About three-quarters of current cigarette smokers want to quit, 40% will attempt to quit annually, and 90% of self-initiated attempts will be unsuccessful. Mean weight gain after smoking cessation may be as much as 13 pounds at 1 year, and 21 pounds over 5 years.

Population data suggest that more than one-half of women and one-third of men with a previous attempt to quit smoking report that weight gain was one of the primary reasons for relapse back to smoking.

Developing effective approaches to the prevention of post-cessation weight gain (PCWG) may increase the likelihood of sustained smoking abstinence and may engage “weight-concerned smokers” in the quitting process. Bupropion SR has the greatest effect for preventing PCWG, but nicotine replacement therapies may have an effect as well while they are being used. Varenicline has no effect on PCWG.

Lorcaserin is a 5-HT2c (serotonin) receptor agonist FDA-approved for weight loss. Varenicline is the most effective monotherapy for smoking cessation and targets the alpha-4 beta-2 nicotinic acetylcholine receptor.

Ryan Hurt, MD , and his colleagues recently completed a pilot clinical trial evaluating the potential efficacy of combining varenicline and lorcaserin for the prevention of PCWG in obese and overweight smokers ( Nicotine Tob Res. 2016 Nov 16. doi: 10.1093/ntr/ntw304 ).

In this study, 20 smokers with a body mass index of 27-40 kg/m2 received varenicline and lorcaserin for 12 weeks.

Fifty percent of subjects were abstinent from smoking at 12 weeks, among whom weight gain was only +1.1 ± 3.9 kg (90% confidence interval, –0.9 to +3.1). The most-common side effect of the combination was sleep disturbance, reported by five patients.

The study was limited by the small sample size and the absence of a control group or placebo.

As clinicians, we frequently employ combination therapy in chronic diseases such as diabetes and hypertension when single-agent therapy is ineffective. By combining drugs with different therapeutic targets, we can achieve our treatment goals.

In tobacco dependence treatment, we use combination pharmacotherapy for heavier smokers or for those who have tried and failed to quit previously. Interestingly, lorcaserin has been demonstrated in another pilot study to increase smoking cessation rates by itself.

The combination of lorcaserin and varenicline holds promise for the treatment of tobacco dependence by attacking tobacco dependence through two different mechanisms and preventing PCWG, which may prevent relapse back to smoking.

Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author and do not necessarily represent the views and opinions of the Mayo Clinic. The opinions expressed in this article should not be used to diagnose or treat any medical condition, nor should they be used as a substitute for medical advice from a qualified, board-certified practicing clinician. Dr. Ebbert has no relevant financial disclosures about this article.

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