Understanding GLP-1 Weight Loss Drugs

GLP-1 (glucagon-like peptide-1) receptor agonists are a class of medications originally developed to manage type 2 diabetes. In recent years, they have gained significant attention for promoting weight loss, especially for individuals struggling with obesity. Additional benefits related to the weight loss for these drugs include a lower risk of high blood pressure, heart disease, stroke, fatty liver disease, several cancers, and others

Patients and readers are always asking my thoughts on these drugs since I provide a holistic and integrative analysis that goes beyond the headlines by an often corrupt media. Do we prescribe these drugs at the Stengler Center? Yes. However, we prescribe them judiciously and with caution. There is a place for these medications for people struggling with Type 2 diabetes and obesity since these diseases skyrocket ones risk for all the major chronic and serious diseases. For the person who has 10-20 pounds to lose due to diet and lifestyle factors, we do not recommend them. The reason I do not prescribe these drugs to anyone who wants them is due to two facts:

1. The weight gain comes back after discontinuation of the medications. Unless diet, lifestyle, and hormonal issues are addressed, the weight will come back. Research has even shown that the long-term use of these drugs leads to weight regain even with lifestyle intervention! I will have a video or article coming out on this subject very soon.

2. I am always concerned about potential long-term side effects of relatively new medications. How many times have superstar drugs come on the market, only to learn of serious side effects in the future. Drug companies are masters in putting out positive information on drugs and obscuring concerning side effects.

What Are GLP-1 Drugs?

GLP-1 is a hormone naturally produced in the gut that regulates blood sugar levels, appetite, and digestion.� Most of these drugs are given by injection. It works by:

1. Stimulating Insulin Secretion: GLP-1 helps the pancreas release insulin in response to elevated blood sugar levels.
2. Suppressing Glucagon Release: It reduces the secretion of glucagon, a hormone that increases blood sugar.
3. Delay Stomach Emptying: Slower digestion helps individuals feel full for longer periods.
4. Acting on the Brain: GLP-1 impacts the hypothalamus to reduce appetite.

Synthetic GLP-1 receptor agonists mimic these effects, providing benefits beyond blood sugar control.

Popular GLP-1 Medications

1. Semaglutide (Ozempic, Wegovy): Approved for both diabetes and obesity management, semaglutide has shown significant weight loss results in clinical trials.
2. Tirzepatide (Mounjaro, Zepbound)-approved for chronic weight management in adults with obesity and Type 2 diabetes. Contains GLP-1 agonist and another peptide known as GIP (glucagonlike peptide 1 (GLP1) to synergistically control appetite, insulin control, and reduced fat storage.
3. Liraglutide (Saxenda, Victoza): Initially approved for diabetes, it later gained approval for chronic weight management. The generic version of this medication was recently approved.
4. Dulaglutide (Trulicity): Primarily for diabetes, there is ongoing research into its potential for weight loss.

Clinical Evidence

Numerous studies have demonstrated the efficacy of GLP-1 drugs for weight loss. On average, these medications result in a loss of 5% to 15% of body weight. The SURMOUNT-4 Randomized Clinical Trial demonstrated that a once-weekly injection of Tirzepatide in overweight or obese women resulted in a mean weight reduction of 20.9% of body weight over 36 weeks. From week 36 to 88, there was an additional 5.5% mean weight reduction, while those on placebo had an increase of 14%.

Potential Side Effects

The most common side effects of GLP-1 agonists are digestive-related and may include:

Nausea (the most common side effect)

Loss of appetite

Vomiting

Diarrhea

Additional potential side effects which are less common:

Dizziness

Increased heart rate

Infections

Headaches

Indigestion

Severe but rare side effects may include:

Pancreatitis

Medullary thyroid cancer (although this side effects was shown in rats and to date has not shown in human data)

Kidney injury

Worsening of diabetes-related retinopathy

Allergic reactions

Accessibility and Cost

One of the main challenges with GLP-1 drugs is their cost. Without insurance coverage, these medications can be prohibitively expensive, with monthly prices ranging from $800 to $1,500. Efforts are underway to improve affordability and expand access. Patients often have problems with insurance coverage and often prescribe through compounding pharmacies where the cost is significantly lower.

Conclusion

GLP-1 receptor agonists have become very popular in a world that is plagued by obesity and diabetes. This class of drugs can be effective for significant weight loss and diabetes improvement. Digestive side effects are common and long-term side effects still need to be confirmed. Patients should be aware that regaining weight is common for those who use and then discontinue these medications.

References

Abdullah bin Ahmed, I. (2024). A comprehensive review on weight gain following discontinuation of glucagon-like peptide-1 receptor agonists for obesity. Journal of Obesity, 2024, 18. https://doi.org/10.1155/2024/8056440�

Aronne, L. J., Sattar, N., Horn, D. B., Bays, H. E., Wharton, S., Lin, W.-Y., Ahmad, N. N., Zhang, S., Liao, R., Bunck, M. C., Jouravskaya, I., Murphy, M. A., Fretes, J. O., Coronel, M. J., Gutnisky, L. L., Frechtel, G. D., Gelersztein, E., Aizenberg, D., Maldonado, N., & Nardandrea, J. P. (2024). Continued treatment with Tirzepatide for maintenance of weight reduction in adults with obesity. JAMA, 331(1), 38. https://doi.org/10.1001/jama.2023.24945�

GLP-1 agonists. Cleveland Clinic. (2024, October 11). https://my.clevelandclinic.org/health/treatments/13901-glp-1-agonists�

Koenig, D. (2024, November 26). Side effects of GLP-1 drugs: What doctors should know. Medscape. https://www.medscape.com/viewarticle/side-effects-glp-1-drugs-what-doctors-should-know-2024a1000l8r?ecd=mkm_ret_241228_mscpmrk_pcp_top-content_etid7124114&uac=130325DZ&impID=7124114�

Rao, M., Shaunhessy, A., & Sokol, R. (n.d.). Prescribing GLP-1 Agonists for Weight Loss: Wrestling With Our Philosophical Angst. American Family Physician, 110(4).�