What does this research mean for the field?

In real-world settings, GLP-1 receptor agonists produce clinically meaningful but more modest reductions in HbA1c and body weight in patients with type 2 diabetes compared to clinical trials, with the majority of improvements occurring within the first 6 months. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This study aims to evaluate the real-world effectiveness of glucagon-like peptide-1s on glycemic control and body weight in adults with type 2 diabetes.

June 7, 2026

20-PUB: A Meta-Analysis of Real-World Effectiveness of Glucagon-Like Peptide 1s among Patients with Type 2 Diabetes in the United States

Key Points

This study aims to evaluate the real-world effectiveness of glucagon-like peptide-1s on glycemic control and body weight in adults with type 2 diabetes.
Systematic review of observational studies from 2014 to 2025 reporting HbA1c and body weight changes
Meta-analysis using restricted maximum likelihood random effects modeling to estimate pooled means
Inclusion of 23 studies assessing changes in HbA1c and/or body weight among adults with type 2 diabetes
Pooled mean HbA1c reduction was -1.03% (95% CI: -1.17%, -0.89%) at 6 months and -0.90% (95% CI: -1.10%, -0.70%) at 12 months
Mean body weight decreased by -2.49 kg (95% CI: -3.35, -1.64) at 6 months and -3.01 kg (95% CI: -3.88, -2.14) at 12 months
Findings show clinically meaningful reductions in HbA1c and consistent weight loss, particularly noticeable by 6 months.

Abstract

Introduction and Objective: Clinical trials of glucagon-like peptide-1-based treatments (GLP-1s) demonstrate robust improvements in glycemic control and body weight. However, suboptimal real-world persistence may attenuate effectiveness, which has not been comprehensively evaluated. This systematic literature review aimed to summarize real-world changes in HbA1c and body weight among adults with type 2 diabetes (T2D) treated with GLP-1s. Methods: PRISMA guidelines were used to identify observational studies (2014-2025) reporting mean changes in body weight (kg) and HbA1c (%) among adults with T2D initiating a GLP-1. Meta-analyses of HbA1c and weight changes using restricted maximum likelihood random effects modeling were performed to estimate overall pooled means and 95% confidence intervals (CI). Results: Twenty-three studies reporting changes in HbA1c and/or body weight were included. Across all GLP-1s (dulaglutide, liraglutide, and semaglutide), pooled mean HbA1c changed -1.03% (95% CI: -1.17%, -0.89%) at 6 months and -0.90% (95% CI: -1.10%, -0.70%) at 12 months. Mean body weight changed -2.49 kg (95% CI: -3.35, -1.64) at 6 months and -3.01 kg (95% CI: -3.88, -2.14) at 12 months. Clinically meaningful reductions in HbA1c (0.5%) and consistent weight loss were observed, with the majority of improvements occurring by 6 months and minimal incremental change thereafter. Despite known efficacy differences among individual GLP-1s and persistent heterogeneity after stratification, effect estimates were directionally consistent across drugs. Conclusion: Across diverse real-world studies, GLP-1s produce meaningful but more modest reductions in HbA1c and body weight compared to clinical trials, potentially reflecting lower persistence in routine practice. These findings underscore the need for therapeutic options and care strategies that support sustained treatment use and help patients achieve clinical benefits more comparable to those observed in randomized trials. Disclosure N. Rasouli: Advisory Panel; Current; Eli Lilly and Company. Research Support; Current; Eli Lilly and Company. Advisory Panel; Current; Novo Nordisk. Research Support; Current; Novo Nordisk. Advisory Panel; Current; Amgen Inc. Research Support; Current; SomaLogic, Inc. L. Perreault: Advisory Panel; Current; Novo Nordisk, Eli Lilly and Company, Boehringer Ingelheim International GmbH. Speaker's Bureau; Current; Novo Nordisk, Eli Lilly and Company, Boehringer Ingelheim International GmbH, Ascendis Pharma A/S. F. Sanogo: Employee; Current; Amgen Inc. L. Bylsma: Research Support; Current; Amgen Inc. N. Movva: Research Support; Current; Amgen Inc., Idorsia Pharmaceuticals Ltd. M. Suh: Research Support; Current; Amgen Inc., Idorsia Pharmaceuticals Ltd. H. Reichert: Research Support; Current; Amgen Inc., Idorsia Pharmaceuticals Ltd. M. Donsmark: Employee; Current; Amgen Inc. Stock/Shareholder; Current; Novo Nordisk A/S. M. Girguis: Employee; Current; Amgen Inc. C. Frankenfeld: Consultant; Current; Amgen Inc. Other - Editorial Board Member: Journal of Nutrition and Annals of Epidemiology; Current; Elsevier.

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