# Do GLP-1 Drugs Help Antipsychotic Weight Gain? 9.8% Off, Half Back | This GLP

Do GLP-1 drugs help antipsychotic weight gain? A 76-week schizophrenia study, a 764,115-pair mortality emulation and a 14,694-person bipolar cohort | what each shows.

Publisher: This GLP Editorial Team
Canonical: https://thisglp.com/research/do-glp1-drugs-help-antipsychotic-weight-gain
Updated: 2026-09-17
Published: 2026-09-16

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Evidence

# Do GLP-1 Drugs Help Antipsychotic Weight Gain? 9.8% Off, Half Back

In 26 people with schizophrenia on clozapine or olanzapine, semaglutide took off about 10.1 kg over 24 weeks. A year after it stopped, roughly half had returned.

[This GLP Editorial Team](https://thisglp.com/about)September 20269 min readUpdated September 2026

Weight against baseline · 0% · −9.8% · −5.1% · start · week 24 (drug ends) · week 76 · 26 enrolled · 17 completed the intervention · open-label, no control

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Yes, by about 10.1 kg, and roughly half of it came back. A 24-week open-label study gave nurse-administered semaglutide to people with schizophrenia taking clozapine or olanzapine [\[1\]](https://thisglp.com/research/do-glp1-drugs-help-antipsychotic-weight-gain#ref-1). Weight fell 9.8% on an intention-to-treat basis (95% CI −12.7% to −6.8%). A year after the drug stopped, participants were 5.1% below baseline. Twenty-six people enrolled and fifteen finished the trial, with no control group.

## Key takeaways

-   An open-label study gave nurse-administered semaglutide for 24 weeks to people with schizophrenia taking clozapine or olanzapine, then followed them to week 76.
-   Weight fell 9.8% by the end of the intervention (95% CI -12.7% to -6.8%), about 10.1 kg.
-   A year after the drug stopped, weight was 5.1% below baseline (95% CI -8.3% to -1.9%) — roughly half of what was lost had returned.
-   Twenty-six enrolled, 17 completed the intervention, 15 completed the trial. No control group and no blinding.
-   In a 764,115-pair emulation, four-year mortality among people with serious mental illness was 4.91% against 6.45%.
-   In 14,694 people with bipolar disorder, semaglutide tracked lower psychiatric hospitalization; liraglutide and dulaglutide did not.

Clozapine and olanzapine cause substantial weight gain. For many people they are also the antipsychotics that work, so they are not substitutable. That leaves a population carrying drug-induced obesity with no way to stop the cause.

## What the intervention produced

Weight fell 9.8% on an intention-to-treat basis, around 10.1 kg. Waist circumference fell 7.3%. HbA1c fell too but did not reach significance (P = 0.055).

The dose was 1.0 mg weekly. That is a diabetes dose, not the 2.4 mg used for weight management. These figures are therefore not comparable to obesity-trial numbers, a distinction that changes the ranking of these drugs. The ordering is set out in [the network meta-analysis of nineteen drugs](https://thisglp.com/research/the-best-losers-are-the-worst-tolerated).

The number most studies do not publish

At week 76, a year after the intervention ended, participants were 5.1% below their starting weight (95% CI -8.3% to -1.9%). Roughly half of what came off had come back. Most small open-label studies stop at the end of treatment and report the 9.8%. This one reported both, and the second number is the more useful one.

## How small the study is

Twenty-six people enrolled. Seventeen completed the intervention and fifteen completed the trial. There was no control group and no blinding.

In a population where medication adherence is the central clinical difficulty, a 65% completion rate is itself a finding. It means the weight figures describe those who stayed.

One result points in an unexpected direction. Gut microbial alpha diversity decreased as time on semaglutide increased, with one species enriched. Lower diversity is usually characterized as unfavorable in metabolic research. Nobody measured a health outcome from it, so it is an observation rather than a harm. It belongs beside the other things these drugs turn out to do that nobody designed them for, as in [the inflammation substudy](https://thisglp.com/research/do-glp1-drugs-reduce-inflammation).

## What happens to mortality in this population

People with schizophrenia, bipolar disorder and major depression die substantially earlier than everyone else, mostly of cardiovascular disease. A target trial emulation matched 764,115 pairs starting a GLP-1 drug or an SGLT2 inhibitor. Of those pairs, 195,184 had serious mental illness [\[2\]](https://thisglp.com/research/do-glp1-drugs-help-antipsychotic-weight-gain#ref-2).

Four-year mortality in that cohort was 4.91% against 6.45%. The hazard ratio was 0.76 and the absolute difference 1.54 percentage points. The comparator is not placebo: SGLT2 inhibitors reduce mortality themselves, so this is one effective drug measured against another. The same paper's one-year figure is 1.46% against 2.84%. That is too large to believe, and the reasons are in [the four-year mortality gap](https://thisglp.com/research/a-mortality-gap-in-serious-mental-illness).

## Whether the psychiatric course changes

A nationwide cohort covered 14,694 people with bipolar disorder and diabetes or obesity. It compared each person against their own periods on and off these drugs [\[3\]](https://thisglp.com/research/do-glp1-drugs-help-antipsychotic-weight-gain#ref-3). Semaglutide tracked a 21% lower risk of psychiatric hospitalization (adjusted HR 0.79, 95% CI 0.69 to 0.91). Liraglutide and dulaglutide showed no such association.

One outcome did not move at all. Sick leave for psychiatric reasons showed no association with any of the drugs studied. Hospitalization depends on admission thresholds and bed availability; sick leave tracks whether someone can work. The full reading is in [the bipolar cohort](https://thisglp.com/research/do-glp1-drugs-help-bipolar-disorder).

One randomized psychiatric result exists. A trial in major depressive disorder found semaglutide reduced the felt cost of effort, measured on an effort-based decision-making task [\[4\]](https://thisglp.com/research/do-glp1-drugs-help-antipsychotic-weight-gain#ref-4). It was a secondary finding, and it is described in [the effort and reward trial](https://thisglp.com/research/motivation-in-depression-a-secondary-finding).

## What this establishes

Feasibility, in a group usually excluded from obesity trials altogether. Nurse-administered treatment in a public mental health setting produced real weight loss in people taking the most metabolically damaging antipsychotics.

Whether it should be continued indefinitely rather than for 24 weeks is the question the 76-week figure raises and cannot answer. The same question runs through [what comes back when you stop](https://thisglp.com/research/what-else-comes-back-when-you-stop-a-glp1). No seller on this roster prescribes for schizophrenia, and an intake form is not where a clozapine history belongs.

## Frequently asked

Do GLP-1 drugs help antipsychotic weight gain?

In a 24-week open-label study of people on clozapine or olanzapine, weight fell 9.8%, about 10.1 kg. Twenty-six people enrolled, fifteen finished, and there was no control group.

Does the weight stay off after stopping?

Not fully. A year after the drug stopped, participants were 5.1% below their starting weight, so roughly half of what came off had returned.

What dose was used?

1.0 mg of semaglutide weekly. That is a diabetes dose rather than the 2.4 mg used for weight management, so the figures do not transfer to obesity-trial numbers.

Do these drugs reduce deaths in serious mental illness?

A 764,115-pair emulation put four-year mortality at 4.91% against 6.45%, a hazard ratio of 0.76. The comparator was an SGLT2 inhibitor, which lowers mortality itself, not a placebo.

Do they change the psychiatric course?

In 14,694 people with bipolar disorder, semaglutide tracked a 21% lower risk of psychiatric hospitalization. Liraglutide and dulaglutide did not, and sick leave for psychiatric reasons did not move for any of them.

## Sources

1.  \[1\] Lappin JM, Bolton P, Smith G, Chua XY, et al. (2026). Weight loss and gut microbial changes associated with semaglutide among people living with schizophrenia receiving clozapine or olanzapine: An open-label 24-week semaglutide intervention and 76-week trial Schizophrenia Research. [PMID 42372344](https://pubmed.ncbi.nlm.nih.gov/42372344/)
2.  \[2\] McIntyre RS, Zhang-James Y, Kwan ATH (2026). Glucagon-Like Peptide 1 Receptor Agonists, Mortality, and Cardiovascular Outcomes in Serious Mental Illness JAMA Psychiatry. [PMID 42647034](https://pubmed.ncbi.nlm.nih.gov/42647034/)
3.  \[3\] Taipale H, Taylor M, Lähteenvuo M, Mittendorfer-Rutz E, Tanskanen A (2026). Use of Glucagon-Like Peptide 1 Receptor Agonists and the Associated Risk of Hospitalisation in Bipolar Disorder, From a Nationwide Cohort, 2009-2024 Acta Psychiatrica Scandinavica. [PMID 42324672](https://pubmed.ncbi.nlm.nih.gov/42324672/)
4.  \[4\] Gill H, Badulescu S, Shah H, Brudner RM, et al. (2026). Semaglutide and Effort-Based Decision-Making in Major Depressive Disorder: A Randomized Clinical Trial JAMA Psychiatry. [PMID 42054055](https://pubmed.ncbi.nlm.nih.gov/42054055/)

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