GLP-1 Agonist Benefits and Risks
As we know, over the past 30 years, rates of overweight and obesity in the U.S. have more than doubled, creating a growing public health crisis. Projections suggest that by 2050, 213 million adults and 43 million children will face overweight or obesity. Researchers have been emphasizing that urgent action is needed to address this issue.
A recent Medscape article looks into one promising intervention that involves glucagon-like peptide-1 receptor agonists (GLP-1 RAs), initially developed for diabetes and now approved for weight loss. These drugs have seen a dramatic rise in popularity, with prescriptions increasing by 132.6% from late 2022 to late 2024. Public awareness has also surged, with 32% of surveyed U.S. adults reporting familiarity with GLP-1 RAs in 2024, compared to just 19% in 2023.
GLP-1 RAs and their effectiveness
GLP-1 RAs, including tirzepatide (which targets additional receptors beyond GLP-1), have demonstrated effectiveness in weight loss. A 2022 analysis of 22 trials involving over 17,000 participants found that 50.2% achieved at least a 5% weight loss, while 17.5% experienced a ≥10% weight reduction compared to placebo. A subsequent 2023 review of 41 trials confirmed significant reductions in weight, BMI, and waist measurements.
Dr. Andres Acosta from the Mayo Clinic highlighted the long-standing use of GLP-1 RAs and the growing enthusiasm for their application in treating obesity. However, experts like Dr. Daniel Drucker from Mount Sinai Hospital caution that while these medications are highly effective, not everyone benefits. Approximately 10% of users may experience minimal weight loss or intolerable side effects.
Dr. Drucker said,
[W]e know some people don’t lose much weight when taking these medicines and others don’t feel well and can’t take them… [It’s} essential for us to identify who will be the best responders, as we do with medications for other conditions, such as cancer and cardiovascular disease.
Understanding obesity phenotypes
Dr. Acosta’s research has identified four obesity phenotypes that can guide treatment approaches:
- Hungry Gut (HG). Patients experience rapid gastric emptying and feel hungry shortly after meals.
- Hungry Brain. Individuals have impaired satiety and tend to overeat during meals.
- Emotional Hunger. Emotional or hedonic eating behaviors dominate.
- Slow Burn. Patients have a sluggish metabolism and burn fewer calories.
In a study of 312 patients, those receiving phenotype-specific treatments achieved significantly greater weight loss (15.9% vs. 9.0%) after one year. Acosta’s lab has developed a genetic test to predict the best responders to GLP-1 RAs, showing promise in identifying individuals who might benefit most. It’s licensed by Dr. Acosta’s lab and available through Phenomix Sciences.
His group has also studied which lifestyle interventions are most effective for each phenotype. Dr. Acosta said,
When a unique lifestyle intervention targeting each phenotype was applied, patients lost more weight and had greater metabolic improvement.
Concerns about side effects
Despite their benefits, GLP-1 RAs carry risks. Common side effects include nausea, diarrhea, and constipation, while more serious issues like pancreatitis and gallbladder diseases have been reported. Additionally, cases of compounded GLP-1 RAs from pharmacies have been linked to fatalities. These risks emphasize the need for cautious use, especially as discontinuation rates are high due to cost (over $12,000 annually) and side effects.
Optimizing treatment
Experts like Dr. Marc-Andre Cornier stress that GLP-1 RAs should be part of a broader strategy that includes lifestyle changes, such as a high-protein diet and resistance exercise to prevent muscle loss. Furthermore, precision medicine approaches tailored to individual phenotypes may enhance treatment success and minimize trial-and-error prescribing. Recently published recommendations can help healthcare experts guide patients taking GLP-1 RAs to optimize nutrition.
Public attitudes and sustainability
Despite rising interest, a recent survey found that most Americans prefer alternative methods, such as plant-based diets, over weight-loss injections. Moreover, many discontinue GLP-1 RAs within a year, raising concerns about long-term effectiveness and potential weight cycling.
Dr. Acosta highlighted the importance of identifying ideal candidates for these medications to maximize benefits while addressing cost and insurance coverage challenges. Tailored approaches are key to ensuring sustainable, effective obesity treatment.
Your responses and feedback are welcome!
Source: “As GLP-1 Use Surges, Clinicians Weigh Benefits and Risks,” Medscape, 11/22/24
Source: “Metabolic Bariatric Surgery in the Era of GLP-1 Receptor Agonists for Obesity Management,” JAMA Network, 10/25/24
Source: “Reasons for discontinuation of GLP1 receptor agonists…,” Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 9/29/17
Image by Towfiqu barbhuiya on Unsplash
