What are the risks and benefits associated with these agents?
Modest weight loss is seen with the use of SGLT2 inhibitors. Initial weight loss is believed to be related to volume loss, but more sustained weight loss is thought to be from loss of fat mass.6 This is not surprising, as excreting glucose means excreting calories through urine.
Risk for hypoglycemia is extremely low, which makes this therapeutic class an attractive option. However, caution should be exercised when SGLT2 inhibitors are combined with other agents known to cause hypoglycemia (sulfonylureas and insulin).6
The most common adverse effect is genital mycotic infection. Women with a history of recurrent genital mycotic infection and uncircumcised men are at the greatest risk.6
Due to increased glycosuria, which results in an osmotic diuresis, modest blood pressure improvement has been seen (3 to 4 mm Hg systolic and 1 to 2 mm Hg diastolic7,8) in patients taking SGLT2 inhibitors, which is an additional benefit for hypertensive diabetic patients.6 On the other hand, use of SGLT2 inhibitors can also cause dehydration and volume depletion and can raise serum creatinine in patients who are already taking diuretics (particularly loop diuretics).6 Drug tolerance and adherence can be improved by advising patients to expect transient increased urination (approximately 135 to 350 mL/d increase from baseline5,9) and emphasizing the importance of good hydration and maintaining good genital hygiene.
A slight increase in LDL cholesterol was seen in clinical trials of the SGLT2 inhibitors, although this phenomenon is poorly understood. However, HDL cholesterol increased as well, maintaining the LDL:HDL ratio.6 No long-term cardiovascular outcome data are available at this time; as with any new antidiabetic medication, postmarketing studies, as required by the FDA, are currently ongoing.6
What are the options in this therapeutic category, and how are they distinct?