Navigating the benefits and harms of GLP-1 and GLP-1/GIP agonists in obesity.
Level 5 - mechanism / opinion, no new human data
Narrative review without systematic search or meta-analytic methods
PubMed 41513440 · doi:10.1136/dtb.2025.000039
What was done
This narrative review summarizes the reported clinical benefits, adverse effects, discontinuation rates, and management considerations for GLP-1 and GLP-1/GIP receptor agonists in the treatment of obesity and related comorbidities.
What was found
The review reports short-term improvements in type 2 diabetes mellitus, cardiovascular disease, and metabolic dysfunction-associated steatotic liver disease. Adverse effects include gastrointestinal symptoms (nausea, vomiting, acute pancreatitis, dehydration, malnutrition), reduced efficacy of oral contraceptives, allergic reactions, and rare occurrences of thyroid cell tumours and non-arteritic anterior ischaemic optic neuropathy. Up to 33% of weight lost is lean mass (muscle and bone). Discontinuation rates reach up to 80% after 2 years, with subsequent weight regain of up to two-thirds of lost weight, primarily as fatty tissue. Co-prescription with supervised exercise and dietetic advice is recommended.
Why it matters
It highlights that substantial lean tissue loss and high real-world discontinuation rates with rapid fat regain complicate incretin-based weight loss, reinforcing the necessity of concurrent lifestyle support.
Limits
This is a narrative review with no systematic search strategy, meta-analytic pooling, or risk-of-bias assessment reported. Sample sizes, primary trial characteristics, and precise statistical estimates with confidence intervals are absent in the abstract. Comparative differences between individual GLP-1 and GLP-1/GIP agents are not detailed.
Cited by
- supports GLP-1 receptor agonist medications cause muscle loss and digestive problems as potential side effects.