Two trials, two names
The label calls them Trial 1 (NCT05869903) and Trial 2 (NCT05872620). On ClinicalTrials.gov, the US public trial registry, Eli Lilly and Company lists them as the phase 3 studies ATTAIN-1 and ATTAIN-2 [1][2][3].
The label adds a technical note: the trials used an investigational formulation of orforglipron, and the results are shown as the equivalent once-daily Foundayo™ doses. That is why the tables speak of 5.5 mg, 9 mg and 17.2 mg [1].
Same trial, two sets of numbers
If you read the published ATTAIN-1 paper next to the label, the doses and some figures look different. The paper reports the trial doses of 6, 12 and 36 mg, which the label converts into Foundayo™ tablet strengths; the abstract of a later trial, ACHIEVE-4, states the equivalence for the top dose directly, 36 mg capsule to 17.2 mg tablet [1][4][11].
| Measure | US label (Foundayo™ doses) [1] | NEJM paper (trial doses) [4] |
|---|---|---|
| Doses | 5.5, 9 and 17.2 mg | 6, 12 and 36 mg |
| Average weight change | −7.4%, −8.3%, −11.1%; placebo −2.1% | −7.5%, −8.4%, −11.2%; placebo −2.1% |
| Lost at least 10%, top dose | 54.5%; placebo 13% | 54.6%; placebo 12.9% |
| Lost at least 20%, top dose | 18.4%; placebo 2.9% | 18.4%; placebo 2.8% |
| Stopped because of side effects | 8% across Trials 1 and 2; placebo 3% | 5.3% to 10.3% by dose; placebo 2.7% |
How the trials were set up
Both were randomised and double-blind, with a placebo group. In Trial 1, people were assigned in a 3:3:3:4 ratio to the three doses or placebo; in Trial 2 the ratio was 1:1:1:2. Doses were raised step by step, as in section 2.1 of the label [1].
Every participant, including those on placebo, received standard lifestyle support: advice on a reduced-calorie diet and physical activity counselling with a recommended minimum of 150 minutes a week. The main outcome was the average percent change in body weight from the start to week 72 [1].
Who was enrolled
- Trial 1: adults with a BMI of 30 or more, or 27 to under 30 together with a weight-related condition, for example high blood pressure or sleep apnea. People with type 2 diabetes were excluded. Average age 45, 64% women, average weight 103.2 kg [1].
- Trial 2: adults with a BMI of 27 or more and type 2 diabetes, with an HbA1c between 7% and 10%. People using DPP-4 inhibitors, GLP-1 receptor agonists or injected glucose-lowering medicines such as insulin were excluded. Average age 57, 47% women, average weight 101.4 kg, average HbA1c 8%; 11% had diabetic eye disease [1].
Beyond the average
At week 72 the average weight change at 17.2 mg was −11.1% against −2.1% on placebo in Trial 1, and −9.6% against −2.5% in Trial 2. The label adds that weight fell regardless of age, sex, race, ethnicity, starting BMI or blood sugar status [1].
Averages hide a wide spread, so the label also counts how many people crossed set thresholds. The table shows the highest dose; at 5.5 mg in Trial 1, for example, 32.5% lost at least 10% [1]. The label marks some of the higher-threshold comparisons as not controlled for multiplicity, so treat those as supportive rather than formal findings.
| Weight lost | Trial 1: placebo | Trial 1: 17.2 mg | Trial 2: placebo | Trial 2: 17.2 mg |
|---|---|---|---|---|
| At least 5% | 26.8% | 71.5% | 26.8% | 67% |
| At least 10% | 13% | 54.5% | 9.2% | 45.6% |
| At least 15% | 6% | 35.9% | 3.1% | 25.9% |
| At least 20% | 2.9% | 18.4% | 0.7% | 10.8% |
Reading the cumulative chart
Figures 3 and 4 plot, for every possible amount of weight change, the share of each group that reached at least that much. The label explains how to read them with an example: draw a vertical line at −10% in Trial 1 and it meets the 17.2 mg curve at about 55% and the placebo curve at about 13% [1].
The useful lesson is that people on the same dose ended up in very different places, and some people on placebo lost a meaningful amount too. Neither trial says what any one person will lose.
Stopping early and missing weights
Not everyone stayed on the trial drug. In Trial 1, 22% to 24% of those on Foundayo™ stopped it, compared with 30% on placebo. In Trial 2, the figures were 19% to 22% against 20% [1].
The results count everyone who was randomised (intent-to-treat). The week-72 weight was missing for 24% of the placebo group and 14% to 16% of the dose groups in Trial 1, and for 13% and 7% to 13% in Trial 2. Missing values were estimated statistically from people in the same group, including those who were still weighed after stopping the drug [1]. This is standard practice, but it is one reason to treat each figure as an estimate.
Other measurements
Table 7 of the label reports changes beyond weight. The rows below are for the top dose; the label marks the blood pressure, pulse and blood fat results as not controlled for multiplicity [1].
| Measure | Trial 1: placebo | Trial 1: 17.2 mg | Trial 2: placebo | Trial 2: 17.2 mg |
|---|---|---|---|---|
| Waist (cm) | −3.1 | −10 | −2.8 | −8.3 |
| Systolic blood pressure (mm Hg) | −1.4 | −6.4 | −1.5 | −4.6 |
| Pulse (beats per minute) | +0.6 | +4.6 | +0.4 | +3.6 |
| HbA1c (percentage points) | −0.1 | −0.3 | −0.4 | −1.7 |
| Non-HDL cholesterol (%) | −2 | −7.7 | −3 | −9.7 |
Safety in the pooled trials
The label pools the two trials for safety, covering 3,155 people on Foundayo™. Side effects led 8% to stop, against 3% on placebo; digestive effects of any kind affected 60% to 69% by dose against 37%, and caused 3% to 6% to stop, against 0.7% [1]. Of those with digestive effects, 60% rated them mild, 36% moderate and 4% severe [1].
Less common findings include acute pancreatitis confirmed by adjudication in 6 people on Foundayo™ against 1 on placebo, and gallstones in 1% against 0.7% [1]. Our symptom pages go through the individual side effects.
The wider trial programme
Several other orforglipron trials have been published as peer-reviewed papers. Most report doses of the investigational formulation, such as 3, 12 or 36 mg, rather than tablet strengths, and none of them is described in the US label. The table summarises each from its abstract.
| Trial | Who, and for how long | Compared with | Design | Main result in the abstract |
|---|---|---|---|---|
| Phase 2, obesity [6] | 272 adults with obesity or overweight, no diabetes; 36 weeks | Placebo | Double-blind, dose-finding | Weight −9.4% to −14.7% at week 36, against −2.3% |
| ACHIEVE-1 [7] | 559 adults with early type 2 diabetes on diet and exercise; 40 weeks | Placebo | Double-blind | HbA1c −1.24 to −1.48 points against −0.41; weight −4.5% to −7.6% against −1.7% |
| ACHIEVE-2 [8] | 962 adults with type 2 diabetes on metformin; 40 weeks | Dapagliflozin 10 mg | Open-label, orforglipron dose blinded | HbA1c −1.23 to −1.56 points against −0.81; stopped the study drug 15% to 20% against 6% |
| ACHIEVE-3 [9][10] | 1,698 adults with type 2 diabetes on metformin; 52 weeks | Oral semaglutide 7 or 14 mg | Open-label | HbA1c −1.71 and −1.91 points against −1.23 and −1.47; weight on treatment −6.7% and −9.2% against −3.7% and −5.3% |
| ACHIEVE-4 [11] | 2,749 adults with type 2 diabetes and heart or kidney disease; median 2 years | Insulin glargine | Open-label, event-driven | Major cardiovascular events 4.2% against 5.0%, hazard ratio 0.84, meeting the non-inferiority margin |
| ACHIEVE-5 [12] | 546 adults with type 2 diabetes on insulin glargine; 40 weeks | Placebo | Double-blind | HbA1c −1.58 to −1.88 points against −0.79 |
| ATTAIN-MAINTAIN [13] | 376 adults who had lost weight on tirzepatide or semaglutide injections; 52 weeks | Placebo | Double-blind, phase 3b | Among those whose weight had plateaued, kept 74.7% (after tirzepatide) and 79.3% (after semaglutide) of the earlier loss, against 49.2% and 37.6% |
How to read these studies
- Group results: every figure above is an average or a share of a group, and none predicts what one person will lose or how their blood sugar will move [1].
- Open-label designs: in ACHIEVE-2, ACHIEVE-3 and ACHIEVE-4 participants knew which medicine they took, which matters most for reported side effects [8][9][11].
- Comparators: ACHIEVE-3 used oral semaglutide at the 7 mg and 14 mg diabetes doses, not a weight-management dose, and its weight figure in the registry counts only time on the study drug [9][10]. None of the trials listed here compares orforglipron with a weight-management injection.
- Safety rather than benefit: ACHIEVE-4 was built to rule out excess cardiovascular risk against insulin glargine, not to show that orforglipron lowers it [11].
- Maintenance: ATTAIN-MAINTAIN had no group that stayed on the injection and lasted one year; its authors name both as limitations [13].
- Subgroups: a post hoc analysis of 616 people aged 65 or older in ATTAIN-1 and ATTAIN-2 found weight changes similar to younger participants; post hoc analyses describe, they do not confirm [14]. A pooled analysis of seven phase 3 trials, with 11,220 participants, found no case meeting the criteria for drug-induced liver injury [15].
Foundayo™ is a trademark of Eli Lilly and Company. PepLabo is not affiliated with or endorsed by Eli Lilly and Company.
