Adding Empagliflozin to Insulin Cuts A1C in Type 1 Diabetes, Reduces CV Risk in Study

A study from Spain has found that when managed carefully, the use of the sodium glucose cotransporter 2 (SGLT2) inhibitor empagliflozin can give patients with type 1 diabetes (T1D) greater glycemic control than they get with insulin alone, along with improved time in range.

Results from the study, published this week in Diabetes Technology & Therapeutics, are likely to add to the debate over whether the SGLT2 class is appropriate for use in T1D. The small prospective study involved just 27 patients, for whom empagliflozin was added off-label per a protocol within clinical practice. The primary end point was the change in glycated hemoglobin (A1C), although blood pressure, weight, and safety issues were also assessed.

Discussions during the recent meeting of the European Association for the Study of Diabetes (EASD) took up the topic of SGLT2 inhibitors in T1D, and for several years abstracts presented at the American Diabetes Association (ADA) have raised the possibility that this drug class that has become a standard in type 2 diabetes care could also aid patients with T1D.

But when given the opportunity this year to approve a dual SGLT1/2 inhibitor for T1D, the FDA balked, following the divided vote of an advisory panel. European regulators have approved the drug for T1D patients who are overweight or obese.

The advantage of empagliflozin, and the SGLT2 class generally, is that its unique mechanism expels excess glucose through the urine, thus offering the possibility of reducing glucose variability—eliminating the “roller coaster” effect that many with T1D experience that can cause long-term microvascular damage. Increasingly, diabetes experts say a patient’s time in range, more so than the A1C measure, may be a better indicator of long-term health, cardiovascular risk, and the likelihood of complications such as blindness or kidney failure.

But studies in T1D patients taking sotagliflozin and another SGLT2 inhibitor, canagliflozin, showed an elevated risk of diabetic ketoacidosis (DKA); this risk prompted FDA’s rejection of the sotagliflozin application. Advocates for T1D were frustrated, saying that patients with this disease are already at increased risk of hypoglycemia and measures beyond A1C must be given consideration.

In this new study, only 1 of the 27 patients had a mild DKA incident, which caused discontinuation. There were no reported incidents of severe hypoglycemia.

After 52 weeks, results showed the following:

• Adding empagliflozin reduced A1C from 8.0% ±0.7% to 7.2% ±0.8% (P&thinsp; <&thinsp;.001).
• The mean percentage time in range for capillary glucose monitoring increased from 50% to 62% (P = .008) while patients were taking less insulin, —0.08 IU/kg per day, (P = .031).
• Patients lost weight, with an average loss of 8 kg, and systolic blood pressure (BP) dropped from 134 to 127 mmHg (P <.001), meaning the average went from just above new recommended targets from the American College of Cardiology/American Heart Association to within normal BP range.

Consistent with the known adverse effects of the SGLT2 inhibitor class, the most common side effects were genitourinary infections (10 cases over 52 weeks).

The authors concluded: “Our results suggested that the use of empagliflozin following a strict off-label protocol may represent an effective and safe option in real life among patients with T1D, improving metabolic control, and ameliorating some cardiovascular risk factors.”

Reference

Bayona Cebada A, Nattero-Chavez L, Alonso Diaz S, Escobar-Morreale HF, Luque-Ramirez M. Efficacy and safety of SGLT2 inhibitors in type 1 diabetes after the introduction of an off-Label use protocol for clinical practice [published online October 23, 2019]. Diabetes Technol Ther. 2019; doi: 10.1089/dia.2019.0316.