Diabetes drug metformin could impair progression of pancreatic cancer, research suggests

The diabetes drug metformin could be used to inhibit the progression of pancreatic cancer, according to American researchers.
Researchers at Massachusetts General Hospital aimed to investigate how metformin – a commonly used type 2 diabetes drug which lowers blood glucose levels – could treat pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer.
As for why they used metformin in their study, the researchers wrote: “It is frequently prescribed to diabetic pancreatic cancer patients and has been shown to associate with a better outcome.”
The researchers noted that previous studies have shown that type 2 diabetes patients taking metformin have a reduced risk of developing pancreatic cancer. Furthermore, metformin treatment among patients who develop the tumour could reduce the risk of death.
Prior to this study, though, the mechanisms of how metformin worked against pancreatic were unclear, as no reports had provided evidence of any potential biomarkers of response.
Decreased inflammation
In cellular and animal models, metformin was found to decrease the inflammation and fibrosis characteristics of PDAC.
The researchers observed that levels of hyalurona, a compound which provides strength within the extracellular matrix, were 30 per cent lower in tumour samples from overweight or obese type 2 diabetes patients with PDAC taking metformin compared to those not taking the drug.
Preventing the activation of pancreatic stellate cells (PSCs) and alleviating desmoplasia are beneficial strategies in treating PDAC, and in obese animal models of pancreatic cancer, those that received metformin had fewer activated PSCs.
Additionally, the researchers wrote: “We found that metformin alleviates desmoplasia – an accumulation of dense connective tissue and tumour-associated immune cells that is a hallmark of pancreatic cancer – by inhibiting the activation of the pancreatic stellate cells that produce the extracellular matrix and by reprogramming immune cells to reduce inflammation.”
Metformin also reduced levels of tumour-associated macrophages in obese animal models by 60 per cent, which correlates with reduced disease progression.
The study authors highlighted that the tumour-related effects of metformin might be independent from its effects on glucose metabolism and body weight.
“Nearly 200 clinical trials are currently underway investigating the effect of metformin on tumours in both diabetic and non-diabetic patients,” said co-senior author Rakesh K. Jai, PhD.
“Understanding the mechanism behind metformin’s effects on pancreatic and other cancers may help us identify biomarkers – such as patient body weight and increased tumour fibrosis – that can identify the patients for whom metformin treatment would be most beneficial.”
The findings were published in the online journal Plos One.