Prevention of Type 2 Diabetes in Subjects With Prediabetes and Metabolic Syndrome Treated With Phentermine and Topiramate Extended Release

• Published in: Diabetes care Vol. 37; no. 4; pp. 912 - 921
• Main Authors: Garvey, W. Timothy, Ryan, Donna H., Henry, Robert, Bohannon, Nancy J.V., Toplak, Hermann, Schwiers, Michael, Troupin, Barbara, Day, Wesley W.
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.04.2014
• Subjects: Anti-Obesity Agents - administration & dosage; Anti-Obesity Agents - therapeutic use; Biological and medical sciences; Blood pressure; Current Concepts of Type 2 Diabetes Prevention; Delayed-Action Preparations; Development and progression; Diabetes; Diabetes Mellitus, Type 2 - prevention & control; Diabetes therapy; Diabetes. Impaired glucose tolerance; Disease prevention; Drug therapy; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Fructose - administration & dosage; Fructose - analogs & derivatives; Fructose - therapeutic use; Humans; Life Style; Male; Medical sciences; Metabolic diseases; Metabolic syndrome; Metabolic Syndrome - complications; Metabolic Syndrome - drug therapy; Middle Aged; Miscellaneous; Other metabolic disorders; Pharmaceutical industry; Phentermine - administration & dosage; Phentermine - therapeutic use; Placebos; Prediabetic state; Prediabetic State - complications; Prediabetic State - drug therapy; Prescription drugs; Prevention; Prevention and actions; Public health. Hygiene; Public health. Hygiene-occupational medicine; Topiramate; Type 2 diabetes; Weight; Weight reducing preparations; France; United States; Switzerland; Amphetamine derivatives; Endocrinopathy; Type 2 diabetes; Human; Topiramate; Nutrition; Controlled release form; Phentermine; Cardiovascular disease; Metabolic diseases; Anticonvulsant; Metabolic syndrome; Prevention; Treatment; Anorectic; Endocrinology
• DOI: 10.2337/dc13-1518
• ISSN: 0149-5992; 1935-5548

OBJECTIVE To evaluate over 108 weeks the effect of phentermine and topiramate extended release (PHEN/TPM ER) treatment on progression to type 2 diabetes and/or cardiometabolic disease in subjects with prediabetes and/or metabolic syndrome (MetS) at baseline. RESEARCH DESIGN AND METHODS Subanalysis of a phase 3, randomized, placebo-controlled, double-blind study of overweight/obese subjects (BMI ≥27 to ≤45 kg/m(2)) with two or more comorbidities. Subjects were randomized to placebo, PHEN 7.5 mg/TPM ER 46 mg (7.5/46), or PHEN 15 mg/TPM ER 92 mg (15/92) plus lifestyle modifications for 108 weeks. Percent weight loss in the intent-to-treat population using multiple imputation (ITT-MI), annualized incidence rate of progression to type 2 diabetes, and changes in glycemia, lipid parameters, blood pressure, and waist circumference were evaluated. RESULTS At baseline, 475 subjects met the criteria for prediabetes and/or MetS. After 108 weeks, subjects with prediabetes and/or MetS in the placebo, 7.5/46, and 15/92 groups experienced mean percent weight loss of 2.5, 10.9, and 12.1%, respectively (ITT-MI; P < 0.0001 vs. placebo), associated with reductions of 70.5 and 78.7% in the annualized incidence rate of type 2 diabetes for those receiving 7.5/46 and 15/92, respectively (ITT, P < 0.05), versus placebo. The ability of PHEN/TPM ER to prevent diabetes was related to degree of weight lost and was accompanied by significant improvements in cardiometabolic parameters. PHEN/TPM ER was well tolerated by this subgroup over 2 years. CONCLUSIONS PHEN/TPM ER plus lifestyle modification produced significant weight loss and markedly reduced progression to type 2 diabetes in overweight/obese patients with prediabetes and/or MetS, accompanied by improvements in multiple cardiometabolic disease risk factors.