ACHIEVE-3: orforglipron versus oral semaglutide in 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 non-peptide GLP-1 receptor agonist designed as a daily pill with no food or water restrictions. This trial compared it directly with oral semaglutide, the tablet form of semaglutide (Wegovy, Ozempic are the injectable forms). Head-to-head trials like this are rare and useful, because they compare two medicines in the same people under the same conditions. The primary question was blood sugar, not weight.

Who was in the study

The trial enrolled 1698 adults aged 18 or older with type 2 diabetes that was inadequately controlled by metformin at 1500 mg a day or more. Their HbA1c was between 7.0% and 10.5%, and the average at the start was 8.3%. HbA1c is a blood test that reflects average blood sugar over about three months. Their BMI was at least 25. BMI, or body mass index, is weight in kilograms divided by height in metres squared. The trial was run at 131 centres in Argentina, China, Japan, Mexico and the USA, with a treatment period of 52 weeks.

What the researchers did

This was a phase 3, randomized, open-label, active-controlled, non-inferiority trial. Randomized means people were assigned to groups by chance. Open-label means participants and staff knew which pill each person was taking; there was no placebo. Active-controlled means the comparison was with another real medicine.

Participants were assigned in equal numbers to orforglipron 12 mg (424 people), orforglipron 36 mg (423), semaglutide 7 mg (426) or semaglutide 14 mg (425), all taken by mouth once a day. There was a lead-in period of up to 4 weeks, then 52 weeks of treatment.

The primary objective was non-inferiority of orforglipron 36 mg versus semaglutide 14 mg, and of orforglipron 12 mg versus semaglutide 7 mg, for the change in HbA1c at week 52. Non-inferiority means showing that the new medicine is not meaningfully worse than the comparator. The margin was 0.3 percentage points. If non-inferiority was met, the plan allowed a test for superiority. The main analysis used the treatment-regimen estimand, which counts everyone who was randomized regardless of what happened during the trial. An estimand is the precise question the statistics answer.

What they found

From a starting HbA1c of 8.3%, the average change at week 52 was -1.71 percentage points with orforglipron 12 mg, -1.91 with orforglipron 36 mg, -1.23 with semaglutide 7 mg and -1.47 with semaglutide 14 mg.

The estimated difference for orforglipron 12 mg versus semaglutide 7 mg was -0.48 percentage points (95% confidence interval -0.65 to -0.31). For orforglipron 36 mg versus semaglutide 14 mg it was -0.44 (95% CI -0.62 to -0.26) (R32-C77). A confidence interval is the range of values the data are reasonably consistent with. Both non-inferiority tests were met, and both orforglipron doses were superior to both semaglutide doses. Even orforglipron 12 mg versus semaglutide 14 mg showed a difference of -0.24 (95% CI -0.41 to -0.072). Orforglipron 36 mg versus semaglutide 7 mg showed -0.68 (95% CI -0.85 to -0.50).

The published summary we reviewed does not report body-weight results, so this page cannot say how the two pills compared on weight.

Side effects and people who stopped

Gastrointestinal events, meaning stomach and bowel symptoms, were the most frequent side effects. They were reported by 249 of 424 people (59%) on orforglipron 12 mg, 245 of 423 (58%) on orforglipron 36 mg, 157 of 426 (37%) on semaglutide 7 mg and 193 of 425 (45%) on semaglutide 14 mg. Most were mild to moderate.

More people stopped treatment because of side effects on orforglipron: 37 (9%) on 12 mg and 41 (10%) on 36 mg, compared with 19 (4%) on semaglutide 7 mg and 21 (5%) on semaglutide 14 mg (R32-C76). The average increase in pulse rate was also larger with orforglipron: 3.7 beats per minute at 12 mg and 4.7 at 36 mg, versus 1.0 at semaglutide 7 mg and 1.5 at 14 mg. Four deaths occurred: one in each orforglipron group and two in the semaglutide 7 mg group.

What this study does not tell you

• Orforglipron is not approved in Canada as of September 2026.
• The trial was open-label. Knowing which pill you are taking can affect how side effects are reported.
• The summary reports no weight results, so this page cannot tell you which pill led to more weight loss.
• The comparison was with oral semaglutide at 7 and 14 mg. It does not tell you how orforglipron compares with injectable semaglutide or with other medicines.
• Everyone was on metformin. Results may differ in people on other treatments.
• The trial ran for 52 weeks and does not show longer-term blood sugar control or safety.
• The higher rates of stomach side effects, stopping and pulse increase with orforglipron are a real trade-off that the abstract itself highlights.
• The trial was funded by the company that makes orforglipron.

What it means in Canada

Orforglipron is not approved in Canada as of September 2026. Semaglutide in its various forms is a different matter, and you can read about it on our semaglutide in Canada page. For emerging medicines, see our medicines page. For how diabetes and weight-management medicines are paid for, see public drug coverage by province.

Related reading

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

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