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

• Published in: The American journal of clinical nutrition Vol. 95; no. 2; pp. 297 - 308
• Main Authors: Garvey, W Timothy, Ryan, Donna H, Look, Michelle, Gadde, Kishore M, Allison, David B, Peterson, Craig A, Schwiers, Michael, Day, Wesley W, Bowden, Charles H
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 01.02.2012; American Society for Nutrition; American Society for Clinical Nutrition, Inc
• Subjects: Adult; adults; adverse effects; analogs & derivatives; Anti-Obesity Agents; Anti-Obesity Agents - adverse effects; Anti-Obesity Agents - pharmacology; Anti-Obesity Agents - therapeutic use; Biological and medical sciences; Cardiorespiratory; Cardiovascular Diseases; Cardiovascular Diseases - complications; Cardiovascular Diseases - drug therapy; Chronic diseases; Clinical trials; complications; Delayed-Action Preparations; Diabetes; Diabetes Mellitus; Diabetes Mellitus - epidemiology; Diabetes Mellitus - prevention & control; Double-Blind Method; Drug Combinations; drug effects; drug therapy; epidemiology; Feeding. Feeding behavior; Female; Fructose; Fructose - adverse effects; Fructose - analogs & derivatives; Fructose - pharmacology; Fructose - therapeutic use; Fundamental and applied biological sciences. Psychology; Humans; Incidence; Intention to Treat Analysis; least squares; Least-Squares Analysis; Lifestyle; Lifestyles; Male; Metabolic Diseases; Metabolic Diseases - prevention & control; Metabolic disorders; Middle Aged; Nutrition; Obesity; Obesity - complications; Obesity - drug therapy; Obesity and Eating Disorders; Overweight; Overweight - complications; Overweight - drug therapy; Patient Dropouts; pharmacology; Phentermine; Phentermine - adverse effects; Phentermine - pharmacology; Phentermine - therapeutic use; placebos; prevention & control; Self efficacy; therapeutic use; Time; Topiramate; Vertebrates: anatomy and physiology, studies on body, several organs or systems; volunteers; Weight control; weight loss; Weight Loss - drug effects; AE; LOCF; LS; T2D; ITT; 7.5/46; 15/92; CVD; TEAE; SAE; PHEN/TPM CR; Hb A1c; bpm; C-SSRS; Human; Extension; Obesity; Nutrition disorder; Weight loss; Adult; Nutritional status; Release; Overweight
• ISSN: 0002-9165; 1938-3207; 1938-3207
• DOI: 10.3945/ajcn.111.024927

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. Design: 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. Conclusion: 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.