For individuals with type 2 diabetes (T2DM), the long-term combined effects of lifestyle habits and glucagon-like peptide-1 (GLP-1) receptor agonists on cardiovascular outcomes remain uncertain. A prospective cohort study published in The Lancet Diabetes & Endocrinology evaluated the combined association of GLP-1 receptor agonist use and adherence to eight low-risk lifestyle habits with major adverse cardiovascular events (MACE).

The study enrolled individuals with T2DM between January 10, 2011, and September 30, 2023, who had no previous history of myocardial infarction, stroke, or advanced chronic kidney disease. Of the 963,753 veterans enrolled, 98,261 participants met the inclusion criteria. The eight low-risk lifestyle habits assessed were higher quality diet, being physically active, not smoking, restful sleep, no heavy alcohol intake, good stress management, social connection and support, and no opioid use disorder. The primary endpoint was MACE, defined as non-fatal stroke or myocardial infarction, or cardiovascular death. Cox proportional hazards regression models were used to estimate multivariable-adjusted hazard ratios.

During 632,543 person-years of follow-up, 10,443 participants developed MACE. Compared with participants adopting one lifestyle habit or fewer, those adhering to all eight low-risk lifestyle habits had a multivariable-adjusted hazard ratio of 0.40 (95% CI, 0.30-0.54). GLP-1 receptor agonist use was associated with a multivariable-adjusted hazard ratio of 0.84 (95% CI, 0.76-0.92) compared with non-use. Participants using GLP-1 receptor agonists and adhering to six to eight low-risk lifestyle habits had a hazard ratio of 0.57 (95% CI, 0.46-0.71) compared with those with three or fewer low-risk lifestyle habits and no GLP-1 receptor agonist use.

These findings indicate that adherence to low-risk lifestyle habits combined with GLP-1 receptor agonist use was associated with a greater reduction in MACE risk than either approach alone.