Humans; Internal Medicine; Life Sciences; Meta-analysis; Micro- and macrovascular complications; Mortality; Randomized clinical trials; Randomized Controlled Trials as Topic; Type 2 diabetes
• ISSN: 1262-3636; 1878-1780
• DOI: 10.1016/j.diabet.2016.09.005

Abstract Background 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. Methods A 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. Results A 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). Conclusion There 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.