Type 2 diabetes and risk of heart failure: a systematic review and meta-analysis from cardiovascular outcome trials

Aim: We performed a meta-analysis of randomized controlled trials (RCTs) that evaluated the effect of dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and sodium glucose co-transporter-2 inhibitors (SGLT-2i) on heart failure (HF) risk in patients with type 2 diabetes (T2D). Methods and results: The electronic search was carried out until 10 November 2018. RCTs were included if they compared add-on therapy with any DPP-4i, GLP-1 RAs, or SGLT-2i with placebo, and included in the outcome hospitalization for HF, and other outcomes required for cardiovascular safety studies. Risk of HF was the primary outcome for this meta-analysis. We used a random-effect model to calculate hazard ratio (HR) and 95% CI. Twelve trials were identified, involving 120,765 patients. Compared with placebo, HF risk showed a non-significant 10% reduction with the newer anti-hyperglycemic drugs (HR = 0.90, 0.80–1.01); use of DPP-4i and GLP-1 RAs was associated with nonsignificant modifications of the HF risk (+5% and −9%, respectively), while the use of SGLT-2i was associated with a significant 31% reduction of the HF risk (HR = 0.69, 0.61–0.79, P < 0.001), with no heterogeneity (I 2 = 0%, P = 0.741), suggesting a class effect. The meta-regression analysis of all 12 trials showed no association of reductions of hemoglobin A1C with HF risk. Conclusion: In T2D, SGLT-2i can reduce the risk of HF that is unrelated to improved glycemic control; DPP-4i and GLP-1 RAs behave as neutral.