Responders Vs. Non-Responders or How to Predict the Response to GLP-1 or GLP-1/GIP Receptor Agonist Therapy.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing existing literature without systematic quantitative pooling.
PubMed 42634284 · doi:10.1111/dom.71226
What was done
The authors performed a narrative review of human studies indexed in PubMed from 2005 to May 2026 investigating biological, genetic, metabolic, hormonal, behavioral, and psychosocial predictors of treatment response to GLP-1 receptor agonists and dual GLP-1/GIP receptor agonists across three clinical contexts: glycemic control in type 2 diabetes (T2D), weight loss in overweight or obesity without T2D, and dual metabolic response in individuals with both conditions.
What was found
Weight-loss non-response (<5% total body weight loss) affects approximately 10% of participants in clinical trials, with higher rates observed in real-world cohorts; glycemic non-response in T2D is less frequent. Early on-treatment response is the only actionable predictor currently established. Genome-wide association findings linking *GLP1R* and *GIPR* variants to weight loss and gastrointestinal adverse events remain single-cohort, self-reported, and unreplicated; metabolic, microbiome, and neuroendocrine markers remain preliminary.
Why it matters
Clinicians cannot currently rely on pre-treatment genetic, metabolic, or microbiome testing to predict GLP-1 or GLP-1/GIP receptor agonist efficacy. Assessing early on-treatment response remains the only evidence-based approach to guide therapy individualization.
Limits
The publication is a narrative review without systematic pooling, meta-analytic estimates, or reported study counts in the abstract. Candidate predictors are currently limited by single-cohort designs, reliance on self-reported outcomes, and a lack of prospective replication.
Cited by
- supports A study found genetic differences in individuals that influence their therapeutic responsiveness and nausea severity when taking GLP-1 receptor agonists.