One of the loudest open questions in the incretin space is not how much weight these drugs can take off. We know that now. The question is what happens after, and whether the field can design a maintenance phase that is not simply the same injection forever. Gan & Lee Pharmaceuticals, a Chinese company most people outside the space have never heard of, threw an unusual answer at that question this week: switch people to one injection a month.
The company announced topline results from GRADUAL-3, a phase 3b study of bofanglutide, its long-acting GLP-1 receptor agonist, on 4 November 2026. The claim is that once-monthly dosing held the weight steady for 24 weeks after participants completed 52 weeks of fortnightly injections, while the placebo group regained.
What the Research Says
- GRADUAL-3 is the first completed phase 3b study worldwide to evaluate weight-loss maintenance with once-monthly dosing under a randomised controlled design, according to the company’s announcement.
- Participants first completed 52 weeks of once-fortnightly bofanglutide in the GRADUAL-1 trial, then were randomised by last dose (24 mg or 48 mg) to either monthly bofanglutide or monthly placebo for 24 weeks.
- Over those 24 weeks, mean body weight changed by +0.41% in the 24 mg monthly group and -0.12% in the 48 mg monthly group, against +8.52% in the placebo group, with both active arms significant versus placebo (P<0.0001).
- Monthly dosing also maintained improvements in waist circumference, blood pressure and lipids, per the topline announcement.
- Full results are slated for presentation at future scientific conferences and peer-reviewed publication, meaning none of this is citable yet beyond the press release.
Why a maintenance trial matters
The weight-regain problem is the field’s awkward truth. The STEP 1 extension showed most of the lost weight returns within about a year of stopping semaglutide, and the general read across the class is that weight trajectories follow the drug. Stopping means regaining. That pushes everyone toward indefinite treatment, which is a hard sell for cost, for injection fatigue, and for supply systems already straining under demand. Our weight regain coverage walks through that evidence base.
Most answers to this have been “take the drug longer” or “take a higher dose longer.” GRADUAL-3 is testing something structurally different: dial the frequency down rather than the efficacy down. If a monthly injection can hold weight where a placebo group regained over 8%, that is a genuine maintenance paradigm, not just a dosing convenience.
The placebo comparison is the right one to read here. An 8.52% regain over 24 weeks in the placebo arm is consistent with what the withdrawal studies elsewhere in the class have shown, which gives the between-group contrast some credibility even before the full dataset lands.
The caveats
They are substantial. Topline only means we do not have confidence intervals, no per-participant scatter, no discontinuation rates, no safety signal breakdown beyond a company statement that cardiometabolic parameters held. The population is Chinese participants with obesity or overweight, which matters for generalisability until the dataset is published. And Gan & Lee has every commercial incentive to frame 0.41% and -0.12% as equivalent outcomes when the numbers are technically different directions.
There is also the quieter question of whether bofanglutide’s long half-life is doing the work here. A monthly injection is really a slow fortnightly-equivalent drip, so the honest framing may be less “a new paradigm” and more “this compound’s pharmacokinetics let us stretch the interval.” That would still be useful, but it would be compound-specific rather than a class-level answer to maintenance.
Where this fits for Australia
Bofanglutide has no TGA presence. It is not approved, not scheduled, not under assessment, and there is no grey-market signal around it worth reporting yet. The reason to cover it is that the maintenance question is universal, and the Australian half-million-user GLP-1 population we have covered before (UNSW study) will eventually face the same after-the-drug question that GRADUAL-3 is trying to answer. Whatever works for maintenance, monthly or otherwise, is going to be relevant here, whether it arrives through the PBS or not.
Our semaglutide and retatrutide pages carry the comparator datasets for anyone who wants to see how the weight-loss numbers stack against the majors.
The Grey Highway Telegram group has a running thread on maintenance strategies and what the community is seeing on the ground.
Sources
Source: Gan & Lee Pharmaceuticals, “A New Paradigm for Long-Term Weight Management: Once-Monthly Bofanglutide Maintenance Therapy Delivers Positive Results in Weight Control and Maintenance Over 24 Weeks - GRADUAL-3 Study Meets Its Primary Endpoint”, PR Newswire, 4 November 2026: https://aapnews.aap.com.au/aapreleases/cision20261104AE87483
Source: Gan & Lee Pharmaceuticals, GRADUAL-1 trial announcement and study background (press materials referenced in the GRADUAL-3 release above).
Disclaimer: This article is for educational and informational purposes only. It does not constitute medical advice, therapeutic recommendations, or endorsements of any compound. Grey Highway is a research-education community. We do not sell, supply, or promote the use of research compounds. Always consult a qualified healthcare professional regarding health decisions. For Australian regulatory information, visit the TGA website.