Improved Glycemic Control and Weight Loss with Naltrexone SR/Bupropion SR Combination Therapy in Overweight/Obese Subjects with Type 2 Diabetes
Abstract Number: 2633-PO
Authors: ALOK K. GUPTA, PRISCILLA HOLLANDER, HAROLD BAYS, MARIA GUTTADAURIA, JANELLE ERICKSON, DENNIS KIM, EDUARDO DUNAYEVICH
Institutions: Baton Rouge, LA, Dallas, TX, Louisville, KY, New York, NY, Indianapolis, IN, La Jolla, CA
Results: Therapies that reduce body weight are often associated with improved glycemic control in subjects with type 2 diabetes mellitus (T2DM). The COR-Diabetes Ph. 3, double-blind, multicenter, placebo (PBO)-controlled, 56-wk study examined the efficacy/safety of naltrexone sustained-release (SR)/bupropion SR in overweight/obese T2DM subjects (baseline HbA1c 7-10%) using oral (or no) anti-diabetes medications (OADs). Subjects (N=505) were randomized 2:1 to NB32 (32mg naltrexone SR/360mg bupropion SR daily) or PBO. Wk 56 endpoints included changes from baseline in weight, HbA1c, fasting blood glucose (FBG), insulin, and HOMA-IR, and the % of subjects with HbA1c <7% and <6.5% (modified ITT-LOCF: subjects with ≥1 post-baseline weight measurement on study drug; NB32 n=265, PBO n=159). Baseline characteristics were similar between groups (mean: age 54y; 54% female; 80% Caucasian; weight 106kg; BMI 37kg/m2; HbA1c 8.0%; FBG 161mg/dL; insulin 14.9μIU/mL; HOMA-IR 5.7; 10%, 31%, and 59% of subjects were using 0, 1, ≥2 OADs). Weight loss was -5.0% NB32 vs.-1.8% PBO (P<0.001). NB32-treated subjects (vs. PBO) experienced greater improvements in HbA1c (-0.6% vs. -0.1%; P<0.001), with a higher proportion achieving HbA1c <7% (44.1% vs. 26.3%; P<0.001) and <6.5% (20.7% vs. 10.2%; P<0.01). In subjects with baseline HbA1c >8% (mean 8.9%) or >9% (mean 9.5%), HbA1c improvements were -1.1% NB32 (n=88) vs. -0.5% PBO (n=52; P<0.01), and -1.2% NB32 (n=29) vs. -0.3% PBO (n=23; P<0.05), respectively. There was a numerical trend in FBG, insulin, and HOMA-IR favoring NB32 vs. PBO. Fewer NB32-treated subjects required rescue medications for glycemic control (22.3% vs. 35.2%, P<0.01). The most frequent adverse events with NB32 (vs. PBO) were nausea (42.3% vs. 7.1%), constipation (17.7% vs. 7.1%), and vomiting (18.3% vs. 3.6%). Nausea occurred early, was transient and mostly mild/moderate in severity. NB32 was not associated with increases vs. PBO in depression, suicidal ideation, or hypoglycemia adverse events. In conclusion, NB32 therapy in overweight/obese subjects with T2DM was generally well-tolerated, improved glycemic control, and reduced weight.