Which Weight-Loss Drug Works Best?


Some medications may work better than others in those looking to lose weight.

Some medications may work better than others in those looking to lose weight.

A recent study published in the Journal of the American Medical Association pitted the 5 FDA-approved weight-loss drugs (orlistat, lorcaserin, naltrexone/bupropion, phentermine/topiramate, and liraglutide) against each other to determine which medication was associated with the most weight loss after 1 year.

The meta-analysis included data from 30,000 obese (BMI ≥30) and overweight (BMI ≥27). Each patient had at least 1 weight-related comorbidity, such as hypertension, hyperlipidemia, or type 2 diabetes.

At the end of the 1-year study, the researchers found that a median 23% of participants taking the placebo saw at least 5% weight loss. Meanwhile, 75% of participants taking phentermine/topiramate, 63% of participants taking liraglutide, 55% taking naltrexone/bupropion, 49% taking lorcaserin, and 44% taking orlistat lost 5% of their baseline body weight by the end of the study.

“Ultimately, given the differences in safety, efficacy, and response to therapy, the ideal approach to weight loss should be highly individualized, identifying appropriate candidates for pharmacotherapy, behavioral interventions, and surgical interventions” the researchers wrote.

Despite the availability of 5 FDA-approved options, recent research results show that just 1% of obese patients who are eligible for weight-loss drugs are actually prescribed them. Other research has found that a very small number of health care providers write most of the prescriptions for those weight-loss drugs, suggesting that most providers are either unaware of their availability or don’t consider them to be standard practice yet. Obese patients may also lack awareness of the pharmacological options available to them.

Jennifer L. Costello, PharmD, BCPS, BC-ADM, previously told Pharmacy Times that the “risks and benefits [of weight-loss drugs] is an important area for pharmacists to know and review with patients to help educate them on their disease state.”

Pharmacists should review the following drug profiles to determine which option is best for a specific patient.


The FDA approved orlistat in 1999, and prior to 2012, it was the only FDA-approved medication for the long-term management of obesity. Today, orlistat is available as both a prescription (Xenical) and OTC product (Alli).

Because the triacylglycerol lipase inhibitor leads to weight loss by preventing the absorption of dietary fat, patients have to ingest dietary fat in order for the drug to be effective. Pharmacists should also note that orlistat has been associated with the potential to block other medications from absorption, so any interacting agents should be administered separately.


Approved in 2012, lorcaserin (Belviq) is a serotonin 2C receptor agonist that is taken twice a day with or without food.

Since Belviq works on serotonin, it’s associated with an increased risk for serotonin syndrome. Therefore, pharmacists should be mindful of possible drug interactions with serotonergic medications.

Results of a phase 2 clinical study in 2014 suggested that lorcaserin is also an effective smoking cessation aid.


Naltrexone/bupropion (Contrave) was approved in late 2014 as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults.

Contrave is a combination of naltrexone, an opioid antagonist, and bupropion, an antidepressant. The drug requires a 4-week dose titration schedule, and because it consists bupropion, it carries a black box warning for Suicidality and Antidepressant Drugs, as well as Neuropsychiatric Reactions in Patients Taking Bupropion for Smoking Cessation.

Other counseling points for Contrave include:

  • Swallow tablets whole, and don’t cut, chew, or crush. Tell your health care provider if you can’t swallow tablets whole.
  • Don’t take Contrave with high-fat meals, as it may increase your risk of seizures.
  • If you take a urine drug-screening test, Contrave may make the test result positive for amphetamines.


Phentermine/topiramate (Qsymia) was approved in 2012 and is a combination of phentermine, a sympathomimetic amine anorectic, and topiramate extended-release, an antiepileptic medication.

Qsymia is taken once a day, and pharmacists should counsel patients to take it in the morning with or without food in order to avoid insomnia. Because the product contains topiramate, patients may notice concentration, memory, and speech difficulties. It’s also critically important for pharmacists to counsel patients about the dangers of stopping Qsymia suddenly, as doing so can increase the risk for seizures.

Notably, Qsymia was the only high-profile drug to be excluded in its therapeutic category on CVS’s 2016 formulary. Express Scripts also excluded Qsymia on its 2016 Preferred Formulary.


Liraglutide (Victoza) was originally approved as a treatment for type 2 diabetes, but in December 2014, the FDA approved liraglutide injection (Saxenda) as a treatment option for chronic weight management.

Saxenda is a glucagon-like peptide-1 receptor agonist that shouldn’t be used in combination with any other drug belonging to this class. Although Saxenda and Victoza contain the same active ingredient at different doses, Saxenda isn’t indicated for the treatment of type 2 diabetes, as its safety and efficacy for this indication hasn’t been established.

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