Gianluigi Savarese1, Pasquale Perrone-Filardi2, Carmen D'Amore2, Cristiana Vitale3, Bruno Trimarco2, Luca Pani4, Giuseppe M C Rosano5. 1. Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy; IRCCS San Raffaele Roma, Italy. 2. Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy. 3. IRCCS San Raffaele Roma, Italy. 4. Italian Medicines Agency (AIFA), Italy. 5. IRCCS San Raffaele Roma, Italy; Cardiovascular and Cell Sciences Research Institute, St George's University, London, UK. Electronic address: giuseppe.rosano@gmail.com.
Abstract
BACKGROUND: Dipeptidyl peptidase-4 inhibitors (DPP-4is) improve glucose control in patients with type 2 diabetes mellitus (DM); however, only few studies were properly designed to evaluate their cardiovascular (CV) effects. The purpose of this study was to assess the impact of DPP-4i treatment on CV morbidity and mortality. METHODS: Randomized clinical trials enrolling more than 200 patients, comparing DPP-4 versus placebo or active treatments in patients with DM and reporting at least one event among all-cause and CV mortality, myocardial infarction (MI), stroke and new onset of heart failure (HF) were included in the analysis. RESULTS: Ninety-four trials enrolling 85,224 patients (median follow-up=29weeks) were included in the analysis. Compared to control, treatment with DPP-4i did not affect all-cause and CV mortality, as well as stroke, in the short and long terms (< and >=29weeks, respectively). DPP-4i reduced the risk of MI in the short (RR: 0.584 [95% CI: 0.361 to 0.943]; p=0.028), but not in the long term. Additionally, long-term treatment with DPP-4 was associated with a 15.8% increased risk of HF (RR: 1.158 [CI: 1.011 to 1.326]; p=0.034). No heterogeneity among studies or publication bias was detected. CONCLUSIONS: DPP4is do not affect all cause- and CV-mortality and stroke in diabetic patients; the reduction in MI observed with short-term treatment does not persist in the long term. Long-term use of DPP-4i in diabetic patients is associated with increased risk of HF.
BACKGROUND:Dipeptidyl peptidase-4 inhibitors (DPP-4is) improve glucose control in patients with type 2 diabetes mellitus (DM); however, only few studies were properly designed to evaluate their cardiovascular (CV) effects. The purpose of this study was to assess the impact of DPP-4i treatment on CV morbidity and mortality. METHODS: Randomized clinical trials enrolling more than 200 patients, comparing DPP-4 versus placebo or active treatments in patients with DM and reporting at least one event among all-cause and CV mortality, myocardial infarction (MI), stroke and new onset of heart failure (HF) were included in the analysis. RESULTS: Ninety-four trials enrolling 85,224 patients (median follow-up=29weeks) were included in the analysis. Compared to control, treatment with DPP-4i did not affect all-cause and CV mortality, as well as stroke, in the short and long terms (< and >=29weeks, respectively). DPP-4i reduced the risk of MI in the short (RR: 0.584 [95% CI: 0.361 to 0.943]; p=0.028), but not in the long term. Additionally, long-term treatment with DPP-4 was associated with a 15.8% increased risk of HF (RR: 1.158 [CI: 1.011 to 1.326]; p=0.034). No heterogeneity among studies or publication bias was detected. CONCLUSIONS: DPP4is do not affect all cause- and CV-mortality and stroke in diabeticpatients; the reduction in MI observed with short-term treatment does not persist in the long term. Long-term use of DPP-4i in diabeticpatients is associated with increased risk of HF.