Genetic biomarkers could predict GLP-1 efficacy response, results show. 

Human omics company Ovation.io and precision medicine company PrecisionLife have released findings from the first phase of their collaboration, showing biomarkers can predict the efficacy, safety and tolerability of GLP-1 therapies. 

Using Ovation’s longitudinal clinical and omics datasets and PrecisionLife’s AI-driven combinatorial analytics platform, the partners identified underlying genetic drivers of GLP-1 efficacy to predict and stratify strong and weak responders within a large real-world population.  

The insights provide a better understanding of the genetic and biological drivers of GLP-1 responses. The findings also shed light on new biomarkers for drug development, refined patient enrolment in clinical trials, and the potential for a payor-facing test to inform reimbursement policy for these widely prescribed drugs based on a patient’s potential to tolerate and respond to a specific therapy. 

“While questions have been raised in the literature about the impact of genetics on GLP-1 patient responses, Phase I of the PrecisionLife/Ovation collaboration demonstrated that we can identify genetic biomarkers associated with strong and weak responders to GLP-1 RA drugs and quantitatively predict the level of efficacy based on their degree of response measured by BMI and HbA1c changes,” said Steve Gardner, CEO of PrecisionLife. 

“While we see many known pathways, a number of the genes identified are outside of the “defined” GLP-1RA mechanisms of action and novel in the literature.  

“We believe this initial effort demonstrates our combined ability to provide solutions in high value disease states where precision medicine and therapy selection improve outcomes and address unmet needs.”  

Findings could ‘improve patient outcomes’

GLP-1 therapies are among the fastest-growing drug classes globally, yet approximately 50% of patients discontinue treatment within 12 months, often losing previously achieved metabolic benefit. With figures showing US spending on GLP-1 medicines exceeds $70 billion annually, variable response and high discontinuation rates create significant clinical and economic challenges for payors, providers, and pharmaceutical developers. 

Phase I of the collaboration, initiated in December 2025, utilised 4,600 patients’ data and generated over 2,500 genetic signatures associated with GLP-1 RA-mediated efficacy. These signatures were mapped to 1,100 genes with 15 main genetic mechanisms driving efficacy.  

These markers of strong responses to GLP-1 drugs were also associated with type 2 diabetes, cardiovascular disease, lipid metabolism and other disease states. The biomarkers of efficacy were identified in 100% of the patients. 

Based on these results, PrecisionLife and Ovation have agreed to expand their partnership into Phase II, scaling the dataset to up to 25,000 patients toand incorporate more detailed clinical phenotype data. This next phase will validate and refine efficacy signals and identify predictive markers of safety and tolerability, including drug-specific response differences.  

“Our initial, hypothesis free results suggest that by combining Ovation’s unique normalised and standardised longitudinal data sets and clinical records with PrecisionLife’s mechanistic patient stratification analysis platform, we can identify specific combinations of genetic and biological drivers that create different “response-defined” subgroups within this crucial therapeutic category,” said Curt Medeiros, CEO of Ovation.io.  

“These real-world, in-the-wild, data can be of significant value to our biopharma clients as well providing important clinically facing markers that improve patient outcomes.  

“Matching patients to specific therapies based on their individual risk and response mechanisms, rather than treating them as a homogeneous population, enables more targeted, de-risked development programmes and more accurate patient prescriptions.”