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Obesity: New guidelines rank best weight loss drugs

  • Researchers conducted a meta-analysis of different FDA-approved anti-obesity drugs.
  • They recommended four drugs alongside lifestyle changes to treat obesity when lifestyle interventions alone are insufficient.
  • Expert commentators note that access due to cost remains a hurdle for these drugs becoming mainstream.

The prevalence of obesity in the United States increased from 30.5% in 1999–2000 to 41.9% in 2019–2020. Obesity is related to many health complications, including cardiovascular disease, stroke, and certain kinds of cancer, including colon cancer.

While lifestyle interventions are key to managing obesity, they have limited efficacy and durability for many. Pharmaceutical interventions have thus been developed and approved for long-term management of the condition.

However, such drugs are limited in use. A small number of providers make up over 90% of prescriptions, partially due to a lack of familiarity with existing medications and limited insurance coverage.

Half of US adults live with obesity

Recently, the American Gastroenterological Association (AGA) analyzed current pharmaceutical therapies for obesity and created new guidelines on to treat the condition.

They noted that for adults with overweight and obesity who do not respond adequately to lifestyle interventions, long-term pharmacological therapy is recommended.

“Obesity is now affecting close to 50% of U.S. adults and is emerging as a major global pandemic with real health and economic impacts,” Dr. Yuval Cohen, cofounder and CEO of Corbus Pharmaceuticals, not involved in the study, told Medical News Today.

“The combination of education, awareness, social action, and medicinal therapy — where needed — should be a top global healthcare priority,” he added.

“The new guidelines were greatly needed as the previous ones were based on older and outdated data; new research has shown that lowering the criteria for surgery will have a huge, beneficial impact on a larger group of patients,” Dr. Mir Ali, bariatric surgeon and medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, CA, not involved in the study, also told MNT.

The new guidelines appear in Gastroenterology.

New guidelines for obesity management 

The researchers analyzed various studies investigating nine Food and Drug Administration (FDA)-approved anti-obesity medications to treat adults with a body mass index (BMI) of 27 kilograms per square meter (kg/m2) and above.

After analyzing the results, the researchers found that four drugs approved for long-term use have moderate or large weight loss effects with few negative side effects. The drugs were:

  • semaglutide, 2.4 milligrams (mg)
  • liraglutide, 3 mg
  • phentermine-topiramate extended-release (ER)
  • naltrexone-bupropion ER.

They noted that, when used alongside lifestyle interventions, each of the drugs was linked to a total body weight loss of between 3% and 10.8%.

Some studies also reported 15% total body weight loss, although the researchers noted this outcome was comparably rarer.

Dr. Chrisopher McGowen, board-certified gastroenterologist, internist, and obesity medicine specialist at True You Weightloss, not involved in the study, told MNT:

“[Semaglutide and liraglutide] are a tremendous advance for the treatment of obesity. Weight loss of 15% in 1 year is phenomenal and can have a true impact on patient health and medical comorbidities. We simply did not have these options in the past, aside from surgical modalities.”

The researchers noted, however, that FDA-approved anti-obesity medications should not be used by pregnant women, and that the drugs may increase the risk of hypoglycemia in those with type 2 diabetes.

They further wrote that doctors should exercise caution when treating those taking medications to lower blood pressure, as well as those with eating disorders.

The researchers noted that orlistat should be avoided for those with obesity or overweight with weight-related complications due to generally small weight loss results — 2,78% total body weight loss — and negative side effects, including flatulence and fecal incontinence.

Underlying mechanisms 

“Semaglutide is a class of drugs originally designed to treat type 2 diabetes,” explained Dr. Benjamin F. Voight, associate professor of systems pharmacology and translational therapeutics and genetics at the University of Pennsylvania, not involved in the study.

“Previous work has suggested that the mechanism could include reduced appetite and food cravings, better control of eating, and lower relative preference for fatty, energy-dense foods,” he added.

“Liraglutide is a GLP-1 agonist and functions as an appetite suppressant. This is thought to be mediated through both peripheral and central nervous system pathways, by modulating different types of neurons important for controlling recognition of appetite satiety,” he noted.

Dr. Aleem Kanji, board-certified internist and endocrinologist at Ethos Endocrinology, Houston, TX, not involved in the study, told MNT that “[p]hentermine-topiramate ER (Qsymia) has mechanisms from each medication of the combination drug. Phentermine increases the release of norepinephrine in the brain resulting in appetite suppression.”

“Topiramate is believed to also result in appetite suppression through enhancement of GABA (gamma-aminobutyric acid) and other mechanisms in the brain,” he explained.

“Weight loss mechanisms of naltrexone-bupropion ER (Contrave) are thought to be decreased appetite through activation of the POMC [proopiomelanocortin] neurons and decreased food cravings through the mesolimbic dopamine pathway, known as the reward pathway,” noted Dr. Kanji.

Why medication?

When asked why some people with obesity may not respond to lifestyle changes alone, Dr. Lucas Carr, associate professor in the Department of Health and Human Physiology at the University of Iowa, not involved in the study, told MNT:

“Obesity is a complex disease with biological, genetic, environmental, and behavioral causes. Some individuals simply have a higher inherited risk of being obese due to their genetic makeup. Many individuals live an environment that contributes to their weight — e.g. toxic food environment, low access to resources.”

“There is a lot of variability in the quality of lifestyle weight loss interventions available. Some are based on sound scientific evidence, while others are not. In both cases, these are barriers that are mostly out of the individual’s control and not a case of low willpower, which is a common stereotype,” he added.

Dr. Jaime Almandoz, medical director at the Weight Wellness Program and Associate Professor of Internal Medicine at the University of Texas Southwestern Medical Center, not involved in the study, also told MNT that “[b]eyond this, when we lose weight, there are many biological changes that increase our risk for weight recurrence, called metabolic adaptation.”

“This can include changes in appetite, satiety, and energy expenditure, which promote the positive energy balance that drives weight gain,” he said.

Dr. McGowen explained how biological changes can increase the risk of weight recurrence. He said:

“Once a person is affected by overweight or obesity, the body has numerous intrinsic hormonal and neuroregulatory mechanisms designed to preserve that weight. When an individual diets and begins losing weight, there is an immediate compensatory increase in appetite and hunger driven by a rise in the hunger hormone, ghrelin. Similarly, the satiety hormone leptin decreases with weight loss, leading to less fullness when eating.”

“And finally, as one loses weight, their body becomes more efficient and uses less energy, meaning fewer calories expended. The combined result is that weight regain is near-inevitable following a diet and lifestyle program. This is exactly why pharmacotherapy and bariatric and metabolic surgery treatments are needed — to counteract these intrinsic weight-promoting mechanisms,” he added.

Limitations 

When asked about the guidelines’ limitations, Dr. Almandoz said: “The primary limitation to these guidelines is patient access to the anti-obesity medications that are recommended. Less than 2% of the eligible US population receives prescription anti-obesity medications, and when they do, the average duration of treatment is for less than 3 months.”

“This is due to many factors,” he noted, “which include healthcare providers and patients believing that anti-obesity medications are either ineffective or dangerous.”

“Insurance coverage of anti-obesity medications is a major barrier to treating obesity as the majority of people with commercial health insurance do not have anti-obesity medications on formulary. Although Medicare covers bariatric surgery, it does not cover any anti-obesity medications. Many of the newer anti-obesity medications (e.g. liraglutide and semaglutide), cost over a thousand dollars per month and are inaccessible to people without prescription coverage for these medications,” he added.

Dr. Voight further noted that as pharmacological interventions are relatively new, more study is needed to ascertain their safety and efficacy in pediatric patients.

Implications

Considering how these guidelines could influence treatment options for obesity, Dr. Kanji noted: “Treatment plans should take into account an individual’s medical conditions, presence of weight-related complications, dietary and cultural preferences, physical limitations, potential medication side effects, benefits and risks of each medication, and cost of medication.”

“These guidelines add to the current evidence the effectiveness of anti-obesity medications as part of a comprehensive treatment plan. It is my hope that the guidelines further demonstrate the need for anti-obesity medications to be more cost-effective and widely covered by health insurers,” he added.

Dr. Sameer Murali, obesity medicine specialist at University of Texas Health Houston and Memorial Hermann, not involved in the study, agreed that treatment plans should be personalized, he told MNT:

“[A] patient who struggles with night eating would likely be a poor responder to phentermine monotherapy given phentermine is a stimulant, suppresses appetite during the day, and may have little or no effect on appetite at night. A patient who is consuming a majority of their calories from sugar-sweetened beverages and/ or alcohol may be a poor responder to medication regimens largely aimed at reducing caloric intake from food.”

“Appropriate evaluation of mood disorders and disordered eating behavior may reveal additional pharmacologic targets that could enhance therapy,” he noted.

“Given the scope of the obesity problem around the world, we certainly need more medical specialties offering evidenced-based treatments or, at a minimum, providing referrals to reputable programs and treatments,” Dr. David Sarwer, associate dean for research and director of the Center for Obesity Research and Education at the College of Public Health at Temple University in Philadelphia, not involved in the study, also commented.

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