A large observational study suggests additive effects on clinical outcomes.

Glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors, when used individually, each lower risk for adverse cardiorenal outcomes and mortality in patients with diabetes. But the combined effect of these drugs on such outcomes has not been studied extensively.

Using UK databases, investigators identified 6700 patients (mean age, 57 years) with longstanding diabetes who started GLP-1 agonists during an eight-year period and added SGLT-2 inhibitors either at the same time or later. These patients were matched, using propensity scores, with 6700 patients who started GLP-1 agonists and did not add SGLT-2 inhibitors. Similarly, 8900 patients who started SGLT-2 inhibitors and added GLP-1 agonists were matched with 8900 patients who started SGLT-2 inhibitors and did not add GLP-1 agonists. Median follow up for both comparisons was about nine months.

Compared with patients who took GLP-1 agonists alone, patients who took drugs from both classes had significantly lower risk for major adverse cardiovascular events and serious adverse renal events. Compared with patients who took SGLT-2 inhibitors alone, those who took drugs from both classes had significantly lower risk for major adverse cardiovascular events and nonsignificantly lower risk for serious adverse renal events. Absolute differences for the significant comparisons were roughly three events prevented per 1000 person-years.

Comment: With different and complementary mechanisms of action, these two drug classes appear to have additive beneficial effects for preventing major adverse cardiorenal events. However, in this study with average follow up shorter than one year, absolute risk reductions were small; tracking whether additive benefits increase substantially over time will be important. Finally, side effects and costs are additional relevant factors in considering simultaneous use of both drug classes.

Bruce Soloway, MD, Associate Professor Emeritus of Family and Social Medicine, Albert Einstein College of Medicine, Bronx, New York, USA.

Simms-Williams N, et al. Effect of combination treatment with glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors on incidence of cardiovascular and serious renal events: population based cohort study. BMJ 2024 Apr 25; 385: e078242.

This summary is taken from the following Journal Watch titles: General Medicine, Cardiology, Ambulatory Medicine.