High-Dose Semaglutide: Balancing Marginal Glycemic Benefits With Tolerability Trade-Offs

We read with interest the recent report on a phase 2 trial by Aroda et al. (1), which evaluated high-dose semaglutide (up to 16 mg weekly) in individuals with type 2 diabetes and overweight or obesity. The study highlights a critical dilemma in glucagon-like peptide 1 receptor agonist therapy: the balance between incremental efficacy and tolerability when exceeding approved doses. While higher doses yielded modest glycemic improvements and greater weight loss, they also caused substantially increased gastrointestinal adverse events, underscoring the need for careful patient selection.