Augusto Lavalle-Cobo1,2,3, Walter Masson4,5,6, Martín Lobo4,5,6,7, Gerardo Masson4,5,6,7,8, Graciela Molinero4. 1. Council of Epidemiology and Cardiovascular Prevention, Argentine Society of Cardiology, Azcuenaga 980, Buenos Aires, Argentina. augustolavallecobo@hotmail.com. 2. Cardiology Department, Sanatorio Finochietto, Av. Córdoba 2678, Buenos Aires, Argentina. augustolavallecobo@hotmail.com. 3. , 926 7B, Ayacucho, Argentina. augustolavallecobo@hotmail.com. 4. Council of Epidemiology and Cardiovascular Prevention, Argentine Society of Cardiology, Azcuenaga 980, Buenos Aires, Argentina. 5. Cardiology Department, Sanatorio Finochietto, Av. Córdoba 2678, Buenos Aires, Argentina. 6. Cardiology Department, Hospital Italiano de Buenos Aires. Tte. Gral, Juan Domingo Perón 4190, Buenos Aires, Argentina. 7. Cardiology Department, Hospital Militar Campo de Mayo. Tte. Gral. Ricchieri S/N, Buenos Aires, Argentina. 8. Cardiology Department, Instituto Cardiovascular San Isidro-Sanatorio Las Lomas, Von Wernicke 3031, San Isidro, Argentina.
Abstract
INTRODUCTION: Sodium Glucose Co-transporter 2 inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1RAs) were associated with a reduction in cardiovascular disease events in cardiovascular outcomes trials (CVOTs) in type 2 diabetes. Most of the patients included in these trials received metformin as background therapy. AIM: To evaluate the effect of glucagon-like peptide 1 receptor agonists on major cardiovascular events (MACE) and mortality in metformin-naïve patients with type 2 diabetes. METHODS: A systematic review and meta-analysis of randomized controlled clinical trials of GLP-1RAs on type 2 diabetes population was performed, after searching the PubMed/MEDLINE, Embase, Scielo, Google Scholar and Cochrane Controlled Trials databases. The primary endpoint was MACE. The secondary endpoints were cardiovascular death and all-cause mortality. A meta-analysis of time-to-event outcomes was performed. This meta-analysis was registered in PROSPERO (CRD42021260040) RESULTS: Seven trials, including 11510 patients, were identified and considered eligible for the analyses. GLP-1RAs were associated with a significant reduction in MACE incidence (HR: 0.86, 95% confidence interval: 0.79-0.94; I2: 0%). The secondary endpoints analysis showed a non-significant reduction in all-cause mortality (HR: 0.86, 95% confidence interval: 0.73-1.00 I2: 0%) and cardiovascular mortality (HR: 0.81, 95% confidence interval: 0.63-1.05; I2: 0%). CONCLUSIONS: In this meta-analysis, GLP-1RAs reduced the incidence of MACE in patients with type 2 diabetes without metformin at baseline, without significant reduction in all-cause mortality and cardiovascular mortality. These results support the fact that when a GLP-1RAs is administered, the benefit on cardiovascular outcomes is independent of the use of metformin.
INTRODUCTION: Sodium Glucose Co-transporter 2 inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1RAs) were associated with a reduction in cardiovascular disease events in cardiovascular outcomes trials (CVOTs) in type 2 diabetes. Most of the patients included in these trials received metformin as background therapy. AIM: To evaluate the effect of glucagon-like peptide 1 receptor agonists on major cardiovascular events (MACE) and mortality in metformin-naïve patients with type 2 diabetes. METHODS: A systematic review and meta-analysis of randomized controlled clinical trials of GLP-1RAs on type 2 diabetes population was performed, after searching the PubMed/MEDLINE, Embase, Scielo, Google Scholar and Cochrane Controlled Trials databases. The primary endpoint was MACE. The secondary endpoints were cardiovascular death and all-cause mortality. A meta-analysis of time-to-event outcomes was performed. This meta-analysis was registered in PROSPERO (CRD42021260040) RESULTS: Seven trials, including 11510 patients, were identified and considered eligible for the analyses. GLP-1RAs were associated with a significant reduction in MACE incidence (HR: 0.86, 95% confidence interval: 0.79-0.94; I2: 0%). The secondary endpoints analysis showed a non-significant reduction in all-cause mortality (HR: 0.86, 95% confidence interval: 0.73-1.00 I2: 0%) and cardiovascular mortality (HR: 0.81, 95% confidence interval: 0.63-1.05; I2: 0%). CONCLUSIONS: In this meta-analysis, GLP-1RAs reduced the incidence of MACE in patients with type 2 diabetes without metformin at baseline, without significant reduction in all-cause mortality and cardiovascular mortality. These results support the fact that when a GLP-1RAs is administered, the benefit on cardiovascular outcomes is independent of the use of metformin.
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