Efficacy and safety of DPP-4 inhibitors in patients with type 2 diabetes: Meta-analysis of placebo-controlled randomized clinical trials - 04/02/17
, 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
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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 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.
Le texte complet de cet article est disponible en PDF.Keywords : DPP-4 inhibitors, Meta-analysis, Micro- and macrovascular complications, Mortality, Randomized clinical trials, Type 2 diabetes
Abbreviations : CI, EXAMINE, FDA, GLP-1, HbA1c, DPP-4I, RCT, RR, SAVOR–TIMI, TECOS, T2D
Plan
Vol 43 - N° 1
P. 48-58 - février 2017 Retour au numéro
Article précédent
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