The World Health Organization (WHO) 2025 global guideline on the use of GLP-1 medications recommended their use for adults (excluding pregnant women) living with obesity, as part of long‑term obesity treatment (9).
Whilst GLP-1 medications are effective for weight loss, how well they work varies depending on factors such as the type of GLP-1 used, dose, treatment duration, adherence, and the individual (10).
In real‑world settings—where the structured support of clinical trials is absent—weight loss tends to be lower, averaging about 12%. It is important to note that these estimates are based on observational data, not clinical trial evidence.
To put this into perspective, lifestyle (diet and physical activity) changes alone usually lead to about 3–5% weight loss in 6–12 months. While more intensive programs, such as very low-calorie diets, can help people lose around 6–8% if they stay engaged (12).
It is important to recognise that obesity is a chronic condition that is difficult to manage long-term, and weight regain is common once treatment ends without sustained dietary and lifestyle support (13).
As one would expect, when GLP-1 medications are stopped, weight regain is common (6). A study reported that one year after stopping taking GLP-medications (and without further diet and lifestyle changes), participants regained, on average, two-thirds of their prior weight loss (10).
In a recent large analysis, it was estimated that in those who stopped taking GLP-1 medications, body weight would return to pre-treatment levels in less than two years (15).
While GLP‑1 medications can support meaningful weight loss, sustaining these benefits long‑term is more likely when paired with ongoing diet and lifestyle, and behavioural change support.
In addition to their established role in improving blood glucose control in people with diabetes, clinical studies show that GLP‑1 medications can reduce the higher risk of heart disease faced by people living with obesity (19, 20).
Research also suggests that GLP-1 medications may help support kidney health (16), and emerging research suggests they may offer neuroprotective benefits (17).
Because living with overweight or obesity increases the risk of several cancers, some preliminary studies have explored whether GLP‑1s might reduce the risk of obesity‑related cancers (18).
However, the evidence for these potential benefits—including kidney, neurological, and cancer‑related effects—comes largely from observational studies and is not yet proven.
Like most medications, GLP‑1 medications can cause side effects. Clinical trials show that more than 70% of patients experience adverse events—most often mild gastrointestinal symptoms (14).
GLP-1 medications have also been associated with an increased risk of pancreatitis (inflammation of the pancreas). However, the current evidence from clinical trials is not strong (22).
It has been suggested that the cases of pancreatitis may be due to weight‑loss‑induced gallstones rather than a direct drug effect (23). Although weight loss in general has been shown to reduce the risk of gallstones, rapid weight loss increases the risk of developing gallstones (24).
By reducing hunger and increasing fullness, GLP‑1 medications often lead to lower overall food intake. Although the evidence in this area is emerging, available data show that GLP-1s reduce calorie (energy) intake by approximately 16%–39% (25). This can make it harder to meet nutrient needs, particularly if dietary variety is limited. Consequently, maintaining diet quality (how healthy the diet is) becomes essential to ensure nutritional needs are met despite reduced calorie intake (1).
A cross-sectional study of adults using GLP-1 medications found widespread nutrient shortfalls, with over 90% failing to meet recommended intakes for key micronutrients such as vitamin D, potassium, and choline (25).
In one study, nutritional deficiencies were diagnosed in 13% of patients within 6 months and 22% within 12 months of starting to take GLP-1 medications – the most common nutritional deficiency was vitamin D (26). In part, this may be due to people having a lower intake of vitamin D-rich foods.
A growing concern with people taking GLP‑1 medication is that it can reduce lean body mass, including muscle.
For those using GLP-1 medications, maintaining adequate protein intake becomes especially important. A higher‑protein diet can help offset losses in lean mass, improve muscle quality, and help support long‑term weight‑loss maintenance (28, 29).
Alongside prioritising protein, strategies that preserve muscle—such as regular resistance-based exercise—can help reduce losses in muscle, strength, and physical function during GLP‑1‑induced weight loss (29).
See part 3 which delves into how the GLP-1 medications are changing consumers' food preferences and how the food industry is responding.
9. WHO issues global guideline on the use of GLP-1 medicines in treating obesity Available from: https://www.who.int/news/item/01-12-2025-who-issues-global-guideline-on-the-use-of-glp-1-medicines-in-treating-obesity
10. Wilding JPH, Batterham RL, Davies M, Van Gaal LF, Kandler K, Konakli K, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes, Obesity and Metabolism. 2022;24(8):1553–64.
11. Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, et al. Tirzepatide Once Weekly for the Treatment of Obesity. New England Journal of Medicine. 2022;387(3):205–16.
12. Perreault L, Kramer ES, Smith PC, Schmidt D, Argyropoulos C. A closer look at weight loss interventions in primary care: a systematic review and meta-analysis. Front Med. 2023;10:1204849.
13. Wadden TA, Chao AM, Machineni S, Kushner R, Ard J, Srivastava G, et al. Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial. Nat Med. 2023;29(11):2909–18.
14. Rodriguez PJ, Zhang V, Gratzl S, Do D, Goodwin Cartwright B, Baker C, et al. Discontinuation and Reinitiation of Dual-Labeled GLP-1 Receptor Agonists Among US Adults With Overweight or Obesity. JAMA Network Open. 2025;31;8(1):e2457349.
15. West S, Scragg J, Aveyard P, Oke JL, Willis L, Haffner SJP, et al. Weight regain after cessation of medication for weight management: systematic review and meta-analysis. BMJ. 2026;392.
16. Colhoun HM, Lingvay I, Brown PM, Deanfield J, Brown-Frandsen K, Kahn SE, et al. Long-term kidney outcomes of semaglutide in obesity and cardiovascular disease in the SELECT trial. Nat Med. 2024;30(7):2058–66.
17. Monney M, Jornayvaz FR, Gariani K. GLP-1 receptor agonists effect on cognitive function in patients with and without type 2 diabetes. Diabetes & Metabolism. 2023;49(5):101470.
18. Dai H, Li Y, Lee YA, Lu Y, George TJ, Donahoo WT, et al. GLP-1 Receptor Agonists and Cancer Risk in Adults With Obesity. JAMA Oncol. 2025;11(10):1186–93.
19. Zushin PJH, Wu JC. Evaluating the benefits of the early use of GLP-1 receptor agonists. The Lancet. 2025;405(10474):181–3.
20. Lincoff AM, Brown-Frandsen K, Colhoun HM, Deanfield J, Emerson SS, Esbjerg S, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. New England Journal of Medicine. 2023;389(24):2221–32.
21. Kim JA, Yoo HJ. Exploring the Side Effects of GLP-1 Receptor Agonist: To Ensure Its Optimal Positioning. Diabetes Metab J. 2025;49(4):525–41.
22. Xie H, Jiang L, Peng J, Hu H, Han M, Zhao B. Drug-induced pancreatitis: a real-world analysis of the FDA Adverse Event Reporting System and network pharmacology. Front Pharmacol. 2025;16:1564127.
23. Lomeli LD, Kodali AM, Tsushima Y, Mehta AE, Pantalone KM. The incidence of acute pancreatitis with GLP-1 receptor agonist therapy in individuals with a known history of pancreatitis. Diabetes Research and Clinical Practice. 2024;215:111806.
24. Mehta AE, Lomeli LD, Pantalone KM. Glucagon-like peptide-1 receptor agonists and pancreatitis: A reconcilable divorce. Cleve Clin J Med. 2025 ;92(8):483–9.
25. Spreckley M, Ruggiero CF, Brown A. Nutrition Strategies for Next-Generation Incretin Therapies: A Systematic Scoping Review of the Current Evidence. Obesity Reviews. 2025;e70079.
26. Scott Butsch W, Sulo S, Chang AT, Kim JA, Kerr KW, Williams DR, et al. Nutritional deficiencies and muscle loss in adults with type 2 diabetes using GLP-1 receptor agonists: A retrospective observational study. Obesity Pillars. 2025;15:100186.
27. Memel Z, Gold SL, Pearlman M, Muratore A, Martindale R. Impact of GLP- 1 Receptor Agonist Therapy in Patients High Risk for Sarcopenia. Curr Nutr Rep. 2025;14(1):63.
28. Prado CM, Phillips SM, Gonzalez MC, Heymsfield SB. Muscle matters: the effects of medically induced weight loss on skeletal muscle. The Lancet Diabetes & Endocrinology. 2024;12(11):785–7.
29. Neeland IJ, Linge J, Birkenfeld AL. Changes in lean body mass with glucagon-like peptide-1-based therapies and mitigation strategies. Diabetes, Obesity and Metabolism. 2024;26:16–27.
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