GLP-1s in Focus with Bariatric Surgery: Part 2

In the first article of our series, we explored the basics of GLP-1 medications, including how they work, their applications, and their role in weight management, particularly in conjunction with bariatric procedures. 

Now, let’s go deeper.

If you’ve seen one GLP-1 med, have you seen them all? Not quite. While they all share the same mechanism of mimicking the glucagon-like peptide-1 hormone to regulate insulin, slow digestion, and reduce appetite, they don’t all perform the same. With a growing list of GLP-1 options on the market, how do you decide which one is best?

Specific GLP-1 RAs for Weight Loss

Currently, the only FDA-approved GLP-1 medications for weight loss include liraglutide (Saxenda), semaglutide (Wegovy), and tirzepatide (Zepbound).

It’s important to understand that GLP-1s are typically prescribed according to their FDA-approved indications. For example, although Wegovy and Ozempic both contain semaglutide, Wegovy is specifically approved for chronic weight management, whereas Ozempic is approved primarily for the treatment of type 2 diabetes. Both drugs can lead to weight loss, but their primary FDA-approved uses differ. 

Off-label prescribing is common, especially in patients with overlapping, or potentially developing, conditions like obesity with diabetes or obesity with cardiovascular risks. In these cases, choosing a GLP-1 medication that addresses the primary diagnosis ensures that treatment aligns with FDA labeling while still providing beneficial effects, such as weight loss.

Since our focus here is weight loss, we’ll concentrate on the GLP-1s that are FDA-approved specifically for this purpose.

The Research

The result we’re concerned with here is weight loss, but how the meds get you there isn’t the same. This translates to varying degrees of effectiveness in clinical studies, as well as in real-world applications.

For people without diabetes, semaglutide led to an average weight loss of 6.9% and liraglutide followed closely behind at 6.6%. But the same study suggests that tirzepatide may be the new frontrunner. In an extensive U.S. study of more than 18,000 adults with obesity, researchers found that tirzepatide users lost nearly double the weight of semaglutide users – 15.3% vs. 8.3% after 12 months, to be exact.¹ 

If we consider this study alone, it is easy to assume that tirzepatide is the best choice, with semaglutide close behind, especially when compared to liraglutide. It’s a fair takeaway, but the whole picture is a bit more layered.

Diabetes

Several studies have shown a difference in weight loss outcomes between individuals with and without diabetes. For example, a meta-analysis showed semaglutide led to 17.4% weight reduction in non-diabetic participants, but only 4 to 6.2% in participants with type 2 diabetes.² Similar findings also appear in large clinical studies that tested semaglutide for weight management. 

Researchers are unclear about the mechanism behind these results, but they speculate that diabetes itself may cause changes in metabolism and gut function that could reduce the effectiveness of GLP-1 drugs in promoting weight loss.² 

Patient Demographics

Age and gender also influence how effectively GLP-1s help with shedding pounds. Research suggests that older adults typically lose less weight and see smaller improvements in body measurements compared to younger patients using the same treatments. When it comes to gender differences, women generally achieve greater weight loss than men when on these medications.³ 

Starting Weight

Starting weight and BMI also make a difference. In a review of randomized controlled trials, individuals with a higher starting weight tended to lose more weight and experience greater reductions in waist size when using GLP-1 meds. In other words, the higher the starting BMI, the more effective the medication seemed to be.³ 

Differing Formulations

One more thing: not all GLP-1 products work the same way. For example, tirzepatide differs from traditional GLP-1s because it is a dual agonist that targets both the GLP-1 receptor and the glucose-dependent insulinotropic polypeptide (GIP) receptor. (It has other functions, but the primary role of GIP is insulin secretion.) This dual action may enhance appetite control and metabolism beyond what GLP-1-only drugs can achieve, potentially leading to greater weight loss.⁴ Additionally, the medications vary in their dosing schedules and how patients tolerate them, which can also affect overall effectiveness.

The Lab vs. The Real World

Clinical trials provide controlled environments that often highlight the best-case scenario, but real-world experience can look quite different. Unlike trial participants, who follow strict medication schedules and monitoring, many patients in real life may take lower doses, come up against cost barriers, or discontinue the medication early for other reasons. 

Side effects also differ between drugs; some patients tolerate semaglutide better than tirzepatide, or vice versa, which can influence adherence and outcomes.⁴ 

When patients do use GLP-1s consistently and at effective doses, comparative real-world data generally support what clinical trials have found: semaglutide tends to produce more weight loss than liraglutide or dulaglutide, and tirzepatide may offer even greater reductions in weight.⁵ 

Choosing the Right One

The first step is to have appropriate medical oversight.

With multiple GLP-1 options available, selecting the best medication depends on individual factors, including underlying health conditions, lifestyle, and treatment goals. It’s important to note that GLP-1 medications are intended for people who meet specific criteria for obesity or overweight status with related health risks. They are not appropriate for everyone, especially those who fall outside these parameters.

Careful about Compounding

We’ll go into it in greater detail in the next part of the series, but it’s worth a mention here. Be cautious of compounded versions of GLP-1 drugs. These are not FDA-regulated, which means they may pose safety risks and lack the proven efficacy of approved medications. Be sure to talk to your provider in detail about using compounded GLP-1 medicines so that you fully understand the risks and benefits.

If you’re considering GLP-1 therapy for weight management or want to learn more about how these medications might fit into your health plan, the team at MIIS Weight Loss Institute is here to guide you. 

1. Thomsen, R. W., Mailhac, A., Løhde, J. B., & Pottegård, A. (2025). Real-world evidence on the utilization, clinical and comparative effectiveness, and adverse effects of newer GLP-1RA-based weight-loss therapies. Diabetes, obesity & metabolism, 27 Suppl 2(Suppl 2), 66–88. https://doi.org/10.1111/dom.16364. 
2. Jensterle, M., Rizzo, M., Haluzík, M., & Janež, A. (2022). Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review. Advances in therapy, 39(6), 2452–2467. https://doi.org/10.1007/s12325-022-02153-x. 
3. Wong, H. J., Sim, B., Teo, Y. H., Teo, Y. N., Chan, M. Y., Yeo, L. L. L., Eng, P. C., Tan, B. Y. Q., Sattar, N., Dalakoti, M., & Sia, C.-H. (2025). Efficacy of GLP-1 Receptor Agonists on Weight Loss, BMI, and Waist Circumference for Patients With Obesity or Overweight: A Systematic Review, Meta-analysis, and Meta-regression of 47 Randomized Controlled Trials. Diabetes Care, 48(2), 292–300. https://doi.org/10.2337/dc24-1678. 
4. Jensterle, M., Rizzo, M., Haluzík, M., & Janež, A. (2022). Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review. Advances in therapy, 39(6), 2452–2467. https://doi.org/10.1007/s12325-022-02153-x. 
5. Thomsen, R. W., Mailhac, A., Løhde, J. B., & Pottegård, A. (2025). Real-world evidence on the utilization, clinical and comparative effectiveness, and adverse effects of newer GLP-1RA-based weight-loss therapies. Diabetes, obesity & metabolism, 27 Suppl 2(Suppl 2), 66–88. https://doi.org/10.1111/dom.16364.