Where Do SGLT2 Inhibitors Fit in Diabetes Care?

New Class of Drugs 'Turns Glucosuria on Its Head'

Clifford J. Bailey, PhD


October 15, 2013

In This Article

Safety and Tolerability of SGLT2 Inhibitors

What do we know in terms of safety and tolerability from the trials? Hypoglycemic risk does not appear to be increased when these agents are used as monotherapy or in combination with agents that don't cause hypoglycemia. Of course, the risk for hypoglycemia is still present if these agents are combined with drugs that can cause hypoglycemia, such as the sulfonylureas and insulin, but nevertheless, one still sees the glucose-lowering effect irrespective of what other agents are used, whether the SGLT2 inhibitor is being given as monotherapy or combined with metformin, a sulfonylurea, a dipeptidyl peptidase-4 (DPP-4) inhibitor, or insulin. Hypoglycemic risk appears to be under control and this can be partly explained by the mechanism. As the blood glucose level falls, the amount of available glucose falls, so the amount that is reabsorbed will tend to fall because the SGLT2 plus SGLT1 (which is in the more distal part of the proximal tubule) will be able to reabsorb most of that glucose.

When glucose is eliminated in the urine, this also raises the risk for infection. Genital infections such as thrush are more common in patients with type 2 diabetes who have glucosuria. This has been noticed with these agents and so they may not be appropriate for individuals who have a history of these types of events. In most individuals this either doesn't occur or the infections are mild, and if recognized early, manageable. The same holds true for urinary tract infections. In the trials there was a very small increase in the incidence of urinary tract infection with the use of these agents when they cause glucosuria. We have no real evidence of hypotension, and although osmotic diuresis can occur, we have no evidence of dehydration, but of course you would not use these agents in individuals who are already predisposed to a reduction in their fluid volume.


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