This letter discusses the safety of using the drug phentermine for long-term obesity treatment. It argues that contrary to common assumptions, phentermine does not typically elevate blood pressure and may even reduce it. The letter cites clinical trials and observational studies showing blood pressure declines in phentermine-treated patients, especially those with preexisting hypertension who lost weight. The authors conclude that long-term phentermine use is safer than assumed and should be the first-line pharmacotherapy considered for many obese patients. They call for additional long-term clinical trials of over 1 year to further evaluate phentermine's efficacy and safety profile.

1. letter to the editor
Diabetes, Obesity and Metabolism 13: 963–964, 2011.
© 2011 Blackwell Publishing Ltd
Phentermine therapy for obesity does not elevate blood
pressure
To the Editor: The preponderance of published evidence suggests that
The report by Kang et al. [1] of a clinical trial with a new blood pressure elevation because of phentermine is rare rather
diffuse-controlled release of phentermine for obesity is timely than common in the context of obesity management.
because phentermine is currently one of the few remaining Phentermine was approved for obesity treatment in 1959,
approved drugs for obesity pharmacotherapy. We agree that long before the chronicity of obesity was acknowledged and
the study data supports the authors’ conclusions that this the Food and Drug Administration (FDA) began to require
formulation of phentermine is a safe and effective treatment long-term clinical trials for obesity drugs. In response to a long
adjunct for treating obesity. We also agree that further long- simmering controversy, and after an extensive reevaluation
term studies of phentermine should be undertaken. In our of these obesity drugs, in 1977 the FDA formally reaffirmed
opinion, phentermine pharmacotherapy for obesity is much amphetamine and its congeners, including phentermine, to
safer than is commonly assumed. Phentermine offers a high be effective for obesity treatment. However, in response
potential of substantial benefit to obese patients, particularly to controversy regarding the addiction potential of the
those with moderate elevations of blood pressure, and it amphetamine congeners, and because most of the patients
should be the first choice medicine when pharmacotherapy in clinical trials had only taken the drugs for 12 weeks, the FDA
is considered for most obese patients. decided that these drugs should be used only a ‘few weeks’ [6].
Kang et al. mentioned that phentermine may elevate blood At that time, many private practice obesity treatment specialists
pressure, even though they observed the opposite effect. Other already had 18 years of experience with these amphetamine
than a few anecdotes, there is little or no evidence in the congeners, had found them to be both effective and safe, and
peer-reviewed medical literature to support the often repeated were using them long term for patients in their practices. Few
conjecture that phentermine, when chronically administered, of these practitioners discontinued their patients’ medications
when the FDA relabeled them for short term use only. (W.L.
to the editor
can elevate blood pressure. The clinical trial reports cited by
Asher, pers. comm.). Although the notion that phentermine
letter
Kang et al. either did not report blood pressures or reported that
should be used beyond 12 weeks did not begin to gain traction
phentermine-treated subjects had declines in blood pressure.
in the medical literature until after Weintraub et al.’s studies
The meta-analyses cited discuss elevations of blood pressure
appeared beginning in 1984 [7], occasional earlier reports had
as adverse effects but provide no supporting data. Average
suggested that the drugs could be used for longer durations than
blood pressures are known to decline when obese patients
12 weeks [8]. A recent survey of obesity treatment specialists
lose weight without pharmacotherapy [2]. Obesity treatment
in the US revealed that the majority of the specialists polled
specialists experienced with phentermine have known for
now use phentermine, diethylpropion, and phendimetrazine
some time that average blood pressures also decline in
long term [9]. We conclude that long-term phentermine
patients when phentermine is added to weight loss therapy. use has long been common in the US despite the FDA
These observations have recently been confirmed in two labeling.
observational reports from private practices, one short term [3] We concur with Kang et al., that additional phentermine
and the other long term [4]. In clinical trials for Qnexa, a efficacy and safety studies should be conducted. Since many
combination of phentermine and topiramate, investigators also physicians already use phentermine long term, the studies
observed that the blood pressure declined in treated patients should be long term, at least 1 year in length.
with the most pronounced declines occurring in patients
with preexisting hypertension [5]. The long-term phentermine
E. J. Hendricks∗
study mentioned above [4] found that phentermine-treated
Center for Weight Management, Roseville, CA 95661, USA
patients with preexisting hypertension had the greatest declines
in blood pressure, patients with preexisting prehypertension
had lesser declines, while patients with initial optimum
R. B. Rothman
blood pressures (<120/80) had no significant blood pressure
Belite Medical Center, Fairfax, VA 22030, USA
changes. Long-term phentermine-treated patients had better
success with weight loss maintenance and had blood pressure ∗ Center for Weight Management, 2510 Douglas Boulevard,
declines that were persistent so long as weight loss was Suite 200, Roseville, CA 95661, USA
maintained. E-mail: edhendricks@surewest.net

2. letter to the editor DIABETES, OBESITY AND METABOLISM
Conflict of Interest 4. Hendricks EJ, Greenway FL, Westman EC, Gupta AK. Blood pressure and
heart rate effects, weight loss and maintenance during long-term
Dr Hendricks wrote the draft and Dr Rothman revised the phentermine pharmacotherapy for obesity. Obesity (Silver Spring) 2011
letter. Both authors agreed on the final draft and have no [Epub ahead of print].
conflicts of interest. 5. Gadde KM, Allison DB, Ryan DH et al. Effects of low-dose, controlled-
release, phentermine plus topiramate combination on weight and
associated comorbidities in overweight and obese adults (CONQUER):
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964 doi:10.1111/j.1463-1326.2011.01435.x Volume 13 No. 10 October 2011