Cadisegliatin (oral glucokinase activator)

Insulin is the only therapy most people with type 1 diabetes ever take — and insulin cannot tell the difference between a rising blood sugar and a falling one. Adjunct drugs are the attempt to give the body back some of the machinery insulin does not replace. Nearly all of them are borrowed from type 2 diabetes, and nearly all of them are sold on HbA1c or weight. Cadisegliatin is the unusual one: it was developed for type 1 from the beginning, and the thing it is trying to fix is hypoglycemia.

What it actually does. Cadisegliatin (formerly TTP399) is an oral, liver-selective glucokinase activator.¹ Glucokinase is the enzyme that acts as the liver's glucose sensor — it decides when the liver should soak up glucose and store it as glycogen, and when it should release it. In type 1 diabetes that sensing is impaired, partly because the liver never sees the surge of insulin that a working pancreas would deliver straight into the portal vein. Cadisegliatin turns glucokinase back up, in the liver only, so the liver stores glucose more readily after meals and — crucially — has more glycogen in the tank to release when glucose falls.¹ It is a tablet taken alongside insulin, not a replacement for it. Nobody stops injecting.

What the phase 2 data showed. The published phase 1b/2 SimpliciT1 study tested TTP399 800 mg against placebo in adults with type 1 diabetes.¹ Two results stand out:

• HbA1c fell modestly but significantly. Placebo-adjusted, HbA1c improved by 0.7 percentage points in Part 1 and 0.21 points in Part 2 at week 12.¹ The Part 2 figure is the more sober one, and it is small.
• Lows fell substantially. The frequency of severe or symptomatic hypoglycemia dropped by about 40% versus placebo in Part 2 — the larger of the two parts (85 participants).¹ This — not the HbA1c number — is why the drug is in phase 3.

The ketone result is the one to notice. The best-known danger of adding a drug to insulin in type 1 diabetes is euglycemic diabetic ketoacidosis — ketoacidosis that develops while glucose still looks normal, so it hides from your meter and your CGM. It is why SGLT2 inhibitors, effective as they are, remain a fraught choice in type 1. In SimpliciT1, cadisegliatin went the other way: plasma beta-hydroxybutyrate and urinary ketones were lower on the drug than on placebo.¹ That is a genuine differentiator, and it is the main reason we score safety here well above where we would score an SGLT2 inhibitor. It is not a guarantee — the studies were small and short, and DKA incidence is being formally tracked in phase 3.²

Phase 3: CATT1. The confirmatory trial (NCT06334133) is randomized, double-blind and placebo-controlled: cadisegliatin 800 mg once or twice daily versus placebo, over six months, in roughly 150 adults aged 18 and over with type 1 diabetes, at up to 25 US sites. The first participant was randomized in August 2025.²³ The design detail that matters most: the primary endpoint is hypoglycemia itself — the incidence of level 2 events (glucose below 54 mg/dL, 3.0 mmol/L) and level 3 events (severe lows needing someone else's help). HbA1c, time in range and DKA incidence are secondary.² Trials in this field almost always put HbA1c first. This one does not, and that tells you what the drug is for.

Where things stand. vTv says enrolment is on track to complete in Q3 2026, with topline data expected in the second half of 2026, and that it has cash to reach that readout.⁴ Treat those as company expectations rather than facts — trial timelines slip. vTv also states that cadisegliatin carries FDA Breakthrough Therapy designation for type 1 diabetes, which speeds review but says nothing about whether the drug works.² A separate phase 2a crossover study is planned in people already using hybrid closed-loop systems — the fair test of whether an oral drug still adds anything once an algorithm is doing the minute-to-minute work.

Our read. A ~40% reduction in severe and symptomatic hypoglycemia — the Part 2 result, from one study — would, if it replicates, be worth more to most people's daily life than another fraction of a percentage point off an HbA1c — fewer 3 a.m. juice boxes, fewer episodes that need help, less of the fear that quietly shapes every dosing decision. But phase 2 is not phase 3, one published study is not a body of evidence, and this drug is currently reachable only by joining a trial. Come back for the H2 2026 readout.

References

1. Klein KR, Freeman JLR, Dunn I, et al. The SimpliciT1 Study: A Randomized, Double-Blind, Placebo-Controlled Phase 1b/2 Adaptive Study of TTP399, a Hepatoselective Glucokinase Activator, for Adjunctive Treatment of Type 1 Diabetes. Diabetes Care 2021;44(4):960-968 (PMID 33622669). https://doi.org/10.2337/dc20-2684 ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶

2. vTv Therapeutics. vTv Therapeutics Announces First Study Participant Randomized in CATT1 Phase 3 Trial of Cadisegliatin in Type 1 Diabetes (press release, 7 Aug 2025). https://www.globenewswire.com/news-release/2025/08/07/3129170/0/en/vTv-Therapeutics-Announces-First-Study-Participant-Randomized-in-CATT1-Phase-3-Trial-of-Cadisegliatin-in-Type-1-Diabetes.html ↩ ↩² ↩³ ↩⁴

3. Managed Healthcare Executive. Cadisegliatin, an Oral Drug For Type 1 Diabetes, Begins Phase 3 Trial. https://www.managedhealthcareexecutive.com/view/cadisegliatin-an-oral-drug-for-type-1-diabetes-begins-phase-3-trial ↩

4. vTv Therapeutics. vTv Therapeutics Reports First Quarter 2026 Financial Results and Provides Corporate Update (press release, 13 May 2026; CATT1 enrolment on track to complete Q3 2026, topline data expected H2 2026). https://www.globenewswire.com/news-release/2026/05/13/3294394/0/en/vtv-therapeutics-reports-first-quarter-2026-financial-results-and-provides-corporate-update.html ↩