Drugs for Diabetes: Part 8 SGLT2 Inhibitors

Alison MacEwen; Gerard A McKay; Miles Fisher


Br J Cardiol. 2012;19(1):26-29. 

In This Article

Other Considerations

Extrapolation from the mechanism of action of SGLT2 inhibitors raises the possibility of side effects such as dehydration and electrolyte loss, although this is generally not supported by the results of the studies discussed above. Familial renal glycosuria (FRG) is a rare condition caused by a mutation in the SGTL2 gene. Subjects with FRG exhibit varying degrees of glycosuria, however, remain asymptomatic, do not become dehydrated or become hypoglycaemic.[8] This disease model of SGLT2 inhibition is reassuring in terms of adverse long-term outcomes.

12 weeks' treatment with 20 mg/day of dapagliflozin resulted in a mean increase in daily urine output of 107–375 ml/day secondary to a mild osmotic diuresis.[12] Study populations were counselled about symptoms of dehydration and their avoidance with adequate fluid consumption, and this generally seemed effective. One patient in a phase II study with dapagliflozin developed dehydration and renal impairment. This resolved with oral rehydration and withholding their angiotensin-converting enzyme (ACE) inhibitor and diuretic treatment.[15] In contrast to individuals with FRG, a relatively high proportion of patients with diabetes are likely to be treated with ACE inhibitors and diuretic therapy, and are likely to have an increased prevalence of comorbidities, such as renal impairment, cardiovascular disease and autonomic neuropathy, and, thus, further evidence from phase III studies is still required to evaluate the safety and efficacy of SGLT2 inhibition in the long term, including possible effects on cancer.


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