CV Risks in Obesity and Diabetes Not Increased With Nalxtrexone/Bupropion
After the second interim analysis, the study was terminated with 50% of the major adverse cardiovascular event (MACE) data collected.
In 2 related studies, extended-release naltrexone/bupropion improved glycemic control, promoted additional weight loss, and did not increase cardiovascular risks for patients with both type 2 diabetes and elevated cardiovascular risk.1,2
These results were presented at the American Diabetes Association (ADA) 77th Scientific Sessions, held June 9 to 13 in San Diego, California.
As J.B. Buse, MD, PhD, from the University of North Carolina in Chapel Hill, and fellow researchers pointed out, extended-release naltrexone 32 mg/bupropion 360 mg has been indicated as an adjunctive therapy to diet and physical activity for chronic weight management.1
The participants were randomly assigned to naltrexone 32 mg/bupropion (n=3784) or placebo (n=3803) and received an Internet-based weight management program. To continue study medication, participants were required to lose ≥2% body weight by 16 weeks "without a sustained increase in blood pressure."
Of the total population, more than half were women (56.7%) and were a mean age of 60.7 years. The mean body mass index of participants was 37.4 kg/m2, and more than 20% had cardiovascular disease. The participants' mean hemoglobin A1c (HbA1c) level was 7.4%, and the median disease duration was 7.8 years.
After the second interim analysis, the study was terminated with 50% of the major adverse cardiovascular event (MACE) data collected. At that point, 2.0% of patients in the placebo group had experienced MACE vs 1.8% of patients in the naltrexone/bupropion group (hazard ratio [HR], 0.87; 99.7% CI, 0.53-1.42). The subcategories of cardiovascular death, nonfatal stroke, and nonfatal myocardial infarction had HRs of 0.54, 1.06, and 1.00, respectively.
Furthermore, in an "on treatment" analysis, MACE occurred in 0.7% of patients in the placebo group vs 0.8% of patients in the naltrexone/bupropion group, which excluded events that occurred more than 30 days after the last dose of study medication.
Serious adverse events and adverse events were similar between participants with and without type 2 diabetes; gastrointestinal disorders were the most common adverse events leading to the discontinuation of naltrexone/bupropion.
"In this older population with [type 2 diabetes] and elevated [cardiovascular] risk, [naltrexone/bupropion] did not demonstrate any evidence for increased [cardiovascular] risk compared to [placebo]," the researchers concluded.
In the study led by Raymond Plodkowski, MD, from Orexigen Therapeutics, Inc. in La Jolla, California, researchers, conducted efficacy analyses to determine weight loss and glycemic effects in patients who were considered "early responders," defined as patients who achieve ≥5% of weight loss at week 16.2
At baseline, patients a had mean body mass index of 36.6 kg/m2, HbA1c levels of 8.0%, and fasting plasma glucose of 161 mg/dL. More than half (54%) were women, and the mean age was 54 years.
At week 16, 41% of patients in the naltrexone/bupropion group (n=265) achieved weight loss of ≥5% compared with 13% of patients in the placebo group (n=159). Nearly all the early responders (88%) completed 56 weeks of treatment. These patients had a mean weight loss of 8.5 pounds at 16 weeks, and by the end of treatment, 9.1 pounds from baseline. The patients in the early responders group also had several improved glycemic parameters, including a least squares mean change of −1.01% in HbA1c compared with the placebo group (0.14) and a decrease in fasting plasma glucose levels of 19.5 mg/dL compared with 4.0 mg/dL in the placebo group. Changes in high-density lipoprotein levels were more substantial in early responders vs placebo (5.4 mg/dL vs −0.3 mg/dL).
Similar to the previous study, patients who discontinued medication did so because of adverse events (29% in the naltrexone/bupropion group vs 15% in the placebo group).
"The majority [of patients treated with naltrexone/bupropion] continued treatment to study end, supporting the use of the [week] 16 criteria to predict longer term outcomes in patients with [type 2 diabetes]," the researchers concluded.
Disclosures: Researchers report financial relationships with Orexigen Therapeutics, Inc., Janssen Pharmaceuticals, Novo Nordisk, Eli Lilly and Company, and Johnson & Johnson.
- Buse JB, Smith SR, Gilder K, Shan K, Halseth A. Effect of naltrexone/bupropion on cardiovascular events in overweight and obese participants with type 2 diabetes and cardiovascular risk factors in a large, randomized, double-blind study. Presented at: American Diabetes Association (ADA) 77th Scientific Sessions; June 9-13, 2017; San Diego, CA. Abstract 2121-P.
- Plodkowski R, Hollander PA, Acevado L, Gilder, Halseth A. Early achievement of significant weight loss with naltrexone/bupropion is associated with additional weight loss and improved glycemic control at one year in patients with type 2 diabetes. Presented at: American Diabetes Association (ADA) 77th Scientific Sessions; June 9-13, 2017; San Diego, CA. Abstract 2123-P.