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metformin + sirolimus
- Development stage
- Discontinued
- Lead developer
- University of Chicago
- Modality
- Small Molecules
- Administration
- Oral
01
Overview
Metformin + sirolimus is an investigational drug combination evaluated by the University of Chicago for the treatment of advanced solid tumors. Metformin, a biguanide traditionally used for type 2 diabetes, acts as an AMPK activator which indirectly inhibits the mTOR pathway. Sirolimus (also known as rapamycin) is a direct inhibitor of the mTORC1 complex. In the context of oncology, this combination was hypothesized to provide synergistic mTOR inhibition while potentially mitigating sirolimus-induced metabolic adverse effects, such as hyperglycemia and hypertriglyceridemia, through metformin's insulin-sensitizing properties. A Phase 1 pharmacodynamic study (NCT01529593) utilized an extended-release formulation of metformin in combination with daily sirolimus. However, the study was terminated after an interim analysis indicated that the addition of metformin did not significantly improve pharmacodynamic biomarkers in patients with advanced solid tumors.
- Other names
- Metformin XR + SirolimusMetformin XL + SirolimusSirolimus and Metformin
02
Targets
FKBP1AAMPK (Adenosine monophosphate–activated protein kinase)Mechanistic target of rapamycin complex 1
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