Efficacy and safety of semaglutide versus placebo for people with schizophrenia on clozapine with obesity (COaST): a phase 2, multi-centre, participant and investigator- blinded, randomised controlled trial in Australia.

Siskind D, Baker A, Arnautovska U, Warren N, Russell A, DeMonte V, Halstead S, Iyer R, Korman N, McKeon G, Medland S, Parker S, Stedman T, Trott M

The lancet. Psychiatry1 Jul 2025Cited by 37 (Europe PMC)

PMID40506208DOI10.1016/s2215-0366(25)00129-4PepBankPUB-40506208

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Summary

The text of this summary is not shown here, because the article license does not allow reuse. Read it at the source (opens in a new tab)

Text rights: Publisher copyright. Results still quote short attributed sentences.

Results from this study6

6 results from studies that gave the peptide. 6 results from people.

01HumanRandomized controlled trialEfficacy outcome
In adults with schizophrenia on clozapine and obesity, semaglutide reduced body weight by 13·88% versus 0·42% with placebo at week 36 (difference -13·46%).
In plain wordsIn adults with schizophrenia taking clozapine, semaglutide led to much more weight loss than placebo.
Peptide
Semaglutide
Outcome
DecreasePercentage body weight change at 36 weeks
Study
n = 31
Comparator
Placebo
Analysis
Primary
Outcome group
Body weight · Metabolic and weight
Studied dose
titrated to 2·0 mg once weekly · subcutaneous · 36 weeksAs given in this study (human).
Measurements
Body weight reduction
13.88%
semaglutide
Body weight reduction
0.42%
placebo
Between-group difference
−13.46%
semaglutide versus placebo
Source sentences
Summary
At week 36, semaglutide yielded a 13·88% (SE 0·90) body weight reduction compared with 0·42% (SE 0·93) for placebo (between-group difference: -13·46%; p<0·0001).
2 context sentences(design, population, supporting numbers)
Summary · context
Adults (aged 18-64 years) across six sites were randomly assigned (1:1) to once weekly subcutaneous semaglutide titrated to 2·0 mg or placebo for 36 weeks.
Summary · context
166 individuals were screened for eligibility, 135 were excluded, and the remaining 31 were randomly assigned to either the semaglutide group (n=15) or the control group (n=16).
Report a problemFND-4050620801
02HumanRandomized controlled trialPharmacokinetics
In adults with schizophrenia on clozapine, semaglutide did not change clozapine concentrations versus placebo.
In plain wordsIn adults with schizophrenia, semaglutide did not change clozapine blood levels compared with placebo.
Peptide
Semaglutide
Outcome
No significant changeClozapine concentration
Study
n = 31
Comparator
Placebo
Analysis
Secondary
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
titrated to 2·0 mg once weekly · subcutaneous · 36 weeksAs given in this study (human).
Source sentences
Summary
No differences were observed in clozapine or norclozapine concentrations or PANSS scores.
2 context sentences(design, population, supporting numbers)
Summary · context
Adults (aged 18-64 years) across six sites were randomly assigned (1:1) to once weekly subcutaneous semaglutide titrated to 2·0 mg or placebo for 36 weeks.
Summary · context
166 individuals were screened for eligibility, 135 were excluded, and the remaining 31 were randomly assigned to either the semaglutide group (n=15) or the control group (n=16).
Report a problemFND-4050620802
03HumanRandomized controlled trialPharmacokinetics
In adults with schizophrenia on clozapine, semaglutide did not change norclozapine concentrations versus placebo.
In plain wordsIn adults with schizophrenia, semaglutide did not change norclozapine blood levels compared with placebo.
Peptide
Semaglutide
Outcome
No significant changeNorclozapine concentration
Study
n = 31
Comparator
Placebo
Analysis
Secondary
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
titrated to 2·0 mg once weekly · subcutaneous · 36 weeksAs given in this study (human).
Source sentences
Summary
No differences were observed in clozapine or norclozapine concentrations or PANSS scores.
2 context sentences(design, population, supporting numbers)
Summary · context
Adults (aged 18-64 years) across six sites were randomly assigned (1:1) to once weekly subcutaneous semaglutide titrated to 2·0 mg or placebo for 36 weeks.
Summary · context
166 individuals were screened for eligibility, 135 were excluded, and the remaining 31 were randomly assigned to either the semaglutide group (n=15) or the control group (n=16).
Report a problemFND-4050620803
04HumanRandomized controlled trialEfficacy outcome
In adults with schizophrenia on clozapine, semaglutide did not change PANSS scores versus placebo.
In plain wordsIn adults with schizophrenia, semaglutide did not change psychosis symptom scores compared with placebo.
Peptide
Semaglutide
Outcome
No significant changePsychosis symptoms (PANSS score)
Study
n = 31
Comparator
Placebo
Analysis
Secondary
Outcome group
Psychiatric symptoms · Mental health and mood
Studied dose
titrated to 2·0 mg once weekly · subcutaneous · 36 weeksAs given in this study (human).
Source sentences
Summary
No differences were observed in clozapine or norclozapine concentrations or PANSS scores.
2 context sentences(design, population, supporting numbers)
Summary · context
Adults (aged 18-64 years) across six sites were randomly assigned (1:1) to once weekly subcutaneous semaglutide titrated to 2·0 mg or placebo for 36 weeks.
Summary · context
166 individuals were screened for eligibility, 135 were excluded, and the remaining 31 were randomly assigned to either the semaglutide group (n=15) or the control group (n=16).
Report a problemFND-4050620804
05HumanRandomized controlled trialSafety outcome
In adults with schizophrenia on clozapine, semaglutide was well tolerated, with no serious adverse events deemed related to the treatment.
In plain wordsIn adults with schizophrenia taking clozapine, semaglutide was well tolerated with no serious side effects judged related to it.
Peptide
Semaglutide
Outcome
No significant changeSerious adverse events related to treatment
Study
n = 31
Comparator
Placebo
Outcome group
Adverse events · Whole body
Studied dose
titrated to 2·0 mg once weekly · subcutaneous · 36 weeksAs given in this study (human).
Source sentences
Summary
Semaglutide was well tolerated, with no serious adverse events that were deemed to be related to the treatment
2 context sentences(design, population, supporting numbers)
Summary · context
Adults (aged 18-64 years) across six sites were randomly assigned (1:1) to once weekly subcutaneous semaglutide titrated to 2·0 mg or placebo for 36 weeks.
Summary · context
166 individuals were screened for eligibility, 135 were excluded, and the remaining 31 were randomly assigned to either the semaglutide group (n=15) or the control group (n=16).
Report a problemFND-4050620805
06HumanRandomized controlled trialSafety outcome
In adults with schizophrenia on clozapine, semaglutide was associated with low rates of constipation.
In plain wordsIn adults with schizophrenia taking clozapine, constipation was uncommon on semaglutide.
Peptide
Semaglutide
Outcome
Not applicableConstipation
Study
n = 31
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
titrated to 2·0 mg once weekly · subcutaneous · 36 weeksAs given in this study (human).
Source sentences
Summary
and low rates of constipation.
2 context sentences(design, population, supporting numbers)
Summary · context
Adults (aged 18-64 years) across six sites were randomly assigned (1:1) to once weekly subcutaneous semaglutide titrated to 2·0 mg or placebo for 36 weeks.
Summary · context
166 individuals were screened for eligibility, 135 were excluded, and the remaining 31 were randomly assigned to either the semaglutide group (n=15) or the control group (n=16).
Report a problemFND-4050620806

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
11 Oct 2026, 00:04 UTC
Study results updated
Version 1
9 Oct 2026, 03:06 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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