J Korean Diabetes.  2024 Mar;25(1):9-15. 10.4093/jkd.2024.25.1.9.

SGLT2 Inhibitors and Diabetes: Where Does It Come from and Where Does It Go?

• Kim JY
• Kim SG

• KMID: 2554116
• DOI: http://doi.org/10.4093/jkd.2024.25.1.9

Abstract

Sodium glucose cotransporter 2 (SGLT2) inhibitors have emerged as powerful medications in the past decade. Numerous clinical trials have reported their cardio-renal protective effects and associated reductions in mortality. The beneficial effects of SGLT2 inhibitors in mediating heart failure and chronic kidney disease progression have been consistent across patients with and without diabetes regardless of ejection fraction. Therefore, SGLT2 inhibitors are not only antidiabetic drugs but also medications for heart failure and chronic kidney disease. However, adverse events such as genital infections and diabetic ketoacidosis should be considered. In this review, we explore the journey of SGLT2 inhibitors, often referred to as the “statins of the 21st century,” from their inception to the present day. We introduce the strengths and weaknesses of this medication and discuss unresolved issues that should be taken into considerations when prescribing SGLT2 inhibitors.

Keyword

Diabetes mellitus; Heart failure; Hypoglycemic agents; Renal insufficiency, chronic; Sodium-glucose transporter 2 inhibitors

Figure

• 

  Fig. 1. Comparison of large-scale clinical trials of statins and SGLT2 inhibitors. Statins have proven cardiovascular benefits, including the primary and secondary prevention of MACE. SGLT2 inhibitors have demonstrated efficacy not only in preventing MACE but also in primary and secondary prevention of hospitalization for heart failure, even in environments where statins and RAS inhibitors are commonly used. Moreover, they have proven efficacy in reducing cardiovascular mortality and demonstrated a renal protective effect. SGLT2, sodium glucose cotransporter 2; MACE, major adverse cardiovascular event; RAS, renin-angiotensin system; RASi, renin-angiotensin system inhibitor; ASCVD, atherosclerotic cardiovascular disease; SGLT2i, sodium-glucose cotransporter 2 inhibitor; HHF, hospitalization for heart failure; CVD, cardiovascular disease; CV, cardiovascular; CKD, chronic kidney disease.

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  Fig. 2. Determining Appropriate Candidates for SGLT2 inhibitor therapy. SGLT2 inhibitors should be considered for patients with heart failure or CKD and could also be a great option for those who need weight loss (blue box). However, cautious use is needed, especially for patients who have experienced frequent or consistent genital infections or those with frailty (red box). Those marked with a question mark (?) represent populations that are still under investigation or require further study to establish a concrete conclusion. Additionally, other antidiabetic agents could be considered for further intensification of glycemic control (gray box). SGLT2, sodium glucose cotransporter 2; CKD, chronic kidney disease; SGLT2i, sodium-glucose cotransporter 2 inhibitor; eGFR, estimated glomerular filtration rate; ESKD, end-stage kidney disease; MI, myocardial infarction; NAFLD, non-alcoholic fatty liver disease; BMI, body mass index; T1DM, type 1 diabetes mellitus; LADA, latent autoimmune diabetes in adults; KT, kidney transplantation; DPP-4i, dipeptidyl peptidase-4 inhibitor; TZD, thiazolidinedione; SU, sulfonylurea; GLP-1RA, glucagon-like peptide-1 receptor agonist. a3P symptoms: polyuria, polydipsia, polyphagia.

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