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Randomized Clinical Trials of Deutaleglitazar in Healthy Participants and in Patients with Diabetic Kidney Disease

In brief

Deutaleglitazar improved glucose and lipids in 18 patients, but lowered eGFR

In three short randomized studies, 18 people with diabetic kidney disease received deutaleglitazar for up to 14 days; glucose and lipid measures improved, while estimated kidney function fell and recovered after treatment stopped. Few adverse events were reported, though neutropenia increased with dose. These early studies do not show whether the metabolic changes translate into lasting kidney benefit.

Journal
Kidney international reports (Q1)
Published
20 August 2026
Study design
Randomized controlled trial
Evidence level
Level 1, High (CEBM 1b)
Authors
Vlado Perkovic, Sam L Francis, Hong Zhang, Ying Gao, Jicheng Lv, Haiyan Li, et al.
PMID
42774918
DOI
10.1016/j.ekir.2026.107037

Why clinicians should know about it

  • Picked for Nephrology (paper of the day, 26 September 2026): PPAR agonist trial in diabetic kidney disease

Abstract

INTRODUCTION: Deutaleglitazar (AP303) is a novel dual peroxisome proliferator-activated receptor (PPAR) α and γ agonist, which has the potential to offer the combined clinical benefit on diabetic kidney disease (DKD) management by normalizing the elevated glomerular capillary pressure, ameliorating podocyte depletion, as well as correcting diabetic dyslipidemia and hyperglycemia. METHODS: A total of 3 single-center, randomized, placebo-controlled single-ascending-dose and/or multiple-ascending-dose studies investigated its pharmacokinetics (PK), pharmacodynamic, safety, and tolerability in healthy participants with different ethnicities and in patients with DKD and reduced kidney function. RESULTS: A total of 80 healthy participants, and 18 patients with DKD and estimated glomerular filtration rate (eGFR) 30-60 ml/min per 1.73 m2 from Australia and China received either placebo, a single oral dose, or multi-dose of deutaleglitazar for 14 days. Deutaleglitazar exposure increased in a dose-dependent manner both after a single dose and at steady state, with no accumulation. Minor differences of PK profiles in Caucasian versus Asian participants, and in those with normal versus reduced kidney function are considered unlikely to be clinically significant. Reduction in eGFR with reversibility after drug discontinuation was evident. Improvement in diabetic dyslipidemia and hyperglycemia were observed. Few adverse events were reported; only neutropenia was dose related. CONCLUSIONS: The PPARα and PPARγ related effects occurred over similar dose ranges, indicating that deutaleglitazar is a balanced agonist of the 2 receptor subtypes targeting on the root cause and multi-pathway of DKD progression.

Abstract as published, via PubMed.

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For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.