Our aim was to compare once-weekly semaglutide to incretin-based therapies – defined as either dipeptidyl peptidase-4 inhibitors (DPP-4i) or other glucagon-like peptide-1 receptor agonist (GLP-1RA) – in patients with type 2 diabetes.

We searched for randomized trials comparing once-weekly semaglutide to other incretin-based therapies in patients with type 2 diabetes. We pooled trials that compared semaglutide to other GLP-1RA together, and those comparing semaglutide to DPP-4i together. The primary outcome was the change in haemoglobin A_1c over time.

Five trials met our inclusion criteria. There was a significantly greater reduction in haemoglobin A_1c favouring semaglutide when compared to other GLP-1RA or DPP-4i [MD (95% CI) = −0.38% (−0.62, −0.15) and −1.14% (−1.53, −0.75) respectively]. There was a significantly greater weight loss favouring semaglutide when compared to other GLP-1RA or DPP-4i [MD (95% CI) = −2.50 kg (−3.91, −1.09) and −3.19 kg (−3.66, −2.72) respectively]. The proportion of patients achieving glycaemic goals and goal weight loss was greater in semaglutide-treated patients when compared to either other GLP-1RA or DPP-4i. However, semaglutide-treated patients had a significantly higher incidence of gastrointestinal side effects.

While both once-weekly semaglutide and other incretin-based therapies can reduce haemoglobin A_1c, semaglutide causes a more potent haemoglobin A_1c reduction and greater weight loss when compared to other incretin-based therapies. However, this potent effect of semaglutide was associated with a higher incidence of gastrointestinal side effects. Additional studies are needed to determine whether this marked reduction in both haemoglobin A_1c and body weight may translate into improved cardiovascular outcomes.