EFFECTIVENESS OF SEMAGLUTIDE IN OBESITY TREATMENT AND THE ROLE OF LIFESTYLE INTERVENTIONS

Keywords: Obesity, GLP-1 Receptor Agonist, Semaglutide, Weight Loss, Lifestyle Intervention, Pharmacotherapy

Abstract

Background: Obesity is a global epidemic, affecting ~13% of adults and driving type 2 diabetes, cardiovascular disease, and other comorbidities (World Health Organization, 2021). In Europe and the U.S., prevalence reaches 30–40%, with >20% in Poland (Gajewska & Harton, 2023). Lifestyle interventions alone often fail to ensure durable results, creating demand for adjunctive pharmacotherapy.

Aim: To review obesity epidemiology and evaluate once-weekly semaglutide 2.4 mg regarding mechanism, efficacy, safety, and synergy with lifestyle changes.

Materials and Methods: Narrative review of publications (2018–2025) from PubMed, Google Scholar, and other databases on obesity, GLP-1 analogs, and lifestyle trials. STEP program data, meta-analyses, and guidelines were included.

Results: Risk factors include genetics, aging, sedentary lifestyle, and poor diet. Semaglutide, a GLP-1 receptor agonist, enhances insulin secretion, delays gastric emptying, and reduces appetite  (Papakonstantinou et al., 2024). In STEP Phase 3 trials, semaglutide 2.4 mg weekly produced ~15% mean weight loss over 68 weeks, versus ~2–5% with placebo  (Wilding et al., 2021) (Davies et al., 2021). About 69–79% achieved ≥10% loss, over half ≥15%  (Davies et al., 2021). Safety was consistent with GLP-1 class, dominated by mild-to-moderate gastrointestinal events  (Davies et al., 2021). Lifestyle modification alone yields 5–10% reduction, but in STEP 3, semaglutide plus intensive behavioral therapy achieved 16.0% versus 5.7% with lifestyle alone  (Wadden et al., 2021). Continued lifestyle support is crucial to maintain outcomes and limit post-withdrawal regain.

Conclusions: Semaglutide represents a breakthrough in obesity pharmacotherapy, approaching bariatric surgery efficacy in some patients. Optimal outcomes occur with integration of diet, activity, and education. Future dual/triple agonists may enhance efficacy, but issues of cost, access, and adherence persist. Broad, equitable availability is essential for public health.

References

Aronne LJ, Horn DB, le Roux CW, et al. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity (SURMOUNT-5). N Engl J Med. 2025;393(1):26-36. https://doi.org/10.1056/nejmoa2416394

Clément K, van den Akker E, Argente J, et al. ODP607 Long-term Efficacy of Setmelanotide in Patients With POMC or LEPR Deficiency Obesity. J Endocr Soc. 2022;6(Suppl 1):A14–A15 https://doi.org/10.1210/jendso/bvac150.030

Davies M, Færch L, Jeppesen OK, Pakseresht A, Pedersen SD, Perreault L, Rosenstock J, Shimomura I, Viljoen A, Wadden TA, Lingvay I. Efficacy and Safety of Semaglutide 2.4 MG Once-Weekly in Adults With Overweight or Obesity and Type 2 Diabetes (STEP 2). Journal of the Endocrine Society. 2021;5(Suppl_1):A10–A11. https://doi.org/10.1210/jendso/bvab048.019

Enebo LB, Berthelsen KK, Kankam M, et al. Safety, tolerability, and pharmacodynamic effects of co-administering the amylin analog cagrilintide with semaglutide 2.4 mg for weight management: a randomized phase 1b trial. Lancet. 2021;397(10286):1736-1748. https://doi.org/10.1016/s0140-6736(21)00845-x

Gajewska D, Harton A. Current nutritional status of the Polish population – focus on body weight status. J Health Inequal. 2023;9(2):154-160. https://doi.org/10.5114/jhi.2023.133899

Garvey WT, Mechanick JI, Brett EM, et al. American Association of Clinical Endocrinology (AACE) Guidelines for Medical Care of Patients with Obesity. Endocr Pract. 2016;22(Suppl 3):1-203. https://doi.org/10.4158/ep161365.gl

Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022;387(3):205-216. https://doi.org/10.1056/nejmoa2206038

Jastreboff AM, Kotz CM, Kahan S, et al. Triple–Hormone-Receptor Agonist Retatrutide for Obesity – Phase 2 Trial. N Engl J Med. 2023;389(19):1836-1848. https://doi.org/10.1056/nejmoa2301972

Jensen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults. Circulation. 2014;129(25 Suppl 2):S102-S138. https://doi.org/10.1161/01.cir.0000437739.71477.ee

Johnston BC, Kanters S, Bandayrel K, et al. Comparison of Weight Loss Among Named Diet Programs in Overweight and Obese Adults: A Meta-analysis. JAMA. 2014;312(9):923-933. https://doi.org/10.1001/jama.2014.10397

Knop, F. K., Aroda, V. R., do Vale, R. D., Holst-Hansen, T., Laursen, P. N., Rosenstock, J., Rubino, D. M., Garvey, W. T., & OASIS 1 Investigators (2023). Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet (London, England), 402(10403), 705–719. https://doi.org/10.1016/S0140-6736(23)01185-6

Lasota K, Hołownia-Voloskova M, Casciano R, Walczak J. Is There an Opportunity for Reimbursement of Anti-Obesity Drugs in Central and Eastern Europe? Value Health. 2024;27(Suppl 1):S168. https://doi.org/10.1016/j.jval.2024.10.2192

Lau DCW, Erichsen L, Francisco AM, Satylganova A, le Roux CW, McGowan B, Pedersen SD, Pietiläinen KH, Rubino D, Batterham RL, et al.. Once‑weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double‑blind, placebo‑controlled and active‑controlled, dose‑finding phase 2 trial. Lancet. 2021 Dec 11;398(10317):2160–2172. https://doi.org/10.1016/s0140-6736(21)01751-7

Lincoff AM, Brown-Frandsen K, Colhoun HM, Deanfield J, Emerson SS, Esbjerg S, Hardt-Lindberg S, Hovingh GK, Kahn SE, Kushner RF, Lingvay I, Oral TK, Michelsen MM, Plutzky J, Tornøe CW, Ryan DH; SELECT Trial Investigators. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med. 2023;389(24):2221–2232. https://doi.org/10.1056/nejmoa2307563

Look AHEAD Research Group (Wing RR, et al.). Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med. 2013;369(2):145-154. https://doi.org/10.1056/nejmoa1212914

Papakonstantinou I, Tsioufis K, Katsi V, et al. Spotlight on the Mechanism of Action of Semaglutide. Curr Issues Mol Biol. 2024;46(12):14514-14541. https://doi.org/10.3390/cimb46120872

Puhl, R. M., & Heuer, C. A. (2010). Obesity stigma: important considerations for public health. American journal of public health, 100(6), 1019–1028. https://doi.org/10.2105/AJPH.2009.159491

Rodriguez PJ, Goodwin Cartwright BM, Gratzl S, et al. Semaglutide vs Tirzepatide for Weight Loss in Adults with Overweight or Obesity. JAMA Intern Med. 2024;184(9):1056-1064. https://doi.org/10.1001/jamainternmed.2024.2525

Rubino DM, Greenway FL, Khalid U, O'Neil PM, Rosenstock J, Sørrig R, Wadden TA, Wizert A, Garvey WT; STEP 8 Investigators. Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial. JAMA. 2022 Jan 11;327(2):138-150. https://doi.org/10.1001/jama.2021.23619

Rubino F, Puhl RM, Cottrell J, et al. Joint international consensus statement for ending stigma of obesity. Nat Med. 2020;26(4):485-497. https://doi.org/10.1038/s41591-020-0803-x

Sumithran P, Prendergast LA, Delbridge E, et al. Long-Term Persistence of Hormonal Adaptations to Weight Loss. N Engl J Med. 2011;365(17):1597-1604. https://doi.org/10.1056/nejmoa1105816

Wadden TA, Bailey TS, Billings LK, et al. Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults with Overweight or Obesity (STEP 3). JAMA. 2021;325(14):1403-1413. https://doi.org/10.1001/jama.2021.1831

Wadden TA, Neiberg RH, Wing RR, et al. Eight-Year Weight Losses with an Intensive Lifestyle Intervention: The Look AHEAD Study. Obesity (Silver Spring). 2014;22(1):5-13. https://doi.org/10.1002/oby.20662

Weghuber D, Barrett T, Barrientos-Pérez M, et al. Once-Weekly Semaglutide in Adolescents with Obesity (STEP TEENS). N Engl J Med. 2022;387(24):2245-2257. https://doi.org/10.1056/nejmoa2208601

Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). N Engl J Med. 2021;384(11):989-1002. https://doi.org/10.1056/nejmoa2032183

Wilding JPH, Batterham RL, Davies M, Van Gaal LF, Kandler K, Konakli K, Lingvay I, McGowan BM, Oral TK, Wadden TA, Kushner RF. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obes Metab. 2022;24(8):1553-1564. https://doi.org/10.1111/dom.14725/v1/review2

Wing RR, Phelan S. Long-term weight loss maintenance. Am J Clin Nutr. 2005;82(1 Suppl):222S-225S. https://doi.org/10.1093/ajcn/82.1.222s

World Health Organization (WHO). Obesity and Overweight - Fact Sheet. WHO Newsroom; 2021. Retrieved from https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight

World Health Organization Regional Office for Europe. WHO European Regional Obesity Report 2022. WHO Europe; 2022. Retrieved from https://www.who.int/europe/publications/i/item/9789289057738

World Obesity Federation. World Obesity Atlas 2023. World Obesity Federation; 2023. Retrieved from https://data.worldobesity.org/publications/?cat=19

Wycherley TP, Moran LJ, Clifton PM, et al. Effects of energy-restricted high-protein, low-fat compared with standard-protein, low-fat diets: a meta-analysis of randomized controlled trials. Am J Clin Nutr. 2012;96(6):1281-1298. https://doi.org/10.3945/ajcn.112.044321

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2025-09-30
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Filip Bracichowicz, Igor Winogrodzki, Patryk Kowalczyk, Hanna Paszkiewicz, Kamil Nowak, Aleksandra Gęsińska, Alicja Stryczek-Schlusche, Bartłomiej Trzciński, Oliwia Gugała, & Aleksandra Magdalena Furczyńska. (2025). EFFECTIVENESS OF SEMAGLUTIDE IN OBESITY TREATMENT AND THE ROLE OF LIFESTYLE INTERVENTIONS. International Journal of Innovative Technologies in Social Science, 5(3(47). https://doi.org/10.31435/ijitss.3(47).2025.3931