title: Two-year sustained weight loss and metabolic benefits with controlled-release phentermine/topiramate in obese and overweight adults (SEQUEL): a randomized, placebo-controlled, phase 3 extension study.
abstract: BACKGROUND
  Obesity is a serious chronic disease. Controlled-release phentermine/topiramate (PHEN/TPM CR), as an adjunct to lifestyle modification, has previously shown significant weight loss compared with placebo in a 56-wk study in overweight and obese subjects with ≥2 weight-related comorbidities.
  
  
  OBJECTIVE
  This study evaluated the long-term efficacy and safety of PHEN/TPM CR in overweight and obese subjects with cardiometabolic disease.
  
  
  METHODS
  This was a placebo-controlled, double-blind, 52-wk extension study; volunteers at selected sites continued with original randomly assigned treatment [placebo, 7.5 mg phentermine/46 mg controlled-release topiramate (7.5/46), or 15 mg phentermine/92 mg controlled-release topiramate (15/92)] to complete a total of 108 wk. All subjects participated in a lifestyle-modification program.
  
  
  RESULTS
  Of 866 eligible subjects, 676 (78%) elected to continue in the extension. Overall, 84.0% of subjects completed the study, with similar completion rates between treatment groups. At week 108, PHEN/TPM CR was associated with significant, sustained weight loss (intent-to-treat with last observation carried forward; P < 0.0001 compared with placebo); least-squares mean percentage changes from baseline in body weight were -1.8%, -9.3%, and -10.5% for placebo, 7.5/46, and 15/92, respectively. Significantly more PHEN/TPM CR-treated subjects at each dose achieved ≥5%, ≥10%, ≥15%, and ≥20% weight loss compared with placebo (P < 0.001). PHEN/TPM CR improved cardiovascular and metabolic variables and decreased rates of incident diabetes in comparison with placebo. PHEN/TPM CR was well tolerated over 108 wk, with reduced rates of adverse events occurring between weeks 56 and 108 compared with rates between weeks 0 and 56.
  
  
  CONCLUSIONS
  PHEN/TPM CR in conjunction with lifestyle modification may provide a well-tolerated and effective option for the sustained treatment of obesity complicated by cardiometabolic disease. This trial was registered at clinicaltrials.gov as NCT00796367.
authors.affiliation: Department of Nutrition Sciences, UAB Diabetes Research and Training Center, University of Alabama at Birmingham, 35294-3360, USA. garveyt@uab.edu
authors.forename: W Timothy
authors.initials: WT
authors.lastname: Garvey
authors.forename: Donna H
authors.initials: DH
authors.lastname: Ryan
authors.forename: Michelle
authors.initials: M
authors.lastname: Look
authors.forename: Kishore M
authors.initials: KM
authors.lastname: Gadde
authors.forename: David B
authors.initials: DB
authors.lastname: Allison
authors.forename: Craig A
authors.initials: CA
authors.lastname: Peterson
authors.forename: Michael
authors.initials: M
authors.lastname: Schwiers
authors.forename: Wesley W
authors.initials: WW
authors.lastname: Day
authors.forename: Charles H
authors.initials: CH
authors.lastname: Bowden
mesh_terms: D000328:Adult; D019440:Anti-Obesity Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000150:complications / Q000188:drug therapy*; D003692:Delayed-Action Preparations; D003920:Diabetes Mellitus / Q000453:epidemiology / Q000517:prevention & control; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D005632:Fructose / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D015994:Incidence; D057194:Intention to Treat Analysis; D016018:Least-Squares Analysis; D008297:Male; D008659:Metabolic Diseases / Q000517:prevention & control; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000188:drug therapy*; D050177:Overweight / Q000150:complications / Q000188:drug therapy*; D010352:Patient Dropouts; D010645:Phentermine / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D013995:Time; D000077236:Topiramate; D015431:Weight Loss / Q000187:drug effects*
chemical_list: D019440:Anti-Obesity Agents; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D000077236:Topiramate; D005632:Fructose; D010645:Phentermine