Metformin may improve myocardial perfusion and survival in patients with type 2 diabetes

"The results confirm previous reports that metformin use in adults with type 2 diabetes significantly associates with improved overall survival," the researchers wrote in their study. The study was published in medRxiv as a preprint and has not yet been peer-reviewed.

Metformin is an antihyperglycemic agent for treating type 2 diabetes mellitus (T2DM). T2DM patients are at increased risk of cardiovascular diseases, including coronary microvascular dysfunction (CMD), silent myocardial infarction (MI), and coronary artery disease (CAD). CMR (cardiovascular magnetic resonance) can be used to detect and quantify myocardial perfusion reserve (MPR) and stress myocardial blood flow (MBF), both of which are objective measures of coronary microvascular function.

Noor Sharrack, University of Leeds, Leeds, United Kingdom, and colleagues explored the association between metformin use, MPR, MBF, survival and major adverse cardiovascular and cerebrovascular events (MACCE) in patients with type 2 diabetes. MACCE comprises stroke, all-cause death, MI, coronary revascularization, and heart failure hospitalization.

An automatic artificial intelligence-supported process was used to derive global MBF and MPR. For this purpose, patients with type 2 diabetes and a cohort of healthy controls underwent quantitative myocardial perfusion CMR. Associations between metformin use, MPR, MBF, all-cause death, and MACCE were quantified using Cox proportional hazard models and Multivariable regression analysis.

The study led to the following findings:

• The analysis included 572 patients with T2DM (68% prescribed metformin) with a median follow-up of 851 days.
• Metformin use was tied to an increase in myocardial perfusion reserve of 0.12.
• There was 82 first MACCE in all T2DM patients, including 25 deaths.
• Although the number of first MACCE events was similar for patients prescribed metformin (14% compared to those who were not, 15.8%), there was a total of 9 deaths in patients prescribed metformin compared to 16 in patients who were not, the adjusted hazard ratio 0.29.

"Our study is the first reported clinical study with findings that show a significant association between metformin use and improved coronary microvascular function in type 2 diabetes patients, after adjusting for certain confounding parameters," the researchers wrote.

"Further prospective studies are required to confirm the association between metformin use and improved MPR and reduced mortality and clarify the mechanisms responsible and quantify the dose at these associated outcomes are observed," they concluded.

Reference:

Metformin associates with improved myocardial perfusion reserve and survival in patients with Type 2 Diabetes Mellitus. Noor Sharrack, Kristopher D Knott, Gaurav S Gulsin, Tushar Kotecha, Louise AE Brown, Jian L Yeo, Aldostefano Porcari, Robert D Adam, Sharmaine Thirunavukarasu, Amrit Chowdhary, Eylem Levelt, James C Moon, Gerry P McCann, Marianna Fontana, Peter Kellman, Theresa Munyombwe, Christopher Gale, David L Buckley, John P Greenwood, Peter P Swoboda, Sven Plein. medRxiv 2023.04.13.23288441; doi: https://doi.org/10.1101/2023.04.13.23288441