Yes, in both trials that have asked, and by a margin wide enough that the more interesting question is what the untreated group was doing. Surgery that has underdelivered is one of the few places in this field where somebody has actually run the randomized comparison, rather than looking back at records afterwards.
The semaglutide trial
A double-blind trial randomized 70 people whose weight loss after bariatric surgery had been suboptimal to semaglutide 2.4 mg or placebo, and followed them for 68 weeks [1]. Sixty-three were in the intention-to-treat sample, with 34 and 29 contributing data at the final visit.
Weight fell 18.0% on semaglutide and rose 0.4% on placebo, an adjusted difference of 19.18 percentage points with an interval running from 23.4 to 14.8. Metabolic parameters and quality of life improved alongside it, measured with the kind of instrument this site examined in the health utility analysis.
The liraglutide trial, in a narrower group
An earlier randomized trial gave liraglutide 3.0 mg or placebo to people 18 to 120 months past a Roux-en-Y gastric bypass specifically, with lifestyle counseling for everyone, over 56 weeks [2]. Eighty-nine received the drug and 43 the placebo.
| Liraglutide 3.0 mg | Placebo | |
|---|---|---|
| Total body weight change | −8.8% | +1.1% |
| Lost at least 5% | 76% | 17% |
| Lost at least 10% | 51% | none |
| Lost at least 15% | 26% | none |
| Went below their post-operative low | 21% | none |
That last row is the one worth sitting with. A fifth of the people on liraglutide ended up below the lowest weight their operation had ever taken them to, and nobody on placebo did.
Read the placebo arms before the headlines
What these two trials do not establish
They are small. Seventy people and 132 people, with 63 contributing to the analysis in one of them, is not the scale at which safety signals appear or subgroups separate. The semaglutide trial recorded eight serious adverse events and one suspected unexpected serious adverse reaction, which is what a trial that size can tell you about harm: very little.
The liraglutide trial also lost a lot of people. Only 65% of the drug group and 53.4% of the placebo group completed, which the authors attribute to the pandemic. Serious adverse events occurred less often on liraglutide than on placebo.
They also tested different drugs after different operations. One enrolled mixed bariatric procedures and the other only Roux-en-Y gastric bypass, so they are two answers to adjacent questions rather than a replication. Nobody has compared a GLP-1 drug against a revision operation, which is the choice a person in this position is actually weighing — and the broader surgery-against-drug comparison is in surgery against a GLP-1 on cardiovascular outcomes.
What the trials do support is narrow and useful: when an operation has underdelivered, adding one of these drugs moves weight substantially, and doing nothing does not hold the line. What happens if the drug is later stopped is a separate question, answered in what happens when you stop tirzepatide.