Research
Hormonal
In adults with obesity, treatment with 36 mg of orforglipron for 72 weeks led to a mean body weight reduction of -11.2%, significantly greater than the -2.1% reduction with placebo (P<0.001).
Orforglipron may be an effective treatment option for weight loss in obese adults.
StrongSupportsmedium confidence
The mean change in body weight from baseline to week 72 was -11.2% (95% CI, -12.0 to -10.4) with 36 mg of orforglipron, as compared with -2.1% (95% CI, -2.8 to -1.4) with placebo (P<0.001 for all comparisons with placebo).
Why this rating
Based on a phase 3 randomized controlled trial design.
Source
Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment
Sean Wharton et al. · New England Journal of Medicine · 2025
DOI 10.1056/nejmoa2511774
rct · n=3127Cited 69×
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
More from this paper
- 54.6% of patients in the orforglipron 36-mg group achieved a weight reduction of 10% or more, compared to 12.9% in the placebo group.Strong
- Orforglipron treatment resulted in significant improvements in waist circumference, systolic blood pressure, triglyceride levels, and non-HDL cholesterol levels compared to placebo.Strong
Related findings · Hormonal
- Initial treatment for type 2 diabetes should be a combination of metformin and either an SGLT-2 inhibitor or a GLP-1 receptor agonist to achieve cardiorenal protection, rather than monotherapy or older agents like sulfonylureas.Strong
- For patients with specific monogenic obesity syndromes (leptin deficiency, POMC/PCSK1/LEPR mutations), targeted pharmacotherapy (recombinant leptin or setmelanotide) is highly effective and should be prioritized, unlike in polygenic obesity.Strong
- Continued weekly administration of 2.4 mg subcutaneous semaglutide prevents weight regain and promotes further weight loss in adults with overweight or obesity, whereas switching to placebo results in significant weight regain.Strong
This is one finding among thousands. Every one is graded and traced to its source, so you can see what the evidence actually supports. Browse the research →