Biweekly GLP-1 candidate lowers A1c in type 2 diabetes

Clinical takeaway: Bofanglutide would add something distinct to the crowded GLP-1 field if its biweekly dosing can preserve glycemic and weight benefits while improving treatment convenience. These phase 2b data are encouraging, but GI adverse effects were common, so phase 3 trials will need to confirm the best dose, tolerability, and durability before clinicians can judge its practical role.

Bofanglutide, an investigational GLP-1 receptor agonist designed for longer dosing intervals, lowered A1c in adults with type 2 diabetes in a 24-week phase 2b trial. The study compared several bofanglutide regimens, including once every 2 weeks dosing, with once weekly semaglutide 1 mg in 272 adults in China.

At week 24, A1c decreased by 1.87 to 2.28 percentage points across the biweekly bofanglutide groups, compared with 1.60 percentage points with weekly semaglutide. The largest reduction among the biweekly regimens occurred with bofanglutide 18 mg every 2 weeks.

A1c goal attainment was similar between groups. At week 24, 63% to 75% of participants receiving bofanglutide achieved an A1c below 7%, compared with 70% of those receiving semaglutide. Body weight, fasting glucose, waist circumference, lipid measures, and liver enzymes also improved across treatment groups.

The results suggest that a biweekly GLP-1 regimen may be able to deliver clinically meaningful glycemic effects, but tolerability remains a key issue. Gastrointestinal adverse events, including nausea, vomiting, decreased appetite, and diarrhea, were more common with bofanglutide than with semaglutide. Most were mild or moderate and occurred during dose escalation, but adverse events were the most common reason for trial withdrawal.

Dose selection will also be important. The 24 mg biweekly dose did not clearly outperform the 18 mg biweekly dose and was associated with poorer tolerability and more discontinuation.

“Based on an assessment of the efficacy and AEs seen in this exploratory trial, the 12 mg and 18 mg Q2W target doses have been selected for evaluation in ongoing phase 3 confirmatory trials,” the study authors concluded.

Source: Liu M, et al. (2026 June 30) Ann Intern Med. Weekly and biweekly treatment with bofanglutide versus semaglutide in Chinese patients with type 2 diabetes: a phase 2b randomized clinical trial