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Diabetes, Obesity and Metabolism 13: 963–964, 2011.© 2011 Blackwell Publishing Ltdletter to the editor

Phentermine therapy for obesity does not elevate bloodpressure

To the Editor:The report by Kang et al. [1] of a clinical trial with a newdiffuse-controlled release of phentermine for obesity is timelybecause phentermine is currently one of the few remainingapproved drugs for obesity pharmacotherapy. We agree thatthe study data supports the authors’ conclusions that thisformulation of phentermine is a safe and effective treatmentadjunct for treating obesity. We also agree that further long-term studies of phentermine should be undertaken. In ouropinion, phentermine pharmacotherapy for obesity is muchsafer than is commonly assumed. Phentermine offers a highpotential of substantial benefit to obese patients, particularlythose with moderate elevations of blood pressure, and itshould be the first choice medicine when pharmacotherapyis considered for most obese patients.

Kang et al. mentioned that phentermine may elevate bloodpressure, even though they observed the opposite effect. Otherthan a few anecdotes, there is little or no evidence in thepeer-reviewed medical literature to support the often repeatedconjecture that phentermine, when chronically administered,can elevate blood pressure. The clinical trial reports cited byKang et al. either did not report blood pressures or reported thatphentermine-treated subjects had declines in blood pressure.The meta-analyses cited discuss elevations of blood pressureas adverse effects but provide no supporting data. Averageblood pressures are known to decline when obese patientslose weight without pharmacotherapy [2]. Obesity treatmentspecialists experienced with phentermine have known forsome time that average blood pressures also decline inpatients when phentermine is added to weight loss therapy.These observations have recently been confirmed in twoobservational reports from private practices, one short term [3]and the other long term [4]. In clinical trials for Qnexa, acombination of phentermine and topiramate, investigators alsoobserved that the blood pressure declined in treated patientswith the most pronounced declines occurring in patientswith preexisting hypertension [5]. The long-term phenterminestudy mentioned above [4] found that phentermine-treatedpatients with preexisting hypertension had the greatest declinesin blood pressure, patients with preexisting prehypertensionhad lesser declines, while patients with initial optimumblood pressures (<120/80) had no significant blood pressurechanges. Long-term phentermine-treated patients had bettersuccess with weight loss maintenance and had blood pressuredeclines that were persistent so long as weight loss wasmaintained.

The preponderance of published evidence suggests thatblood pressure elevation because of phentermine is rare ratherthan common in the context of obesity management.

Phentermine was approved for obesity treatment in 1959,long before the chronicity of obesity was acknowledged andthe Food and Drug Administration (FDA) began to requirelong-term clinical trials for obesity drugs. In response to a longsimmering controversy, and after an extensive reevaluationof these obesity drugs, in 1977 the FDA formally reaffirmedamphetamine and its congeners, including phentermine, tobe effective for obesity treatment. However, in responseto controversy regarding the addiction potential of theamphetamine congeners, and because most of the patientsin clinical trials had only taken the drugs for 12 weeks, the FDAdecided that these drugs should be used only a ‘few weeks’ [6].At that time, many private practice obesity treatment specialistsalready had 18 years of experience with these amphetaminecongeners, had found them to be both effective and safe, andwere using them long term for patients in their practices. Fewof these practitioners discontinued their patients’ medicationswhen the FDA relabeled them for short term use only. (W.L.Asher, pers. comm.). Although the notion that phentermineshould be used beyond 12 weeks did not begin to gain tractionin the medical literature until after Weintraub et al.’s studiesappeared beginning in 1984 [7], occasional earlier reports hadsuggested that the drugs could be used for longer durations than12 weeks [8]. A recent survey of obesity treatment specialistsin the US revealed that the majority of the specialists pollednow use phentermine, diethylpropion, and phendimetrazinelong term [9]. We conclude that long-term phentermineuse has long been common in the US despite the FDAlabeling.

We concur with Kang et al., that additional phentermineefficacy and safety studies should be conducted. Since manyphysicians already use phentermine long term, the studiesshould be long term, at least 1 year in length.

E. J. Hendricks∗Center for Weight Management, Roseville, CA 95661, USA

R. B. RothmanBelite Medical Center, Fairfax, VA 22030, USA

∗Center for Weight Management, 2510 Douglas Boulevard,Suite 200, Roseville, CA 95661, USA

E-mail: edhendricks@surewest.net

letter to the editor DIABETES, OBESITY AND METABOLISM

Conflict of InterestDr Hendricks wrote the draft and Dr Rothman revised theletter. Both authors agreed on the final draft and have noconflicts of interest.

References1. Kang JG, Park CY, Kang JH, Park YW, Park SW. Randomized controlled trial to

investigate the effects of a newly developed formulation of phenterminediffuse-controlled release for obesity. Diabetes Obes Metab 2010; 12:876–882.

2. Aucott L, Rothnie H, McIntyre L, Thapa M, Waweru C, Gray D. Long-termweight loss from lifestyle intervention benefits blood pressure? a systematicreview. Hypertension 2009; 54: 756–762.

3. Rothman RB. Treatment of obesity with ‘‘combination’’ pharmacotherapy.Am J Ther 2010; 17: 596–603.

4. Hendricks EJ, Greenway FL, Westman EC, Gupta AK. Blood pressure andheart rate effects, weight loss and maintenance during long-termphentermine pharmacotherapy for obesity. Obesity (Silver Spring) 2011[Epub ahead of print].

5. Gadde KM, Allison DB, Ryan DH et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight andassociated comorbidities in overweight and obese adults (CONQUER):a randomised, placebo-controlled, phase 3 trial. Lancet 2011; 377:1341–1352.

6. Colman E. Anorectics on trial: a half century of federal regulation ofprescription appetite suppressants. Ann Intern Med 2005; 143: 380–385.

7. Weintraub M. Long-term weight control study: conclusions. Clin PharmacolTher 1992; 51: 642–646.

8. Craddock D. Anorectic drugs: use in general practice. Drugs 1976; 11:378–393.

9. Hendricks EJ, Rothman RB, Greenway FL. How physician obesity specialistsuse drugs to treat obesity. Obesity 2009; 17: 1730–1735.

964 doi:10.1111/j.1463-1326.2011.01435.x Volume 13 No. 10 October 2011