Diabetes Metab J.  2014 Aug;38(4):261-273. 10.4093/dmj.2014.38.4.261.

A Novel Therapeutic Agent for Type 2 Diabetes Mellitus: SGLT2 Inhibitor

• Jung CH
• Jang JE
• Park JY

• KMID: 2174102
• DOI: http://doi.org/10.4093/dmj.2014.38.4.261

Abstract

Type 2 diabetes mellitus (T2DM) is a complex endocrine and metabolic disorder, and a major public health problem that is rapidly increasing in prevalence. Although a wide range of pharmacotherapies for glycemic control is now available, management of T2DM remains complex and challenging. The kidneys contribute immensely to glucose homeostasis by reabsorbing glucose from the glomerular filtrate. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, a new class of antidiabetic agents that inhibit glucose absorption from the kidney independent of insulin, offer a unique opportunity to improve the outcomes of patients with T2DM. In this review, we provide an overview of two globally-approved SGLT2 inhibitors, dapagliflozin and canagliflozin, and discuss their effects and safety. This information will help clinicians to decide whether these drugs will benefit their patients.

Keyword

Canagliflozin; Dapagliflozin; Diabetes mellitus, type 2; Glucosuria; SGLT2 inhibitor

MeSH Terms

Absorption
Diabetes Mellitus, Type 2*
Drug Therapy
Glucose
Homeostasis
Humans
Hypoglycemic Agents
Insulin
Kidney
Prevalence
Public Health
Canagliflozin
Glucose
Hypoglycemic Agents
Insulin

Figure

• 

  Fig. 1 Glucose reabsorption in the renal proximal tubule. Under normal physiological conditions, the kidney reabsorbs all of the filtered glucose. This occurs via the actions of sodium-glucose cotransporter 2 (SGLT2) in the early proximal tubule, which reabsorbs most of the filtered glucose load, and SGLT1 in the more distal regions of the tubule, which absorbs the remaining glucose. These cotransporters are located on the luminal epithelium. Glucose transporter 2 (GLUT2) and GLUT1 facilitate glucose transport across the basolateral membrane in the early and the more distal regions of the proximal tubule, respectively.

• 

  Fig. 2 Renal glucose handling before and after sodium-glucose cotransporter 2 (SGLT2) inhibition. SGLT2 inhibition reduces the maximum transport rate (Tm) of glucose. This reduced Tm for glucose through SGLT2 inhibition results in a decrease in glucose reabsorption in the renal proximal tubule and lowers the renal threshold so that glucosuria occurs at a lower plasma glucose concentration.

• 

  Fig. 3 Mean changes in (A) the glycated hemoglobin (HbA1c) level, (B) the fasting plasma glucose (FPG) level, and (C) body weight in clinical trials with dapagliflozin at a dose of 5 or 10 mg/day. Data are adjusted for baseline values. MET, metformin; GLIM, glimepiride; PIO, pioglitazone; INS, insulin; NA, not available. aP<0.05 vs. the placebo.

• 

  Fig. 4 Mean changes in (A) the glycated hemoglobin (HbA1c) level, (B) the fasting plasma glucose (FPG) level, and (C) body weight in clinical trials with canagliflozin at a dose of 100 or 300 mg/day. Data are adjusted for baseline values. MET, metformin; SU, sulfonylurea; PIO, pioglitazone; GLIM, glimepiride; SIT, sitagliptin. aP<0.05 vs. the placebo or active comparator.

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