Is Biweekly Bofanglutide Better Than Weekly Semaglutide?

Managing type 2 diabetes mellitus (T2DM) effectively remains a primary challenge for healthcare providers globally. However, patients often struggle with frequent treatment regimens, highlighting the need for longer-acting options. Therefore, clinical research focuses heavily on novel glucagon-like peptide-1 receptor agonists (GLP-1 RAs) with extended dosing intervals. Specifically, this Phase 2b trial compared bofanglutide versus semaglutide in adults with type 2 diabetes.

Designing the Study for Bofanglutide Versus Semaglutide

In this multicenter, open-label, active-controlled trial, researchers evaluated 272 Chinese adults with T2DM. Initially, these participants were drug-naive or receiving stable oral antidiabetic drugs, with baseline HbA1c levels between 7.0% and 11.0%. The investigators randomly assigned participants to five distinct treatment groups. Specifically, three groups received biweekly (once every two weeks) bofanglutide titrated to targets of 12 mg, 18 mg, or 24 mg. Meanwhile, the fourth group received once-weekly bofanglutide titrated to 24 mg. Finally, the active control group received once-weekly semaglutide titrated to 1 mg.

Key Glycemic Efficacy Outcomes at Week 24

At week 24, all bofanglutide regimens demonstrated substantial reductions in HbA1c levels. For instance, biweekly bofanglutide at 12, 18, and 24 mg lowered HbA1c by 1.87%, 2.28%, and 1.94% respectively. Additionally, once-weekly bofanglutide at 24 mg achieved an impressive 2.32% reduction. In comparison, once-weekly semaglutide at 1 mg reduced HbA1c by 1.60%. Consequently, the treatment differences clearly favored the novel agent. Specifically, the 18 mg biweekly and 24 mg once-weekly bofanglutide groups achieved superior glycemic control compared to semaglutide.

Evaluating Safety, Tolerability, and Side Effects

Both drugs maintained a manageable safety profile during the 24 weeks of active treatment. However, gastrointestinal adverse events occurred more frequently with the novel agent. Specifically, these side effects affected 81.8% to 87.3% of bofanglutide participants, compared to 51.9% in the semaglutide group. Indeed, most of these events were mild or moderate and occurred during dose escalation. Furthermore, patients experienced very low rates of hypoglycemia, and no one experienced severe hypoglycemia. Therefore, the overall tolerability profile supports the continued clinical development of bofanglutide.

Clinical Implications for Practice and Future Research

These findings offer exciting prospects for diabetes care, especially regarding patient adherence. Indeed, biweekly dosing requires fewer injections, which may help patients follow this treatment plan more consistently. Additionally, the superior glucose control of bofanglutide may provide robust clinical advantages over existing options. Nevertheless, the open-label design and short duration of this trial represent important limitations. Furthermore, researchers conducted the study exclusively in Chinese participants, so we need broader global trials. Consequently, ongoing Phase 3 trials are actively evaluating bofanglutide to confirm these promising results across diverse populations.

Frequently Asked Questions

Q1: What is bofanglutide?

Bofanglutide is an investigational, long-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA) that manages type 2 diabetes and obesity. Specifically, its extended half-life allows for biweekly (once every two weeks) dosing, which offers greater convenience than standard weekly treatments.

Q2: How does the efficacy of bofanglutide compare to semaglutide?

According to the Phase 2b trial, bofanglutide demonstrated superior glycemic control compared to semaglutide. Specifically, biweekly bofanglutide at 18 mg reduced HbA1c by 2.28%, whereas weekly semaglutide at 1 mg reduced HbA1c by 1.60%.

Q3: What are the most common side effects of bofanglutide?

The most common side effects are gastrointestinal adverse events, such as nausea, diarrhea, and decreased appetite. However, these events are mostly mild to moderate and generally occur during the dose escalation phase.

References

1. Liu M et al. Weekly and Biweekly Treatment With Bofanglutide Versus Semaglutide in Chinese Patients With Type 2 Diabetes : A Phase 2b Randomized Clinical Trial. Ann Intern Med. 2026 Jun 30. doi: 10.7326/ANNALS-25-04623. PMID: 42372276.
2. Wu H et al. Efficacy and Safety of Bofanglutide (GZR18), a Biweekly GLP-1RA, Compared with Semaglutide in Chinese Patients with T2D. Diabetes. 2025;74(Supplement_1):752-P.
3. Gan & Lee Pharmaceuticals. Gan & Lee Pharmaceuticals Announced First Participant Dosed in a Phase 3 Clinical Study (OPTIMUM-2) of Bofanglutide (GZR18) injection in Chinese Patients with Type 2 Diabetes Mellitus. Published February 14, 2025.