Practical Approach to Initiating SGLT2 Inhibitors in Type 2 Diabetes

Abstract

Sodium-glucose co-transporter 2 (SGLT2) inhibitors are an attractive novel therapeutic option for the treatment of type 2 diabetes. They block the reabsorption of filtered glucose in kidneys, mainly in proximal renal tubules, resulting in increased urinary glucose excretion and correction of the diabetes-related hyperglycemia. Beyond improving glucose control, SGLT2 inhibitors offer potential benefits by reducing body weight and blood pressure. On the basis of the efficacy demonstrated in clinical trials, SGLT2 inhibitors are recommended as second- or third-line agents for the management of patients with type 2 diabetes. Beneficial effects on kidney disease progression, cardiovascular and all-cause mortality, and hospitalization for heart failure have also been demonstrated with one SGLT2 inhibitor (empagliflozin). Potential adverse events resulting from their mechanism of action or related to concomitant therapies are reviewed. A treatment algorithm for the adjustment of concomitant therapies after initiating SGLT2 inhibitors is also proposed.

Keywords: Concomitant; Initiation; Management; SGLT2 inhibitors; Type 2 diabetes.

Fig. 1

Renal hyperfiltration in type 2 diabetes patients and the impact of receiving SGLT2 inhibitors. Modified from Fioretto et al. [5]. SGLT2 sodium-glucose co-transporter 2

Fig. 2

Proposed algorithm for adjusting antidiabetic agents (a) and diuretic/antihypertensive therapy (b) when initiating SGLT2 inhibitors in patients with type 2 diabetes. DPP4i DPP4 inhibitors, GI gastrointestinal, GLP1ra GLP-1 receptor agonists, SU sulfonylureas, SMBG self-monitoring of blood glucose, BP blood pressure. *Avoid insulin withdrawal to minimize the risk of euglycemic diabetic ketoacidosis. **Hemodynamically unstable defined as atrial fibrillation, orthostatic hypotension or blood pressure lability, prior syncope, etc. ***Clinical situation defined by congestive heart failure, edema, renal function