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Randomized controlled trial

ATTAIN-1: orforglipron, a daily GLP-1 pill, for obesity

Orforglipron, an oral small-molecule GLP-1 receptor agonist, reduced weight at 72 weeks by 11.2% with 36 mg (95% CI, −12.0 to −10.4), 8.4% with 12 mg (95% CI, −9.1 to −7.7) and 7.5% with 6 mg (95% CI, −8.2 to −6.8), compared with 2.1% on placebo (95% CI, −2.8 to −1.4).

Wharton S et al. Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment. New England Journal of Medicine, 2025. DOI: 10.1056/NEJMoa2511774

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Key facts

Drug
orforglipron
Design
Randomized controlled trial
Participants
3,127
Duration
72 weeks
Funding
Eli Lilly
Registry
NCT05869903
Population
3,127 adults with obesity (or overweight with at least one weight-related complication), without diabetes.
Primary outcome
Percentage change in body weight at 72 weeks with oral orforglipron 6, 12 or 36 mg daily versus placebo.

What it found

Mean weight loss, % of starting weight · 72 weeks
  • Orforglipron 6 mg daily (oral)95% CI, −8.2 to −6.8−7.5%
  • Orforglipron 12 mg daily (oral)95% CI, −9.1 to −7.7−8.4%
  • Orforglipron 36 mg daily (oral)95% CI, −12.0 to −10.4−11.2%
  • Placebo95% CI, −2.8 to −1.4−2.1%

Difference (Orforglipron 6 mg daily (oral)): −5.4 points vs placebo (subtraction).

Difference (Orforglipron 12 mg daily (oral)): −6.3 points vs placebo (subtraction).

Difference (Orforglipron 36 mg daily (oral)): −9.1 points vs placebo (95% CI, −10.1 to −8.1).

Figures from the paperSee the results in a chart

Orforglipron, an oral small-molecule GLP-1 receptor agonist, reduced weight at 72 weeks by 11.2% with 36 mg (95% CI, −12.0 to −10.4), 8.4% with 12 mg (95% CI, −9.1 to −7.7) and 7.5% with 6 mg (95% CI, −8.2 to −6.8), compared with 2.1% on placebo (95% CI, −2.8 to −1.4). The difference versus placebo with 36 mg was −9.1 percentage points (95% CI, −10.1 to −8.1). The drug was started at 1 mg and increased every 4 weeks up to the assigned dose. The most common adverse effects were digestive.

Limitations

Funded by Eli Lilly. Weight loss is smaller than with the weekly injectables, although they were not compared directly. The trial doses (6, 12 and 36 mg) do not match the dose strengths on the label of the product approved in the United States in 2026 (Foundayo: 5.5, 9 and 17.2 mg), which the FDA treats as equivalent to the trial doses.

What it means for you

ATTAIN-1 showed that orforglipron, a daily GLP-1 pill, reduced weight by an average of 11.2% at the highest dose over 72 weeks, compared with 2.1% on placebo. Figures from different trials cannot be compared directly with those of the injectables. If you are interested in an oral option, talk to your doctor.

Further reading

Related trials

  • orforglipron52 weeks

    ATTAIN-MAINTAIN

    On orforglipron, 74.7% of the weight lost on tirzepatide was maintained, versus 49.2% on placebo.

  • orforglipron72 weeks

    ATTAIN-2

    At 72 weeks, weight changed by −9.6% with orforglipron 36 mg, −7.0% with 12 mg and −5.1% with 6 mg, compared with −2.5% on placebo.

  • orforglipron40 weeks

    ACHIEVE-2

    At 40 weeks, HbA1c fell by 1.23, 1.50 and 1.56 points with orforglipron 3, 12 and 36 mg, compared with 0.81 on dapagliflozin.

  • orforglipron and semaglutide52 weeks

    ACHIEVE-3

    HbA1c fell by 1.71 and 1.91 points with orforglipron 12 and 36 mg, and by 1.23 and 1.47 points with oral semaglutide 7 and 14 mg.

Sources

The original paper and the records consulted for this summary, with the date they were accessed.

  1. New England Journal of Medicine.Wharton S, et al. Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment. N Engl J Med. 2025;393(18):1796-1806.accessed .
  2. National Library of Medicine (PubMed).PubMed record PMID 40960239 (abstract).accessed .