Cancer patients with type 2 diabetes may have worse outcomes on immune checkpoint inhibitor (ICI) therapy, according to a study published in Clinical Cancer Research

Researchers found that, among patients receiving ICIs to treat advanced solid tumors, those who were also taking a glucose-lowering medication (GLM) for type 2 diabetes had shorter overall survival (OS) and progression-free survival (PFS). 

However, a subanalysis revealed that the association with PFS and OS was only significant in patients who were taking metformin and not in those who were taking insulin or other GLMs.

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This study included 1395 patients with advanced solid tumors who received ICIs at 21 institutions between June 2014 and June 2020. The median age of the cohort was 68 (range, 21-91) years, and 63.7% of patients were men. Cancer types included non-small cell lung cancer (54.7%), melanoma (24.7%), renal cell carcinoma (15.0%), and other cancers (5.6%). 

A total of 226 patients were taking a GLM, and 1169 patients were not. Among the patients taking a GLM, 65.0% were taking metformin, 55.3% were taking other oral diabetes medications, and 33.6% were using insulin.

In a multivariate analysis, patients taking any GLM had significantly shorter OS (hazard ratio [HR], 1.29; 95% CI, 1.07-1.56) and PFS (HR, 1.21; 95% CI, 1.03-1.43) than those not taking a GLM. 

When the researchers matched patients receiving either metformin or another GLM with control patients, the team found that metformin use was significantly associated with shortened OS (HR, 1.53; 95% CI, 1.16-2.03) and PFS (HR, 1.34; 95% CI, 1.04-1.72). 

However, there was no significant association between other GLMs and OS (HR, 1.03; 95% CI, 0.75-1.41) or PFS (HR, 0.99; 95% CI, 0.75-1.31).

“[O]ur study is the first, to our knowledge, to report a clear detrimental effect of diabetes on clinical outcomes from ICIs in patients with solid tumors,” the researchers wrote. “In view of the constantly expanding clinical indications of ICI-based therapies across different cancer types and the increasing global burden of metabolic syndrome, obesity, and type 2 diabetes, our findings are of clinical importance and need to be carefully considered in the provision of cancer immunotherapy.” 

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Cortellini A, D’Alessio A, Cleary S, et al. Type 2 diabetes mellitus and efficacy outcomes from immune checkpoint blockade in patients with cancer. Clin Cancer Res. Published online May 1, 2023. doi:10.1158/1078-0432.CCR-22-3116