Understanding Weight Loss Drugs: Benefits, Risks, and Future Implications

Though originally approved for treating type 2 diabetes, semaglutide (OzempicTM and WegovyTM) and tirzepatide (MounjaroTM) have garnered increased attention over the last few years due to their weight loss effects.

These drugs belong to a class known as glucagon-like peptide 1 receptor agonists (GLP-1RAs).

This article will explore the benefits and risks of GLP-1RAs, discussing their future implications and potential alternatives.

How do GLP-1RAs work? Glucagon-like peptide 1 (GLP-1) is a hormone that triggers the release of insulin (lowering the amount of glucose in the blood), blocks the secretion of glucagon (which raises blood sugar levels), slows the emptying of the stomach and increases satiety. GLP-1 agonist drugs mimic this hormone.

GLP-1RAs – successes in diabetes and beyond

Before their use as a weight loss intervention, GLP-1RAs were trialed and approved for their ability to reduce glucose levels effectively in type 2 diabetes.

The first GLP-1RA to be approved by the US Food and Drug Administration (FDA), for type 2 diabetes, exenatide, required twice daily injections. In 2019, semaglutide became the first oral medication of this class to be approved by the FDA. This oral form (RybelsusTM) must be taken once daily. The injectable form (Ozempic and Wegovy) is administered once weekly.

As the use of GLP-1RAs for diabetes management has increased, the discovery of their impact on weight loss has sparked interest in their potential for obesity treatment.

A study published in the New England Journal of Medicine found that adults with obesity had a mean weight loss of 14.9% with semaglutide and lifestyle intervention. This exceeded the loss with placebo plus lifestyle intervention by 12.4 percentage points.

Tirzepatide, a dual-acting GLP-1/glucose-dependent insulinotropic polypeptide (GIP) agonist, has shown greater glucose and weight lowering effects than semaglutide. The drug is also effective at reducing blood pressure, waist circumference, body weight and liver fat content.

“GLP-1RAs have shown impressive clinical benefits in multiple trials. They can lead to an average weight loss of 15%–20%, improve cardiometabolic risk factors and prevent secondary cardiovascular events. They also slow the progression of kidney disease and reduce the severity of obesity-related conditions, like obstructive sleep apnea,” said Dr. David D. Kim, assistant professor of medicine and public health at the University of Chicago.

GLP-1RAs could also provide benefits outside of diabetes and obesity management. A recent study, published in Nature Medicine, found an association between GLP1-RAs and benefits to neurological and behavioral health, with reduced risks of seizures and addiction to alcohol, cannabis, stimulants and opioids. Participants taking the drugs also experienced decreased risks of suicidal ideation, self-harm, bulimia and psychotic disorders such as schizophrenia.

Further studies have shown potential benefits of GLP-1RAs in fatty liver disease, chronic kidney disease and heart disease.

Could GLP-1RAs exacerbate eating disorders?

The success of GLP-1RAs has led to an increase in demand and supply shortages, leading to a rise in counterfeit versions of these products being sold. These products can contain any number of ingredients, potentially leading to unknown adverse events or accidental overdoses.

Legitimate GLP-1RAs can cause nausea, vomiting, diarrhea, dizziness, mild heart rate increase, infections, headaches and indigestion. Rare side effects include pancreatitis, thyroid cancer, kidney injury and worsening diabetes-related retinopathy.

One potential area for concern, according to Dr. Riccardo Dalle Grave, director of the Department of Eating and Weight Disorders at Villa Garda Hospital, Italy, is that these drugs could potentially contribute to the onset or exacerbation of eating disorder symptoms.

“By enhancing feelings of satiety and suppressing hunger, GLP-1RAs may exacerbate dietary restriction (physiological undereating) and dietary restraint (the cognitive effort to limit food intake),” Dalle Grave said.

“This can encourage the adoption of rigid and extreme eating patterns, such as skipping meals, consuming minimal portions or avoiding specific foods altogether. These behaviors are core characteristics and perpetuating factors of eating disorders. Moreover, common side effects of GLP-1RAs, such as nausea, vomiting and diarrhea, can further suppress appetite, reinforcing restrictive eating behaviors.”

For those with existing eating disorders, Dalle Grave explained how “the appetite-suppressing effects of GLP-1RAs may conflict with key eating disorder treatment approaches, which emphasize re-establishing regular eating habits and reducing restrictive behaviors”.

Conversely, some researchers believe GLP-1RAs could be used to treat binge-eating disorder (BED), which is characterized by recurrent binge episodes without compensatory behaviors such as excessive exercise, inducing vomiting or using laxatives.

“Although some evidence suggests they may reduce binge eating, GLP-1RAs are not approved for BED treatment. Their use should be limited to cases where binge episodes are substantially reduced, regular eating patterns are established and healthy lifestyle changes are adopted,” Dalle Grave said. Close monitoring is essential to detect worsening eating disorder symptoms, such as rigid dietary rules or meal skipping,” said Dalle Grave, “the role of GLP-1RAs in obesity when it coexists with BED requires further research.”

The full impact of weight loss drugs on other mental health conditions remains unclear. A Scientific Reports study found that liraglutide and semaglutide increased anxiety and suicidal ideations in females and younger participants in real-world settings. In one case, a patient with a history of depression experienced depressive symptoms after four weeks of treatment with semaglutide, which ceased when treatment stopped.

Another study of the reported adverse events for semaglutide, liraglutide and tirzepatide over a period of 28 months found that while only 1.2% of the total reports were psychiatric adverse events, there were 9 deaths and 11 life-threatening outcomes due to suicide attempts in this time period. Depression, anxiety and suicidal ideation were also reported.

The future of weight loss

Weight loss medications haven’t been around long enough to have a full picture of their long-term effects.

“While clinical trials and post-market studies have provided robust evidence of efficacy and safety over a few years, there is still limited data on the long-term effects of GLP-1RA use. This uncertainty is something we’ll need to continue monitoring as more people use these medications for extended periods,” said Kim. It remains to be seen if these drugs could have impacts on metabolism, mental health or other chronic conditions.

“By reducing obesity-related complications, GLP-1RAs can lower long-term healthcare costs. However, at their current net price in the US, the long-term cost savings don’t fully offset the increased spending on these medications. So, while they offer tremendous health benefits, even with insurance coverage, patients often face substantial out-of-pocket expenses.”

One month supply list prices Ozempic 1 mg (semaglutide): 936 USD Wegovy 2.4 mg (semaglutide): 1,349 USD Rybelsus 7 mg (semaglutide): 936 USD Mounjaro 15 mg (tirzepatide): 1,023 USD

The high cost associated with these drugs is likely one of the factors leading over 50% of users to discontinue use before the one year mark. Over 84% of users without type 2 diabetes discontinued use before two years.

According to Kim, the financial burden and potential side effects of long-term GLP-1RA use highlight the need for an alternative strategy.

Studies have shown that patients can gain weight after discontinuing GLP-1RAs. One study found a significant association between weight re-gain and reinitiation of treatment. According to Kim, “this occurs because GLP-1RAs not only help reduce appetite and improve metabolism while they're active, but they also influence hormonal pathways that regulate hunger and satiety. Once the medication is stopped, these pathways often revert to their pre-treatment state, making it harder for patients to sustain their progress without additional support.”

A paper co-authored by Kim in 2024 suggested that, while potentially less effective than weight loss drugs, weight-maintenance strategies could optimize the clinical benefits of reducing unhealthy weight more efficiently and equitably.

“Weight-maintenance programs, which emphasize lifestyle modifications like diet, exercise and behavioral counseling – often following an initial weight loss phase achieved with GLP-1RAs – offer a more sustainable and affordable alternative to long-term medication use. These programs avoid the high recurring costs associated with GLP-1RAs and eliminate the risks of medication-related side effects,” Kim said.

“This approach is particularly important for disadvantaged populations, who are disproportionately affected by obesity and its complications, and who stand to benefit the most from equitable access to these interventions.”

GLP-1RAs offer transformative health benefits to many patients. However, these medications are not without risks. It will be critical to address gaps in our understanding of their long-term effects and to explore how these medications can be integrated into broader, more sustainable weight management strategies.

The future of weight loss treatments lies not only in advancing pharmacological options but also in ensuring these solutions are accessible, affordable and part of a comprehensive strategy tailored to the diverse needs of patients worldwide.

According to the source: Technology Networks.