Introduction: Two-Year Effects of Semaglutide in Adults with Overweight or Obesity — The STEP 5 Trial
With obesity posing a significant public health burden, long-term therapeutic strategies are essential. Semaglutide, a GLP-1 receptor agonist, has garnered considerable attention for its potent weight-loss effects in adults with obesity or overweight. The STEP 5 trial, titled “Two-Year Effects of Semaglutide in Adults with Overweight or Obesity“ by Garvey et al., published in Nature Medicine in 2022, provides critical insights into the prolonged safety and efficacy of semaglutide over a 104-week period.
This randomized, double-blind, placebo-controlled study aimed to assess sustained outcomes in weight loss, treatment adherence, and adverse events associated with weekly semaglutide 2.4 mg over two years.
Study Design and Participant Profile
Between October 2018 and February 2019, 304 participants were randomized in equal numbers to receive either semaglutide 2.4 mg or placebo. The study followed an intention-to-treat model, tracking outcomes both during the in-trial and on-treatment periods.
Key demographic details:
- Mean age: 47.3 years
- Mean body weight: 106.0 kg
- Mean BMI: 38.5 kg/m²
- Female participants: 77.6%
- White participants: 93.1%
Overall, 282 participants (92.8%) completed the trial, and 243 (79.9%) remained on treatment through week 104.
Results: Clinically Significant Weight Loss
The STEP 5 trial demonstrated robust weight-loss efficacy over two years:
- Participants in the semaglutide group experienced a mean body weight reduction of 11.85% more than placebo recipients.
- Weight reductions were consistent across both in-trial and on-treatment assessments.
- Cardiometabolic risk factors also improved, including waist circumference, blood pressure, and lipid profiles (though detailed secondary endpoints were not specified in the provided summary).
These outcomes affirm semaglutide’s capability to deliver durable weight loss over a prolonged period, making it an attractive option for long-term obesity management.
Adherence and Retention Rates
One of the strengths of STEP 5 was its high completion and adherence rates:
- 92.8% of participants completed the trial
- 89.5% had weight measured at week 104
- 79.9% were still receiving treatment at the study’s end
These figures highlight semaglutide’s tolerability and feasibility for extended use in real-world clinical settings.
Safety Profile: Predominantly Gastrointestinal Side Effects
As observed in prior GLP-1 RA studies, semaglutide’s primary adverse events were gastrointestinal:
- Nausea, vomiting, and diarrhea were the most common complaints
- GI events were 1.59 times more likely in the semaglutide group compared to placebo
Despite these occurrences, the overall safety profile was acceptable, with relatively few discontinuations due to side effects. The majority of GI events were mild to moderate in severity and occurred primarily during dose escalation.
Conclusion: Semaglutide Offers Sustained Weight Loss for Obesity Management
The STEP 5 trial reinforces semaglutide’s long-term efficacy in reducing body weight and improving overall metabolic health. Its ability to maintain weight loss for up to 104 weeks with a high level of adherence speaks to its clinical utility.
While gastrointestinal side effects remain a consideration, these were manageable and consistent with previous studies. For individuals seeking sustained, medically supervised weight management, semaglutide 2.4 mg weekly represents a compelling treatment option backed by strong, long-term data.
References
- Garvey WT, Batterham RL, Bhatta M, et al. Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial. Nat Med. 2022;28(10):2083–2091.
- Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021;384(11):989–1002.
- Lin F, Yu B, Ling B, et al. Weight loss efficiency and safety of tirzepatide: A Systematic review. PLoS One. 2023;18(5):e0285197.
- Kushner RF, Calhoun DA, Rock CL. Approaching Obesity Management as a Chronic Disease. J Clin Endocrinol Metab. 2020;105(9):dgaa399.
- Apovian CM, Aronne LJ, Bessesen DH, et al. Pharmacological Management of Obesity: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2015;100(2):342–362.
