Pharmacotherapy for obesity among ‘best’ approaches to fill treatment gaps

BOSTON — In an overview of the pharmacotherapy options clinicians now have in their arsenal to help patients battle obesity, a presenter here discussed six FDA-approved drugs.

Samuel Klein, MD, chief of the division of geriatrics and nutritional sciences and director of the center for human nutrition at Washington University School of Medicine, St. Louis, Mo., detailed the efficacy and safety of each and the treatment gaps each class of drugs fills.

“People can lose weight, but the Achilles’ heel and the problem of managing obesity is keeping the weight off,” Klein said. “Pharmacotherapy here is really one of our best approaches for helping people not just lose weight, but maintain the weight loss long term.”

However, between physicians who are somewhat reluctant to prescribe them and patients reluctant to pay for the nonreimbursable drugs, few patients with obesity actually receive pharmacotherapy, Klein noted.

“Since obesity is a chronic disease, chronic pharmacotherapy would hopefully be one of the answers to help maintain long-term weight loss,” he said. “This really does have a place in managing and treating obesity.”

Pharmacotherapy round-up

Following a 50-year period during which only approximately 10 drugs were approved to treat obesity, four received FDA go-ahead in just the last 2 years, Klein said.

“Recently we’ve had a plethora compared to the past … which makes it very important for physicians to understand what these medications are, what the can do, what they can’t do and when they should be used,” he said.

Phentermine | FDA-approved in 1959

Recommend dosage. 30 mg once daily; legally approved only for short-term use, with no long-term indication at time of approval.

Clinical efficacy. Phentermine is “surprisingly” effective but has little data due to its early approval. Patients who received even a half dose (15 mg/day) or a quarter dose (7.5 mg/day) had approximately 5% greater weight loss than placebo.

Among the complications. Dry mouth, difficulty sleeping and nervousness; attenuates weight-loss–induced benefits on BP and heart rate, but overcomes these later; contraindicated in those with CV disease, particularly arrhythmia.

Orlistat (Xenical and Alli, GSK) | FDA-approved in 1999

Recommend dosage. Prescription, 120 mg three times daily; over-the-counter, 60 mg three times daily.

Clinical efficacy. Orlistat is a lipase inhibitor that blocks the absorption of fat — for patients on a regular diet, around 30% — and inhibits the digestion and absorption of triglycerides. Whether half a dose or full dose, patients see approximately 3% greater weight loss than placebo.

Among the complications. Gastrointestinal side effects are common. Recidivism occurs over time.

Combination Phentermine-Topiramate | FDA-approved in 2012

Recommend dosage. 7.5 mg phentermine and 46 mg topiramate once daily; given in various doses.

Clinical efficacy. Phentermine-topiramate consistently shows an “impressive” average weight loss of approximately 8% greater than placebo. If a patient does not achieve ≥ 5% weight loss after 12 weeks of the highest dose, it is recommended to stop treatment.

Among the complications. Dry mouth, dizziness, abnormal taste, constipation, insomnia, tingling; cognitive dysfunction can occur, including attention deficits and memory loss; concerns about fetal toxicity; potential glaucoma.

Lorcaserin (Belviq, Eisai) | FDA-approved in 2013

Recommend dosage. 10 mg twice daily.

Clinical efficacy. Lorcaserin is a 5-HT2C agonist shown to reduce weight by approximately 3% to 4% greater than placebo.

Among the complications. Headache, nausea, dizziness, dry mouth and fatigue; can cause hypoglycemia in patients with type 2 diabetes; semi-contraindicated in patients taking SSRIs.

Combination Bupropion-Naltrexone (Contrave, Takeda) | FDA-approved in 2014

Recommend dose. 360 mg bupropion and 32 mg naltrexone twice daily.

Clinical efficacy. Bupropion-naltrexone has demonstrated approximately 4% greater weight loss than placebo. Increasing the dose does not appear to augment the treatment success.

Among the complications. A lengthy list incorporates side effects of both individually approved drugs and includes nausea, headache, constipation, diarrhea, dizziness, vomiting, insomnia, dry mouth, anxiety and tremor; attenuates weight-loss–induced benefits on BP, and increases heart rate; requires altering doses of a variety of other medications.

Liraglutide (Saxenda, Novo Nordisk) | FDA-approved in 2015

Recommend dosage. 3 mg once daily; not the 1.8 mg approved for treating diabetes.

Clinical efficacy. Liraglutide has been shown to lead to an approximate 5% greater weight loss than placebo, with no difference seen between patients with normoglycemia and diabetes.

Among the complications. Mild to moderate nausea and diarrhea.

A class of drugs in context

Although the history of this class was fraught with some missteps, with drugs approved and later withdrawn because the perception that their side effects were not worth the benefits, Klein said we can expect more of these medications.

He made a caveat to the audience that the weigh losses represent averages.

“Some patients will lose a lot of weight. Some will lose very little weight. And you don’t know, there’s no way to predict how your patient will respond to any medication in advance. The only way to know is to try it. For any of these medications, you have a range of responses, so it’s very difficult to say that one medication is more effective than another in any individual patient. And if one medication doesn’t work, a patient may respond to another medication subsequently.”

Klein said patients could even respond to the same medication subsequently, but that has yet to be studied.

The side effects of these drugs are reversible by ceasing medication, Klein said, and sometimes even disappear on their own.

“Even if they are very severe, if you stop the medication, the side effects go away,” he said. “Many times the side effects go away even if you don’t stop the medications, but just lower the dose. And many times, the side effects go away if you continue the same dose.

Klein also noted that using pharmacotherapy to manage obesity does not work as well without behavior therapy for obesity. Taking the drugs while avoiding lifestyle changes, he said, “exposes patients to all the side effects and costs of the medication without the full benefit.”

Further, Klein said these types of therapies should not be considered to “jumpstart” patient treatment or “get them over the hump” because the weight will come back very quickly.

The treatment gaps exist between diet therapy and surgical therapy, as well as in patients who do not respond well to surgical therapy and those who respond well to surgical therapy but then regain the weight.

“There are the potential places where drug therapy may become useful,” Klein said. “And we should not be treating ‘hyperBMIemia’ — we should really be treating a patient.” – by Allegra Tiver

Reference:

Klein S. Pharmacotherapy in the Management of Obesity: New Drugs and Emerging Targets. Presented at: Cardiometabolic Health Congress; October 21-24, 2015; Boston.

Disclosure: Klein reports being a stockholder of Aspire Bariatrics and Human Longevity Inc. and having served on scientific advisory boards for NovoNordisk, Pfizer and Takeda.