Wegovy vs. Zepbound: Comparing GLP-1 Therapies

In the GLP-1 wars over the past couple of years, there has been quite a bit of discussion about which drug is better: Wegovy or Zepbound?

Wegovy (semaglutide) is a GLP-1 receptor agonist. Zepbound (tirzepatide) is a combination GLP-1 and GIP receptor agonist. GLP-1 and GIP are naturally occurring hormones that help regulate appetite, blood sugar, and fat storage. GLP-1 primarily regulates appetite and blood sugar levels, while GIP supports metabolism and the way your body stores fat.

Due to its first-to-market status, Wegovy (essentially Ozempic at a higher dose, with FDA approval for managing body mass) is the best-known GLP-1 weight loss medication, and clinical trials have shown significant body weight loss of approximately 12% to 88%.¹ The wide range in results seems to stem from dosage variability and the initial BMI of the patient.

Zepbound came out later and, similar to the route Ozempic took, it represents a derivative of Eli Lilly’s diabetes drug Mounjaro. Targeting both GLP-1 and GIP pathways, this dual-agonist medication has been shown in pooled analyses to produce greater reductions in body weight, BMI, and waist circumference compared to placebo – with average weight loss of about 25 pounds, and even greater results seen with higher doses and longer treatment durations.²

But do the clinical research numbers hold in reality?

Clinical studies showed the desired effects of both drugs in only a subset of participants, and the past two years of widespread use have made it clear that not everyone experiences dramatic weight loss. In fact, some patients may not lose any weight at all.

A significant factor in long-term weight loss effectiveness is linked to how a patient tolerates the drug. No matter the weight loss potential of a medication, if the side effects are too burdensome or if it simply doesn’t work for a particular patient, we may suggest trying the other drug to see if it produces better results.

Understanding the side effects

Overall, the side effect profiles of the different GLP-1 drugs have been fairly consistent. But with the widespread use of these drugs, new side effects have emerged beyond what was observed in clinical trials. Even though severe side effects are rare, it has long been known that GLP-1 medications, whether they’re used for weight loss or blood sugar control, can cause issues such as gallbladder and pancreatic disease, stomach motility problems like gastroparesis, and, in some cases, concerns related to thyroid cancer. Since their approval, there have also been rare reports of liver inflammation, vision problems, and even suicidal thoughts.

The case for long-term use

While we can expect new obesity treatments to emerge in the coming months and years – including, eventually, oral GLP-1 medications – Zepbound (tirzepatide) and Wegovy (semaglutide) are currently excellent options for helping many patients lose weight.

That said, these drugs appear to have a ceiling in their effectiveness, with most patients reaching their maximum weight loss around one year into treatment. Research also shows that discontinuing therapy often leads to gradual weight regain within months, with many reverting toward their baseline weight over the following year if treatment and/or lifestyle support is not maintained.³

Whether these medications can or should be taken long-term is still unclear. For now, it’s important to be realistic: these drugs are powerful tools, but they are only one part of a broader strategy that includes lifestyle changes, ongoing monitoring, and individualized care planning.

Where bariatric surgery fits into the continuum of care

GLP-1 and GIP drugs have certainly been a game-changer in the weight loss world, but at a certain point, they’re just not effective enough to help some patients, especially those with an elevated BMI. Once a patient’s BMI exceeds 35, the drug’s effectiveness often begins to diminish, and it may not be sufficient to achieve meaningful weight loss when used alone.

BMI cutoff isn’t strict or definitive as to when bariatric surgery is more effective than a GLP-1 medication. However, patients with a BMI over 40 are generally more likely to achieve greater results with surgery than with the drug alone. Despite the limitation, GLP-1 medications can still play an important role as a precursor to surgery by helping patients lose weight beforehand or as a boost to overcome plateaus after surgery.

Used strategically as an adjunct to bariatric surgery, GLP-1 medications have a clear, complementary role in optimizing patient outcomes. Before surgery, these drugs can help patients not only lose additional weight but also reduce liver size, making the procedure safer. After surgery, they can support patients who are experiencing slower-than-expected weight loss or early weight regain, providing a non-surgical option before considering a revision or conversion procedure.

So, is one better than the other?

The short answer is possibly. While both drugs are quite similar, they do have distinct mechanisms of action and, therefore, effectiveness. According to clinical data, Zepbound appears to have an edge over Wegovy in terms of weight loss. However, keep in mind that these results reflect averages across study populations; individual responses can vary widely, and what works best for one patient may not be the same for another.

Both Zepbound (tirzepatide) and Wegovy (semaglutide) are exceptionally effective medications that have become valuable additions to the range of weight loss strategies. To that end, both of these drugs are strong options for helping patients get on track or prepare themselves for a more successful surgical outcome.

Every patient’s weight loss experience is unique, and what works for one person may not work for another. GLP-1 medications can produce meaningful results, but they’re most effective when used as part of a carefully planned approach.

Consulting a weight-loss specialist or bariatric surgeon will help you understand how these medications could fit into your situation. Whether it’s jumpstarting progress, overcoming a plateau, or preparing for surgery, talk with the team at Higa Bariatrics to avoid some trial and error that could limit results or cause unnecessary side effects.

1. Alanazi, M., Alshahrani, J. A., Sulayman Aljaberi, A., Alqahtani, B. A. A., & Muammer, M. (2024). Effect of Semaglutide in Individuals With Obesity or Overweight Without Diabetes. Cureus, 16(8), e67889. https://doi.org/10.7759/cureus.67889. 
2. Rohani, P., Malekpour Alamdari, N., Bagheri, S. E., Hekmatdoost, A., & Sohouli, M. H. (2023). The effects of subcutaneous Tirzepatide on obesity and overweight: a systematic review and meta-regression analysis of randomized controlled trials. Frontiers in endocrinology, 14, 1230206. https://doi.org/10.3389/fendo.2023.1230206.
3. Quarenghi, M., Capelli, S., Galligani, G., Giana, A., Preatoni, G., & Turri Quarenghi, R. (2025). Weight Regain After Liraglutide, Semaglutide or Tirzepatide Interruption: A Narrative Review of Randomized Studies. Journal of clinical medicine, 14(11), 3791. https://doi.org/10.3390/jcm14113791.