Reduction in Multiple Cardiometabolic Risk Factors With Combined Olanzapine/Samidorphan Compared With Olanzapine: Post Hoc Analyses From a 24-Week Phase 3 Study

• Published in: Schizophrenia bulletin 2023-03, Vol.49 (2), p.454-463
• Main Authors: Correll, Christoph U, Stein, Evan, Graham, Christine, DiPetrillo, Lauren, Akerman, Sarah, Stanford, Arielle D, Jiang, Ying, Yagoda, Sergey, McDonnell, David, Hopkinson, Craig
• Format: Article
• Language: English
• Subjects: Adult; Antipsychotic Agents - adverse effects; Benzodiazepines - adverse effects; Cardiometabolic Risk Factors; Cardiovascular Diseases - drug therapy; Humans; Hypertension - drug therapy; Hypertension - epidemiology; Metabolic Syndrome - chemically induced; Metabolic Syndrome - epidemiology; Obesity - chemically induced; Olanzapine - adverse effects; Regular; Weight Gain
• ISSN: 0586-7614; 1745-1701
• DOI: 10.1093/schbul/sbac144

Abstract Background and Hypotheses Weight gain and adverse cardiometabolic effects often limit the clinical utility of olanzapine. In ENLIGHTEN-2, combining olanzapine with the opioid receptor antagonist samidorphan (OLZ/SAM) mitigated olanzapine-associated weight gain. These analyses tested the hypothesis that OLZ/SAM would be associated with reduced adverse cardiometabolic effects compared with olanzapine. Study Design This phase 3 double-blind study randomized adults with schizophrenia to OLZ/SAM or olanzapine for 24 weeks. Post hoc analyses assessed changes from baseline to week 24 in cardiometabolic risk parameters, including body mass index (BMI), risk of developing obesity (BMI ≥30 kg/m2) or metabolic syndrome, waist circumference, along with mean and potentially clinically significant changes in blood pressure, glucose, and lipids. Results After 24 weeks’ treatment, compared with olanzapine, OLZ/SAM was associated with smaller least-squares mean (LSM) changes from baseline in systolic blood pressure (LSM difference, −2.63 mm Hg; 95% CI: −4.78, −0.47), diastolic blood pressure (LSM difference, −0.75 mm Hg; 95% CI: −2.31, 0.80), and BMI (LSM difference, −0.65 kg/m2; 95% CI: −1.01, −0.28). OLZ/SAM treatment was also associated with reduced risk of shifting from normal blood pressure to stage 1/2 hypertension (odds ratio [OR], 0.48; 95% CI: 0.24, 0.96), becoming obese (OR, 0.52; 95% CI: 0.32, 0.82), and developing metabolic syndrome (OR, 0.55; 95% CI: 0.31, 0.99) compared with olanzapine. No treatment group differences were noted for risk of hyperglycemia or hyperlipidemia. Conclusions OLZ/SAM treatment was associated with lower risk of worsening cardiometabolic risk factors related to obesity, hypertension, and metabolic syndrome relative to olanzapine. NCT02694328, https://clinicaltrials.gov/ct2/show/NCT02694328.