March 3, 2014

SGLT2 Inhibitors Seem to Increase Glucose Production

Paradoxes do happen and this is a surprise. Researchers discovered this while studying the newest class of diabetes drugs, sodium glucose cotransporter 2 SGLT2 inhibitors. The result was obtained from dapagliflozin (Farxiga), one of the two FDA approved drugs in the class.

Although they increase the amount of blood sugar dumped into the urine, the newest class of diabetes drugs appears to increase endogenous (proceeding from within; derived internally) glucose production, two studies found.”

The researchers are wisely calling for additional studies to confirm the results they found. The first study was done at the University of Texas Health Sciences Center in San Antonio and involved 18 men. The second study was done at the University of Pisa in Italy, and used the drug empagliflozin. The Italy study used 66 type 2 patients.

The researchers found that the drugs did what they were designed for; increase the glucose excretion in the urine and lower plasma glucose levels. This is when the researchers discovered the substantially increased endogenous glucose production, which was accompanied by an increase in glucagon levels. Patients on the placebo had no change in these levels.

The researchers reported that the increase in endogenous glucose production offset about half of the amount of glucose dumped into the urine. In other words, if the endogenous glucose production could have been prevented, the decrease in glucose caused by dapagliflozin and empagliflozin would have been about double.

By having others replicate this finding, the researchers are suggesting that clinicians may want to use the SGLT2 inhibitors in tandem with incretin therapies, which have effects on glucagon and could reduce the increase in endogenous glucose production. The researchers then ask for further metabolic studies for verification of this.

This research does point to potential problems for SGLT2 and clinicians need to use caution in prescribing this medication until the full effects are understood. As people with diabetes, I would also urge caution in accepting this medication until the full effects are determined. This is one paradox that may have long-term harmful effects.

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