Switching from an injection to oral orforglipron: ATTAIN-MAINTAIN

Why this study matters

Weight tends to come back after injectable weight-management medicines stop. This trial asked whether a daily pill could hold on to some of that earlier weight loss. It is the first randomized study we found that takes people directly from tirzepatide (Zepbound, Mounjaro) or semaglutide (Wegovy, Ozempic) onto an oral medicine. For Canadian readers, it is a glimpse of a possible future option, not a description of anything available now.

Who was in the study

The 376 participants had all completed the 72-week SURMOUNT-5 trial, which compared tirzepatide with semaglutide in adults living with obesity but without type 2 diabetes. They were split into two cohorts based on which medicine they had taken: 205 had taken tirzepatide (cohort 1) and 171 had taken semaglutide (cohort 2). The trial lasted 52 weeks. The main analysis looked at people who had reached a weight plateau, meaning their weight had stopped falling before they switched.

What the researchers did

This was a double-blind, placebo-controlled trial. Within each cohort, people were randomized, meaning assigned by chance, to a daily orforglipron capsule or a placebo capsule that looked the same. Double-blind means neither participants nor researchers knew who received which. The orforglipron dose was 36 mg, or a maximum tolerated dose of 24 or 36 mg, in an investigational capsule formulation. From week 24, people who regained a substantial amount of weight could receive open-label orforglipron as rescue treatment.

The main outcome was the percentage of prior weight reduction that was maintained at 52 weeks among people who had reached a plateau. The trial used a treatment-regimen estimand with imputation for missing values. An estimand is a precise statement of what the trial measures and how it handles people who stop, switch or receive rescue. Here, people who received rescue were assumed to get no further benefit from their assigned treatment.

What they found

In cohort 1, people who had previously taken tirzepatide and had reached a plateau maintained a model-based estimate of 74.7% of their prior weight reduction with orforglipron, compared with 49.2% with placebo (R32-C63). The estimated difference was 25.5 percentage points, with a 95% confidence interval of 14.5 to 36.5. A confidence interval is the range within which the true difference most likely sits.

In cohort 2, people who had previously taken semaglutide maintained an estimated 79.3% with orforglipron, compared with 37.6% with placebo (R32-C64). The estimated difference was 41.7 percentage points (95% CI 24.4 to 59.0).

The abstract reports that all key secondary endpoints were met. Note that neither cohort was compared with simply continuing the injection. The two cohorts came from different prior treatments and should not be compared with each other.

Side effects and people who stopped

The most common side effects were stomach and bowel symptoms, mostly mild to moderate. Before any rescue treatment, stopping because of side effects occurred in 7.3% of people on orforglipron and 2.5% on placebo in the tirzepatide cohort, and in 4.8% and 3.0% in the semaglutide cohort. The published summary we reviewed does not report overall discontinuation for any reason.

What this study does not tell you

• Orforglipron is not approved in Canada as of September 2026, and the capsule studied was an investigational formulation. Results may not apply to any future product.
• There was no group that simply continued tirzepatide or semaglutide, so the trial cannot say how a pill compares with staying on the injection.
• Rescue orforglipron was allowed from week 24, which blurs the placebo comparison in the second half of the trial.
• Participants were selected completers of a previous trial. The main analysis was limited to those whose weight had plateaued.
• The trial lasted one year.
• The summary we reviewed did not include the funding statement or author disclosures, so the sponsor's role in the trial could not be checked.

What it means in Canada

This trial describes a medicine that is not approved in Canada as of September 2026. Nothing here reflects current Canadian prescribing or coverage. For the medicines that are used here, see tirzepatide in Canada and semaglutide in Canada. For an overview of medicines and their status, see medicines. For cost questions, see public drug coverage by province.

Related reading

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

Source