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Friday, March 15, 2013

Diabetes: A new kid on the horizon?

Adding to the not so long list of anti diabetic drugs, is a new promising group -
The SGLT2 inhibitors

Amongst the orals, we have

  • Biguanides like Metformin and Thiazolidinediones like Pioglitazone which reduce the insulin resistance.

  • Sulfonylureas like Glimepiride, Gliclazide, and Glibenclamide and Glinides like Repaglinide which act on insulin secretion.

  • Alpha Glucosidase inhibitors like Acarbose, Miglitol, and Voglibose which reduce the glucose absorption from the gastrointestinal tract.

  • DPP-4 inhibitors like Sitagliptin and Saxagliptin and GLP1 agonist like Exenatide  which act by reducing Glucagon secretion.

Now we have a new group which could potentially act via the kidneys.

The kidney plays an important role in the maintenance of glucose homeostasis by reabsorbing almost all filtered glucose via sodium-glucose cotransporters (SGLTs). The SGLT2 cotransporter is the most important of these, as it mediates 90% of renal glucose reabsorption. Its expression and activity are increased in type 2 diabetes, causing increased amounts of glucose to be reabsorbed into the systemic circulation, thereby adding to the hyperglycemia derived from other pathogenic defects. The SGLT2 cotransporter has therefore been targeted as a site for intervention in the management of hyperglycemia in type 2 diabetes.

Several SGLT2 inhibitors, including dapagliflozin, canagliflozin, empagliflozin, and ipragliflozin have been developed and are currently under investigation for efficacy and safety as treatment for type 2 diabetes.

Dapagliflozin was approved by the European Commission on November 14, 2012, and on January 10, 2013, the USFDA advisory committee recommended approval for canagliflozin as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. These agents reduce plasma glucose concentration by inhibiting SGLT2-mediated reabsorption of filtered glucose at the proximal tubule, leading to glucosuria.

Investigational study data indicate that, in patients with early or long-standing type 2 diabetes, SGLT2 inhibitors are effective in reducing fasting plasma glucose, postprandial plasma glucose, and HbA1c, promote weight loss, and have a low risk of clinically significant hypoglycemia. Because their mechanism of action is independent of insulin, SGLT2 inhibitors complement the action of other antihyperglycemic agents, including insulin and metformin.

The only worry would be the costing of the drug. Like its predecessor, the DPP-4 inhibitor, if its priced equally high, the benefits to society at large would be equally low.


  1. very intersting post.thanx for explaining the action of SGLT2 inhibitors in a short and comprehensive way.i would like to know the contra indications.most of the chronic diabetics have impaired kidney functions....nephropathy as we term they have any role if the patients hv impaired kidney functions?

    1. Very imp point. Most of the oral antidiabetics are ruled out in chronic kidney diseases. The status of this group will be revealed once the trials are over.