Hormonal
GCGR/GLP-1 dual agonists (e.g., mazdutide, survodutide) and GCGR/GLP-1/GIP triple agonists (e.g., retatrutide) elicit substantial body weight reduction (up to 24.2%) and improve liver health in patients with obesity and MASLD/MASH.
For individuals with obesity and liver fat, newer once-weekly injections targeting the glucagon and GLP-1 receptors (and sometimes GIP) are showing remarkable results, with some patients losing over 20% of their body weight and seeing improvements in liver health. These are prescription medications requiring medical supervision, but they represent a significant advancement over older treatments.
In early clinical trials, several GCGR-based multi-agonists (mazdutide, survodutide [being developed by the sponsor of this review], retatrutide) demonstrated substantial efficacy for eliciting weight loss in people with obesity while improving liver health in those with MASLD.
Why this rating
Supported by multiple phase 2 and 3 clinical trials, though long-term safety and chronic effects are still being delineated.
Source
Shared mechanistic pathways of glucagon signalling: Unlocking its potential for treating obesity, metabolic dysfunction‐associated steatotic liver disease, and other cardio‐kidney‐metabolic conditions
Guy Neff · Diabetes Obesity and Metabolism · 2025
DOI 10.1111/dom.70148
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