A complete breakdown of the ATTAIN and ACHIEVE Phase 3 programs — what was studied, what the data showed, and what it means for patients.
Orforglipron has been studied in two major Phase 3 programs: ATTAIN (focused on obesity) and ACHIEVE (focused on type 2 diabetes). Together these programs enrolled thousands of patients across dozens of countries and generated the data underpinning Lilly's NDA submission.
| Trial | Population | Duration | Key Result | Published |
|---|---|---|---|---|
| ATTAIN-1 | Obesity, no diabetes (n=3,127) | 72 weeks | 12.4% weight loss (36mg) | NEJM, Sep 2025 |
| ATTAIN-2 | Obesity + type 2 diabetes (n=1,600+) | 72 weeks | 10.5% weight loss (36mg) | Lancet, Nov 2025 |
| ATTAIN-MAINTAIN | Post-injectable weight maintenance | 52 weeks | Maintained prior weight loss | Announced Dec 2025 |
| ACHIEVE-1 | Type 2 diabetes | 40 weeks | Significant A1C reduction | NEJM, Jun 2025 |
| ACHIEVE-3 | T2D vs. oral semaglutide | — | Superior to oral semaglutide | Sep 2025 |
The pivotal obesity trial enrolled 3,127 adults with obesity or overweight plus at least one weight-related condition (hypertension, dyslipidemia, sleep apnea, or cardiovascular disease) who did not have diabetes. Participants received once-daily orforglipron at 6mg, 12mg, or 36mg, or placebo, alongside diet and physical activity guidance for 72 weeks.
Primary result: All three doses met the primary endpoint of superior weight reduction vs. placebo. At the highest 36mg dose, participants lost an average of 12.4% of their body weight (27.3 lbs) compared to 0.9% with placebo. 59.6% of participants on 36mg lost at least 10% of body weight; 39.6% lost at least 15%.
| Dose | Avg. Weight Loss | ≥10% Achieved | ≥15% Achieved | ≥20% Achieved |
|---|---|---|---|---|
| Placebo | -0.9% (-2.2 lbs) | 12.9% | 5.9% | 2.8% |
| 6 mg | -7.5% | — | — | — |
| 12 mg | -8.4% | — | — | — |
| 36 mg | -11.2% to -12.4% | 54.6–59.6% | 36–39.6% | 18.4% |
Notable finding: Among the 1,127 participants who had prediabetes at the start of the study, up to 91% of those taking orforglipron achieved near-normal blood sugar levels, compared to 42% of those taking placebo. This suggests a meaningful diabetes prevention benefit.
ATTAIN-2 studied orforglipron in over 1,600 adults with both obesity and type 2 diabetes. The highest dose (36mg) produced 10.5% weight loss (22.9 lbs) compared to 2.2% with placebo. A1C was reduced by 1.8 percentage points at the highest dose, with 85.1% of participants achieving an A1C below 7%, compared to 23% on placebo.
This innovative trial addressed one of the most pressing questions in obesity medicine: when patients stop taking injectable GLP-1 drugs, they typically regain most of their weight. Could orforglipron serve as a lower-cost, easier oral maintenance therapy?
Participants who had completed 72 weeks on injectable Wegovy or Zepbound (from the SURMOUNT-5 head-to-head trial) were switched to orforglipron or placebo for 52 weeks. The result: patients who switched from Wegovy to orforglipron maintained all but 0.9 kg of their prior weight loss — essentially holding their results. Placebo patients regained 9.4 kg over the same period.
This positions orforglipron as a potentially valuable step-down maintenance therapy — patients could achieve significant weight loss on more powerful injectables, then switch to the more convenient and affordable oral pill to maintain results long-term.
The ACHIEVE program evaluated orforglipron specifically for blood sugar control in type 2 diabetes. ACHIEVE-1 results published in the NEJM in June 2025 showed significant A1C reductions across all doses. ACHIEVE-3, announced in September 2025, was a direct head-to-head comparison against oral semaglutide (Rybelsus) — orforglipron demonstrated superior results, providing strong evidence for its potential as a first-line oral diabetes therapy without the dosing restrictions of Rybelsus.