Disclosures: Simmons reports being an employee of Alkermes Inc. and owning stock/options in the company.
May 14, 2021
2 min read

Olanzapine/samidorphan treatment reduces weight gain for several schizophrenia subgroups

Disclosures: Simmons reports being an employee of Alkermes Inc. and owning stock/options in the company.
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Olanzapine/samidorphan combination treatment reduced weight gain across several subgroups of individuals at increased risk for weight gain with olanzapine, according to results of a subgroup analysis.

Researchers presented the results at the Congress of the Schizophrenia International Research Society.

Adam Simmons

“The combination of olanzapine and samidorphan provides the antipsychotic effect of olanzapine but mitigates some of the weight gain associated with it,” Adam Simmons, MPH, director of clinical program management at Alkermes, told Healio Psychiatry. “Most of the data that we've published focused on weight as an endpoint and looked at studies as a whole, but now we're starting to focus on some additional data, which we presented in this subgroup analysis. We know in the literature that there are certain subgroups based on age, race, baseline BMI and sex that are at higher risk for olanzapine weight gain, so we had pre-identified that those were subgroups of interest, and we’re showing how those subgroups performed.”

Simmons and colleagues conducted a 24-week, phase 3, multicenter, double-blind study to assess weight gain among outpatients with schizophrenia according to DSM-5 diagnosis who were aged 18 to 55 years and had stable body weight. They excluded individuals who were antipsychotic naïve or treatment resistant or who had less than 1 year having elapsed since the initial onset of schizophrenia symptoms. Participants received either olanzapine/samidorphan (Lybalvi, Alkermes) (n = 266), formerly called ALKS 3831, or olanzapine alone (n = 272). Both groups received an initial olanzapine dose of 10 mg, with dose titration allowed until week 4. Percent change from baseline in body weight at week 24 and proportion of participants with 10% or higher weight gain at week 24 served as the co-primary endpoints. The researchers prespecified exploratory analyses of the co-primary endpoints according to the following: male or female; older than age 30 years or age 30 years or younger; Black or non-Black; and BMI of lower than 27 kg/m2 or BMI of 27 kg/m2 or higher.

Results showed Lybalvi treatment significantly mitigated weight gain compared with olanzapine alone among outpatients with schizophrenia. At 24 weeks, 29.8% of patients who received olanzapine exhibited weight gain of 10% or higher vs. 17.8% among those who received Lybalvi, and the percent change in weight from baseline was 6.6% vs. 4.2% among the Lybalvi and olanzapine groups, respectively.

In the prespecified subgroup analyses, demographics between treatment groups were similar. For percent change in weight at week 24, Lybalvi was linked to a lower mean percent change in weight compared with olanzapine across all evaluated subgroups, with an overall least squares mean difference of -2.38 (95% CI, -3.88 to -0.88). Further, for weight gain of 10% or greater at week 24 across subgroups, the researchers noted smaller weight gain among patients who received Lybalvi compared with those who received olanzapine, with an overall odds ratio of 0.5 (95% CI, 0.31-0.8).

Simmons and colleagues noted several limitations, including small sample sizes for some subgroups that may have contributed to wider confidence intervals; a lack of data on obese patients, since study enrollment was limited to individuals with a BMI of 18 to 30 kg/m2; and the subgroups not being stratified at randomization.

“The great thing is that among all the risk factors that we looked at that are known for increasing risk for weight gain, we saw the same mitigation effect across all of them,” Simmons said. “This may be helpful for clinicians when they’re looking at somebody who is at increased risk for olanzapine-induced weight gain.”


Simmons A. Olanzapine/samidorphan mitigates weight gain across subgroups of patients known to be at increased risk for weight gain with olanzapine treatment. Presented at: Congress of the Schizophrenia International Research Society; April 17-21, 2021 (virtual meeting).