Tirzepatide once weekly for the treatment of obesity: results from the SURMOUNT-1 study
Tirzepatide is an innovative medication for the treatment of obesity that simultaneously activates GLP-1 and GIP receptors. This allows it to influence appetite regulation, glucose levels, and the body’s energy balance.
Obesity is a chronic disease that significantly increases the risk of cardiovascular diseases, type 2 diabetes, and overall mortality. That is why new pharmacological approaches to its treatment are being actively investigated.
Study design of SURMOUNT-1
The SURMOUNT-1 study (NEJM, 2022) is a randomized, double-blind, placebo-controlled phase 3 trial.
It included 2,539 adult participants with:
- obesity (BMI ≥30)
- or overweight (BMI ≥27) with complications
- without type 2 diabetes
Participants were randomly assigned to 4 groups:
- Tirzepatide 5 mg once weekly
- Tirzepatide 10 mg once weekly
- Tirzepatide 15 mg once weekly
- Placebo
The treatment duration was 72 weeks, including a dose-escalation period of up to 20 weeks.
All participants also received basic lifestyle recommendations:
- caloric deficit of approximately 500 kcal/day
- at least 150 minutes of physical activity per week
Results: weight reduction
The average change in body weight after 72 weeks was:
- 5 mg: −15.0% (≈ −15.0 kg on average)
- 10 mg: −19.5%
- 15 mg: −20.9%
- Placebo: −3.1%
The difference between tirzepatide and placebo was statistically significant across all doses (p < 0.001).
Clinically meaningful weight loss outcomes
Key weight loss thresholds:
- ≥5% body weight: achieved by 85–91% of participants in tirzepatide groups
- ≥10%: a majority of participants in the 10–15 mg groups
- ≥20%: 50–57% in higher dose groups
- ≥25%: up to 36% in the 15 mg group
For comparison, in the placebo group these outcomes occurred in only 1–3% of participants.
Metabolic effects
In addition to weight loss, tirzepatide improved several metabolic parameters:
- reduction in waist circumference
- lower blood pressure
- improved insulin levels
- reduced lipid levels
In more than 95% of participants with prediabetes, glucose levels normalized by the end of the study.
Body composition changes
In a subgroup where body composition was measured, the following was observed:
- ≈33.9% reduction in fat mass in the tirzepatide group
- ≈8.2% reduction in the placebo group
The fat-to-lean mass ratio improved significantly, indicating a qualitative improvement in body composition.
Side effects
The most common adverse reactions were gastrointestinal:
- nausea
- diarrhea
- constipation
- vomiting
These symptoms:
- were generally mild to moderate
- occurred most often during dose escalation
- tended to decrease over time
Serious adverse events were rare and comparable between groups.
Serious adverse events
- overall rate of serious events: ~6%
- rare cases of pancreatitis
- low incidence of gallstone disease
- a small number of treatment discontinuations due to side effects
Some serious events were also related to COVID-19, as the study was conducted between 2019–2022.
Study conclusions
Tirzepatide administered once weekly demonstrated:
- significant weight loss (up to ~21%)
- high rates of clinically meaningful weight reduction
- improved metabolic profile
Compared to existing obesity treatments, tirzepatide showed one of the highest levels of efficacy in clinical trials.
Conclusion: the drug may become one of the key tools in pharmacological treatment of obesity, but it requires medical supervision.
Source: SURMOUNT-1, New England Journal of Medicine (2022), DOI: 10.1056/NEJMoa2206038