There is significant overlap between obesity and type 2 diabetes (T2DM). Incretin agents (dipeptidyl peptidase 4 (DPP-4) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1RAs)) are recommended as second-line to metformin in patients with T2DM due to their glucose-lowering effects, low risk of hypoglycemia, and favorable effect on weight. Naltrexone/bupropion (NB) is a combination therapy approved in North America and Europe for chronic weight management. This is an exploratory analysis of the efficacy and safety of NB in T2DM subjects enrolled in two double-blind, placebo-controlled Phase III studies (N=1344), that were stable on an incretin agent prior to randomization. At 1 year, mean weight change was -4.6% ± 0.21% in NB (N=700) compared to -1.1% ± 0.15% in placebo (N=644). In subjects randomized to NB that achieved at ≥5% weight loss at week 16 (early responders, N=269), mean weight change at 1 year was -8.8% ± 0.34%. An analysis of covariance using LOCF adjusting for age, sex, baseline BMI, baseline weight, and responder status revealed no significant interaction between incretin agent and weight treatment medication (p=0.1317), a significant treatment NB vs. placebo effect (p<0.0001), but not a significant incretin agent effect (p=0.1388). Safety and tolerability profiles were in line as previously observed in the broader population.
In conclusion, NB is efficacious and safe in reducing weight in patients with obesity and T2DM on DPP-4 inhibitors and GLP-1RAs, and may be an effective addition when weight loss is a focus in treatment.
S. Wharton: Advisory Panel; Self; Bausch Health Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc. P. Yin: Employee; Self; Bausch Health. F. Camacho: Consultant; Self; Bausch + Lomb, Janssen Pharmaceuticals, Inc. M. Burrows: Employee; Self; Bausch Health. J. Blavignac: Employee; Self; Bausch Health Canada. M. Barakat: Employee; Self; Bausch Health.