Medications widely used as diabetes treatments have raised the possibility of influencing the occurrence and progression of cancer beyond their therapeutic purpose of blood sugar control. It is already known that diabetes itself is associated with an increased risk of several cancers, but recently, attention has focused on the possibility that diabetes medications may directly engage in cancer biology.
A research team led by Professor Lin Nong Ji from the Endocrinology Department at Peking University People's Hospital in China comprehensively analyzed how anti-diabetic drugs might affect cancer growth, immune response, and inflammatory response, presenting these possibilities in the December issue of the international journal ⟪Precision Clinical Medicine⟫.
Cancer Not Explained by Blood Sugar and Weight Alone... Comprehensive Analysis of Major Anti-Diabetic Drugs and Cancer-Related Research
Type 2 diabetes is associated with an increased risk of several cancers, including liver cancer, colorectal cancer, and breast cancer. Until now, this association has primarily been explained by hyperglycemia and obesity, but studies have increasingly shown that blood sugar and weight control alone cannot fully explain the phenomenon of increased cancer risk in diabetes patients. Consequently, the research team deemed it necessary to examine the possibility that diabetes medications could independently influence cancer occurrence and progression.
The research team analyzed existing experimental and clinical studies focusing on widely used anti-diabetic medications such as metformin, SGLT2 inhibitors, and GLP-1 receptor agonists, addressing their effects on biological pathways related to cancer. The analysis focused on cancer biological mechanisms beyond blood sugar control effects, including cell proliferation, immune response, inflammation regulation, and changes in the tumor microenvironment.
The analysis revealed that metformin, the primary oral hypoglycemic agent, has the most accumulated research evidence, suggesting it may inhibit cancer cell proliferation, alter the tumor microenvironment, and enhance anti-cancer immune responses. In particular, it was observed to affect key signaling pathways regulating cell growth and survival, such as AMPK, mTOR, and PI3K/AKT, leading to effects related to cell proliferation inhibition, induction of cell death, and regulation of neovascularization.
Metformin has shown results associated with a reduced risk of colorectal and liver cancer in some studies, but its effects were inconsistent for other cancer types, such as breast cancer. The research team explained that these differences could vary depending on the type of cancer, stage, and the patient's metabolic state.
SGLT2 inhibitors and GLP-1 receptor agonists have also reported results associated with changes in cancer cell growth, reduced inflammation, and increased cell death, but not all cancers exhibited effects in the same direction. Results varied by drug class and individual components, and in some cases, it was difficult to confirm clear clinical benefits.
Professor Lin Nong Ji stated, "Anti-diabetic medications are essential for diabetes management, but the long-term effects on cancer are not yet fully elucidated," adding, "This review summarizes the complex biological mechanisms through which these drugs may influence cancer progression, and the current evidence is mixed." He further noted, "The long-term effects and potential for therapeutic strategies in cancer patients need to be validated through additional clinical research."
Importance of 'Drug Selection' in Patients with Concurrent Diabetes and Cancer
In other words, while diabetes medications may influence cancer growth and immune/inflammatory responses beyond blood sugar control, it is not yet the stage to definitively state that they are uniformly 'good' or 'bad' for all cancers. The research team evaluated that this analysis suggests the importance of personalized treatment strategies for patients with both diabetes and cancer. If the effects of specific anti-diabetic medications on the biological characteristics of cancer are better understood, it may be possible to refine treatment choices and prevention strategies more precisely.
In patients with both diabetes and cancer, the choice of which diabetes medication to use can be a factor in treatment strategy, and additional clinical research is needed to clarify this. However, the research team emphasized that at this stage, using anti-diabetic medications for cancer prevention or treatment lacks sufficient evidence.
