Trial results promising, but DKA still a concern with use of new once-daily pills.
One study examined Farxiga, an SGLT-2 inhibitor, a once daily pill that had FDA approval for type 2 diabetes in 2014. The other study examined sotagliflozin, an SGLT-1/2 dual inhibitor, also a once-daily pill that has not yet been approved as a treatment for type 1 diabetes. Phase 3 trial results of both studies showed greater HbA1c reductions and weight loss benefit, which is a great push for FDA approval as an add-on to insulin therapy for patients with type 1 diabetes.
In the DEPICT 1 trial, a total of 833 patients with type 1 diabetes were followed for 24 weeks. They had an average HbA1c of 8.5%. In addition to a daily dose of 60 units regular insulin, patients also received either a lower dose of 5 mg Farxiga, a higher dose of 10 mg Farxiga, or placebo.
Overall, Farxiga lowered HbA1c by 0.4% to 0.5% and patients lost 3% to 4% more weight, compared to placebo group. Farxiga also helped to decrease total daily insulin dose by 9% to 13%. There were no substantial differences in the rates of hypoglycemia, severe hypoglycemia or potential development of diabetic ketoacidosis (DKA) in patients on Farxiga (1% to 2%) or on placebo (1%). The lower rate of DKA in patients taking Farxiga could be due to specific instructions for doctors that insulin dose reduction for the new adjunctive therapy should not be more than 20%. Further, one-third of the patients taking Farxiga had 2 to 3 more hours in range compared to placebo, measured by continuous glucose monitoring (CGM). While Farxiga shows promising results in DEPICT 1 trial, more results from DEPICT 2 and DEPICT 1 extension are needed for its approval as an add-on therapy for patients with type 1 diabetes.
The Tandem 3 trial studied sotagliflozin. This drug has a dual mechanism of action. Its SGLT-1 inhibitor function delays glucose from being absorbed by the intestines, while its SGLT-2 inhibitor function helps further lower blood glucose level by making the kidney excrete excess glucose.
Half of the 1,402 patients with type 1 diabetes in the Tandem 3 trial were given sotagliflozin, while the other half received a placebo. Study results showed sotagliflozin lowered A1c to less than 7% without severe hypoglycemia or DKA in 29% of patients compared to 15% of patients in the placebo group. 3% of the patients taking sotagliflozin developed hypoglycemia compared to 2% in the placebo group. While sotagliflozin reduced an average of 5 pounds over a 6-month period, the patients receiving placebo gained an average of 2 pounds. These results were similar to inTandem 1 and inTandem 2 trial; however, inTandem 3 did not include an “insulin optimization period,” which refers to training for best insulin administration. DKA is a concern in theTandem 3 trial as 3% of the patients taking sotagliflozin developed DKA compared to 0.6% of the patients receiving placebo. Participants received DKA risk management education, but the information on type of DKA risk management education is unclear.
Given the promising results of greater reduction in HbA1c, weight loss, and amount of insulin needed, these drugs could be a promising add-on therapy for patients with type 1 diabetes. With a unique “mechanism of action,” Sotagliflozin is glucose-responsive and insulin independent. It can lower blood glucose when the level is high and stops working when the level is low. If these drugs are approved, they can help healthcare providers safely reduce insulin doses and monitor ketones.
- Sotagliflozin and Farxiga are two once-daily pills that showed promising A1c reduction and weight loss benefit in patients with type 1 diabetes.
- The risk of diabetic ketoacidosis (DKA) development is a concern and still remains in discussion.
- Both drugs are not currently approved by the FDA as an adjunctive therapy. Once getting the approval from FDA, these drugs can be beneficial for patients with type 1 diabetes.
Emma R, Jeemin K. Can An Add-on Pill for Type 1 Diabetes Improve A1c and Weight Loss?. diatribe. 2017 Sep 24.
Kay Lynn Tran, PharmD candidate L|E|C|O|M SOP Bradenton ’18