Comparing cardiovascular benefits between GLP-1 receptor agonists and SGLT2 inhibitors as an add-on to metformin among patients with type 2 diabetes: A retrospective cohort study

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).…”

“…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].…”

Commentary: SGLT2is vs. GLP1RAs reduce cardiovascular and all-cause mortality

“…In this updated meta-analysis, we included a total of eighteen large cohort studies ( 2 – 19 ). We identified that compared with GLP1RAs, SGLT2is were associated with a 10% increase in risk of stroke (HR 1.10, 95% CI 1.01–1.19; P for effect size = 0.04; Figure 1A ), a 21% reduction in risk of HHF (HR 0.79, 95% CI 0.71–0.88; P for effect size <0.01; Figure 1B ), and a 17% reduction in risk of CKO (HR 0.83, 95% CI 0.70–0.99; P for effect size = 0.04; Figure 1C ).…”

“…By implementing a meta-analysis ( 1 ) based on nine large cohort studies ( 2 – 10 ) directly comparing cardiovascular and renal endpoints between sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists (GLP1RAs) in patients with type 2 diabetes (T2D), Qiu et al ( 1 ) identified an interesting and clinically relevant finding that compared with GLP1RAs, SGLT2is were associated with significantly decreased risks of cardiovascular death (CVDH) [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.68–0.99] and all-cause mortality (ACM) (HR 0.92, 95% CI 0.85–0.99). Nowadays, nine new relevant cohort studies ( 11 – 19 ) are available and yield some inconsistent findings. For example, the studies by Fu et al ( 11 ) and Ueda et al ( 12 ) show similar risk of CVDH between SGLT2is and GLP1RAs, while the studies by Alkabbani et al ( 13 ) and Tang et al ( 14 ) show similar risk of ACM.…”