Metformin + Simvastatin + Digoxin combination

The combination of metformin, simvastatin, and digoxin (C3) is a novel repurposed drug combination that has been investigated primarily for targeted treatment of pancreatic ductal adenocarcinoma (PDAC) and potentially other solid tumors[1][2]. This combination consists of three FDA-approved drugs that were identified to effectively target PDX1 and BIRC5 in human pancreatic cancer tumors[1]. ## Mechanism of Action The C3 combination works by targeting specific genes involved in pancreatic cancer: - It targets pancreaticoduodenal homeobox1 (PDX1) and baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5)[1] - The drugs were selected using super-promoters of the target genes to interrogate an FDA approved drug library[1] - The combination has been shown to effectively suppress the proliferation of pancreatic cancer cells[2] ## Development Status The combination is currently in clinical development: - A Phase IB trial is underway for patients with pancreatic cancer and other advanced solid tumors[5] - The trial is designed as an open-label, single-arm dose escalation study with subjects accrued in 3-subject dose escalation cohorts[5] - Patients with treated advanced solid tumors showing disease progression on established standard therapy are being enrolled[5] ## Safety Profile Safety data for this combination appears promising: - In a retrospective study of 72 patients taking the three drugs concurrently for 18 months, the combination appeared to confer no significant toxicity[3] - The adverse drug reaction profile was comparable to package insert criteria and a negative cohort[3] - The average Modified Marshall Scoring System for Organ Failure was 0.7, revealing minimal toxicity[3] - Several unexpected long-term cancer survivors were identified in the cohort[3] ## Dosing Information In the clinical trial setting: - Metformin is taken at breakfast and dinner time (as applicable) - Simvastatin is taken at bedtime - Digoxin is taken once daily[5] - All three are administered as oral pills within recommended package insert safe levels[5] This combination represents an interesting approach to drug repurposing, taking three well-established medications with known safety profiles and applying them to a new therapeutic area with significant unmet need.

Other names

metformin + simvastatin + digoxin