GZGI TRIAL
Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity
Phase 2, randomized, double-blind, placebo-controlled trial
Objective:
To assess the efficacy and safety of orforglipron, an oral non-peptide GLP-1 receptor agonist, for weight reduction in adults with obesity, or with overweight plus at least one weight-related health condition, and without diabetes.
272 Patients
Inclusion Criteria:
- Age 18-75 years
- BMI ≥30 kg/m², BMI ≥27 kg/m² and <30 kg/m² with at least 1 weight-related comorbidity
Exclusion Criteria:
- Diabetes
- Prior surgical treatment for obesity
- eGFR <30
- Pancreatitis
- Severe psychiatric disorders (except stable MDD or generalized anxiety disorder)
Groups:
- Orforglipron (12, 24, 36, or 45 mg): n = 222
- Placebo: n = 50
Primary Outcome:
- The mean change from baseline in body weight at week 26 (%):
- Orforglipron: -8.6 to -12.6%
- Placebo: -2.0%
Secondary Outcomes:
- The mean change from baseline in body weight at week 36 (%):
- Orforglipron: -9.4 to -14.7%
- Placebo: -2.3%
- Weight reduction of at least 10% by week 36 (%):
- Orforglipron: 46 to 75%
- Placebo: 9%
Conclusion:
Daily oral orforglipron, a nonpeptide GLP-1 receptor agonist, was associated with weight reduction. Adverse events reported with orforglipron were similar to those with injectable GLP-1 receptor agonists.