Phentermine and topiramate combination for chronic weight management: a review
Keywords:Obesity, Pharmacotherapy, Phentermine, Topiramate
Obesity is a major public health concern and one of the leading preventable causes of death worldwide. It has manifold adverse health consequences, potentially involving all major organ systems thus leading to a reduced life expectancy. The long-term successful management of obesity remains a herculean task and invariably requires a multifaceted approach including lifestyle and behavioral modification, increased physical activity, and adjunctive pharmacotherapy and bariatric surgery. However, effective pharmacological options are limited because of the previous history of several failed agents as well as the fact that presently available agents are few, and utilized only as monotherapy. The recent Food and Drug Administration (FDA) approval of the fixed drug combination of phentermine and extended release topiramate marks the first FDA approved combination pharmacotherapeutic agent for obesity. This review details the various pharmacological aspects of the use of phentermine and topiramate combination along with the results of clinical trials done so far and also the present role of this combination in the management of obesity. Beyond the significant improvement in weight, the findings from various clinical trials also show improvement in metabolic and glycemic parameters, blood pressure, and lipid profile suggesting its added utility in cardiovascular risk modification. The acceptability of this combination would usher in a new era in the pharmacotherapy of obesity that utilizes combination therapy to improve efficacy, enhance synergism and concurrently minimize the risk of adverse effects. As with any newly marketed drug, there may be yet-unknown benefits and risks associated with this combination, which would be known only after its long-term use.
Barness LA, Opitz JM, Gilbert-Barness E. Obesity: genetic, molecular, and environmental aspects. Am J Med Genet A. 2007;143A(24):3016-34.
Caballero B. The global epidemic of obesity: an overview. Epidemiol Rev. 2007;29(1):1-5.
Obesity and Overweight. World Health Organisation. Available from: http://www.who.int/mediacentre/factshe. [Last accessed on 2013 Aug 05].
Flier JS, Flier EM. Biology of obesity. In: Longo DL, Kasper DL, Jameson JL, Fauci AS, Hauser SL, Loscalzo J, editors. Harrison’s Principles of Internal Medicine. New York: McGraw-Hill; 2012: 462-8.
Kelly T, Yang W, Chen CS, Reynolds K, He J. Global burden of obesity in 2005 and projections to 2030. Int J Obes. 2008;32(9):1431-7.
Derosa G, Maffioli P. Anti-obesity drugs: a review about their effects and their safety. Expert Opin Drug Saf. 2012;11(3):459-71.
Greenway FL, Bray GA. Combination drugs for treating obesity. Curr Diab Rep. 2010;10(2):108-15.
Topiramate. Drug Bank. Available from: http://www.drugbank.ca/drugs/DB00273 [Last accessed on 2013 Aug 11].
Phentermine. Drug Bank. Available from: http://www.drugbank.ca/drugs/DB00191. [Last accessed on 2013 Aug 21].
Qsymia. Available from: https://www.qsymia.com/pdf/prescribing-information.pdf. [Last accessed on 2013 Aug 05].
Allison DB, Gadde KM, Garvey WT, Peterson CA, Schwiers ML, Najarian T, et al. Controlled-Release Phentermine/Topiramate in Severely Obese Adults: a randomized controlled trial (EQUIP). Available from: http://www.vivus.com/images/stories/downloads_newsroom/equipobesityoct2011.pdf. [Last accessed on 2013 Aug 04].
Gadde KM, Allison DB, RyaN DH, Peterson CA, Troupin B, Schwiers ML, et al. Effects of low-dose, controlled-release phentermine plus topiramate combination on weight and associated co morbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled phase trial. Available from: http://www.vivus.com/images/stories/downloads_newsroom/lancet.pdf. [Last accessed on 2013 Aug 05].
Garvey WT, Ryan DH, Look M, Gadde KM, Allison DB, Peterson CA, et al. 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. Available from: http://www.vivus.com/images/stories/downloads_newsroom/garvey-sequel.pdf. [Last accessed on 2013 Aug 05].
Ryan DH, Peterson C, Troupin B. Weight loss at 6 months with V1-0521 (PEN/TPM combination) treatment. Paper Presented at the 69th Annual Scientific Sessions of the American Diabetes Association; 2009.
VIVUS I. VIVUS Reports Topline Findings from FORTRESS, Dec 21, 2011. [media release on the Internet]Available from: http://www.ir.vivus.com/releasedetail.cfm? ReleaseID=634920. [Last accessed on 2014 Mar 16].
Hunt S, Russell A, Smithson WH, Parsons L, Robertson I, Waddell R, et al. Topiramate in pregnancy: preliminary experience from the UK Epilepsy and Pregnancy Register. Neurology. 2008;71(4):272-6.
Winslow DH, Bowden CH, DiDonato KP, McCullough PA. A randomized, double-blind, placebo-controlled study of an oral, extended-release formulation of phentermine/topiramate for the treatment of obstructive sleep apnea in obese adults. Sleep. 2012;35(11):1529-39.