gut microbiome diet

Adherence and Persistence with GLP-1-Based Therapies: International Real-World Evidence and the Role of Nutritional and Lifestyle Support-A Narrative Review

30 May 2026

Dziewierz A, Siudak Z.

Summary

What the study found

This review highlights a significant gap between the high success of GLP-1 medications in clinical trials and their low success in the real world due to high discontinuation rates. Researchers concluded that long-term weight management is unlikely to succeed without an integrated care model that prioritizes structured nutritional support.

Key findings

Real-world persistence rates are often very low, with some patient groups showing less than 15% adherence after 24 months of treatment.
The most common drivers for stopping the medication include gastrointestinal intolerance and the high economic burden of treatment.
Rapid weight loss associated with these drugs increases the risk of lean mass loss, necessitating a specific focus on protein intake.
Effective treatment requires Medical Nutrition Therapy that targets micronutrient density and meal composition to improve drug tolerability.

Practical takeaways

To maximize the benefits of GLP-1 therapies for longevity, you should focus on high protein intake to protect your muscle mass during weight loss. Implementing gastric-sparing feeding techniques, such as adjusting meal size and composition, is essential for managing side effects and staying on the treatment long-term.

Limitations

The current evidence for these nutritional strategies is largely extrapolated from general obesity studies rather than GLP-1-specific randomized trials. Furthermore, real-world data is heavily influenced by regional reimbursement policies, making global generalizations difficult.

Abstract

Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have transformed type 2 diabetes mellitus (T2DM) and obesity care, with clinical trials demonstrating weight loss exceeding 15%. However, real-world effectiveness lags trial efficacy, largely owing to high discontinuation rates. We characterize the global persistence gap and propose a framework integrating Medical Nutrition Therapy (MNT) to improve adherence. Methods: We conducted a narrative review of real-world evidence from North America, Europe, Asia, and Latin America, synthesized with physiological, nutritional, and behavioral data to distinguish established contributors to discontinuation from strategies that remain partly extrapolated from related populations. Results: Global persistence varies widely: from approximately 75-80% at 12 months in reimbursed T2DM cohorts (Sweden, Denmark) to below 10% in obesity-focused or high out-of-pocket-cost settings (Poland, Colombia), with intermediate rates in the United States and United Kingdom; in several cohorts, persistence falls below 15% by 24 months. The primary drivers are gastrointestinal intolerance and economic barriers. Meal size, dietary composition, and gastric-emptying effects influence gastrointestinal tolerability; inadequate protein intake during rapid weight loss raises concern for lean mass loss. Conclusions: Pharmacotherapy alone is unlikely to sustain long-term obesity management. Narrowing the persistence gap will require an integrated care model in which structured nutritional support-targeting protein intake, micronutrient density, and gastric-sparing feeding-is systematically offered rather than treated as an optional adjunct, while recognizing that most supporting evidence is extrapolated from primary trials in obesity and cardiometabolic disease rather than derived from GLP-1-specific randomized trials.

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