Do they help or hurt? The new world of weight management medications.

Written by Julia Pines, BA and Evelyn Attia, MD.

While Instagram, X (formerly Twitter), and TikTok have long been full of people documenting their weight loss “transformations,” there has been a hashtag explosion as a class of drugs known as glutides earned government approval in various countries for the treatment of obesity and weight management. The social media landscape and the medical news coverage shift between hype and fearmongering. Some important context and basic information about these medications, such as their history and how they work, is getting lost in the shuffle.

Here at the Columbia Center for Eating Disorders, we are also thinking about how this latest version of weight loss chatter and the new choices available (including to some individuals not appropriate for considering these medications) may impact those vulnerable to eating disorders. We are also wondering about what happens with eating behavior for those without eating disorders who have lost significant amounts of weight.

How were glutides discovered and how do they work?

Glutides, formally known as glucagon-like peptide 1 (GLP-1) receptor agonists, are a type of medication that treats type-2 diabetes by stimulating insulin secretion.  In 1964, scientists learned that they could promote greater and longer-lasting insulin release when glucose (sugar) is taken by mouth rather than administered into the bloodstream. When glucose is given through the veins, cells in the pancreas produce insulin to lower the concentration of glucose in the blood. But how consuming glucose by mouth produced more and lasting insulin was a mystery until years later. Eventually, scientists detected a glucagon-like substance in tissues of the digestive system called GLP-1. GLP-1 leads to insulin release when glucose is ingested.

GLP-1 is an incretin, which is a class of gut hormones. The enhanced release of insulin in response to the consumption of glucose is now known as the incretin effect.

Individuals with type-2 diabetes have an impaired incretin effect. Scientists wondered how they could enhance the natural function of GLP-1s. They sought to promote the incretin effect and induce more insulin release. Enter the creation of GLP-1 receptor agonists (aka glutides), which bind to the GLP-1 receptors and increase their activity.

It may surprise you to learn that these medications have been around for a while. The first glutide called exenatide was approved by the US Food and Drug Administration (FDA) in 2005 for the treatment of type-2 diabetes. Since then, several other glutides have been FDA-approved for type-2 diabetes (such as lixisenatide, dulaglutide, albiglutide, semaglutide). More recently, two glutides have been approved for the treatment of obesity (semaglutide and liraglutide). They have snagged the spotlight. This is likely due to a combination of factors, including the high prevalence of obesity globally and, in Western cultures, an idealization of thinness.

What are the effects of glutides?

Besides increasing the production of insulin, glutides have other effects on the digestive and cardiovascular systems. For example, in patients with type-2 diabetes, exenatide:

• decreases fasting and blood glucose,
• slows gastric emptying,
• increases fullness, and
• reduces risk factors for cardiovascular events – such as heart attacks or strokes – by improving blood pressure and cholesterol levels.

Cardiovascular disease is the number one cause of death among individuals with type-2 diabetes. Naturally, benefit to cardiovascular health is increasing everyone’s attention on this class of medications for this clinical group. Even so, the American Diabetes Association lists metformin, an older treatment available for type-2 diabetes, as the first-line therapy. Glutides are mostly recommended for patients with a contraindication or intolerance to metformin.

Once individuals who are prescribed glutides stop taking them, they may no longer benefit from the effects. People who discontinue these medications do so for lots of reasons including

• limitations in insurance coverage,
• side effects, or
• concern about being on medication long term without clarity about possible associated risks for this kind of use.

According to several studies, individuals who discontinue glutides regain much of the weight initially lost while on the medication, with associated rises in blood glucose and cholesterol levels. This is also a deterrent for many people to even start them. More research into the effects of these medications will be useful to evaluate the risks and benefits of taking them.

What are researchers looking to learn next about glutides?

There is still a lot to learn. As all of us sitting on the sidelines reading about this in the popular press can attest, scientists are quickly working to answer questions about the mechanism of action and potential uses of these medications other than for diabetes. 

Mechanisms of interest

Researchers are trying to understand the mechanisms by which glutides affect the digestive system and the brain. Anecdotally, people taking these medications describe a dampening of “food noise” in their heads (i.e., thoughts about food or eating throughout the day). They also describe changes to appetite, cravings, and feelings of fullness. Some individuals seem to appreciate these effects while others find them off-putting or disorienting. Why people have these various subjective experiences while taking glutides is a mystery.

Scientists are looking into the specific brain circuits and neurons that may be impacted by glutide administration. Or, those responsible for its effects. Some are investigating the action of glutides in the gut. For example, what mechanisms occur after GLP-1 is released? What about before it is degraded? Studying the mechanisms of action and effects of glutides is important. It can help to understand potential contraindications to use of these medications. It can also provide evidence for other possible conditions helped by these medications.

To date, researchers have found that glutides influence the brain’s reward system and lead to a reduction in the rewarding quality of food. This finding has sparked ongoing research into the effects of glutides on addiction. Multiple studies have been conducted using animal models of addiction. Some have found that the administration of glutides leads to a reduction in the intake of substances such as alcohol and cocaine. Building upon these results in animals, researchers are investigating the effects of glutides on drug use in people with substance use disorders. A pilot study found that exenatide decreased incidence of smoking and reduced tobacco craving among individuals with tobacco use disorder in conjunction with a nicotine patch.

Effectiveness/tolerability

There has also been active research into the effectiveness and tolerability of glutides in treating individuals with obesity. Multiple active clinical trials are currently underway. Here at the Columbia Center for Eating Disorders, we are collaborating with researchers at Drexel University and the University of Pennsylvania on a study of the eating patterns and brains, fat, and muscle cells of individuals without eating disorders trying to prevent weight regain after weight loss.

Conclusions

Glutides have a clear track record at helping individuals with type-2 diabetes and obesity management. But, they only work for as long as they are taken. Some elements of the mechanism of action for these medications remain mysterious, and long-term effects are unknown.

As with any medication, the benefits for use must be weighed against its risks. We know next to nothing about the use of these medications in individuals who are vulnerable to or have a history of disordered eating. Glutides may promote overly restrictive eating, preoccupation with appearance or weight, and extreme fear of weight regain. These medications may also reignite old patterns. For example, restrictive eating behavior and thinking for individuals with an eating disorder in the past.

For all of us, it is important to be cognizant of these medications as the latest promotion of a thin ideal. We must appreciate the nuances between medically indicated recommendations for reducing weight versus goals for body acceptance or neutrality at any size and reducing weight stigma.

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