ATTAIN-2: oral orforglipron for obesity in people with type 2 diabetes

ATTAIN-2 repeats the pattern seen with every incretin drug: the same doses that produce a given weight loss in people without diabetes produce less in people with it.

What the trial asked

Whether once-daily oral orforglipron reduces body weight compared with placebo in adults with type 2 diabetes and a BMI of 27 or higher.

Design

Phase 3, double-blind, placebo-controlled, 72 weeks, at 136 sites in ten countries. Randomised 1:1:1:2 to orforglipron 6 mg, 12 mg, 36 mg or placebo, after a dose-escalation phase, as an adjunct to lifestyle modification. Primary endpoint: mean percent change in body weight to week 72. The treatment-regimen estimand (all randomised participants regardless of intercurrent events) was primary; an efficacy estimand was supportive.

Who was enrolled

2859 screened between June 2023 and February 2024; 1613 randomised: 329 to 6 mg, 332 to 12 mg, 322 to 36 mg, 630 to placebo. 757 (46.9 percent) female. Entry required HbA1c 7 to 10 percent. Baseline weight 101.4 kg (SD 22.5), BMI 35.6 (SD 6.6), HbA1c 8.05 percent (SD 0.75). 1444 (89.5 percent) completed the study.

Primary endpoint and result

Treatment-regimen estimand, week 72:

All p less than 0.0001.

Key secondary results

The abstract states that all prespecified weight and cardiometabolic measures, including HbA1c, improved significantly with orforglipron, without giving values.

Adverse events and discontinuation

The most common adverse events were mild to moderate gastrointestinal events, mostly during dose escalation. Treatment discontinuation because of adverse events: 6.1 to 9.9 percent with orforglipron versus 4.1 percent with placebo. Ten deaths during the study: six on orforglipron, four on placebo. Investigators judged all unrelated to treatment except one placebo case and one 12 mg case; for the orforglipron case the abstract states no treatment-related association was reported.

Funding and registration

Eli Lilly and Company. ClinicalTrials.gov NCT05872620.

What this trial does not show

• Compare 36 mg here (-9.6 percent) with 36 mg in ATTAIN-1 (-11.2 percent). Same drug, same dose, same duration; the diabetes population lost less. The trial documents that; it does not explain it.
• No active comparator, so nothing about orforglipron against injectable GLP-1s or oral semaglutide in this population.
• HbA1c change is described as significant but not quantified in the abstract.

Where the numbers come from

PubMed abstract of the primary paper (PubMed 41275875), fetched 4 September 2026. See the weight-management versus diabetes trials guide for the pattern across STEP 2, SURMOUNT-2, REDEFINE 2 and this trial.