Related Experiment Video
Updated: Feb 8, 2026
Predictive Immune Modeling of Solid Tumors
Published on: February 25, 2020
A pharmacodynamic study of sirolimus and metformin in patients with advanced solid tumors
Amikar Sehdev1,2, Theodore Karrison3, Yuanyuan Zha4
1Section of Hematology Oncology, Department of Medicine, University of Chicago, 5841 S. Maryland Avenue, MC 2115, Chicago, IL, 60637, USA. asehdev@iupui.edu.
Background:
Sirolimus is a mammalian target of rapamycin (mTOR) inhibitor. Metformin may potentiate mTOR inhibition by sirolimus while mitigating its adverse effects. We conducted a pilot study to test this hypothesis.
Methods:
Patients with advanced solid tumor were treated with sirolimus for 7 days followed by randomization to either sirolimus with metformin (Arm A) or sirolimus (Arm B) until day 21. From day 22 onwards, all patients received sirolimus and metformin. The primary aim was to compare the change in phospho-p70S6K (pp70S6K) in peripheral blood mononuclear cells (PBMC) from day 8 to day 22 using a two-sample t test. Secondary aims were objective response rate, toxicity, and other serum pharmacodynamic biomarkers (e.g., fasting glucose, triglycerides, insulin, C-peptide, IGF-1, IGF-1R, IGF-BP, and leptin).
Results:
24 patients were enrolled, with 18 evaluable for the primary endpoint. There was no significant difference in mean change in pp70S6K in arm A vs. arm B (- 0.12 vs. - 0.16; P = 0.64). Similarly, there were no significant differences in other serum pharmacodynamic biomarkers. There were no partial responses. There were no dose-limiting or unexpected toxicities.
Conclusions:
Adding metformin to sirolimus, although well tolerated, was not associated with significant changes in pp70S6K in PBMC or other serum pharmacodynamic biomarkers.
Impact:
Combining metformin with sirolimus did not improve mTOR inhibition.
Insights
Combining metformin with sirolimus did not enhance mammalian target of rapamycin (mTOR) inhibition in patients with advanced solid tumors. This pilot study found no significant differences in key biomarkers or adverse effects between groups.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Sirolimus is a mammalian target of rapamycin (mTOR) inhibitor used in cancer therapy.
- Metformin, a common diabetes drug, may enhance mTOR inhibition and reduce sirolimus side effects.
- A pilot study was designed to investigate this potential synergy.
Purpose of the Study:
- To determine if metformin potentiates mTOR inhibition by sirolimus.
- To assess if metformin mitigates adverse effects of sirolimus.
- To evaluate changes in pharmacodynamic biomarkers and clinical response.
Main Methods:
- A pilot study involving patients with advanced solid tumors.
- Patients received sirolimus, then were randomized to sirolimus with or without metformin.
- Primary endpoint: change in phospho-p70S6K (pp70S6K) in PBMCs; secondary: response rate, toxicity, and biomarkers.
Main Results:
- 18 patients were evaluable for the primary endpoint.
- No significant difference in pp70S6K change between sirolimus alone and sirolimus with metformin.
- No significant differences in other biomarkers, response rates, or toxicities observed.
Conclusions:
- Adding metformin to sirolimus was well-tolerated.
- Metformin did not significantly enhance mTOR inhibition as measured by pp70S6K.
- The combination did not alter other pharmacodynamic biomarkers or clinical outcomes.
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