Mechanism of Action and Clinical Analysis of Semaglutide in Weight Loss

Authors

  • Xinyu Yu
  • Aocheng Leo Zheng

DOI:

https://doi.org/10.61173/v87vyz34

Keywords:

Semaglutide, weight loss, type 2 diabetes mellitus

Abstract

Semaglutide is a long-acting Glucagon-Like Peptide-1 Receptor Agonist (GLP-1RA). It was initially applied in the treatment of type 2 diabetes mellitus, and later widely used in obesity management due to its prominent weightloss effect. As a novel long-acting GLP-1RA weight-loss drug, compared with traditional GLP-1RAs, it undergoes molecular structural modification to achieve reversible albumin binding, which reduces renal clearance and degradation by dipeptidyl peptidase Ⅳ. Meanwhile, it maintains high affinity to GLP-1 receptors, extending its half-life to 156 hours. The long half-life supports onceweekly injection, greatly improving patients' treatment compliance. Its structure is highly similar to natural human GLP-1, with an amino acid sequence homology of 94%. For the above reasons, it has attracted increasing attention. Accordingly, there is a growing demand for comparing the efficacy of semaglutide with that of other weightloss drugs. This article systematically summarizes the core weight-loss mechanism of semaglutide, efficacy data from large-scale clinical trials, characteristics of adverse reactions and clinical safety, and compares semaglutide with several other weight-loss drugs to clarify their differences and efficacy gaps. It aims to provide objective scientific evidence for the rational clinical application of relevant drugs and scientific weight loss for the public.

References

[1] Chinese Center for Disease Control and Prevention. Report on Nutrition and Chronic Diseases Status of Chinese Residents (2020) [R]. Beijing: People’s Medical Publishing House, 2020.

[2] Chinese Society of Endocrinology. Guidelines for the Prevention and Control of Obesity in China (2021 Edition) [J]. Chinese Journal of Endocrinology and Metabolism, 2021, 37(4): 288-347.

[3] Wilding J P H, Batterham R L, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity [J]. New England Journal of Medicine, 2021, 384(11): 989-1002.

[4] National Medical Products Administration. Announcement on the Approval of Semaglutide Injection for Weight Loss Indication [EB/OL]. (2024-06-20) [2025-01-10].

[5] Müller T D, Finan B, Bloom S R, et al. Glucagon-like peptide 1 (GLP-1) [J]. Molecular Metabolism, 2019, 30: 72-130.

[6] Li L, Wang G. Research progress on the metabolic regulatory mechanisms of GLP-1 receptor agonists in obese patients [J]. Chinese Journal of Diabetes, 2022, 30(8): 621-625.

[7] Zhang X Y, Zhao J J. Effects of semaglutide on lipid metabolism and its clinical significance [J]. Chinese Journal of Cardiology, 2023, 51(3): 310-314.

[8] Wilding J P H, et al. Once-weekly semaglutide in adults with overweight or obesity [J]. N Engl J Med, 2021, 384: 989-1002.

[9] Davies M, Færch L, Jeppesen O K, et al. Semaglutide 2.4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, doubledummy, placebo-controlled, phase 3 trial [J]. The Lancet, 2021, 398(10299): 981-994.

[10] Wadden T A, Berkowitz R I, Yanovski S Z, et al. Effect of subcutaneous semaglutide vs placebo as an adjunct to intensive behavioral therapy on body weight in adults with overweight or obesity: The STEP 3 randomized clinical trial [J]. JAMA, 2021, 326(15): 1503-1515.

[11] Rubino D, Ryan D H, Wilding J P H, et al. Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance in adults with overweight or obesity: The STEP 4 randomized clinical trial [J]. JAMA, 2021, 326(15): 1516-1526.

[12] Garvey W T, Batterham R L, Bhatta M, et al. Two-year effects of semaglutide in adults with overweight or obesity: The STEP 5 trial [J]. Nature Medicine, 2022, 28(10): 2083-2091.

[13] Novo Nordisk. STEP UP study data on the weight-loss efficacy of semaglutide 7.2 mg [EB/OL]. (2023-09-15) [2025- 01-12].

[14] Wilding J P H, Astrup A, Birkebaek N H, et al. Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): A randomised, double-blind, placebocontrolled, phase 3 trial [J]. The Lancet, 2023, 402(10398): 1191-1202.

[15] U.S. Food and Drug Administration (FDA). Warning on the Risks of Pancreatitis and Gallbladder Disease Associated with GLP-1 Receptor Agonists [EB/OL]. (2022-04-01) [2025-01-15].

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Published

2026-08-13