Weight loss pills for obesity: New guidelines rank best drugs

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The prevalence of obesity in the United States increased from 30.5%Trusted Source in 1999–2000 to 41.9% in 2019–2020. Obesity is related to many health complications, including cardiovascular diseaseTrusted Source, strokeTrusted Source, and certain kinds of cancer, including colon cancerTrusted Source.
While lifestyle interventions are key to managing obesity, they have limited efficacyTrusted Source 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%Trusted Source 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“The new guidelines were greatly needed as the previous ones were based on older and outdated data; new research has shown that lowering the criteria for surgery will have a huge, beneficial impact on a larger group of patients,” Dr.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 agonistTrusted Source 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.