CATT1: First Participant Randomized in Cadisegliatin T1D Trial With Klara Klein, MD, PhD

The CATT1 phase 3 trial investigating cadisegliatin for the treatment of type 1 diabetes (T1D) randomized its first participant on August 7, 2025, marking a major step for vTv Therapeutics Inc.’s potential first-in-class oral, liver-selective glucokinase activator.1

This randomized, double-blind, placebo-controlled study is being conducted at 23 sites across the US. With recruitment ongoing, investigators expect an enrollment total of roughly 150 participants. It includes 2 different dose regimens of cadisegliatin (800 mg once or twice daily), which will be compared to placebo in patients currently being treated with multiple daily insulin injections or continuous subcutaneous insulin infusion.1

Although medical devices for T1D have advanced exponentially in recent years, actual therapeutic advances have been few and far between. The primary treatment for T1D is still insulin therapy, which has been at the top of the cascade for almost a century. With multiple implicit limitations surrounding insulin therapy, clinicians and patients alike have been waiting for a new potential frontline treatment to emerge.

“There are issues associated with using exogenous insulin – it causes low blood sugars, which is why we use it in type 1 diabetes,” said Klara Klein, MD, PhD, in an interview with HCPLive. “But if you take too much insulin, you can get low blood sugars. The half-life of exogenous insulin is much longer than what is produced endogenously. And so as we can deliver insulin, which you can’t live without, it’s not the same as what the body actually does.”

Cadisegliatin (TTP399) is a novel, oral small molecule, liver-selective glucokinase activator currently under investigation as the first oral adjunctive treatment for T1D. In previous, non-clinical studies, cadisegliatin, acting selectively on the liver, raised glucokinase activity independent of insulin, which supports clinical investigation of improvement in glycemic control through hepatic glucose uptake and glycogen storage.1

To be included in the trial, patients must be ≥18 years of age, have a diagnosis of T1D with a minimum of 5 years since diagnosis, have had ≥1 hypoglycemic event of Level 2 (glucose level <54 mg/dL) or Level 3 (defined as severe hypoglycemia with altered mental state and/or physical status requiring assistance) in the last 2 months prior to screening. Patients must also exhibit an HbA1c value of <9.5% at screening and be on CSII or MDI for at least 6 months prior to screening.2

Patients are excluded if they have type 2 diabetes, maturity-onset diabetes of the young, or other unusual or rare forms of diabetes, or if they had been hospitalized for diabetic ketoacidosis (DKA) within 3 months prior to screening, among other exclusion criteria. Additionally, patients with uncontrolled hypertension are excluded.2

The primary endpoint is incidence of level 2 or 3 hypoglycemic events in patients treated with cadisegliatin compared to placebo, while secondary endpoints include reduction in hemoglobin A1C, time in target range of glycemic control, and incidence of DKA.1

“Again, all of this is early days, and we’re really looking forward to seeing what happens in this phase 3 study and other studies that come,” Klein said. “We really need better therapies to help people living with type 1 diabetes.”

Investigators expect to release topline data in the second half of 2026.1

References

1. vTv Therapeutics, Inc. vTv Therapeutics Announces First Study Participant Randomized in CATT1 Phase 3 Trial of Cadisegliatin in Type 1 Diabetes. August 7, 2025. Accessed September 5, 2025. https://ir.vtvtherapeutics.com/news-releases/news-release-details/vtv-therapeutics-announces-first-study-participant-randomized

2. vTv Therapeutics, Inc. Cadisegliatin as Adjunctive Therapy to Insulin in Participants With Type 1 Diabetes (CATT1). ClinicalTrials.gov identifier: NCT06334133. Updated July 18, 2025. Accessed September 5, 2025. https://clinicaltrials.gov/study/NCT06334133