Effect of adding GLP-1RA on mortality, cardiovascular events, and metabolic outcomes among insulin-treated patients with type 2 diabetes: A large retrospective UK cohort study

Background Combining a GLP-1 receptor agonist (GLP-1RA) with insulin is often an effective treatment strategy for overweight patients with type 2 diabetes (T2D), but little is known about the longer-term effects on cardiovascular and mortality outcomes in routine clinical practice in the United Kingdom. We therefore compared the times to a major nonfatal cardiovascular (CV) event and all-cause mortality among overweight patients with T2D treated with insulin alone versus insulin + GLP-1RA in a large UK database. Methods A retrospective cohort study was conducted in 18,227 patients with insulin-treated T2D from UK General Practices using The Health Improvement Network database. The 5-year risk of mortality and a 3-point composite of all-cause mortality and nonfatal CV outcomes (myocardial infarction or stroke) was compared between a propensity score-matched cohort of those on insulin alone (n = 1,793) and insulin + GLP-1RA (n = 1,793), irrespective of other diabetes therapies, providing a total of 12,682 person-years of follow-up. Cox proportional hazard models were used to estimate the hazard ratios of the outcomes. Results Hemoglobin A1c reduction was similar between both groups (-0.42 vs -0.33%, P = .089 at 12 months). Overall, 3-point composite events of all-cause mortality and CV events (major adverse cardiovascular even) were 98 versus 55 for the insulin alone versus insulin + GLP-1RA groups, respectively (14.7 vs 9.2 per 1,000 person-years; adjusted hazard ratio [aHR]: 0.64; 95% CI: 0.42-0.98; P = .038). Corresponding composite nonfatal CV events were 33 versus 28 (6.0 vs 5.6 per 1,000 person-years; aHR: 0.76; 95% CI: 0.41-1.42; P = .393), whereas all-cause mortality events were 49 versus 13 (6.9 vs 2.0 per 1,000 person-years; aHR: 0.35; 95% CI: 0.17-0.73; P = .005). Conclusion Based on a large UK cohort in routine clinical practice, adding a GLP-1RA to insulin therapy is associated with a reduction in risk of composite CV events and all-cause mortality but a nonsignificant higher risk of hospitalization for heart failure in overweight patients with T2D.