Many potent antipsychotics, such as olanzapine (OLZ), can cause significant and rapid weight gain as a potential side effect. This can lead to medication non-adherence and recurrence of psychiatric outcomes, or developing cardiometabolic risk factors that increase the risk of heart disease. The olanzapine-samidorphan (OLZ/SAM) drug combination has demonstrated ability to mitigate the weight gain caused by OLZ. However, olanzapine-metformin (OLZ/MET) combinations have also been studied for weight gain problems before the introduction of OLZ/SAM. The authors will review the similarities and differences between OLZ/SAM and OLZ/MET combinations regarding weight gain.

In this literature review, we conducted a non-systematic search in PubMed and Google Scholar, utilizing specific key words, such as “Olanzapine”, “Metformin”, “Samidorphan”, and “Weight Gain.” Case reports/series and narrative reviews were excluded, and only English-language studies reporting weight change or rate of weight change outcomes were included. Data extraction and qualitative synthesis were performed for the selected studies.

OLZ/SAM has shown the ability to effectively reduce weight gain in non-obese populations, however, OLZ/MET has shown the ability to decrease weight gain in both obese and non-obese populations. Both drug combinations displayed these benefits after approximately 7 weeks. OLZ/MET’s weight mitigation was largely commensurate with increases in both dosage and duration of treatment. OLZ/SAM’s most efficacious dosage was not readily apparent. The maximum reduction in weight gain was achieved when MET was titrated to a daily dose of 2000 mg, although significant prevention of weight gain has been reported with lower doses as well. The mean weight change for OLZ/MET over 24 weeks was +5.5 lbs on 2000 mg per day. The mean weight change for OLZ/SAM over 24 weeks was +7.0 lbs., however, the average dose of OLZ/SAM was not reported. These results were seen in both adult and non-adult populations. OLZ/MET is considerably more affordable in comparison to OLZ/SAM. Other notable differences included dosage flexibility and scheduling, contraindications in select populations, and common side effects, among others.

Weight gain is a serious side effect of many antipsychotics and can greatly impair a patient’s quality of health and life. Drug combinations such as OLZ/SAM and OLZ/MET are crucial to help minimize the morbidity caused by medication-induced obesity. Both combinations showed effectiveness in reducing rates of weight gain but these effects were delayed until approximately 7 weeks. OLZ/MET’s effectiveness was positively correlated with increased dosages and duration, unlike OLZ/SAM in which no such relation could be convincingly established. OLZ/SAM’s relatively high cost is likely prohibitive for many persons, especially considering mental illness’ often devastating socioeconomic impact.

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