Obesity Treatment Choice Depends on Medication Side Effects, Patient Characteristics

The range of medication choices to treat obesity is expanding, and a rational prescribing plan requires a solid grasp of medication side effects.

Caroline M. Apovian, MD, director of the Center for Nutrition and Weight Management at Boston Medical Center, said in addition to the approved prescriptions being used, off-label use of medications may be considered in some cases. She presented these options during a pharmacology-focused session at Obesity Week in Boston, MA on November 5, 2014.

Apovian reminded attendees that non-drug interventions, including lifestyle, diet, and behavior modification counseling, should be used for at least 6 months before considering use of medication in individuals with obesity. These interventions should continue during pharmacotherapy and are considered the cornerstone of effective weight management programs.

Discussing newer agents, she began with Lorcaserin, a selective serotonin 2c receptor agonist. This is a novel agent that promotes feelings of satiety. Lorcaserin tends to produce a modest total weight loss of 3-5% of body weight, but some patients will have a robust response: approximately 25% of patients will lose at least 10% of their body weight. Clinicians should assess weight loss at 3 months and move the patient to another medication if at least 5% weight loss has not occurred at that point. Side effects, overall, tend to be modest: fatigue is common, and headache and dizziness also occur in about one in six patients. Lorcaserin is dosed at 10 mg twice daily.

Phentermine and topiramate, both previously approved agents, are now available in an extended-release combination format. Phentermine, the sympathomimetic moiety, suppresses appetite, while topiramate acts on GABA receptors and is a carbonic anhydrase inhibitor, promoting satiety. Each medication tends to counterbalance the side effect profile of the other. Nevertheless, insomnia or somnolence may still occur, and patients sometimes report bothersome paresthesias, probably related to topiramate’s carbonic anhydrase inhibition. Dosing for phentermine/topiramate begins at 3.75/23 mg for two weeks, then may be escalated to a mid-range dose of 7.5/46 mg. the maximum dose is 15/92 mg. Discontinuation should involve a taper.

Another combination of previously available agents, naltrexone/bupropion, also takes advantage of synergy between the two components. Bupropion inhibits uptake of both norepinephrine and dopamine, promoting satiety; naltrexone, a mu opioid agonist, blocks inhibition of feedback to allow satiety signals to be processed. Naltrexone alone has never been used as a weight loss agent. Side effects, which can include nausea, constipation, headache, and dry mouth, tend to moderate over time and can be mitigated with the suggested graduated dosing schedule. Since a transient increase in blood pressure (mean elevation, 1.5 mm Hg) can occur, patient characteristics should be considered before prescribing. Patients take one pill with 8 mg naltrexone and 90 mg bupropion once daily for a week, then add one pill per week to reach a twice daily 16/180 mg dose at the end of four weeks.

An agent currently approved for type 2 diabetes mellitus (T2DM), liraglutide, is expected to be approved for the treatment of obesity soon. This glucose-like peptide-1 (GLP-1) receptor agonist is thought to regulate appetite through hypothalamic action. Nausea is a common side effect that tends to abate over time; in general, liraglutide is well tolerated. When studied for use in individuals with obesity, medication adherence was not affected by the fact that this is a daily injectable medication.

Moving to a discussion of off-label use of medications to treat obesity, Apovian framed the discussion in terms of synergy with treatment for other conditions. For example, individuals with T2DM may expect some weight loss with metformin; exenatide and liraglutide may also produce weight loss. Other agents to consider include the novel class of sodium- glucose cotransporter 2 (SGLT2) inhibitors and pramlintide.

Apovian advocated considering bupropion as first-line treatment for individuals with depression and obesity, even before using a selective serotonin reuptake inhibitor. She advised avoiding Paxil in depressed individuals with obesity, noting that data are strongest for weight gain with this medication.

Beta blockers should be avoided in hypertensive individuals with obesity when possible, Apovian advised, since they can promote weight gain. Similarly, if insomnia is an issue for a patient with obesity, they should not take antihistamines for sleep.

Moving to the practical issue of the cost of some of the newer combination medications, Apovian pointed out that each component may be prescribed separately if insurance coverage and cost are an issue. If phentermine and topiramate are prescribed, she advised instructing patients to take phentermine in the morning and topiramate near bedtime, to avoid daytime sedation and insomnia. However, she also noted that expert guidelines on the use of this and other anti-obesity medications will soon be forthcoming and that the guidelines will recommend that only obesity experts should prescribe drugs off-lable for weight loss.