Two Weight-Loss Drugs Have Highest Odds for 5% Reduction

Marcia Frellick

June 15, 2016

All five drugs approved by the US Food and Drug Administration (FDA) for long-term use in obese or overweight people were associated with a 5% reduction in weight at 1 year vs placebo, but two — controlled-release phentermine and topiramate (Qsymia, Vivus) and liraglutide (Saxenda, Novo Nordisk) — had the highest odds of hitting that mark, according to a new meta-analysis, published in the June 14 issue of the Journal of the American Medical Association. The five drugs are approved for use in obesity (body mass index [BMI] of at least 30 kg/m2) or in overweight people (BMI of at least 27 kg/m2) who have at least one weight-related comorbidity (type 2 diabetes, hypertension, hyperlipidemia).

Rohan Khera, MD, from the department of internal medicine, University of Iowa Carver College of Medicine, Iowa City, and colleagues analyzed 28 randomized clinical trials that included 29,018 patients (median age, 46 years; 74% women; median baseline weight, 100.5 kg [221.6 lbs]; median baseline BMI, 36.1).

Among the placebo group, 23% achieved 5% weight loss.

Drugs' Performance

Study drug Participants showing at least 5% weight loss (%) Average weight loss at 1 year (lbs) Odds ratio of 5% loss at 1 year*
Phentermine-topiramate 75 19.4 9.22
Liraglutide 63 11.7 5.54
Naltrexone-bupropion 55 11 3.96
Lorcaserin 49 7.1 3.1
Orlistat 44 5.7 2.7
*Compared with placebo
Most Bang for the Buck for Qsymia?

The systematic review suggests phentermine-topiramate has several advantages for losing weight.

However, coauthor Siddharth Singh, MD, of the School of Medicine at University of California, San Diego, told Medscape Medical News there are several factors beyond the amount of weight loss obtained that patients and physicians should consider.

He said about phentermine-topiramate, "Overall…I think that's where the most bang for your buck is" but noted that weight loss is different for each patient and different drugs may be more effective or desirable for different patients.

For instance, liraglutide, which is also a medicine for type 2 diabetes and has glucose-lowering effects, may be a more appropriate choice for people who have diabetes, Dr Singh explained.

However, liraglutide is delivered by subcutaneous injection for weight loss, and that may push some people toward a different drug, he added.

And naltrexone-bupropion (Contrave, Orexigen Therapeutics) may be associated with neuropsychiatric properties, such as a potential increased risk of suicide, which must be considered when choosing an agent for certain patients, particularly those with chronic alcohol or drug dependence.

How to Choose

"The approach as to whether to use a particular medication has to be more nuanced," Dr Singh said. "This just gives an idea of what the magnitude of weight loss across all these medications is."

Cost is also a consideration. Orlistat, for instance, costs less than the others, but it was associated with the lowest amount of weight loss. Orlistat is available as an over-the-counter medication (Alli, GlaxoSmithKline); it was initially approved as a prescription medicine (Xenical, Roche).

The main outcome evaluated was 5% weight loss, but researchers also looked at 10% weight loss at 1 year.

The ranking among the drugs in terms of estimated percentage of participants who achieved 10% weight loss over 1 year was: phentermine-topiramate, 54%; liraglutide, 34%; naltrexone-bupropion, 30%; lorcaserin (Belviq, Arena Pharmaceuticals), 25%; and orlistat, 20%.

Comparison With Placebo on Adverse Events

Phentermine-topiramate was more likely to help people achieve both 5% and 10% weight loss than all the other drugs, and there was no significant difference in odds of discontinuation from adverse events among phentermine-topiramate, liraglutide, and naltrexone-bupropion.

Compared with placebo, all five drugs had 1.3 to 2.95 higher odds of being associated with discontinuation due to adverse events. Compared with placebo, lorcaserin had the lowest odds of being discontinued (OR, 1.34). Liraglutide and naltrexone-bupropion had the highest odds, at 2.95 and 2.64, respectively.

Among study limitations is the fact that four of the five agents were approved by the FDA within the past 3 years and because there is no weight-loss standard for comparing drugs as part of approval, direct-comparison trials are lacking.

That's why a network meta-analysis was advantageous, Dr Singh said, so they could compare the drugs with each other.

The next step for the researchers is to compare the same drugs in terms of improving cholesterol levels and blood pressure and "all the things that go into cardiovascular risk," Dr Singh said. They also need to figure out how the drugs fit with other interventions, such as surgery.

They also add a caution about the need for long-term surveillance: "Historically, concerns regarding the long-term safety profile of pharmacotherapy for weight loss have limited their clinical use, particularly among medications with significant adrenergic actions or central appetite-suppressing actions.

"Short-term clinical trials may not provide comprehensive information on the long-term safety of these agents, and prospective postmarketing surveillance studies are warranted," they conclude.

Dr Khera reports no relevant financial relationships. Dr Singh is supported by National Library of Medicine training grant. Disclosures for the coauthors are listed in the article.

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JAMA. 2016;315:2424-2434. Abstract

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