Diabetes, Antidiabetic Medications and Cancer Risk in Type 2 Diabetes: Focus on SGLT-2 Inhibitors

Abstract

In the last decade, cancer became the leading cause of death in the population under 65 in the European Union. Diabetes is also considered as a factor increasing risk of cancer incidence and mortality. Type 2 diabetes is frequently associated with being overweight and obese, which also plays a role in malignancy. Among biological mechanisms linking diabetes and obesity with cancer hyperglycemia, hyperinsulinemia, insulin resistance, increased levels of growth factors, steroid and peptide hormones, oxidative stress and increased activity of pro-inflammatory cytokines are listed. Antidiabetic medications can modulate cancer risk through directly impacting metabolism of cancer cells as well as indirectly through impact on risk factors of malignancy. Some of them are considered beneficial (metformin and thiazolidinedions—with the exception of bladder cancer); on the other hand, excess of exogenous insulin may be potentially harmful, while other medications seem to have neutral impact on cancer risk. Inhibitors of the sodium-glucose cotransporter-2 (SGLT-2) are increasingly used in the treatment of type 2 diabetes. However, their association with cancer risk is unclear. The aim of this review was to analyze the anticancer potential of this class of drugs, as well as risks of site-specific malignancies associated with their use.

The Intricate Crosstalk Between Insulin and Pancreatic Ductal Adenocarcinoma: A Review From Clinical to Molecular

“…The overexpression of SGLT-2 was observed in pancreatic cancer cells ( Scafoglio et al, 2015 ). By blocking SGLT-2, a reduced PDA risk was found in SGLT-2 inhibitor users, and a decreased cancer proliferation in preclinical pancreatic cancer models when treated with SGLT-2 inhibitor ( Dicembrini et al, 2019 ; Dąbrowski, 2021 ).…”

High-Concentration Metformin Reduces Oxidative Stress Injury and Inhibits the Growth and Migration of Clear Cell Renal Cell Carcinoma

“…Studies have found that patients who use metformin have a lower risk of cancer and lower cancer-related mortality [ 10 , 11 ]. Some experimental studies have found that metformin can inhibit the proliferation of prostate cancer cells [ 12 ], breast cancer cells [ 13 ], pancreatic cancer cells [ 14 ], and melanoma cells [ 15 ] in vitro .…”

Diabetes and skin cancers: Risk factors, molecular mechanisms and impact on prognosis

“…Anti-diabetic drugs can affect cancer risk both directly and indirectly by affecting cancer cell metabolism and risk factors. Metformin has beneficial effects in many site-specific cancers, lowering the incidence of liver, gastric, colorectal, endometrial and breast cancers, with reducing the mortality and improving the survival from lung, colorectal, prostate, endometrial, pancreatic and breast cancers[ 86 ]. Metformin reduces the risk of neoplastic and pre-neoplastic cell proliferation by decreasing production of hepatic glucose and increasing glucose uptake peripherally, primarily by the muscle cells.…”