Sodium–Glucose Cotransporter-2 Inhibitors Versus Glucagon-like Peptide-1 Receptor Agonists and the Risk for Cardiovascular Outcomes in Routine Care Patients With Diabetes Across Categories of Cardiovascular Disease

Cardiovascular and Renal Effectiveness of GLP-1 Receptor Agonists vs. Other Glucose-Lowering Drugs in Type 2 Diabetes: A Systematic Review and Meta-Analysis of Real-World Studies

“…In agreement with randomized controlled trials results, real-world studies confirmed that SGLT-2i were significantly more effective than GLP-1RA in the prevention of hospitalization for heart failure (HR 0.71, 95% CI 0.66-0.76, I 2 = 0%) (Figure 3D), both in patients with previous cardiovascular disease [30,31] and at low cardiovascular risk [31,33,35,36]. Despite lacking the statistical power to reliably assess the singular components of the composite cardiovascular outcome, SGLT-2i, and GLP-1RA initiators were at a similar risk of myocardial infarction (HR 0.95, 95% CI 0.83-1.10, I 2 = 60%) and stroke (HR 1.01, 95% CI 0.93-1.10, I 2 = 0%) (Figure 3E,F).…”

“…However, most real-world studies are limited by the lack of information regarding diabetes duration [17,19,20,22,31] and HbA1c levels [17][18][19]25,31], which are relevant contributors to cardiovascular risk [22], as well as other anthropometric and metabolic features. Lugner et al reported similar effects of SGLT-2i and GLP-1RA both on metabolic endpoints and cardiovascular outcomes [32]; conversely, Longato et al found a greater improvement in HbA1c in GLP-1RA vs. SGLT-2i initiators (−0.5% vs −0.4%, p = 0.001), while changes in systolic blood pressure and lipid profile significantly favored SGLT-2i users [36].…”

“…Overall, our meta-analysis found no significant difference in the risk of composite cardiovascular outcome (HR 0.97, 95% CI 0.88-1.08, I 2 = 56%) or MACE (HR 0.96, 95% CI 0.84-1.08, I 2 = 46%) in type 2 diabetic patients treated with GLP-1RA vs. SGLT-2i (Figure 3A,B). Indeed, most real-world studies showed a similar effect of GLP-1RA vs. SGLT-2i on composite cardiovascular outcomes in patients at low cardiovascular risk [17,[30][31][32][33][34][35], with the exception of the study by Longato et al, in which a 22% reduction in the incidence of MACE over a median follow-up of 13 months in SGLT-2i vs. GLP-1RA users was noted (Table 2) [36]. The Authors found that the SGLT-2i benefit was particularly clear in patients with ascertained cardiovascular disease [36].…”

“…The Authors found that the SGLT-2i benefit was particularly clear in patients with ascertained cardiovascular disease [36]. Accordingly, DeRemer et al and Patorno et al showed that SGLT-2i initiators in secondary prevention had a significantly lower risk of composite cardiovascular outcomes vs. GLP-1RA initiators [30,31]. Furthermore, SGLT-2i initiation was associated with greater protection from all-cause death (HR 0.67, 95% CI 0.57-0.79, I 2 = 87%) vs. GLP-1RA; a subgroup analysis of included studies showed that this benefit was particularly clear in patients with ascertained cardiovascular disease [31,35].…”

Comparative cardiovascular effectiveness of glucagon‐like peptide‐1 receptor agonists versus sodium‐glucose cotransporter‐2 inhibitors in patients with type 2 diabetes: A population‐based cohort study

“…[45][46][47][48] One network meta-analysis of CVOTs showed that the use of GLP-1RAs was associated with a similar risk of myocardial infarction to that of SGLT2 inhibitors. 49 Patorno et al and Pineda et al also demonstrated no material differences in the risk of myocardial infarction when comparing GLP-1RAs and SGLT2 inhibitors using US healthcare databases, [13][14][15][16] although Longato et al suggested that SGLT2 inhibitors may lower the risk of myocardial infarction compared to GLP-1RAs using Italian healthcare data. 17 In contrast to these existing Western real-world studies, [13][14][15][16][17] our study population identified from an Asian population-based database was younger (mean age 53 years).…”