Orforglipron, an oral small-molecule GLP-1 receptor agonist, for the treatment of obesity in people with type 2 diabetes (ATTAIN-2): a phase 3, double-blind, randomised, multicentre, placebo-controlled trial.
Deborah B Horn, Donna H Ryan, Sanja Giljanovic Kis et al.
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In 30 seconds
ATTAIN-2 was a 72-week, phase 3, double-blind, randomised, multicentre, placebo-controlled trial of once-daily oral orforglipron added to lifestyle modification in adults with type 2 diabetes and BMI of at least 27 kg/m². Among 1613 participants, mean bodyweight change at week 72 was -5·1%, -7·0%, and -9·6% with orforglipron 6 mg, 12 mg, and 36 mg, respectively, versus -2·5% with placebo; each dose was statistically superior to placebo. Cardiometabolic measures, including HbA1c, also improved. Gastrointestinal adverse events were common, and adverse-event-related discontinuations were more frequent with orforglipron.
Key findings
- At week 72, mean bodyweight change was -5·1% with 6 mg, -7·0% with 12 mg, and -9·6% with 36 mg, versus -2·5% with placebo.
- All prespecified weight and cardiometabolic measures, including HbA1c, improved statistically significantly with orforglipron.
- Adverse-event-related treatment discontinuations occurred in 6·1-9·9% of orforglipron groups versus 4·1% with placebo; gastrointestinal events were most common.
Why it matters
The trial provides phase 3 evidence that an oral, non-peptide GLP-1 receptor agonist can reduce bodyweight in adults with overweight or obesity and type 2 diabetes, alongside improvements in cardiometabolic measures. The dose-related weight reductions may inform evaluation of oral options for this population, while gastrointestinal effects and treatment discontinuations remain relevant when considering tolerability.
What to keep in mind
Follow-up was limited to 72 weeks, so the abstract does not establish longer-term weight outcomes or safety.