Pipeline Review: Emerging Drugs to Prevent Muscle Loss During GLP-1 Therapy | Research

The takeaway

15-40% of GLP-1/GIP drug weight loss is lean muscle; emerging therapeutics including SARMs, myostatin/TGF-β inhibitors, and siRNA therapies aim to preserve muscle mass during treatment.

15-40% is muscle
Up to 40% of weight lost on GLP-1/GIP drugs is lean muscle mass, driving urgent need for muscle-sparing co-therapies

What the researchers found

15-40% of incretin-induced weight loss is lean mass; pipeline solutions include SARMs, myostatin/TGF-β inhibitors, and siRNA; current limitations: parenteral delivery, short trials, sparse functional outcomes, FDA focus on total weight not composition.

Why it matters

Muscle loss undermines the metabolic benefits of weight loss and increases frailty risk. The field urgently needs muscle-sparing co-therapies.

How the study worked

Review of emerging therapeutics pipeline for preserving lean mass during GLP-1/GIP agonist therapy.

What this study cannot tell us

Most pipeline agents are early-stage. Functional muscle outcomes rarely measured. Regulatory path for muscle-preserving claims unclear.

How to read the evidence

Pipeline review with preclinical and early clinical evidence. Most candidates are pre-approval.

When this study was published

Published in 2025.

The bigger picture

The next frontier in obesity pharmacotherapy is not just losing more weight, but losing the right kind of weight — fat, not muscle.

Questions still open

Which muscle-preserving agent will reach market first?
Should regulatory endpoints be changed to include body composition?
Can exercise + protein supplementation adequately substitute for pharmacological approaches?

Common questions

Why does losing muscle matter during weight loss?

Muscle burns calories, improves blood sugar, and prevents falls. Losing 15-40% of weight as muscle undermines these benefits and increases frailty risk, especially in older adults.

What drugs could prevent muscle loss on GLP-1 therapy?

Several are in development: SARMs (anabolic agents), myostatin inhibitors like bimagrumab (block muscle-wasting signals), and siRNA therapies (silence muscle-degrading genes). None are approved yet for this use.

Read the original research

Mitigating loss of lean muscle in GLP-1 and dual GLP-1/GIP agonists: Pipeline opportunities and limitations.

Biochimica et biophysica acta. Molecular basis of disease, 1872(4), 168172

View on PubMed ↗Publisher’s paper ↗

Citation

Hierholzer, Justin; Benson, Harrison; Ewida, Heba A; Ahmed, Mahmoud Salama. (2026). Mitigating loss of lean muscle in GLP-1 and dual GLP-1/GIP agonists: Pipeline opportunities and limitations.. Biochimica et biophysica acta. Molecular basis of disease, 1872(4), 168172. https://doi.org/10.1016/j.bbadis.2026.168172