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SGLT2 Inhibitor Misconceptions

SGLT2 Inhibitors are a new class of drugs aimed at type 2 diabetes. This class of medications is based on blocking the re-uptake of glucose by the kidneys. SGLTs function to ensure that glucose entering the kidneys is returned to the bloodstream instead of being passed in the urine. SGLT-2 inhibitors inhibit this reabsorption and excess glucose is passed. In people with type 2, persistent hyperglycemia can lead to an increased reabsorption of glucose through SGLT2 co-transporters.

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This defect appears to occur in patients with diabetes at a much higher rate than the general population and led to the development of this class of drugs. For many clinicians this seems to be a logical way to help diabetes patients as, according to Richard Aguilar, MD, Medical Director, Diabetes Nation, and Diabetes Care Foundation, these drugs can cause a patient to remove between 65 and 95 grams of glucose a day. However, some prescribers we’ve interviewed seem to feel that that using these classes of drugs is “cheating” in the care of patients and might just make their diabetes worse. When I spoke to a couple of endocrinologists about this and other misconceptions, one endo reported that he had been asked if this method of glucose removal could cause the body to release more glucose into the blood stream to compensate. Another clinician asked if this would cause a permanent increase in glucose re-uptake by the liver. The answer to both seems to be, “No.”

Another endocrinologist had an interesting way of looking at the new drugs, explaining that this drug works similar to metformin, and when I asked him to explain he pointed out that the release of glucose from the liver is accelerated in patients with diabetes and that we use metformin to slow down this release, and in a sense, we are using canagliflozin (an SGLT2 Inhibitor) to do a similar thing by slowing down glucose re-uptake.

The biggest misconceptions, however, surround the data on urinary tract infections. Many clinicians have reported that they would not consider using the drug and when asked why, they indicated that there was a 25 to 30 percent incidence of fungal infections. However, the actual pooled analysis of four phase 3 studies showed the increase in UTI was 1.9% with Invokana 100mg, and 0.3% increased with Invokana 300mg when compared to placebo completely dispelling the idea that everyone who takes the medication will get a UTI.

These misconceptions may partly explain why there has been a slower than expected use of these medications by primary care physicians.