title: Effects of naltrexone sustained-release/bupropion sustained-release combination therapy on body weight and glycemic parameters in overweight and obese patients with type 2 diabetes.
abstract: OBJECTIVE
  To assess the efficacy and safety of 32 mg naltrexone sustained-release (SR)/360 mg bupropion SR (NB) in overweight/obese individuals with type 2 diabetes with or without background oral antidiabetes drugs.
  
  
  METHODS
  This was a 56-week, double-blind, placebo-controlled study in which 505 patients received standardized lifestyle intervention and were randomized 2:1 to NB or placebo. Coprimary end points were percent weight change and achievement of ≥5% weight loss. Secondary end points included achievement of HbA1c <7% (53 mmol/mol), achievement of weight loss ≥10%, and change in HbA1c, waist circumference, fasting blood glucose, and lipids.
  
  
  RESULTS
  In the modified intent-to-treat population (54% female, 80% Caucasian, and mean age 54 years, weight 106 kg, BMI 37 kg/m(2), and HbA1c 8.0% [64 mmol/mol]), NB resulted in significantly greater weight reduction (-5.0 vs. -1.8%; P < 0.001) and proportion of patients achieving ≥5% weight loss (44.5 vs. 18.9%, P < 0.001) compared with placebo. NB also resulted in significantly greater HbA1c reduction (-0.6 vs. -0.1% [6.6 vs. 1.1 mmol/mol]; P < 0.001), percent of patients achieving HbA1c <7% (53 mmol/mol) (44.1 vs. 26.3%; P < 0.001), and improvement in triglycerides and HDL cholesterol compared with placebo. NB was associated with higher incidence of nausea (42.3 vs. 7.1%), constipation (17.7 vs. 7.1%), and vomiting (18.3 vs. 3.6%). No difference was observed between groups in the incidence of depression, suicidal ideation, or hypoglycemia.
  
  
  CONCLUSIONS
  NB therapy in overweight/obese patients with type 2 diabetes induced weight loss, which was associated with improvements in glycemic control and select cardiovascular risk factors and was generally well tolerated with a safety profile similar to that in patients without diabetes.
authors.affiliation: Corresponding author: Priscilla Hollander, priscilh@baylorhealth.edu.
authors.forename: Priscilla
authors.initials: P
authors.lastname: Hollander
authors.forename: Alok K
authors.initials: AK
authors.lastname: Gupta
authors.forename: Raymond
authors.initials: R
authors.lastname: Plodkowski
authors.forename: Frank
authors.initials: F
authors.lastname: Greenway
authors.forename: Harold
authors.initials: H
authors.lastname: Bays
authors.forename: Colleen
authors.initials: C
authors.lastname: Burns
authors.forename: Preston
authors.initials: P
authors.lastname: Klassen
authors.forename: Ken
authors.initials: K
authors.lastname: Fujioka
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects*; D016642:Bupropion / Q000008:administration & dosage*; D003692:Delayed-Action Preparations; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009271:Naltrexone / Q000008:administration & dosage*; D009292:Narcotic Antagonists / Q000008:administration & dosage; D009765:Obesity / Q000097:blood / Q000150:complications / Q000188:drug therapy; D050177:Overweight / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D012189:Retrospective Studies; D012307:Risk Factors; D016896:Treatment Outcome; D015431:Weight Loss; D055815:Young Adult
chemical_list: D018687:Antidepressive Agents, Second-Generation; D001786:Blood Glucose; D003692:Delayed-Action Preparations; D009292:Narcotic Antagonists; D016642:Bupropion; D009271:Naltrexone