Cadisegliatin, an Oral Drug For Type 1 Diabetes, Begins Phase 3 Trial

A phase 3 clinical trial has begun enrolling patients to assess a potential first-in-class oral therapy to treat patients with Type 1 diabetes that has the potential to improve glycemia and reduce the risk of hypoglycemia. Developed by vTV Therapeutics, cadisegliatin is being studied as an adjunct to the use of insulin in adults with Type 1 diabetes.

Type 1 diabetes is an autoimmune disease where the immune system destroys insulin-producing beta cells in pancreatic islets. About 2 million Americans have Type 1 diabetes. Hypoglycemia is a serious complication where glucose levels become too low. Most patients with Type 1 diabetes experience several episodes of mild-to-moderate hypoglycemia each week with about 4% of patients using insulin experiencing severe hypoglycemia.”

Klara Klein, M.D., Ph.D.

“Although there have been major advances in medical devices for the treatment of Type 1 diabetes, there is a huge unmet need to identify therapies that improve glycemia without increasing the risk of ketosis or hypoglycemia,” Klara Klein, M.D., Ph.D., who is an assistant professor of Medicine at the University of North Carolina at Chapel Hill, said in a news release. “People with Type 1 diabetes continue to walk a tightrope between hyper- and hypoglycemia.”

In nonclinical studies, cadisegliatin was found to act selectively on the liver, increasing the activity of glucokinase independently from insulin. Glucokinase is an enzyme that plays a role in regulating blood glucose levels.

Cadisegliatin has been well-tolerated in more than 500 patients with up to six months of treatment. In a phase 2 study in patients with Type 1 diabetes, those treated with the combination of cadisegliatin and insulin had 50% fewer symptomatic episodes and no ketoacidosis. Additionally, cadisegliatin with insulin reduced hemoglobin A1C by 0.36% compared with insulin alone, and 40% of patients treated with cadisegliatin with insulin had reductions of total daily insulin compared with insulin alone.

The CATT1 phase 3 trial is being conducted at up to 25 sites in the United States and will enroll approximately 150 patients. Two different dose regimens (800 mg once or twice daily) of cadisegliatin will be assessed in patients currently being treated with multiple daily insulin injections or continuous subcutaneous insulin infusion. Continuous glucose monitors (CGM) will be provided to all patients.

The primary endpoint is the incidence of level 2 and 3 hypoglycemia, or low blood sugar, in patients receiving cadisegliatin and insulin compared with insulin alone. Select secondary endpoints include reduction in hemoglobin A1C, time in target range of glycemic control, and incidence of diabetic ketoacidosis. Time-in-range is a measurement to assess how long patients are within a targeted blood glucose range. Diabetic ketoacidosis is a serious complication of Type 1 diabetes where the body is not able to use sugar for energy.

Company officials said they are expecting topline data from the phase 3 study in the second half of 2026.

The FDA in July 2024 had placed a clinical hold on the phase 3 trial based on the discovery of a chromatographic signal in a recent human absorption, distribution, metabolism, and excretion (ADME) study, which provides a picture of how a drug is processed in the body. The clinical hold was lifted in March 2025 after company officials determined the signal was the result of a "experimental artifact," a defect in the experiment that can be ascribed to contamination or equipment failure.

An amendment for the CATT1 phase 3 trial has reduced the overall duration of the trial from 12 to 6 months, as well as the use of continuous glucose monitors to assess the clinical endpoint.