Obesity reviews : an official journal of the International Association for the Study of ObesityNov 16, 2023

Using high-dose GLP-1 drugs and combined GLP-1 treatments to manage type 2 diabetes, obesity, and fatty liver disease

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 28, 2026

Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are already approved for managing Type 2 diabetes (T2D) and obesity.

GLP-1RAs may provide clinical benefits for Type 2 diabetes, obesity, and nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH).
Higher doses of GLP-1RAs and novel GLP-1RA-based co-agonists are being evaluated for their potential to reduce glycated hemoglobin (HbA1c) and body weight.
Ongoing trials are assessing the impact of high-dose GLP-1RAs and multi-hormonal strategies in populations with T2D, obesity, or NASH.
Available trial findings suggest clinical efficacy and safety of GLP-1RAs, aligning with preclinical observations.
Expansion of GLP-1R-based drug classes could address the interconnected challenges of T2D, obesity, and NASH.

Simplified

Type 2 diabetes (T2D), obesity, and nonalcoholic fatty liver disease/nonalacoholic steatohepatitis (NAFLD/NASH) share mutual causalities. Medications that may offer clinical benefits to all three conditions are being developed. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are approved for the management of T2D and obesity and there is great interest in evaluating higher doses of available GLP-1RAs and developing novel GLP-1RA-based co-agonists to provide greater reductions in glycated hemoglobin (HbA1c) and body weight as well as modifying NAFLD/NASH complications in clinically meaningful ways. High-dose GLP-1RAs and multi-hormonal strategies including GLP-1R agonism have either already been approved or are in development for managing T2D, obesity, or NASH. We provide a mechanistic outline with a detailed summary of the available clinical data and ongoing trials that are adjudicating the impact of high-dose GLP-1RAs, unimolecular, and multimolecular GLP-1R-based co-agonists in populations living with T2D, obesity, or NASH. The available trial findings are aligned with preclinical observations, showing clinical efficacy and safety thus providing optimism for the expansion of GLP-1R-based drug classes for managing the triad of T2D, obesity and NASH. Development, access, and wide-spread utilization of these new therapeutic approaches will offer important opportunities to markedly improve the collective global burden of T2D, obesity, and NASH.

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Using high-dose GLP-1 drugs and combined GLP-1 treatments to manage type 2 diabetes, obesity, and fatty liver disease

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