Four weight loss medications ranked in order of effectiveness by AGA guidelines

The prevalence of obesity has increased manifold globally over the last twenty years. Diet and exercise fail for most adults who try to lose weight in the long-term and in all such obese patients there is need for pharmacological interference.

The American Gastroenterological Association (AGA) has released new evidence-based guidelines strongly recommending that these patients with obesity should use recently approved medications paired with lifestyle changes. The guidelines have been published in the journal Gastroenterology.

The American Gastroenterological Association has ranked four "anti-obesity medications" in order of effectiveness. The medications, paired with healthy eating and regular physical activity, are first-line medical options and result in moderate weight loss as noted as a percentage of body weight.

1. Semaglutide (Wegovy®), weight loss percentage: 10.8%

Semaglutide is already approved for the treatment of type 2 diabetes mellitus, and it has demonstrated glucoregulatory and cardioprotective benefits that would further promote its use. But the guideline also made note of the possibility of delayed gastric emptying with the use of this drug, with side effects of nausea and vomiting.The AGA guideline panel made a conditional recommendation for the use of semaglutide due to potential varying weight loss in patients with type 2 diabetes.

2. Phentermine-topiramate ER (Qsymia®), weight loss percentage: 8.5%

Extended-release phentermine-topiramate as the second most effective anti-obesity agent has received a conditional AGA recommendation with a moderate certainty of evidence.

AGA has noted that topiramate can be preferentially used for patients with comorbid migraines as it has shown efficacy in treating migraine headaches. But this combination "should be avoided in patients with a history of cardiovascular disease and uncontrolled hypertension."cautions AGA panel.The panel also suggested that blood pressure and heart rate of the user should be checked periodically.

Further women of reproductive age should be advised to use contraception consistently while receiving the medication as topiramate is teratogenic."

Based on lower-certainty evidence, phentermine and diethylpropion monotherapy along with lifestyle interventions are also suggested for use in treatment of obesity," Davitkov said. "[However,] these medications are approved by the FDA for short-term use (12 weeks), and longer use will be off-label."

3. Liraglutide (Saxenda®), weight loss percentage: 4.8%

Liraglutide 3 mg has been approved for the treatment of type 2 diabetes mellitus and has demonstrated reduction of morbidity and mortality in patients with type 2 diabetes at risk for cardiovascular disease.

The AGA panel determined the drug to have a moderate weight loss benefit and small magnitude for potential adverse effects with an effective total body weight loss of 4.8%. However, the guideline did note that liraglutide has been linked to an increased risk for pancreatitis and gallbladder disease and side effects consisting mostly of nausea and vomiting.

4. Naltrexone-Bupropion ER (Contrave®), weight loss percentage: 3.0%

Extended-release naltrexone-bupropion may hold moderate benefit for weight loss with a small magnitude for adverse events, according to AGA. Further naltrexone-bupropion may be considered for the treatment of overweight or obesity in patients attempting smoking cessation as well as in patients with depression.

However this combination "should be avoided in patients with seizure disorders and used with caution in patients at risk of seizures," cautious AGA panel. Also this combination should not be used concomitantly with opiates and blood pressure and heart rate of the user should be checked periodically, especially during the initial 12 weeks of treatment.

"These medications treat a biological disease, not a lifestyle problem. Obesity is a disease that often does not respond to lifestyle interventions alone in the long-term," says author Eduardo Grunvald, MD, University of California San Diego. "Using medications as an option to assist with weight loss can improve weight-related complications like joint pain, diabetes, fatty liver and hypertension."

"There have been changes in obesity treatment in recent years. This guideline is the first since diabetes drugs were approved for obesity treatment and provides clear information for doctors and their adult patients who struggle to lose weight or keep it off with lifestyle changes alone," says Perica Davitkov.

Reference:

Eduardo Grunvald, Raj Shah, Ruben Hernaez, Apoorva Krishna Chandar, Octavia Pickett-Blakely, Levi M. Teigen, Tasma Harindhanavudhi, Shahnaz Sultan, Siddharth Singh, Perica Davitkov,  DOI:https://doi.org/10.1053/j.gastro.2022.08.045