Trial results for a real-world evidence study on the cardiovascular safety of CONTRAVE® (naltrexone 8mg and bupropion 90mg) in Obesity patients were posted on ClinicalTrials.gov on 2025-06-17, showing 26 major adverse cardiovascular events (MACE) for CONTRAVE®/MYSIMBA® initiators compared to 36 for lorcaserin initiators.
Background
Obesity is a complex chronic disease characterized by excessive body fat, which significantly increases the risk of numerous health problems, including cardiovascular disease, type 2 diabetes, certain cancers, and musculoskeletal disorders. Managing obesity often involves lifestyle modifications, but pharmacological interventions are also crucial for many patients to achieve and maintain weight loss. CONTRAVE®, a fixed-dose combination of naltrexone and bupropion, is one such medication approved for chronic weight management. Given the strong link between obesity and cardiovascular risk, assessing the cardiovascular safety of weight management medications in real-world clinical practice is essential for informing treatment decisions and ensuring patient safety.
Trial design
This completed real-world evidence study enrolled 31889 participants with Obesity. The study aimed to generate real-world evidence from electronic health records and linked claims data to assess the cardiovascular safety of CONTRAVE® and all combined use of naltrexone and bupropion (NB) in usual clinical practice. The intervention involved the fixed-dose combination of naltrexone 8mg and bupropion 90mg extended-release oral tablet, marketed as CONTRAVE® in the U.S., and also included combined use of naltrexone and bupropion (NB). The comparator arm consisted of initiators of lorcaserin.
Key results
The trial assessed the incidence of Major Adverse Cardiovascular Events (MACE) between initiators of CONTRAVE®/MYSIMBA® or N&B and initiators of Lorcaserin. Key measurements reported include:
- For initiators of CONTRAVE®/MYSIMBA®, 26 MACE events were observed, compared to 36 events for initiators of Lorcaserin, and 10 events for initiators of Naltrexone and Bupropion (N&B).
- In another measurement, initiators of CONTRAVE®/MYSIMBA® had 6 MACE events, compared to 5 events for initiators of Lorcaserin, and 5 events for initiators of Naltrexone and Bupropion (N&B).
- A further measurement reported 0 MACE events for initiators of CONTRAVE®/MYSIMBA®, 0 events for initiators of Lorcaserin, and 1 event for initiators of Naltrexone and Bupropion (N&B).
What this means
The real-world evidence from this large study involving over 31889 participants provides insights into the cardiovascular safety profile of CONTRAVE® and combined naltrexone and bupropion for obesity management. The findings indicate that initiators of CONTRAVE®/MYSIMBA® experienced a lower incidence of MACE (26 events) compared to initiators of lorcaserin (36 events) in one key analysis. Other analyses showed comparable or slightly different event counts across the groups. These real-world data can help clinicians and patients evaluate the cardiovascular safety considerations when choosing pharmacological treatments for obesity, suggesting that CONTRAVE® may offer a favorable cardiovascular safety profile relative to lorcaserin in certain contexts.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for the study NCT06090461, titled "Real-World Evidence on the Cardiovascular Safety of CONTRAVE® in the United States (U.S.)", were posted on 2025-06-17 on clinicaltrials.gov.