SGLT2i, Pioglitazone, and Ketone Production in T1D

Description

The purpose of this research study is to investigate the effects of Dapagliflozin and Pioglitazone in the body – specifically, on liver glucose production, breakdown of fat, and ketone production in Type 1 Diabetic patients treated with insulin. Subjects with type 1 diabetes mellitus (T1DM) can’t make insulin because their pancreas doesn’t work properly. This means they need insulin injections to control their blood sugar. But using insulin can sometimes cause low blood sugar and weight gain, making it harder for insulin to work and requiring higher doses. Finding other medicines that can help lower blood sugar in people with T1DM and can be used along with insulin would make it easier to manage their blood sugar.

Dapagliflozin is in a class of drugs known as Selective Glucose Cotransporter 2 inhibitors (SGLT2i) and has been shown to effectively lower blood sugar concentration in type 1 diabetes mellitus (T1DM) patients. These drugs lower blood glucose levels by preventing or reducing the re-absorption of glucose in the kidneys. This results in the release of glucose into the urine. At the same time, Selective Glucose Transporter 2 Inhibitor (SGLT2i) drugs stimulate glucose production by the liver, which helps compensate for the loss of glucose into the urine. Also, the use of dapagliflozin in patients with type 1 diabetes was associated with increased risk of ketoacidosis. Ketoacidosis is a serious condition that occurs when the body produces high levels of ketones, leading to increased acidity in the blood. Pioglitazone is in a class of thiazolidinediones and is commonly used to treat high blood sugar levels caused by type 2 diabetes. The investigators believe that the addition of pioglitazone, to dapagliflozin will prevent the risk of ketoacidosis associated with dapagliflozin, and will cause a large reduction in plasma glucose concentration in type 1 diabetes (T1DM) patients.