M B Rehman1, B V Tudrej2, J Soustre2, M Buisson3, P Archambault2, D Pouchain4, H Vaillant-Roussel5, F Gueyffier6, J-L Faillie3, M-C Perault-Pochat7, C Cornu3, R Boussageon2. 1. Cardiology department, CHU de Poitiers, 2, rue de la Milétrie, 86000 Poitiers, France. Electronic address: michaela.rehman@gmail.com. 2. Department of General Practice, Faculty of Medicine, 6, rue de la Milétrie, 86000 Poitiers, France. 3. Inserm, CIC1407, CHU Lyon, 69000 Lyon, France. 4. Department of General Practice, University François Rabelais, 37000 Tours, France. 5. Department of General Practice, Faculty of Medicine of Clermont-Ferrand University, 28, place Henri-Dunant, 63000 Clermont-Ferrand, France; Investigation Center, INSERM CIC 1401, Clermont-Ferrand University Hospital, 58, rue Montalembert, 63000 Clermont-Ferrand, France. 6. UMR 5558, laboratoire de biométrie et biologie évolutive, Claude-Bernard Lyon 1 University, CNRS, 69000 Lyon, France. 7. Inserm CIC-1402, CHU de Poitiers, 86021 Poitiers, France.
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.
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.
Authors: Stacey A Seggelke; Mark C Lindsay; Ingrid Hazlett; Rebecca Sanagorski; Robert H Eckel; Cecilia C Low Wang Journal: Curr Diab Rep Date: 2017-08 Impact factor: 4.810
Authors: Stephen J Greene; Muthiah Vaduganathan; Muhammad Shahzeb Khan; George L Bakris; Matthew R Weir; Jonathan H Seltzer; Naveed Sattar; Darren K McGuire; James L Januzzi; Norman Stockbridge; Javed Butler Journal: J Am Coll Cardiol Date: 2018-03-10 Impact factor: 24.094