ACHIEVE-1: the orforglipron pill in early type 2 diabetes

Why this study matters

Orforglipron is an experimental medicine. It is not approved in Canada as of September 2026, and this study is research only. It is a GLP-1 receptor agonist taken as a daily pill. ACHIEVE-1 was the first phase 3 trial of orforglipron in people with type 2 diabetes. It looked at people early in the disease who were not yet taking any diabetes medicine. For Canadian readers, the question is whether a pill can do what the injectable GLP-1 medicines do for blood sugar, and what happens to weight along the way.

Who was in the study

The trial enrolled 559 adults with type 2 diabetes that was being managed with diet and exercise alone. Their HbA1c was at least 7.0% and no more than 9.5%, and the average at the start was 8.0%. HbA1c is a blood test that reflects average blood sugar over about three months. Their BMI was at least 23.0. BMI, or body mass index, is weight in kilograms divided by height in metres squared. The trial ran for 40 weeks. The published summary we reviewed does not report the age range, the countries, or the average starting weight.

What the researchers did

This was a phase 3, randomized, double-blind, placebo-controlled trial. Randomized means people were assigned to groups by chance. Double-blind means neither participants nor staff knew who was getting the medicine. A placebo is an inactive pill.

Participants were assigned in equal numbers to orforglipron at 3 mg, 12 mg or 36 mg, or placebo, taken once a day for 40 weeks. The primary end point, meaning the main result the trial was designed to test, was the change in HbA1c from the start to week 40. The percentage change in body weight was a key secondary end point. The published summary we reviewed does not describe the lifestyle support the groups received.

What they found

At week 40, the estimated average change in HbA1c was -1.24 percentage points with 3 mg, -1.47 with 12 mg and -1.48 with 36 mg, compared with -0.41 with placebo. All three doses were superior to placebo. The differences from placebo were -0.83 percentage points (95% confidence interval -1.10 to -0.56) for 3 mg, -1.06 (95% CI -1.33 to -0.79) for 12 mg and -1.07 (95% CI -1.33 to -0.81) for 36 mg, each with P below 0.001. A confidence interval is the range of values the data are reasonably consistent with. The average HbA1c at week 40 was 6.5% to 6.7% across the orforglipron groups.

Body weight, the key secondary outcome, changed by -4.5% with 3 mg, -5.8% with 12 mg and -7.6% with 36 mg, compared with -1.7% with placebo (R32-C65).

The published summary we reviewed does not report a between-group difference in weight with a confidence interval.

Side effects and people who stopped

The most common side effects were mild to moderate gastrointestinal events, meaning stomach and bowel symptoms, and most happened while the dose was being increased. No episodes of severe hypoglycaemia (low blood sugar) were reported. Permanent stopping of the study pill because of side effects occurred in 4.4 to 7.8% of people taking orforglipron and 1.4% of those taking placebo. The published summary we reviewed does not give the rate for each dose, or the overall number of people who left the trial.

What this study does not tell you

• Orforglipron is not approved in Canada as of September 2026.
• Weight was a secondary outcome. The trial was designed around HbA1c, and the people enrolled were chosen for early diabetes, not for weight.
• Everyone had early type 2 diabetes managed without medicines. The results do not describe people on metformin, insulin or other treatments.
• The trial ran for 40 weeks and cannot show longer-term blood sugar control or safety.
• Our summary is based on the abstract only. Age, countries, starting weight and stopping rates by dose are not available to us.
• Do not compare these results with numbers from trials of injectable medicines, or with the weight results from ATTAIN-1, which enrolled a different group of people.
• The trial was supported by the company that makes the medicine.

What it means in Canada

Orforglipron is not approved in Canada as of September 2026, and this trial describes a medicine still under development. You can follow emerging medicines on our medicines page. For medicines available in Canada, see semaglutide in Canada and tirzepatide in Canada, and public drug coverage by province.

Related reading

Other studies in this library that bear on the same question.

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