Eli Lilly and Company has reported new findings from a Phase 3b clinical trial suggesting a deeper biological connection between psoriasis and obesity, with combined treatment using Taltz and Zepbound linked to broader immune and metabolic biomarker changes than Taltz alone.
The exploratory analysis from the TOGETHER-PsO trial, presented at the 2026 Fall Clinical Dermatology Conference in Las Vegas, examined adults with moderate-to-severe plaque psoriasis who also had obesity or were overweight with at least one additional weight-related comorbidity.
The findings point to differences in inflammatory pathways when the two medicines were used together, strengthening scientific interest in the potential relationship between immune and metabolic health.
In the United States, approximately 61% of people with psoriasis also have obesity or are overweight with at least one weight-related comorbidity, underscoring the overlap between the two conditions.
"People living with psoriasis and obesity carry a compounded burden that extends beyond what is visible, yet these conditions are too often viewed through separate treatment lenses," said Mark Genovese, senior vice president of Lilly Immunology development.
"The broader biomarker changes observed with Taltz and Zepbound, including those associated with skin clearance, may point to a meaningful relationship between immune and metabolic biology. Along with previously reported clinical outcomes, these findings support a more comprehensive approach to psoriasis care that also addresses obesity for people managing both conditions."
Researchers analysed circulating proteins and gene expression in blood samples to better understand the biological changes associated with taking Taltz and Zepbound together, compared with Taltz alone.
By Week 36, the combination-treatment group showed changes in substantially more proteins and genes than the Taltz-only group. The analysis identified 482 differentially expressed proteins with the combination treatment, compared with 140 with Taltz alone. For gene expression, the corresponding figures were 467 and 16.
Broader biomarker responses were observed as early as Week 12, according to the analysis.
At Week 36, changes in psoriasis-related, immune and metabolic biomarkers across both treatment groups were consistent with the known biological effects of the medicines when used for their approved indications.
The combination was also associated with greater reductions in inflammatory immune activity, including changes involving neutrophils, immune cells that play a role in inflammation.
Researchers further found that changes in a subset of neutrophil-associated markers accounted for part of the additional improvement in the Psoriasis Area and Severity Index (PASI) observed with Taltz and Zepbound compared with Taltz alone.
"This analysis provides new insights into the potential connected immune and metabolic biology in people with psoriasis and obesity," said James G. Krueger, Professor and Laboratory Head, The Rockefeller University.
"What is most compelling is these findings identified differences in inflammatory pathways when patients received concomitant treatment with Taltz plus Zepbound for both conditions. These data at the intersection of psoriasis and obesity highlight immunometabolic health as an important area for continued scientific research."
The new biomarker analysis follows previously reported results from the TOGETHER-PsO trial, which found that Taltz and Zepbound used together delivered superior skin clearance and clinically meaningful weight reduction compared with Taltz alone at the primary endpoint at Week 36.
Those improvements were maintained or further improved through Week 52, while the safety findings remained consistent with the known safety profile of each medicine.
The latest analysis adds a biological dimension to those clinical results, suggesting that treating psoriasis and obesity together may be associated with changes across a broader range of inflammatory and metabolic pathways.
However, the findings are exploratory and do not, on their own, establish a causal relationship between the biomarker changes and clinical improvements.
The results add to ongoing research into immunometabolic health and the potential benefits of addressing psoriasis and obesity as interconnected conditions rather than treating them in isolation.
