Encouraging news about Sotagliflozin use in Type 1 Diabetes
Sotagliflozin is being developed to treat Type 1 diabetes, and it was presented for discussion at the American Diabetes Association (ADA) 2017 Scientific Sessions in June.
To date, researchers have finished three Phase 3 clinical trials on the product. Study results have been good, and thus far, researchers have learned that this investigational drug reduces A1c by roughly 0.5%, in addition to lowering blood pressure and weight. The idea is that this is an oral agent that can possibly be used in addition to insulin in patients with Type 1 diabetes.
One of these trials, the inTandem1 study, was presented in detail at the ADA conference by John B. Buse, MD, PhD, from the University of North Carolina School of Medicine in Chapel Hill. He believes that Sotagliflozin could improve glycemic control in an additional 30% of Type 1 patients, which could translate to fewer complications over time. Used in combination with optimized insulin therapy, Sotagliflozin use can lead to a significant lowering of A1c.
Doctors think that while it looks promising, there are still concerning side effects to consider.
In the 24 week long clinical trial, diabetic ketoacidosis (DKA) developed in 1.1% of patients using the 200 mg dose, and in 3.3% of those given the 400 mg dose. None of the participants in the placebo group developed DKA. It’s also noteworthy that insulin pump users in this study experienced a higher incidence of DKA, particularly at the higher 400 mg dose.
While there are multiple SGLT2 inhibitors on the market, they are approved for treating only Type 2 diabetes.
However, some prescribers use them off-label to treat patients who have Type 1. Some experts warn against using them in the Type 1 population because these drugs are associated with a risk of DKA. Others feel that if great care is taken to chose the right patients, adjust the dose, and monitor for ketones, the DKA risk can be managed. Success depends upon evaluating the personal risk of each particular patient, and that individual’s receptivity to discussing how to ease that risk. An ideal Type 1 candidate might be someone who is middle-aged and overweight with an A1c over 7.5%.
In Type 2 patients, research has revealed that the risk of DKA doubles when these users begin taking an SGLT2 inhibitor, compared to other diabetes medications. That said, the risk is still low, with five to eight patients out of every 1000 going on to end up in DKA.
The ideal outcome of research on an inhibitor of SGLT 1 and 2 in patients with Type 1 diabetes would be that the drug is better than, or, minimally, at least as good as the effect of an SGLT2 inhibitor in Type 1 to control A1c, Blood Pressure (BP), and weight, along with reduced risk of DKA.
SGLT2 affects glucose reabsorption in the kidney, while SGLT1 influences glucose absorption in the gastrointestinal tract. Sotagliflozin lowers blood glucose levels by inhibiting glucose reabsorption in both of these sites. It makes sense to use an inhibitor of both SGLT 1 and 2 in Type 1 because it will eliminate excess glucose from the body.
Some details about the inTandem1 trial:
- there were 793 North American participants with Type 1, with a mean diabetes duration of 24 years and a mean age in their mid-40s.
- Approximately two thirds were insulin pump users, with the remaining third utilizing Multiple Daily Injections (MDI).
- Following six weeks of insulin optimization, average A1c levels fell from an average of approximately 8.2% to 7.6%.
- Participants remained on the optimized regimen and then were randomized to sotagliflozin at 200 mg daily , 400 mg daily, or placebo for 24 weeks.
- The primary endpoint was the percentage lowering in A1c from baseline following 24 weeks of treatment.
- The A1c lowering was 0.08%, 0.43%, and 0.49% for placebo, sotagliflozin 200 mg daily, and sotagliflozin 400 mg daily, respectively.
With both sotagliflozin arms of the trial, there was a significant reduction in body weight, and there was no increase in severe hypoglycemia. There were 18, 11, and 12 events in the placebo, 200 mg daily, and 400 mg daily arms, respectively.
It’s exciting to see research being done on new medications that can improve glycemic control for Type 1 patients, especially when the medication comes in pill form! We are eager to see how things unfold as this drug continues through development.