Effectiveness of GLP ‐1 RAs and SGLT ‐2is for Weight Loss and Glycaemic Control: An Observational Emulation of a Target Trial

ABSTRACT Aims Glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) and sodium‐glucose cotransporter‐2 inhibitors (SGLT‐2is) are both recommended as second‐line treatments for individuals with Type 2 diabetes and obesity, but long‐term head‐to‐head randomized trials in this population are lacking, necessitating a real‐world evaluation of their relative benefits in weight loss and glycaemic control. Materials and Methods Using observational data from Clalit's medical records, separate target trials were emulated comparing three GLP‐1 RAs (liraglutide, dulaglutide and semaglutide) with SGLT‐2is in individuals with Type 2 diabetes and obesity. The main outcomes were absolute changes in body weight and HbA1c during follow‐up (up to 5 years for liraglutide/dulaglutide and 3 years for semaglutide). We used inverse‐probability weighting to adjust for potential confounders. Results We identified 4296, 11 159 and 5041 eligible individuals initiating liraglutide, dulaglutide and semaglutide, respectively. Long‐term weight loss was similar (6.4–7.3 kg at 5 years) for liraglutide and dulaglutide compared with SGLT‐2is; weight loss for semaglutide was 2.6 kg (95% CI: 1.2–4.0) greater than for SGLT‐2is at 18 months. At 18 months, HbA1c reductions were 0.4% (95% CI: 0.3–0.5), 0.7% (95% CI: 0.6–0.8) and 0.6% (95% CI: 0.5–0.8) greater for liraglutide, dulaglutide and semaglutide than SGLT‐2is, respectively; this advantage was maintained throughout follow‐up. Conclusions We estimated that, compared with SGLT‐2is, liraglutide and dulaglutide provided superior glycaemic control and similar weight reduction over 5 years, and that semaglutide produced greater short‐term reductions in both outcomes. Our analyses benchmark the results of short‐term randomized trials and extend the evidence to longer periods.