Pharma companies are testing whether drugs designed for combatting Type 2 diabetes can be used to also treat Type 1 diabetes. The latest attempt involves a class of of oral antidiabetics called SGLT2 inhibitors, first cleared by the Food and Drug Administration on March 29, 2013.
There have been roughly 100 clinical trials involving SGLT2 drugs logged at the National Institutes of Health since researchers first began evaluating canagliflozin. All but two have involved individuals with Type 2 diabetes or those who don’t have diabetes. Recently, there have been studies undertaken to evaluate SGLT2 drugs as an add-on to insulin therapy; the following trials involve people with Type 1 diabetes:
- The drug company Janssen initiated an SGLT2 trial in May 2014 in the U.S. and Canada. 232 participants were enrolled to investigate whether 100 mg and 300 mg canagliflozin doses with insulin would help better control blood sugar levels than insulin alone. Phase II of this trial was completed in June 2015, and the study process came under some criticism, but full results have not been posted.
- In February 2016, Yale Medical School and the National Institutes of Diabetes and Digestive and Kidney Disease (NIDDK) filed for a 20-patient study to administer canagliflozin during interruptions in insulin therapy. Researchers have begun recruiting at the Yale New Haven Hospital Research Unit.
- In December 2015, diaTribe reported the launch of two one-year studies to test the administration of the SGLT2 drug empagliflozin in three different doses. The trial, which is recruiting participants in the U.S., Canada, and the EU, is expected to complete its third phase in September 2017.
- Most recently, diaTribe reported on April 2, 2016 that Phase III international trials have begun to evaluate the SGLT2 drug dapagliflozin for uncontrolled Type 1 diabetes.
These drugs suppress the SGLT2 protein’s ability to carry excess glucose back to the bloodstream. It is instead filtered by the kidney and carried out of the body during urination. They are considered an add-on to more traditional oral diabetes medication regimes, and are available in a single pill that’s combined with metformin.
The medication is currently not recommended for treating Type 1 diabetes, and its FDA label indicates that it should not be administered to patients suffering from or with histories of ketoacidosis. Diabetic ketoacidosis (DKA), rare for people with Type 2, is much more common in people with Type 1.
However, doctors might prescribe the medication for off-label use for people with Type 1. Doctors often have the option to write off-label prescriptions if they think a therapy will benefit their patient. For a separate article, we spoke with Dr. Anne Peters, an endocrinologist who teaches at the Keck School of Medicine at USC. She said SGLT2 drugs can be beneficial to some people with Type 1 diabetes.
“From the beginning, I’ve used SGLT2 inhibitors – off label – in my patients with Type 1 diabetes, and I really saw a benefit,” she said
Dr. Peters starts patients with a low dose, breaking pills into thirds or halves, and slowly adjusts the basal insulin dose downward as patients acclimate. Her patients use serum ketone meters and test at the same time they test their glucose. As long as glucose and ketone levels remain in the safe range, she keeps patients on the therapy. Patient and doctor both stay vigilant for signs of DKA, as well.
There has been some controversy surrounding this class of drug. Canagliflozin has been reportedly linked with cardiovascular and urinary tract complications and hospitalizations for ketosis and ketoacidosis in adverse event reports filed with the FDA. FDA regulators are examining these claims, and have put out a cautionary notice for doctors that the drug might cause some enhanced risk for amputation.
Recently, Type 2 Nation carried a story about legal claims lodged against a leading SGLT2 drugmaker based upon the drug’s reported role in the onset of DKA or kidney damage. It’s not yet been possible to unearth whether patients who’ve initiated suits are in fact those with Type 1 who have been using the drug off-label, and to what extent, or whether the FDA adverse event reports came in from cases of acidosis or ketoacidosis unrelated to diabetic hyperglycemia. As the claims proceed, it may be revealed that some patients were indeed clinical trial participants, or individuals with Type 1 who were prescribed the drug off label under physician supervision.
The pace of trials for SGLT2 drugs has picked up, and the FDA recently relaxed its protocol for when the drug therapy can be initiated. It seems very likely that we’ll be hearing more about this drug for Type 1 use in the future.
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