GLP-1 Agonists for Weight Loss: Do You Need Diabetes to Benefit?

As a primary care physician, I often get asked:

‍"Can GLP-1 Agonists Help with Weight Loss Even If I Don't Have Diabetes?"

The short answer is yes, but let's dive deeper into this fascinating topic. In my practice, I've seen a surge of interest in medications like Wegovy, Saxenda, and the newly approved Zepbound. These drugs, belonging to the class of GLP-1 receptor agonists (and related medications), have been making waves in the world of weight management, even for those without diabetes.

Originally developed to treat type 2 diabetes, these medications have shown remarkable efficacy in weight loss. As someone who's prescribed these drugs and followed their development closely, I can tell you that there has been no other class of medications that has made such a big difference in health for so many people.

Understanding GLP-1 Agonists

First, let's break down what these medications are. GLP-1 (Glucagon-Like Peptide-1) agonists mimic a hormone naturally produced in your body. In my experience explaining this to patients, I often use the analogy of a key fitting into a lock. These medications act like a key, fitting into receptors (the locks) in your body to:

1. Slow down digestion
2. Increase feelings of fullness
3. Reduce hunger
4. Affect brain regions involved in appetite regulation

It's fascinating how closely these drugs can mimic our body's natural processes to achieve weight loss. A key point is that these medications are far more powerful and concentrated than the naturally occurring levels in our bodies, which explains the rapid responses patients often experience.

FDA-Approved Medications for Weight Loss

As of today, the FDA has approved three medications in this class for chronic weight management in non-diabetic individuals:

1. Liraglutide (Saxenda): Approved in 2014
2. Semaglutide (Wegovy): Approved in 2021
3. Tirzepatide (Zepbound): Approved in November 2023

I've prescribed each of these medications, and they all have their unique characteristics which I’ll go into in more detail. Of note, you may see alternate brand names for the same active ingredient. For example, Liraglutide is known by Saxenda for its weight-loss version, and Victoza for its diabetes version. Semaglutide is Wegovy for the weight-loss version, and Ozempic for its diabetes version. Tirzepatide is Zepbound for weight-loss and Mounjaro for diabetes.

As a side note, I find these branding considerations (which are based on regulatory requirements for drug inserts and cautions) to be more confusing than helpful in most cases. But just know that there are several different names for the exact same medication.

The Dual GIP and GLP-1 Mechanism: A Game Changer

Tirzepatide (Zepbound) is particularly interesting because it's a dual GIP and GLP-1 receptor agonist. In simpler terms, it's like having two keys for two different locks. This dual action might explain why, in my clinical experience, some patients respond even more dramatically to this medication.

Here's how it works:

• The GLP-1 effect: Slows stomach emptying, increases feeling of fullness, and stimulates insulin release
• The GIP effect: Improves insulin sensitivity and may directly affect fat tissue

Effectiveness for Weight Loss

The results I've seen in my practice align closely with clinical trial data:

• Semaglutide (Wegovy): Patients typically lose about 15% of their body weight over 68 weeks.
• Liraglutide (Saxenda): Usually results in about 8% body weight loss over 56 weeks.
• Tirzepatide (Zepbound): Some patients lose up to 22.5% of their body weight in 72 weeks.

Remember, these are average results. I've seen some patients lose even more, while others lose less. We still don’t completely understand why some people seem more sensitive to the medications’ effects while others need more time or higher doses. One helpful strategy is combining these medications with lifestyle changes including quality sleep, nutrition, exercise, and stress management.

What Patients Can Expect

When I prescribe these medications, I always prepare my patients for the following:

1. Administration: Most are weekly injections, except Saxenda which is daily. The manufacturer versions are self-injecting pens while compounded versions use small syringes and vials.
2. Side effects: Nausea, vomiting, and diarrhea are not uncommon initially but usually improve.
3. Gradual dose increase: We start low and go slow to minimize side effects.
4. Lifestyle changes: These medications aren't magic bullets. Diet and exercise are crucial.

Important Considerations

As a physician, I have to consider several factors before prescribing:

• Cost: These can be expensive, often over $1,000 per month. Insurance coverage varies and there are strategies to help manage the expense, including drug coupons and patient assistance programs.
• Long-term use: Weight often returns if the medication is stopped without supporting and continuing lifestyle changes.
• Medical history: Not suitable for everyone, especially those with certain thyroid conditions.
• Potential for misuse: I'm cautious about prescribing for purely cosmetic weight loss. While it isn’t completely out of the question, I make sure that patients understand both the known and unknown risks of this relatively new class of drugs before starting them.

The Future of Weight Management

The research in this field is exciting. We're seeing potential applications beyond weight loss, including:

• Possible benefits for heart health
• Potential use in fatty liver disease
• Investigations into neurodegenerative diseases

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References:

1. FDA. (2021, June 4). FDA Approves New Drug Treatment for Chronic Weight Management, First Since 2014. FDA. https://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-treatment-chronic-weight-management-first-2014
2. Nauck, M. A., & Meier, J. J. (2018). Incretin hormones: Their role in health and disease. Diabetes, Obesity & Metabolism, 20 Suppl 1(S1), 5–21. https://doi.org/10.1111/dom.13129
3. Wilding, J. P. H., Batterham, R. L., & Calanna, S. (2021). Once-Weekly Semaglutide in Adults with Overweight or Obesity. The New England Journal of Medicine, 384(11), 989–1002. https://doi.org/10.1056/NEJMoa2032183
4. Pi-Sunyer, X., Astrup, A., Fujioka, K., Greenway, F., Halpern, A., Krempf, M., Lau, D. C. W., le Roux, C. W., Violante Ortiz, R., Jensen, C. B., & Wilding, J. P. H. (2015). A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management. New England Journal of Medicine, 373(1), 11–22. https://doi.org/10.1056/nejmoa1411892
5. Lundgren, J. R., Janus, C., Jensen, S. B. K., Juhl, C. R., Olsen, L. M., Christensen, R. M., Svane, M. S., Bandholm, T., Bojsen-Møller, K. N., Blond, M. B., Jensen, J.-E. B., Stallknecht, B. M., Holst, J. J., Madsbad, S., & Torekov, S. S. (2021). Healthy Weight Loss Maintenance with Exercise, Liraglutide, or Both Combined. New England Journal of Medicine, 384(18), 1719–1730. https://doi.org/10.1056/nejmoa2028198
6. Buse, J. B., Wexler, D. J., Tsapas, A., Rossing, P., Mingrone, G., Mathieu, C., D’Alessio, D. A., & Davies, M. J. (2020). 2019 Update to: Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care, 43(2), 487–493. https://doi.org/10.2337/dci19-0066

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Until next time - Cheers to your health!

Hillary Lin, MD