Biweekly glucagon-like peptide-1 receptor agonist bofanglutide improves glycemic control
1. In this randomized controlled trial, biweekly injections of the novel glucagon-like peptide-1 receptor agonist (GLP-1RA) bofanglutide resulted in greater reductions in hemoglobin A1c (HbA1c) compared with semaglutide in patients with type 2 diabetes mellitus (T2DM).
2. Both treatments were associated with improvements in fasting plasma glucose, body weight, body mass index (BMI), and waist circumference.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Despite improvements in glycemic control, weight loss, and cardiovascular and renal outcomes in patients with type 2 diabetes mellitus (T2DM), current glucagon-like peptide-1 receptor agonist receptor agonists (GLP-1RA) are often limited by a therapeutic gap related in part to the requirement for frequent injections. Bofanglutide is a GLP-1 analogue designed to enable extended dosing intervals. This study evaluated the feasibility and efficacy of high-dose bofanglutide administered once every two weeks for glycemic control in Chinese patients with T2DM and overweight or obesity. Adherence was high in both the bofanglutide and semaglutide groups. Bofanglutide was associated with greater reductions in hemoglobin A1c (HbA1c) compared with semaglutide, particularly among participants not receiving stable oral antidiabetic therapy. Similar proportions of participants in both groups achieved glycemic targets, and both treatments were associated with improvements in fasting plasma glucose, body weight, body mass index (BMI), waist circumference, and other metabolic parameters. Adverse events were common in both groups but were generally mild. Gastrointestinal adverse events, including nausea, vomiting, decreased appetite, and diarrhea, were more frequent with bofanglutide, though they remained mild and typically occurred following dose escalation. The generalizability of these findings is limited by the open-label design, short follow-up duration, restriction to Chinese participants, and absence of formal hypothesis testing or sample size calculation. Nevertheless, these results suggest that bofanglutide may offer improved glycemic outcomes while potentially enhancing treatment convenience through extended dosing intervals.
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In-Depth [randomized controlled trial]: This randomized controlled trial evaluated the feasibility and efficacy of biweekly bofanglutide compared with weekly semaglutide in adults with T2DM across 37 sites in China. Eligible participants were aged 18 to 75 years with T2DM duration ≥3 months, HbA1c 7.0%-11.0%, and BMI ≥18.5 kg/m². Participants were randomized to bofanglutide titrated to 12, 18, or 24 mg biweekly, bofanglutide 24 mg weekly, or semaglutide 1 mg weekly. The primary endpoint was change in HbA1c at week 24. A total of 272 participants were randomized and received at least one dose. Mean age was 50.8 years, 61.0% were male, mean BMI was 27.9 kg/m², mean HbA1c was 8.35%, and mean diabetes duration was 4.3 years. About half received stable oral antidiabetic drugs. Adherence was high across all groups, with nearly all participants maintaining ≥80% dosing compliance. Overall, 75.7% completed the trial. All treatment arms achieved meaningful HbA1c reductions at week 24. Mean HbA1c change with bofanglutide ranged from -1.87% to -2.32%, compared with -1.60% for semaglutide. Treatment differences versus semaglutide ranged from -0.27% to -0.72%. Sensitivity analyses confirmed these findings. Subgroup analyses showed greater HbA1c reductions in drug-naïve participants than in those on background oral therapy. Similar proportions achieved HbA1c targets across groups, including <7.0% (63%-75% vs 70%) and ≤6.5% (58%-69% vs 62%). All groups also showed reductions in fasting glucose, body weight, BMI, waist circumference, lipid parameters, and 7-point glucose profiles. Treatment-emergent adverse events occurred in 97.0% overall (97.7% bofanglutide vs 94.4% semaglutide), were mostly grade 1-2, and primarily gastrointestinal. Discontinuation due to adverse events ranged from 7.5% to 18.5% with bofanglutide and 14.8% with semaglutide. No deaths occurred. Gastrointestinal events were more frequent with bofanglutide, particularly during early dose escalation. Overall, biweekly bofanglutide achieved greater HbA1c reductions than semaglutide and was generally well tolerated, supporting its potential as an extended-interval GLP-1 receptor agonist in T2DM.
Image: PD
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