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Kidney and CV Effectiveness of SGLT2 Inhibitors vs. GLP-1 RAs in Diabetes
Quick Takes
- This multicenter study reports SGLT2i and GLP-1 RAs exert many overlapping kidney and CV effects in people with T2D, although SGLT2i may lead to more improvements in eGFR.
- Given the observational nature of this study, additional clinical trials are indicated to directly compare SGLT2i and GLP-1 RAs in people with and without T2D over longer follow-up durations.
- The large amount of overlapping cardiorenal benefits from these medications in this study suggests that a combination of SGLT2i and GLP-1 RA therapy may be a consideration.
Study Questions:
What are the kidney and cardiovascular (CV) outcomes for new users of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) among people with type 2 diabetes (T2D)?
Methods:
The investigators analyzed electronic health record data from 20 US health systems contributing to PCORnet between 2015 and 2020 using propensity score overlap weighting. The primary kidney outcome was a composite of sustained 40% estimated glomerular filtration rate (eGFR) decline, incident end-stage kidney disease, or all-cause mortality over 2 years or until censoring. In addition, the authors examined CV and safety outcomes. Cox proportional hazards models were used to estimate time to first event and presented weighted incidence rates as number of first events per 1,000 patient-years of follow-up.
Results:
The weighted study cohort included 35,004 SGLT2i and 47,268 GLP-1 RA initiators. Over a median of 1.2 years, the primary outcome did not differ between treatments (hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.81-1.02), although SGLT2i were associated with a lower risk of 40% eGFR decline (HR, 0.77; 95% CI, 0.65-0.91). Risks of mortality (HR, 1.08; 95% CI, 0.92-1.27), a composite of stroke, myocardial infarction, or death (HR, 1.03; 95% CI, 0.93-1.14), and heart failure hospitalization (HR, 0.95; 95% CI, 0.80-1.13) did not differ. Genital mycotic infections were more common for SGLT2i initiators, but other safety outcomes did not differ. The results were similar regardless of chronic kidney disease status.
Conclusions:
The authors report that SGLT2i and GLP-1 RAs led to similar kidney and CV outcomes in people with T2D, though SGLT2i initiation was associated with a lower risk of 40% eGFR decline.
Perspective:
This multicenter study reports SGLT2i and GLP-1 RAs exert many overlapping kidney and CV effects in people with T2D, although SGLT2i may lead to more improvements in eGFR. Given the observational nature of this study, additional clinical trials are indicated to directly compare SGLT2i and GLP-1 RAs in people with and without T2D over longer follow-up durations. The large amount of overlapping cardiorenal benefits from these medications in this study suggests that a combination of SGLT2i and GLP-1 RA therapy may be a consideration. Furthermore, addition of the mineralocorticoid receptor antagonist finerenone may further improve cardiorenal outcomes in these patients.
Clinical Topics: Diabetes and Cardiometabolic Disease, Prevention
Keywords: Diabetes Mellitus, Type 2, Kidney Diseases, Novel Agents
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