Dario Giugliano1, Maria Ida Maiorino2, Miriam Longo3, Giuseppe Bellastella2, Paolo Chiodini3, Katherine Esposito4. 1. Division of Endocrinology and Metabolic Diseases, Department of Advanced Medical and Surgical Sciences, Università della Campania L. Vanvitelli, Naples, Italy. dario.giugliano@unicampania.it. 2. Division of Endocrinology and Metabolic Diseases, Department of Advanced Medical and Surgical Sciences, Università della Campania L. Vanvitelli, Naples, Italy. 3. Medical Statistics Unit, Università della Campania L. Vanvitelli, Naples, Italy. 4. Diabetes Unit, Department of Advanced Medical and Surgical Sciences, Università della Campania L. Vanvitelli, Naples, Italy.
Abstract
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 (I2 = 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.
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 (I2 = 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.
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