canagliflozin + gemcitabine

Canagliflozin + gemcitabine is an investigational combination therapy comprising two small molecule drugs with distinct mechanisms of action. Canagliflozin is a sodium-glucose co-transporter 2 (SGLT2) inhibitor primarily approved for type 2 diabetes, but it has demonstrated antitumor activity in preclinical cancer models by inhibiting glycolysis and suppressing the PI3K/AKT/mTOR signaling pathway, leading to reduced glucose uptake, lactate production, and increased apoptosis in cancer cells. Gemcitabine is a nucleoside analog chemotherapeutic agent that inhibits DNA synthesis by incorporation into DNA and causing masked chain termination, resulting in apoptotic cell death. The combination has shown enhanced efficacy compared to either agent alone in preclinical studies of pancreatic cancer cells and is being evaluated clinically for pancreatic carcinoma[1][2]. This dual approach targets both metabolic pathways (via canagliflozin) and DNA replication (via gemcitabine), aiming to improve antitumor effects.