title: Phentermine, topiramate and their combination for the treatment of adiposopathy ('sick fat') and metabolic disease.
abstract: Positive caloric balance often causes pathologic adipocyte and adipose tissue anatomical and functional changes (termed adiposopathy or 'sick fat'), which may lead to pathogenic adipocyte and adipose tissue responses and metabolic disease. Fat weight loss may improve adiposopathy, and thus improve metabolic disease in overweight patients. Unfortunately, the efficacy of non-surgical weight loss therapies is often limited due to redundant physiological systems that help 'protect' against starvation and/or negative caloric balance. One strategy to overcome these limitations is to combine weight loss drug therapies having complementary mechanisms of action, thereby affecting more than one physiologic process influencing body fat accumulation. Phentermine is a noradrenergic sympathomimetic amine approved for short-term treatment of obesity. Topiramate is a sulfamate-substituted monosaccharide derivative of the naturally occurring sugar monosaccharide D-fructose approved as a treatment for migraine headaches and seizure disorders. Although known to facilitate weight loss since its approval, topiramate monotherapy does not have a regulatory indication as an anti-obesity agent. Phentermine HCl/topiramate controlled-release (PHEN/TPM CR) is a combination agent containing immediate-release phentermine and controlled-release topiramate. Clinical trials involving thousands of patients demonstrate PHEN/TPM CR to be effective in improving the weight of patients, and also effective in improving adiposopathy-associated metabolic diseases. This review examines the pathophysiology of adiposopathy as a contributor to metabolic disease, the data supporting phentermine monotherapy, topiramate monotherapy and their combination as anti-obesity and anti-adiposopathy agents, and the preliminary evidence supporting PHEN/TPM CR as a generally well-tolerated and effective agent to improve metabolic disease.
authors: L-MARC Research Center, 3288 Illinois Avenue, Louisville, KY 40213, USA. hbaysmd@aol.com
authors: Harold
authors: H
authors: Bays
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000503:physiopathology; D050154:Adiposity / Q000187:drug effects; D000818:Animals; D019440:Anti-Obesity Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001067:Appetite Depressants / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001069:Appetite Regulation / Q000187:drug effects; D003692:Delayed-Action Preparations; D017277:Drug Approval; D004338:Drug Combinations; D015507:Drugs, Investigational / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D005632:Fructose / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008659:Metabolic Diseases / Q000188:drug therapy* / Q000503:physiopathology; D009765:Obesity / Q000188:drug therapy* / Q000503:physiopathology; D010645:Phentermine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D017410:Practice Guidelines as Topic; D013566:Sympathomimetics / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000077236:Topiramate; D014481:United States; D014486:United States Food and Drug Administration; D015431:Weight Loss / Q000187:drug effects
chemical_list: D019440:Anti-Obesity Agents; D001067:Appetite Depressants; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D015507:Drugs, Investigational; D013566:Sympathomimetics; D000077236:Topiramate; D005632:Fructose; D010645:Phentermine