Update This article has been updated since its original release.Details
With diabetes labelled as the epidemic of the 21st century1 it is not surprising that a plethora of treatment options has emerged from pharmaceutical R&D pipelines. While mainstay therapies have been available for some time — metformin remains the agent of first choice, with sulfonylurea and insulin available to intensify treatment — many newer add-on options are now available, including the GLP-1 agonists, PPAR-gamma agonists and DPP4 inhibitors.
While all these agents attempt to decrease hyperglycaemia by modifying glucose metabolism, now there is a new class of anti-diabetics, the sodium–glucose co-transporter 2 (SGLT2) inhibitors, which offer a different approach — increasing renal excretion of glucose.
It is ironic that glycosuria, traditionally accepted as a diagnostic hallmark, pathognomonic of uncontrolled diabetes, could now be a reflection of effective management. While possibly counter-intuitive,2 the proposition is simple. By blocking glucose reabsortion in the kidneys, excess glucose is eliminated in urine, improving glycaemic control and at the same time providing a weight-loss advantage, albeit modest.
In this issue of NPS RADAR we review the benefits, harms and place in therapy of two examples of this new class, dapagliflozin and canagliflozin, which are PBS listed from 1 December 2013.
There are some cautions, however. It is well known that glycosuria increases the risk of urinary tract infections. The evidence suggests that in people treated with SGLT2 inhibitors these infections are easily resolved with standard therapy, but for those affected the condition can still be distressing.
Perhaps of greater concern is that the long-term effects of glycosuria induced by SGLT2 inhibitors are not yet documented.
The weight-loss effect is also at risk of being overstated — a potential 1–3 kg loss is not the magnitude of effect required for many in whom obesity and diabetes go hand in hand.
As with most new drugs, only time will tell if the proposition is sound and the long-term safety acceptable.
- Zimmet PZ. Can we avert a diabetes catastrophe in Australia? Med J Aust 2013;199:225–6. .
- Day C, Bailey AV. Glucosuria: a counter intuitive treatment for diabesity. Br J Diabetes Vasc Dis 2013;13:2–6. .