FDA rejects dapagliflozin indication as adjunctive therapy for type 1 diabetes

Helena W. Rodbard, MD, FACP, MACE

It is unfortunate that the FDA has not approved yet another drug from the class of the SGLT inhibitors for people with type 1 diabetes. Following the recent disappointing complete response letter for sotagliflozin, a dual SGLT1 and SGLT2 inhibitor, now the FDA issued a complete response letter for dapagliflozin. These drugs would have been an important addition to our armamentarium and would be addressing some of the unmet needs in type 1 diabetes. Currently, only pramlintide is approved in the U.S. as an adjunct to insulin in people with type 1 diabetes, and it is of limited use.

The principal concern with the SGLT inhibitors is a slightly increased incidence of DKA. This concern has been addressed by a consensus conference on mitigation and recently published recommendations in Diabetes Care (Danne T, et al. Diabetes Care. 2019;doi:10.2337/dc18-2316). With proper selection and education of patients, these drugs can be used very effectively and safely.

Satish K. Garg, MD

There is a great deal of enthusiasm for this class of drugs. However, at the FDA, there is a disconnect with safety vs. efficacy. Efficacy with this drug is clear, in all metrics — blood pressure, weight loss, improvement in HbA1c and hypoglycemia — but there is concern about increased risk for diabetic ketoacidosis. We need to make sure patients have ketone monitoring and education. Just last week, the National Institute for Health Care Excellence (NICE) in the U.K. issued draft final guidance on dapagliflozin with insulin for treating type 1 diabetes. In Europe, dapagliflozin with insulin is recommended as an option for adults with type 1 diabetes with a BMI of at least 27 kg/m² when insulin alone does not provide adequate glycemic control. The draft guideline states that dapagliflozin should be considered only when patients have completed a structured education program that includes information about the risk for DKA, how to recognize risk factors for DKA, how and when to monitor blood ketone levels and what actions to take for elevated blood ketones. This complete response letter gives us an opportunity for the industry to spend money to reduce the background risk for DKA, which is increasing in the U.S. That is the approach Europe is taking, and I don’t know why the U.S. isn’t. In addition, another SGLT2 inhibitor is approved for type 1 diabetes in Japan.