All About SGLT Inhibitors for T1D
What are SGLT inhibitors?
SGLT inhibitors are oral medications that work by decreasing the production of transport proteins and reducing the absorption of glucose by the intestines and kidneys. Up until now, these drugs have been approved exclusively for use in type 2 diabetes. Inhibitors on the market currently include SGLT-2 inhibitors Farxiga, Jardiance, Invokana and Steglatro. While they’re not quite approved across the board by regulatory bodies in the US or internationally, some type 1 diabetes (T1D) patients are already using these medications “off-label”.
On March 22 2019, the U.S. Food and Drug Administration (FDA) declined to approve Zynquista, the first dual SGLT-1 and SGLT-2 inhibitor, for use alongside insulin for people with type 1 diabetes. The drug works to lower the body’s amount of glucose by causing urination that releases excess sugars. This is also how SGLT-2 inhibitors used by those with type 2 diabetes work, though none of them have been previously approved for people with T1D to use. SGLT inhibitors carry an increased risk of diabetic ketoacidosis (DKA), a dangerous complication that normally occurs when the body doesn’t have enough insulin. DKA is less of a risk for patients with type 2 diabetes.
In February of 2019, The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommended an additional indication for dapagliflozin (Farxiga) for use in adults with type 1 diabetes who meet certain criteria, paving the way for SGLT approval for type 1s in Europe. On March 25, 2019, Farxiga (Forxiga in Europe) was approved by the European Commission (EC) for use in in patients with T1D who have a BMI ≥ 27 kg/m2. Farxiga has also been approved for use in patients with T1D in Japan. On April 28, 2019, Zynquista received approval from the European Commission for use in adults with type 1 diabetes and a BMI ≥ 27 kg/m2.
On July 15, 2019, the FDA declined to approve Farxiga for use in people with T1D in the United States.
How they work
SGLT-1 and SGLT-2 dual inhibitors:
- Are dual-functioning drugs that have been tested for use (with insulin) by those with type 1
- Delay and reduce glucose absorption by the intestines and kidneys, increase glucose excretion in urine and lower blood sugar
- Decrease insulin requirements, assist with weight loss and help prevent glucose spikes after meals.
- Brand Names: Zynquista (Sotagliflozin)
- Are drugs used primarily by those with type 2
- Reduce the reabsorption of glucose by the kidneys, increase glucose excretion in urine and lower blood sugar
- Decrease insulin requirements, assist with weight loss and help prevent blood glucose spikes after meals
- Should be taken once at the same time each day, with or without food
- Brand names: Invokana (canagliflozin), Farxiga (dapagliflozin), Jardiance (empagliflozin)
- Reduction in A1C
- Fewer episodes of severe hyperglycemia
- Reduction in total daily insulin needs
- May help with weight loss, glycemic variability and overall quality of life
Clinical trial data showed an increased risk of diabetic ketoacidosis (DKA) in patients with type 1 diabetes. In one trial, 3 percent of patients on sotagliflozin experienced DKA during the study, while only .4% on placebo did. Notably, nearly half of the DKA episodes in patients taking sotagliflozin occurred in blood glucose levels at or below 13.9 mmol/L250 mg/dL. In June 2019, a DKA risk mitigation strategy for people with type 1 diabetes on SGLT inhibitors, the ‘STOP DKA’ protocol was published in Diabetes, Obesity and Metabolism.