Written by: Angie Carter, Health Writer at Shed
If you’ve explored your options for weight-loss medications over the past few years, no doubt you’ve heard about Zepbound® (tirzepatide) and Wegovy® (semaglutide). Both medications are GLP-1 agonists, meaning they mimic the way the hormone glucagon-like peptide 1 (GLP-1) works in the body. GLP-1 helps regulate blood sugar, appetite, and digestion, which can have big implications for weight loss.
So naturally the question arises: which GLP-1 agonist—tirzepatide or semaglutide—is better for weight loss? While earlier clinical trials have shown impressive results for each, a recent study, SURMOUNT-5, put these two medications head-to-head to compare their safety, effectiveness, and side effects.
This study is an important step forward in understanding not just how these GLP-1 medications work, but also their potential to help more people.
Setting the stage: Understanding the SURMOUNT-5 study
The SURMOUNT-5 trial was a randomized, controlled study involving 751 adults with obesity but without type 2 diabetes. Participants received one of the two medications at their maximum approved doses. The trial lasted for 72 weeks and included diet and lifestyle counseling for all participants.
More details on the context surrounding the study:
- The study was led by investigators at Weill Cornell Medicine and NewYork-Presbyterian, conducted with other institutions
- It was conducted across 32 sites in the U.S. and Puerto Rico
- The study was sponsored by Eli Lilly, the company that produces tirzepatide
- The trial was not blinded, meaning participants knew which medication they were taking
Study results: Impressive weight loss with both medications
Both medications led to significant weight loss:
- Tirzepatide: Participants lost an average of 50 pounds, or 20.2% of their baseline weight; 32% achieved at least 25% body-weight reduction.
- Semaglutide: Participants lost an average of 33 pounds, or 13.7% of their baseline weight; 16% achieved at least 25% body-weight reduction.
Participants on both medications also saw reductions to their waist circumference, although those on tirzepatide were more likely to reach specific weight-loss targets.
These results are consistent with previous studies where drugs were evaluated independently.
Why the difference? Single vs. dual action
While both drugs are GLP-1 agonists that are effective for weight loss, results varied slightly, with participants on tirzepatide losing more weight. This is likely due to how the medications interact with the body:
- Semaglutide works by mimicking a single hormone (GLP-1).
- Tirzepatide mimics two hormones: GLP-1 and GIP (glucose-dependent insulinotropic peptide). This dual action may offer added support for hunger regulation and metabolic support.
Each approach taps into the body’s natural regulatory systems to support weight-loss goals and blood sugar regulation. This study is another confirmation that people on either tirzepatide or semaglutide can lose a significant amount of weight.
Side effects
Side effects were similar for both medications, which were mainly gastrointestinal. About 44% of participants in each group experienced nausea, and 25% from both groups reported abdominal pain.
Tolerability can vary from person to person, and side effects can often be managed by starting with lower doses and gradually increasing over time.
Looking ahead: What this means for the future of weight management
The SURMOUNT-5 trial adds important insights to our growing knowledge of GLP-1 drugs, but it’s just one piece of what’s happening in the weight-loss world. Researchers are already testing the next generation of weight-loss drugs, including compounds that mimic three hormones (GLP-1, GIP, and glucagon), like Eli LIlly’s retatrutide. These drugs may be a good alternative for those who don’t respond well to current options, and could be even more effective than tirzepatide and semaglutide.
Trials are also underway to see if tirzepatide can have other long-term health benefits, such as improved cardiovascular outcomes, similar to findings seen with semaglutide.
Final takeaways
The SURMOUNT-5 study confirms that both tirzepatide and semaglutide are highly effective tools for weight loss for people living with obesity. While tirzepatide showed greater average weight loss in this study—likely due to its dual mechanism of action—semaglutide remains a proven and effective treatment with a well-established track record.
While this head-to-head study is beneficial for patients and doctors, it’s important to remember the study was sponsored by the manufacturer of tirzepatide (Eli Lilly) and was not blinded. However, this research adds valuable information to our understanding of these powerful weight-loss medications and points toward future developments in the field that will help even more people.
If you’re interested in starting GLP-1 treatment for weight loss, your doctor will be able to guide you to the best option for you based on your goals, lifestyle, and tolerance levels. Shed offers both tirzepatide and semaglutide options.* Talk to a licensed medical provider today to learn more about your treatment options.
FAQs: Tirzepatide vs. semaglutide
What’s the difference between tirzepatide and semaglutide?
Semaglutide is a GLP-1 agonist, meaning it mimics the GLP-1 hormone your gut already produces. This hormone helps regulate blood sugar and appetite and slows the movement of food through your stomach.
Tirzepatide mimics two hormones: GLP-1 and GIP. This dual action may make tirzepatide more effective at regulating blood sugar levels and appetite, leading to greater metabolic health benefits for some people.
How do GLP-1 agonists work?
GLP-1 injections mimic a natural hormone in your body that helps regulate appetite, blood sugar, and insulin levels. This may lead to decreased hunger, slower digestion, and better glucose control.
How are GLP-1 medications administered?
GLP-1 medications are taken once a week, typically injected into the abdomen or thigh. The dosing will vary from person to person and will be determined by your medical provider. Medication is prescribed only after consultation with a licensed provider to determine appropriateness.
Are tirzepatide and semaglutide safe for long-term use?
Long-term use is considered safe when monitored by a licensed healthcare provider.
Can I switch from one to the other?
If you don’t respond to one medication well, switching to another may be possible.* This transition must be managed and monitored closely by your medical provider.
*Medication is prescribed only after consultation with a licensed provider to determine appropriateness.
This content is for informational purposes and is not medical advice.
