In a meta-analysis, tirzepatide ranked first, and semaglutide was second, for both indications among FDA-approved agents. 

Six glucagon-like peptide-1 (GLP-1) receptor agonists are US Food and Drug Administration approved for managing diabetes; three of these also have been approved for obesity and overweight. However, few trials have compared different GLP-1 receptor agonists. Now, researchers have conducted a network meta-analysis of 76 randomised trials of approved and investigational GLP-1 receptor agonists compared with placebo or each other; 39,000 adults with type 2 diabetes, followed for 12 weeks or longer, were included.

• Tirzepatide, a combined GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist, was the most-effective approved agent for both indications, with mean differences of −2.1% in glycosylated haemoglobin (HbA_1c), −3.11mmol/L in fasting blood glucose and −8.5kg in body weight compared with placebo.
• Semaglutide was second most effective for both indications, with mean differences of −1.4% in HbA_1c, −2.00 mmol/L in fasting blood glucose and −3.1kg in body weight.
• The most-effective agent for weight loss overall was an investigational combination of semaglutide and the amylin analog cagrilintide, which yielded a mean 14.0 kg lower body weight than placebo.
• Most available agents had similar adverse effect profiles, with gastrointestinal effects predominating.

Comment: Tirzepatide is the most effective currently available GLP-1 receptor agonist for both glycaemic control and weight loss in the short and intermediate term; long-term efficacy and safety are still open questions. Future agents in this class might leverage additional mechanisms of action for greater efficacy.

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

Yao H, et al. Comparative effectiveness of GLP-1 receptor agonists on glycaemic control, body weight, and lipid profile for type 2 diabetes: systematic review and network meta-analysis. BMJ 2024; 384: e076410.

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