Where Does Metformin Stand in Modern Day Management of Type 2 Diabetes?

Abstract

Metformin is the most commonly used glucose-lowering therapy (GLT) worldwide and remains the first-line therapy for newly diagnosed individuals with type 2 diabetes (T2D) in management algorithms and guidelines after the UK Prospective Diabetes Study (UKPDS) showed cardiovascular mortality benefits in the overweight population using metformin. However, the improved Major Adverse Cardiovascular Events (MACE) realised in some of the recent large cardiovascular outcomes trials (CVOTs) using sodium-glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have challenged metformin’s position as a first-line agent in the management of T2D. Many experts now advocate revising the existing treatment algorithms to target atherosclerotic cardiovascular disease (ASCVD) and improving glycaemic control as a secondary aim. In this review article, we will revisit the major cardiovascular outcome data for metformin and include a critique of the UKPDS data. We then review additional factors that might be pertinent to metformin’s status as a first-line agent and finally answer key questions when considering metformin’s role in the modern-day management of T2D.

Comparative effectiveness of cardiovascular, renal and safety outcomes of second‐line antidiabetic drugs use in people with type 2 diabetes: A systematic review and network meta‐analysis of randomised controlled trials

“…While the use of sulphonylureas could possibly be further explored for the improvement in ESRD, this must be weighed upon their hypoglycaemic risk. Furthermore, this study could not determine the effects of metformin on renal outcomes 51,70 71,72 .…”

“…Furthermore, this study could not determine the effects of metformin on renal outcomes. 51,70 Nevertheless, additional data from ongoing trials (RenoMet, VA-IMPACT) will hopefully further elucidate the cardiovascular and renal protective effect of metformin. 71,72 As such, further work is required to define the cardiorenal profile of these drugs to better inform clinical practice.…”

Metformin: Is it a drug for all reasons and diseases?

“…In addition: "Metformin prescribing peaked from 55.4% in 2000 to 83.6% in 2013 among all individuals with T2D who were on at least Ahmad et al 2020, [20] Sharma et al, [21] Montvida et al [22] (continued on next page) C.R. Triggle et al skeletal muscle insulin sensitivity (90% versus 55%) [41].…”

Diabetes: how to manage cardiovascular risk in secondary prevention patients

“…Experimental data have demonstrated that metformin reduces inflammation, exerts beneficial effects on lipids, exhibits antithrombotic and anti-atherosclerotic activity, and improves both the gut microbiome and endothelial cell function. 20 In patients with T2D and coronary artery disease, there is evidence to support that metformin exerts a cardioprotective effect by altering cardiac metabolism, which in turn improves cardiac function. 21 …”