Oral Aleniglipron Delivers 11% Weight Loss in Phase 2b
Bristol Myers Squibb’s small-molecule GLP-1 agonist aleniglipron produced double-digit weight loss in the 36-week Phase 2b ACCESS trial.
Oral Aleniglipron Delivers 11% Weight Loss in Phase 2b
In the 36-week Phase 2b ACCESS trial, once-daily aleniglipron — an oral small-molecule GLP-1 receptor agonist — reduced body weight by up to 11.3 % versus placebo in adults with obesity or overweight and at least one comorbidity.(nature.com)
Last updated August 2026
- Drug class: oral small-molecule GLP-1 receptor agonist
- Developer: Bristol Myers Squibb
- Phase 2b weight loss: −8.2 % to −11.3 % placebo-adjusted at 36 weeks(nature.com)
- Maintenance doses studied: 45 mg, 90 mg, 120 mg once daily
- Most common side effects: nausea, diarrhea, vomiting, constipation
- ClinicalTrials.gov identifier: NCT06693843
- Aleniglipron achieved double-digit, dose-dependent weight loss without plateau at 36 weeks.(nature.com)
- Gastrointestinal side effects were mostly mild or moderate and tended to diminish over time.(nature.com)
- The oral, non-peptide structure could lower manufacturing costs and eliminate injections.
- Phase 3 trials will start participants at 2.5 mg to further improve tolerability.
What Is Aleniglipron and How Does It Work?
Aleniglipron (code name GSBR-1290) is a potent, highly selective small-molecule agonist of the glucagon-like peptide-1 (GLP-1) receptor. Unlike peptide-based GLP-1 drugs that must be injected or co-formulated with absorption enhancers, aleniglipron is chemically stable, readily absorbed, and can be taken as a once-daily tablet. By activating the GLP-1 receptor, it boosts insulin secretion, slows stomach emptying, and reduces appetite, leading to lower calorie intake and weight loss.(nature.com)
How Much Weight Loss Did the Phase 2b Trial Show?
The double-blind ACCESS study randomized 230 adults (mean BMI 39.5 kg/m2) to one of three aleniglipron doses or placebo over 36 weeks. The least-squares mean placebo-adjusted percentage change in body weight was:
| Dose | Mean weight loss vs. placebo | Absolute kg change | Participants achieving ≥10 % loss |
|---|---|---|---|
| 45 mg | −8.2 % | −9.2 kg | 46 % |
| 90 mg | −9.8 % | −11.0 kg | 58 % |
| 120 mg | −11.3 % | −12.4 kg | 70 % |
| Placebo | −0.0 % | −0.9 kg | 7 % |
No plateau was seen at week 36, and an interim read-out of the open-label extension showed continued weight loss to week 56 (up to 16.2 % at 90 mg).(nature.com)
Is Aleniglipron Safe and Tolerable?
Adverse events (AEs) were typical for the GLP-1 class and primarily gastrointestinal. Most occurred during early dose escalation and declined thereafter.
| Adverse event | Aleniglipron (all doses) n = 188 | Placebo n = 42 |
|---|---|---|
| Nausea | 34 % | 20 % |
| Diarrhea | 21 % | 14 % |
| Vomiting | 12 % | 5 % |
| Constipation | 11 % | 5 % |
| Discontinuation due to AEs | 10.4 % | 4.8 % |
| Serious AEs | 3.2 % | 5.4 % |
No drug-induced liver injury, pancreatitis, thyroid cancer, or major cardiovascular events were reported. Heart-rate increases (2–3 beats per minute) were small and consistent with other GLP-1 therapies.(nature.com)
How Does Aleniglipron Compare With Other Oral GLP-1 Drugs?
Head-to-head trials are lacking, but published studies provide useful context:
- Orforglipron delivered −10.5 % weight loss at 36 weeks and −12.4 % at 72 weeks in Phase 3 studies.(nejm.org)
- semaglutide">Oral semaglutide (approved for diabetes) produces roughly −3–5 % weight loss at the 14 mg dose.(nejm.org)
Aleniglipron’s 11 % reduction positions it competitively with peptide injectables such as semaglutide 2.4 mg subcutaneous (−15 %) and liraglutide 3 mg (−8 %). However, differences in study design, population, and duration mean indirect comparisons should be interpreted cautiously.(nature.com)
What Are the Next Steps in Development?
Bristol Myers Squibb plans a global Phase 3 program starting later in 2026. Key design features include:
- Starting dose 2.5 mg with slower titration to improve GI tolerability
- Primary endpoint: percent change in body weight at 68 weeks, aligning with FDA chronic weight-management guidance
- Cardiovascular outcomes trial to begin in 2027
Regulatory submissions are targeted for 2029 if Phase 3 is successful.
Who Might Benefit From Oral Small-Molecule GLP-1 Therapy?
Oral options like aleniglipron could suit you if you:
- Prefer tablets over injections
- Have obesity (BMI ≥ 30 kg/m2) or BMI ≥ 27 kg/m2 with a weight-related condition such as hypertension or sleep apnea
- Need a treatment that is easy to store and travel with (no refrigeration)
- Seek a medication potentially less expensive to manufacture at scale
When to Contact Your Healthcare Provider
- Severe or persistent nausea, vomiting, or abdominal pain
- Signs of dehydration (dizziness, dry mouth, reduced urination)
- Sudden vision changes
- Rapid heartbeat or palpitations
- Yellowing of skin or eyes (possible liver injury)
- Thoughts of self-harm or severe mood changes
- Rosenstock J, Lingvay I, Ryan D et al. Oral small-molecule GLP-1 receptor agonist aleniglipron in people with overweight or obesity: a randomized, double-blind, placebo-controlled Phase 2b trial. Nature Medicine. Published June 5 2026.(nature.com)
- Wharton S, Calanna S, Zanchi D et al. Daily oral GLP-1 receptor agonist orforglipron for adults with obesity. N Engl J Med. 2023;389:1338-1349.(nejm.org)
- Hartman M L et al. Orforglipron, an oral small-molecule GLP-1 receptor agonist, in early type 2 diabetes. N Engl J Med. 2025;392:1124-1135.(nejm.org)
- U.S. Food and Drug Administration. Prescription drugs for the treatment of obesity: guidance for industry. February 2023.(nature.com)
- ClinicalTrials.gov. Study of aleniglipron in adults with obesity or overweight (ACCESS). Identifier NCT06693843. Accessed August 2026.
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