Orforglipron FDA Approval Status
Last updated by Judith Stewart, BPharm on April 18, 2025.
FDA Approved: No
Generic name: orforglipron
Company: Eli Lilly and Company
Treatment for: Type 2 Diabetes, Weight Loss (Obesity/Overweight)
Orforglipron is a nonpeptide oral glucagon-like peptide-1 (GLP-1) receptor agonist in development for the treatment of type 2 diabetes, and chronic weight management in people with obesity or overweight.
- Orforglipron is a GLP-1 receptor agonist that works in the treatment of type 2 diabetes and obesity/overweight by stimulating insulin secretion and inhibiting glucagon secretion to lower blood sugar levels. Orforglipron also works to delay gastric emptying, which positively regulates appetite and food intake, eventually leading to weight loss.
- In the Phase 2 study (NCT05048719) which evaluated the efficacy and safety of orforglipron in adults with type 2 diabetes compared to placebo and dulaglutide, orforglipron achieved mean reduction in A1C of up to 2.1% compared to 0.4% with placebo and 1.1% with dulaglutide at 26 weeks. With orforglipron, 65% to 96% of participants achieved an A1C of less than 7.0% at 26 weeks versus 64% in the dulaglutide group and 24% in the placebo group.
- In the Phase 2 study (NCT05051579) which evaluated the efficacy and safety of orforglipron compared to placebo in people with obesity or overweight with at least one weight-related comorbidity, body weight reductions for orforglipron ranged from 8.6% to 12.6% compared to 2.0% for placebo at 26 weeks, and 9.4% to 14.7% for orforglipron compared to 2.3% for placebo at 36 weeks.
- In the phase 2 studies, the safety profile of orforglipron was found to be similar to other incretin-based therapies (including GLP-1 receptor agonists), with gastrointestinal side effects reported as the most common adverse events.
- Lilly has initiated Phase 3 development programs to further study the efficacy and safety of orforglipron for the treatment of type 2 diabetes (ACHIEVE trials) and obesity/overweight (ATTAIN trials).
- In the Phase 3 ACHIEVE-1 study (NCT05971940) which compared the efficacy and safety of orforglipron 3 mg, 12 mg and 36 mg as monotherapy to placebo in adults with type 2 diabetes, orforglipron met the primary endpoint of superior A1C reduction compared to placebo at 40 weeks, lowering A1C by an average of 1.3% to 1.6% from a baseline of 8.0%, and in a key secondary endpoint, more than 65% of participants taking the highest dose of orforglipron achieved an A1C less than or equal to 6.5%. In an additional key secondary endpoint, participants taking orforglipron lost an average of 16.0 lbs (7.9%) at the highest dose. The overall safety and tolerability profile of orforglipron in ACHIEVE-1 was consistent with injectable GLP-1 therapies.
- Orforglipron is also being studied as a potential treatment for obstructive sleep apnea and hypertension in adults with obesity.
Development timeline for orforglipron
Further information
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.