SAN FRANCISCO – At first, the diabetes professionals in the audience at the annual scientific sessions of the American Diabetes Association overwhelmingly raised their hands to say they would support using SGLT2 inhibitors as adjunctive therapy in patients with type 1 diabetes. Then two physicians debated whether the drugs were too risky – predictably, one said yes, the other said no. In the end, most of the audience was unconvinced by one of the doctors. Which one? Well, we’ll get to that.
First, let’s look at the issue that divided the two physicians: Should the sodium-glucose cotransporter 2 (SGLT2) inhibitors canagliflozin (Invokana), dapagliflozin (Farxiga), and empagliflozin (Jardiance) – now commonly used to treat patients with type 2 diabetes – also be prescribed for patients with type 1 diabetes?
The drugs are not cleared in the United States for use in patients with type 1 diabetes, although drug makers are seeking approval. Earlier in 2019, the Food and Drug Administration turned down a request for the approval of sotagliflozin (Zynquista), a dual SGLT1 and SGLT2 inhibitor, for adults with type 1 diabetes. However, the drug has been approved in the European Union for certain overweight patients with type 1 diabetes.
In addition, the drugs are very costly, compared with some of the other diabetes medications, and physicians say that puts them out of reach for some patients.
The case for ...
In arguing that SGLT2 inhibitors would be appropriate as a therapy for patients with type 1 diabetes, Bruce A. Perkins, MD, MPH, professor and clinician-scientist at Leadership Sinai Center for Diabetes at the University of Toronto, emphasized the need for new treatments in type 1 diabetes.
“Even today, people with type 1 tell us they feel isolated, they fear hypoglycemia, they fear complications. And they have this undue burden of self-management,” he said. “We can do much better. Insulin therapy still needs us desperately needing more.”
Dr. Perkins highlighted the drugs’ widely lauded effects on cardiac and renal health and noted that a 2019 meta-analysis of 10 trials found that, compared with placebo, the drugs were associated with mean reductions in hemoglobin A1c (–0.39%; 95% confidence interval, –0.43 to –0.36) and body weight (–3.47%; 95% CI, –3.78 to –3.16).
That analysis also showed a higher risk of genital infection (3.57; 95% CI, 2.97-4.29) and diabetic ketoacidosis (DKA; 3.11; 95% CI, 2.11-4.58) with SGLT inhibitors, but the authors concluded that, despite the adverse events, the available data suggested that adding the inhibitors to basal insulin could be beneficial in patients with type 1 diabetes (Diabetes Metab Res Rev. 2019 Apr 11. doi: 10.1002/dmrr.3169).
In reference to the findings on DKA, Dr. Perkins said recent research has suggested that the DKA risk could be lowered by decreasing the dose of the SGLT2 inhibitors. “[DKA] is a problem, there’s no question, but there’s a background population risk. Whether we introduce an SGLT2 or not, we have to deal with this issue. We can deal with and overcome the excess DKA risk.”
In the big picture, he said, “it would be a crime not to make this treatment available to some patients. Meaningful benefits far outweigh the risks.”