Obesity, Diabetes and Gastrointestinal Malignancy: The role of Metformin and other Anti-diabetic Therapy

Abstract

The association between Diabetes and cancer has been known for decades with obesity and insulin resistance being postulated as the main underlying risk factors for both disorders. With rise of the epidemic of obesity in the USA and around the globe, there has been a rise in diabetes that is currently reaching epidemic proportions. Diabetes is known to be associated with increased risk of several types of malignancy including breast, cervical, pancreatic and colon cancer. In this review, we discuss the epidemic of obesity and its consequential epidemic of diabetes highlighting the pathophysiologic mechanisms of increased cancer in the diabetic population. We will then discuss the role of insulin therapy as well as, other antidiabetic medications, particularly metformin that has been to be associated with lower risk as well as better survival with GI malignancies based on several studies including a study that was recently published by our group.

Adipositas und Krebs

“…Die korrespondierende Endpunktstudie für Semaglutid in der Indikation Adipositas ohne T2 D (SELECT-Studie) wird aktuell durchgeführt, und Ergebnisse sind in den kommenden 2-3 Jahren zu erwarten. Eine antidiabetische Medikation kann das Diabetes-assoziierte Krebsrisiko bei verschiedenen Krebsarten reduzieren, wobei die besten Evidenzen für Metformin bei gastrointestinalen Tumoren [37] und innerhalb dieser Gruppe insbesondere für Dickdarm- [38] und Pankreaskrebs [39] vorliegen (▶ Abb. 1).…”

Adipositas und Krebs

“…Die korrespondierende Endpunktstudie für Semaglutid in der Indikation Adipositas ohne T2D (SELECT-Studie) wird aktuell durchgeführt, und Ergebnisse sind in den kommenden 2-3 Jahren zu erwarten. Eine antidiabetische Medikation kann das Diabetes-assoziierte Krebsrisiko bei verschiedenen Krebsarten reduzieren, wobei die besten Evidenzen für Metformin bei gastrointestinalen Tumoren [37] und innerhalb dieser Gruppe insbesondere für Dickdarm- [38] und Pankreaskrebs [39] vorliegen (▶ Abb. 1).…”

Metformin attenuates diabetic renal injury via the AMPK‑autophagy axis

“…Metformin is a biguanide agent that is commonly used to treat type 2 diabetes ( 16 ). Metformin reinforces hepatic and peripheral tissue sensitivity to insulin and reduces the amount of sugar produced by the liver and released in the bloodstream ( 16 , 17 ). Metformin is an antihyperglycemic agent that is associated with low risk of hypoglycemia compared with other anti-diabetic drugs such as sulfonylurea hypoglycemic agents.…”

“…Considering its favorable effects on serum lipid levels, obese body condition, cardiovascular disease and mortality, metformin is recommended as the first-line pharmacotherapy for patients with type 2 diabetes. The US Food and Drug Administration recommends, therefore, that metformin hydrochloride should be taken for 6 months from the beginning of DN ( 17 ). Metformin has also been reported to be an activator of AMP-activated protein kinase (AMPK) via the increased phosphorylation of AMPK at Thr172, which in turn induces mitophagy and macroautophagy, which protects against DN ( 18 ).…”