Can ipragliflozin treatment help lower insulin dose in patients with T2D receiving insulin therapy?

Is the off-label use of type-2 diabetes medications in type 1 diabetes causing increased rates of diabetic ketoacidosis?


Posted by Medivizor on Dec 9, 2019 in Diabetes mellitus |

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In a nutshell

This study examined the frequency of sodium-glucose cotransporter 2 (SGLT2) inhibitor use in type 1 diabetes (T1D) and the resulting rates of diabetic ketoacidosis (DKA). The study concluded that while the proportion of SGLT2 use in T1D is small, there is a significant associated risk of DKA.

Some background

There are two main types of diabetes. Type 1 is caused by the destruction of insulin-producing cells by the immune system and results in the absence of insulin. In type 2 there is reduced production of insulin. SGLT2 inhibitors such as sotagliflozin (Zynquista) or dapagliflozin (Forxiga) are a type of drug generally employed to treat type 2 DM. They remove glucose from the blood via the kidneys to lower blood glucose. These have not been approved for use in T1D but are sometimes used anyway. This is referred to as off-label use and it is unclear how often it happens.

DKA is a life-threatening complication of diabetes. It has been seen after using SGLT2 inhibitors in both T1D and T2D. Studies have shown DKA risk increases with increased drug dose. As risk is usually tightly controlled in these studies, it is unclear whether the risk remains the same in real life.

Methods & findings

This study included 475 527 patients with diabetes who were new to using SGLT2 drugs. They had been using the drugs for 4-5 months on average. 6 754 patients in total met the criteria for T1D. These patients were put in 2 groups depending on the criteria used for diagnosis. Those in group 1 were diagnosed by broader criteria. They were more likely to have received oral drugs for diabetes immediately after diagnosis. Group 2 had narrow criteria and received insulin treatment. Patients were followed up to see how often DKA occurred.

The percentage of patients with T1D using SGLT2 drugs ranged from 0.47% to 0.98%, depending on the specific drug. Those with T1D using SGLT2 were more likely to be between 12 and 18 years old.

In groups, lower rates of DKA were seen in those not getting insulin. DKA was more common in female patients and in those aged between 25 and 44 years old. Patients between 25 and 44 years of age at the time of starting SGLT2 inhibitors were 2.6 times more likely to experience DKA compared to what would be expected based on clinical trials. 

The bottom line

In conclusion, use of SGLT2 inhibitors in T1D was not as common but was still associated with significant rates of DKA with the off-label use.

The fine print

There is a much lower risk of DKA in T2D, therefore a higher rate of DKA is always expected in T1D. The broad criteria for T1D might have included patients with T2D falsely diagnosed as T1D. This might have influenced the results. 

What’s next?

If you have any concerns or questions regarding your risk of DKA you should speak to your doctor or diabetic nurse.

Published By :

Diabetes Care

Original Title :

Use of Sodium-Glucose Cotransporter 2 Inhibitors in Patients With Type 1 Diabetes and Rates of Diabetic Ketoacidosis.

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