Metformin for endothelial dysfunction in non-diabetic disorders: a scoping review

Area of Science:

• Cardiovascular Research
• Pharmacology
• Endocrinology

Background:

• Metformin, a glucose-lowering drug, demonstrates potential benefits beyond diabetes, particularly in improving endothelial dysfunction.
• Existing literature on metformin's effects on endothelial dysfunction in non-diabetic conditions lacks comprehensive synthesis.
• Endothelial dysfunction is a key factor in various non-communicable diseases (NCDs).

Purpose of the Study:

• To map the extent and nature of research on metformin for endothelial dysfunction in non-diabetic NCDs.
• To identify biomarkers used to measure endothelial dysfunction in studies involving metformin.
• To identify knowledge gaps in the current research landscape.

Main Methods:

• A scoping review was conducted following established methodological frameworks (Arksey and O'Malley, Joanna Briggs Institute).
• Included peer-reviewed studies on adult humans using metformin for endothelial dysfunction in non-diabetic NCDs.
• Excluded narrative reviews, expert opinions, preclinical, and qualitative studies. An extensive database search was performed.

Main Results:

• 56 studies involving 4620 participants were identified, with polycystic ovarian syndrome being the most studied NCD.
• 19 distinct biomarkers of endothelial dysfunction were noted, with flow-mediated dilation being most common.
• Metformin showed a trend towards improvement in 36.8% of biomarkers, but significant differences were more pronounced in studies without active comparators.

Conclusions:

• Growing evidence supports metformin for endothelial dysfunction in non-diabetic NCDs, yet knowledge gaps persist.
• Further research is required for optimal biomarker selection, dosing strategies, and applications in broader NCDs, including in people with HIV.
• Robust primary and secondary research is necessary to quantify metformin's precise effects on endothelial dysfunction.