Cardiovascular outcomes with GLP-1 receptor agonists vs. SGLT-2 inhibitors in patients with type 2 diabetes

Abstract

Aims We examined cardiovascular outcomes associated with initiation of GLP-1RA versus SGLT-2i treatment in a real-world setting among patients with type 2 diabetes. Methods and Results This Danish nationwide registry-based cohort study included patients with type 2 diabetes with a first ever prescription of either GLP-1RA or SGLT-2i from 2013 through 2015 with follow-up until end of 2018. All analyses were standardized with respect to age, sex, diabetes duration, comorbidity, and comedication. The main outcome was a composite of cardiovascular death, myocardial infarction, and stroke. Furthermore, the components of the composite outcome and hospitalization for heart failure were evaluated. Standardized average 3-year risks of outcomes and differences thereof were estimated using doubly robust estimation combining cause-specific Cox regression with propensity score regression. We identified 8,913 new users of GLP-1RA and 5,275 new users of SGLT-2i. The standardized 3-year risk associated with initiating GLP-1RA and SGLT-2i, respectively, was for the composite cardiovascular outcome, 5.6% (95% confidence interval (CI): 5.2–6.1) versus 5.6% (95% CI: 4.8–6.3); cardiovascular mortality, 1.6% (95% CI: 1.3–1.9) versus 1.5% (95% CI: 1.1–1.8); hospitalization for heart failure, 1.7% (95% CI: 1.5–2.0) versus 1.8% (95% CI: 1.2–2.5); myocardial infarction, 2.1% (95% CI: 1.8–2.4) versus 2.1% (95% CI: 1.5–2.6); and stroke, 2.5% (95% CI: 2.2–2.9) versus 2.6% (95% CI: 2.2–3.1). Conclusion In this nationwide study of patients with type 2 diabetes, initiating GLP-1RA versus SGLT-2i was not found to be associated with significant differences in cardiovascular risk.

SGLT2is vs. GLP1RAs Reduce Cardiovascular and All-Cause Mortality

“…In this meta-analysis we included 9 large PSM cohort studies (4)(5)(6)(7)(8)(9)(10)(11)(12). Each of included studies was assessed as high quality according to NOS.…”

Effectiveness and safety of GLP-1 receptor agonists versus SGLT-2 inhibitors in type 2 diabetes: an Italian cohort study

“…Indeed up to 2019 SGLT-2i could be prescribed only in patients with eGFR > 60 ml/min/1.73m 2 while GLP-1 RA in those with eGFR up to 30 and more recently up to 15 ml/min/1.73m 2 . To date, only Lugner et al investigated the renal composite outcome occurrence in GLP-1RA and SGLT-2i initiators, finding no significant differences between groups, even though point estimates for most kidney outcomes favoured SGLT-2i initiators [ 16 ]. Lugner et al enrolled a population with preserved renal function (eGFR > 90 ml/min/1.73m 2 ) [ 16 ], while the baseline eGFR of the patients included in the present study is unknown due to the use of claims data.…”

“…To date, only Lugner et al investigated the renal composite outcome occurrence in GLP-1RA and SGLT-2i initiators, finding no significant differences between groups, even though point estimates for most kidney outcomes favoured SGLT-2i initiators [ 16 ]. Lugner et al enrolled a population with preserved renal function (eGFR > 90 ml/min/1.73m 2 ) [ 16 ], while the baseline eGFR of the patients included in the present study is unknown due to the use of claims data. Even though the proportion of patients with advanced and or acute renal disease at baseline was similar in the two cohorts according to the well-balanced PSM, we cannot exclude that SGLT-2i initiators could have had a better baseline renal function.…”

“…Currently, there are no available headto-head randomized trials comparing the effects of GLP-1RA and SGLT-2i on CV or renal outcomes; hence, despite their recognized limitations-such as the lack of randomization, low quality control surrounding data collection, and susceptibility to multiple sources of bias for comparing outcomes [12]-real-world data may provide guidance in understanding and exploiting the specific clinical properties of these two drug classes. Indeed, several real-world studies (RWS) have been recently carried out in different countries and populations mostly focusing on CV rather than kidney outcomes [13][14][15][16][17][18][19]; these studies have suggested an overall similar benefit of GLP-1 RA and SGLT-2i on CV composite endpoints [20].…”

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

“…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].…”