COR-Diabetes: Naltrexone SR/Bupropion SR Combination Therapy Led to Significant and Sustained Weight Loss and Improved HbA1c in Overweight/Obese Subjects with Type 2 Diabetes
Abstract Number: 56-OR
Authors: PRISCILLA HOLLANDER, RAYMOND PLODKOWSKI, ALOK K. GUPTA, MARIA GUTTADAURIA, JANELLE ERICKSON, DENNIS KIM, EDUARDO DUNAYEVICH
Institutions: Dallas, TX, Reno, NV, Baton Rouge, LA, New York, NY, Indianapolis, IN, La Jolla, CA
Results: COR-Diabetes is a Phase 3, double-blind, placebo (PBO)-controlled, 56-wk study of the efficacy/safety of naltrexone sustained-release (SR)/bupropion SR in overweight/obese subjects with type 2 diabetes (T2DM; baseline HbA1c 7-10%) using oral (or no) anti-diabetes medications (OADs). Subjects (N=505) were randomized 2:1 to oral NB32 (32 mg naltrexone SR/360 mg bupropion SR daily) or PBO. Co-primary endpoints were the % change in weight and the % of subjects with ≥5% weight loss at Wk 56. Secondary endpoints included the % of subjects with ≥10% weight loss, changes in glycemic measures, markers of cardiometabolic risk, and control of eating. Baseline characteristics were similar in both groups (mean: age 54y, 54% female, 80% Caucasian, weight 106 kg, BMI 37 kg/m2, HbA1c 8.0%; modified ITT-LOCF: subjects with ≥1 post-baseline weight measurement on study drug; NB32 n=265, PBO n=159). Study completion rates were 52% NB32/59% PBO. Wk 56 weight loss was -5.0% NB32 vs. -1.8% PBO (P<0.001). More (P<0.001) NB32-treated subjects achieved ≥5% (44.5% vs. 18.9%) and ≥10% (18.5% vs. 5.7%) weight loss. NB32-treated subjects (vs. PBO) had notable improvements in HbA1c: -0.6% vs. -0.1% (P<0.001), and a higher % achieved HbA1C <7%: 44.1% vs. 26.3% (P<0.001). NB32-treated subjects (vs. PBO) experienced greater improvements in waist circumference (P<0.01), triglycerides (P<0.01), and HDL-C (P<0.001). There was a numerical trend in LDL-C, FBG, insulin, and HOMA-IR favoring NB32 vs. PBO. NB32-treated subjects (vs. PBO) reported greater improvements in their ability to control eating (P<0.05). The most frequent adverse events with NB32 were nausea (42.3% NB32 vs. 7.1% PBO), constipation (17.7% vs. 7.1%), and vomiting (18.3% vs. 3.6%). Nausea occurred early, was transient and mostly of mild/moderate severity. There was no meaningful effect of NB32 on depression, suicidal ideation, or hypoglycemia adverse events. In conclusion, NB32 therapy in subjects with T2DM was generally well-tolerated, generated sustained and meaningful weight loss, and improved glycemic control and markers of cardiometabolic risk.