Solriamfetol treatment for patients with obstructive sleep apnea (OSA) or narcolepsy is associated with a decrease in body weight in a dose-related manner, according to analysis findings published in Sleep Medicine.

Insufficient sleep, OSA, and narcolepsy have been associated with weight gain, risks of obesity, and serious adverse cardiac events. Solriamfetol, a dopamine/norepinephrine reuptake inhibitor, has been approved in the US and European Union for treating excessive daytime sleepiness (EDS) associated with OSA (37.5 to 150 mg/day) or narcolepsy (75 to 150 mg/day). Because clinical trials (ClinicalTrials.gov Identifier: NCT02348632) have indicated that solriamfetol treatment of EDS is often associated with decreased appetite and weight loss, researchers sought to characterize weight changes among participants in these clinical trials.

The researchers conducted a retrospective analysis of clinical trial data on adult participants from 2 randomized, placebo-controlled, 12-week trials — 1 involving individuals with OSA (n=474, including 119 receiving placebo) and the other involving individuals with narcolepsy (n=236, including 59 receiving placebo) — in which participants were treated with differing doses of solriamfetol (37.5 [OSA only], 75, 150, or 300 mg/d). The investigators also evaluated data from a 1-year open-label extension trial.


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Data analysis focused on weight change from baseline to the end of study (week 12 or week 40 of the open-label extension). Among participants in the 12-week OSA study, the median percent change in weight from baseline for all solriamfetol dosing levels was -0.84% vs 0.54% for placebo; in participants with narcolepsy, median weight change from baseline was -0.07% of all solriamfetol doses vs 3.08% for placebo.

Analysis of the 1-year open-label extension data found that participants’ overall median percent change in weight from baseline was -1.76%, and that weight changes had a dose-dependent pattern (75mg, 0.57%; 150mg, −1.2%; 300mg, −2.5%). The overall median percent change in weight for participants with OSA was -2.2% and -1.1%. for participants with narcolepsy. Notably, although solriamfetol 300mg daily is not currently approved by the FDA for OSA or narcolepsy, 225 of the 374 extension study participants received this dosage level.

Analysis of the extension study data also showed that after 1 year of solriamfetol treatment, more than 25% of all participants had weight loss of at least 5% relative to baseline, also with a dose-dependent pattern (75mg, 4.5%; 150mg, 17.3%; 300mg, 32.4%). Among participants with OSA, 26.4% experienced at least 5% weight loss, and among those with narcolepsy, 24.2% of participants experienced at least 5% weight loss. Researchers reported no serious weight-related treatment-emergent adverse events.

Study limitations include use of data summarization rather than statistical analyses; lack of a placebo control group in the 1-year study; lack of assessment of potential major adverse events; and the inclusion of 300 mg dose treatment results when the maximum FDA approved solriamfetol dosage for OSA or narcolepsy is 150 mg once daily.

“Solriamfetol treatment was associated with decreases in body weight in a dose-related manner,” the researchers concluded solriamfetol treatment is associated with decreases in body weight among individuals with OSA and narcolepsy — a patient population that includes many who are obese or overweight  —  and that the effect of solriamfetol treatment on body weight is dose dependent. “Further research in prospective randomized controlled studies is required to assess the long-term cardiometabolic impact of solriamfetol treatment,” the researchers added.

Disclosure: This research was supported by Jazz Pharmaceuticals. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Reference

Malhotra A, Strollo PJ, Pépin JL, et al. Effects of solriamfetol treatment on body weight in participants with obstructive sleep apnea or narcolepsy. Sleep Med. Published online August 14, 2022. doi:10.1016/j.sleep.2022.08.005