GLP-1 Agonists for Weight Loss: Effectiveness, Limitations, and the Key Role of Nutritional Support

Weight loss

• May 29, 2026

A blue measuring tape is wrapped around a bottle filled with green and white capsules, with some capsules scattered on a dark surface.

Results and Mechanisms of Action

The introduction of Glucagon-Like Peptide-1 (GLP-1) receptor agonists has enabled weight loss outcomes comparable to certain surgical interventions while avoiding the invasive nature associated with surgery [1]. A systematic review reported average weight loss of up to 13.9% with semaglutide (Wegovy®) and 17.8% with tirzepatide (Mounjaro®) [1]. Weight loss is generally rapid during the first six months, then gradually slows, reaching a plateau around 12 to 18 months [1]. However, real-world results are often more modest, averaging approximately 8% to 11% weight loss among individuals with or without diabetes after 60 weeks of semaglutide treatment [2].

The main mechanisms of action of GLP-1 agonists include [3]:

increased satiety;
reduced appetite;
delayed gastric emptying;
reduced energy intake by approximately 16% to 39%.

The Need for Nutritional Support to Optimize Treatment Effectiveness

Major clinical trials involving GLP-1 agonists all included structured lifestyle interventions combining nutritional counseling, behavioural support, physical activity, and dietary self-monitoring [1].

Structured follow-up with a registered dietitian may:

promote greater weight loss;
improve treatment adherence;
facilitate the management of gastrointestinal side effects;
support adequate long-term nutritional intake;
contribute to the sustainable maintenance of lifestyle changes [1].

Nutritional Challenges:

The use of GLP-1 agonists may lead to several challenges requiring the expertise of a registered dietitian:

Nutritional Challenges	Impact	Possible Interventions / Recommendations
Risk of Nutritional Deficiencies	Significant reduction in appetite and energy intake [2]. Gastrointestinal side effects may decrease nutrient absorption and increase the risk of deficiencies [3]. Nutrients most at risk include iron, calcium, magnesium, zinc, and vitamins A, D, E, K, B1, B12, and C [4].	Regular nutritional follow-up with a registered dietitian to assess dietary intake. Periodic evaluation of biomarkers. Individualized supplementation as needed (vitamine D, calcium, B12, multivitamin).
Gastrointestinal Side Effects	Nausea, vomiting, constipation, and diarrhea are common and may: reduce food intake; promote dehydration; impair treatment adherence [1].	Consume small, frequent meals. Limit high-fat meals, especially at the beginning of treatment. Gradually increase fibre intake. Maintain adequate hydration. Consider magnesium citrate in cases of persistent constipation.
Loss of Muscle Mass	Rapid weight loss leads to loss of lean body mass, representing approximately 25% of total weight loss [5]. Approximately 38% of the weight lost may come from lean mass, corresponding to approximately 20% actual muscle loss according to a clinical trial [6].	Aim for a protein intake of 1.2–1.6 g/kg/day during weight loss [1]. Encourage resistance training ≥3 times/week. Closely monitor individuals at higher risk of sarcopenia (older adults, sedentary individuals, or those with low protein intake).
Bone Health	Rapid weight loss (>14% in 3–4 months) is associated with decreased bone mineral density [4]. GLP-1 agonists also reduce lean mass (including bone mass), accounting for approximately 25% of total weight loss [5].	Ensure adequate intake of protein, calcium, and vitamin D. Incorporate weight-bearing exercises. Aim for ≥150 minutes of physical activity per week to help preserve bone health [7].
Weight Regain and Long-Term Weight Maintenance	Weight cycling may exacerbate lean mass loss and fat mass regain, potentially promoting sarcopenic obesity [1]. Repeated cycles may also negatively influence the relationship with food and body image.	Provide long-term nutritional support (beyond 6 months) to promote maintenance of healthy lifestyle habits. Avoid energy intakes below basal metabolic rate or excessively restrictive caloric deficits. Address behavioural aspects of nutrition. Continue physical activity after treatment discontinuation to maintain weight loss. Promote a diet rich in protein and fibre to reduce meal energy density. Encourage self-monitoring, meal planning, and social support [8].

Long-Term Weight Loss Trends

During Treatment

When treatment is continued long term, weight loss may be maintained for 2 to 4 years [9, 10]. In a recent study (2024), continuous semaglutide use allowed participants to maintain an average weight loss of ~10% over a 4-year period [10].

After Treatment Discontinuation

Discontinuation of GLP-1 agonists is associated with substantial weight regain reaching up to 67% of the weight lost within one year after stopping treatment [11, 12].
A recent meta-analysis reported that participants treated with semaglutide or tirzepatide regained an average of 9.7 kg after treatment discontinuation [13].

Exercise: Protective Effects Against Weight Regain

A clinical study evaluated weight maintenance after discontinuing a one-year liraglutide (Saxenda®) treatment, with or without supervised exercise [14]. The group combining an exercise program with GLP-1 agonist treatment experienced the lowest weight regain (36% of the weight lost regained) one year after treatment cessation, compared to the other groups (61% weight regain in the liraglutide-only group and 81% in the placebo group) [14].

Despite their nombreux bénéfices cliniques, GLP-1 agonists raise new nutritional, metabolic, and behavioural challenges, as well as concerns regarding long-term weight maintenance. These challenges highlight the importance of structured, multidisciplinary support. Registered dietitians play a key role in supporting long-term weight loss, preserving bone and muscle mass, and limiting side effects such as nutritional deficiencies and gastrointestinal disorders.

Help your patients access complementary nutritional support to optimize their long-term weight loss: refer them to a registered dietitian today using our simplified referral form.

References

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Little D, Deckert J, Bartelt K, Ganesh M, Stamp T. Weight Change With Semaglutide. Epic Research.https://epicresearch.org/articles/diabetes-drug-helps-with-weight-loss-…. Accessed on May 20, 2026.
Christensen, S., Robinson, K., Thomas, S., & Williams, D. R. (2024). Dietary intake by patients taking GLP-1 and dual GIP/GLP-1 receptor agonists: a narrative review and discussion of research needs. Obesity Pillars, 11, 100121.
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Iqbal, J., Wu, H. X., Hu, N., Zhou, Y. H., Li, L., Xiao, F., ... & Zhou, H. D. (2022). Effect of glucagon‐like peptide‐1 receptor agonists on body weight in adults with obesity without diabetes mellitus—a systematic review and meta‐analysis of randomized control trials. Obesity Reviews, 23(6), e13435.
Ryan, D. H., Lingvay, I., Deanfield, J., Kahn, S. E., Barros, E., Burguera, B., ... & Kushner, R. F. (2024). Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial. Nature medicine, 30(7), 2049-2057.
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