By Dr. Asnat Raziel, bariatric surgeon specializing in obesity treatment, metabolic health and healthy longevity; Director of the Multidisciplinary Center for Obesity Treatment, Assia Medical, Assuta Ramat HaChayal, Tel Aviv
The SURMOUNT trials: what we’ve learned about tirzepatide and obesity
The SURMOUNT trials are the series of clinical trials that tested tirzepatide, the active ingredient in Mounjaro, as a treatment for obesity. They enrolled thousands of participants and looked at far more than weight loss. They also examined diabetes, sleep apnea, weight maintenance and a head-to-head comparison with another medication. In this article, I’ll summarize what each trial found and what it means for you.
What is tirzepatide and how does it work?
Tirzepatide is a once-weekly injection that mimics two gut hormones: GLP-1 and GIP. In other words, it acts on two receptors at the same time. These hormones increase fullness, slow stomach emptying and improve blood sugar control. As a result, people eat less and experience less “noise” around food.
In practice, treatment starts at 2.5 mg and is gradually increased to 5, 10 or 15 mg a week. Increasing the dose slowly reduces side effects. For a comparison with other medications, see my overview of medication treatment for obesity and metabolic disease.
The SURMOUNT trials: key results
SURMOUNT-1: the main trial
The first trial in the series enrolled 2,539 adults with obesity and without diabetes. After 72 weeks, participants on the 15 mg dose had lost an average of 20.9% of their body weight. On 10 mg the loss reached 19.5%, and on 5 mg, 15.0%. In the placebo group, by contrast, weight loss was only 3.1%. What’s more, about half of the patients on the higher doses lost 20% or more.
Who took part? Adults with a BMI of 30 or more, or 27 or more with at least one weight-related complication, such as high blood pressure. Average starting weight was 104.8 kg, and average BMI was 38.0. In other words, this population closely resembles the patients I see in my clinic every day. The researchers also measured improvements in every metabolic risk factor they examined, including blood pressure, blood sugar and blood lipids.
SURMOUNT-2: obesity with diabetes
People with type 2 diabetes generally lose less weight on medication. In a trial published in The Lancet, 938 participants with obesity and diabetes lost 14.7% on the 15 mg dose and 12.8% on 10 mg. In the placebo group, the loss was 3.2%.
SURMOUNT-3: after a lifestyle program
Here, participants first completed an intensive 12-week program and lost at least 5% of their weight. After that, continued treatment with tirzepatide produced an additional average loss of 18.4%. In the placebo group, on the other hand, weight rose by 2.5%. Put simply, the medication complements lifestyle changes rather than replacing them.
The SURMOUNT trials on weight maintenance
One of the most important findings came from the SURMOUNT-4 trial. All participants received tirzepatide for 36 weeks and lost an average of 20.9%. Then some continued on the medication, while others were switched to placebo. Over the following year, those who continued lost a further 5.5%. Those who stopped, by contrast, regained 14.0% of their body weight.
That’s why I explain to my patients that obesity is a chronic disease. As with high blood pressure, stopping treatment usually brings the problem back. The STEP trials of semaglutide pointed to exactly the same principle.
The SURMOUNT trials beyond weight: diabetes and sleep apnea
A three-year follow-up tracked participants with prediabetes. After 176 weeks, only 1.3% of patients on tirzepatide had developed diabetes, compared with 13.3% in the placebo group. Weight loss was also maintained throughout the entire period.
The SURMOUNT-OSA trial showed another important result. In patients with moderate to severe sleep apnea, the number of breathing interruptions per hour fell by 25.3 to 29.3 events, compared with only about 5 events on placebo. On this basis, the US FDA also approved the medication for treating obstructive sleep apnea. Good sleep matters for brain health as well.
Tirzepatide has also been studied in fatty liver disease, a topic I have covered in a separate article.
The SURMOUNT trials: tirzepatide vs. semaglutide
The SURMOUNT-5 trial compared the two medications head to head in 751 participants without diabetes. After 72 weeks, tirzepatide led to a 20.2% weight loss, compared with 13.7% for semaglutide. Waist circumference also fell by 18.4 cm versus 13.0 cm. Still, personalization matters, and some patients actually respond very well to semaglutide. Meanwhile, newer medications are already being tested, such as CagriSema in the REDEFINE trials.
The SURMOUNT trials: safety and side effects
Across all the trials, the most common side effects were digestive: nausea, diarrhea, constipation and vomiting. Most were mild to moderate and appeared mainly while the dose was being increased. In SURMOUNT-1, for example, 4.3% to 7.1% of patients stopped treatment because of side effects, compared with 2.6% on placebo. I have gathered practical tips in a separate guide to Mounjaro side effects.
It is important to know what is still unknown. The SURMOUNT-MMO trial is now testing, in about 15,000 participants, whether the medication reduces deaths, heart attacks and strokes in people with obesity. Its results have not yet been published.
The bottom line
The SURMOUNT trials showed that tirzepatide leads to an average weight loss of about 15% to 21%, along with improvements in blood sugar, sleep apnea and other risk factors. However, treatment is long term and is combined with nutrition, physical activity and medical follow-up. If you are considering this kind of treatment, it is best to plan it with a doctor who specializes in obesity. You can read about my approach to treatment on the About Dr. Asnat Raziel page.
The information in this article is general and does not replace personal medical advice.
Questions and answers
How much weight did participants lose in the trials?
In SURMOUNT-1, the average loss ranged from 15.0% to 20.9% after 72 weeks, depending on the dose.
What happens when you stop the medication?
In SURMOUNT-4, those switched to placebo regained 14.0% of their body weight within a year. That’s why the maintenance phase is planned in advance.
Did the SURMOUNT trials include people with diabetes?
Yes. SURMOUNT-2 studied people with obesity and type 2 diabetes, and weight loss reached 14.7% on the highest dose.
Does the medication protect the heart?
This is not yet known for certain in people with obesity. A large trial on this question is currently underway.
References
SURMOUNT-1: Tirzepatide Once Weekly for the Treatment of Obesity
SURMOUNT-5: Tirzepatide as Compared with Semaglutide for the Treatment of Obesity
SURMOUNT-OSA: Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity
SURMOUNT-1, three years: Tirzepatide for Obesity Treatment and Diabetes Prevention
The trials were funded by Eli Lilly, the manufacturer of the medication.
