Clinical considerations when adding a sodium-glucose co-transporter-2 inhibitor to insulin therapy in patients with diabetes mellitus.

A consensus meeting was held to discuss add-on therapy of sodium-glucose co-transporter-2 (SGLT2) inhibitors in patients with diabetes mellitus treated with insulin. The objectives were to affirm the efficacy and safety of SGLT2 inhibitors as an add-on to insulin, empower clinicians to minimise the risk of adverse events, and provide clinical guidance. Administration of SGLT2 inhibitors as an add-on therapy to insulin is associated with significant reductions compared with placebo in glycosylated haemoglobin A1c, fasting plasma glucose, insulin dose, and body weight without an increased risk of hypoglycaemia. Compared with traditional therapies, SGLT2 inhibitors have shown cardiovascular and renal benefits. Adding an SGLT2 inhibitor to insulin increases the risk of urinary tract and genital tract infections. The use of SGLT2 inhibitor is also associated with a slightly increased incidence of diabetic ketoacidosis. Patients who may benefit most from add-on therapy with SGLT2 inhibitors include those with established atherosclerotic cardiovascular disease, heart failure, chronic kidney disease, high insulin doses, obesity, and metabolic syndrome. Routine monitoring for diabetic ketoacidosis is controversial, and patient and clinician education is essential to minimise risk. The decision to adjust insulin dose when adding an SGLT2 inhibitor is dependent on patient factors, but the insulin dose should not be reduced beyond 20% prior to the first dose of SGLT2 inhibitor. Patients should temporarily discontinue SGLT2 inhibitors during fasting, acute illness, or low/reduced carbohydrate intake. If ketonuria is detected, SGLT2 inhibitors but not insulin should be immediately discontinued and medical advice sought.