Dapagliflozin: glucuretic action and beyond.
Diabetes mellitus is a greatly challenging disease of the 21 century, and the mortality rate due to this insidious disease is increasing worldwide in spite of availability of effective oral hypoglycemic agents. Satisfactory management of glycemic control in patients afflicted with type 2 diabetes mellitus (T2DM) remains a major clinical challenge. Identification of potential pharmacological target sites is therefore continuing as an integral part of the diabetic research. The sodium-glucose co-transporter type 2 (SGLT2) expressed in the renal proximal tubule plays an essential role in glucose reabsorption. Pharmacological blockade of SGLT2 prevents glucose reabsorption and subsequently induces the elimination of filtered glucose via urine, the process is known as 'glucuresis'. Dapagliflozin is a selective inhibitor of SGLT2. The US FDA approved dapagliflozin in January 2014 to improve glycemic control along with diet and exercise in adult patients afflicted with T2DM. It has a potential to decrease glycated hemoglobin and to promote weight loss. Although the mechanism of action of dapagliflozin is not directly linked with insulin or insulin sensitivity, reduction of plasma glucose by dapagliflozin via induction of glucosuria could improve muscle insulin sensitivity. Moreover, dapagliflozin could cause diuresis and subsequently fall in blood pressure. In addition to general discussion on the pharmacology of dapagliflozin, we propose in this review the possibilities of dual antidiabetic effect of dapagliflozin and its possible additional beneficial actions in hypertensive-obese-T2DM patients through its indirect blood pressure-lowering action and reduction of body calories and weight. Long-term clinical studies are however needed to clarify this contention.
Pharmacology Unit, Faculty of Pharmacy, Asian Institute of Medicine, Science and Technology (AIMST) University, Semeling, 08100 Bedong, Kedah Darul Aman, Malaysia. Electronic address: pbala2006@gmail.com.
Pitchai
P
Balakumar
Pharmaceutical Chemistry Unit, Faculty of Pharmacy, AIMST University, Semeling, 08100 Bedong, Kedah Darul Aman, Malaysia.
Karupiah
K
Sundram
Pharmaceutical Technology Unit, Faculty of Pharmacy, AIMST University, Semeling, 08100 Bedong, Kedah Darul Aman, Malaysia.
Sokkalingam A
SA
Dhanaraj
D000818:Animals; D001559:Benzhydryl Compounds / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D005947:Glucose / Q000378:metabolism*; D005960:Glucosides / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D000077203:Sodium-Glucose Transporter 2 Inhibitors
D001559:Benzhydryl Compounds; D005960:Glucosides; D007004:Hypoglycemic Agents; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C529054:dapagliflozin; D005947:Glucose
Dapagliflozin; Diabetes mellitus; Perspectives; SGLT2 inhibition