Table 1.

Position of the guidelines of the main Scientific Societies on the use of metformin and the ‘new’ antidiabetic drugs (gliflozines and incretins) in patients with Type 2 diabetes mellitus

European Society of Cardiology (ESC)11

In patients with Type 2 diabetes mellitus without a history of major cardiovascular events, renal insufficiency, or heart failure, metformin is recommended as first choice (I B).

In patients with Type 2 diabetes mellitus and previous major cardiovascular events, metformin should still be considered, unless contraindicated (IIa B).

In patients with Type 2 diabetes mellitus and a history of major cardiovascular events, incretins and gliflozines that have demonstrated a benefit on prognosis are recommended with the aim of reducing major cardiovascular and renal events (I A).

In patients with Type 2 diabetes mellitus and signs of end-organ damage, incretins and gliflozins that have demonstrated a benefit on prognosis are recommended with the aim of reducing major cardiovascular events and mortality (IIb B).

In patients with Type 2 diabetes mellitus and chronic renal insufficiency, gliflozines are recommended with the aim of reducing major cardiovascular and renal events (I A).

In patients with Type 2 diabetes mellitus and heart failure with impaired left ventricular function, gliflozins that have demonstrated a benefit on prognosis are recommended with the aim of reducing heart failure hospitalization and cardiovascular mortality (I A).

In patients with Type 2 diabetes mellitus and no prior major cardiovascular events, renal insufficiency or heart failure, incretins and gliflozines should be considered in patients at the highest estimated cardiovascular risk (in the individual patient) (IIa B).

American Diabetes Association/European Association for the study of Diabetes (ADA/EASD)10,14

Metformin is the drug of first choice in patients with Type 2 diabetes, regardless of the level of risk and the condition of primary or secondary prevention.

If heart failure or nephropathy prevails, combine gliflozines with metformin. If these are contraindicated or not tolerated, combine incretins with metformin.

If high risk (age >55 years, left ventricular hypertrophy or carotid, coronary or peripheral artery stenosis >50%) or previous cardiovascular events (no heart failure or nephropathy) prevail, incretins should be added to metformin. If these are contraindicated or not tolerated, add gliflozines to metformin.

In patients at low risk, metformin remains the first-choice drug. If HbA1c is not at target, consider incretins, gliflozines, DPP4-antagonists, or thiazolidinediones or sulfonylureas based on specific considerations for the individual patient (avoid hypoglycaemia, seek weight loss, spend less).

Italian Society of Diabetology and Association of Diabetologists (SID/AMD)

Metformin is the first-choice drug in patients with Type 2 diabetes without previous cardiovascular events. Gliflozines and incretins are second-line drugs.

Metformin, incretins, and gliflozines are drugs of first choice in patients with previous cardiovascular events and without heart failure.

Gliflozines are first-line drugs, and incretins and metformin are second-line drugs, in patients with Type 2 diabetes and heart failure.