Effect of Renal Impairment on the Pharmacokinetics of a Single Oral Dose of Danuglipron in Participants With Type 2 Diabetes

Abstract

Danuglipron (PF‐06882961) is an oral, small‐molecule glucagon‐like peptide‐1 receptor agonist in development for the treatment of type 2 diabetes (T2D) and obesity. Impaired renal function is prevalent in patients with T2D. This phase 1, open‐label study evaluated the effect of renal impairment on the pharmacokinetics, safety, and tolerability of danuglipron (20 mg) in healthy participants with normal renal function (estimated glomerular filtration rate [eGFR] unnormalized for body surface area: ≥90 mL/min), in participants with T2D and normal renal function (eGFR ≥90 mL/min), and in participants with T2D and mild (eGFR 60–89 mL/min), moderate (eGFR 30–59 mL/min), or severe (eGFR <30 mL/min) renal impairment (N = 39). Log–linear regression analyses and analyses of variance showed no evidence of a clinically significant effect of reduced renal function on danuglipron pharmacokinetics. Renal clearance of unchanged danuglipron was minimal (<1% across all renal function groups). Danuglipron pharmacokinetics were similar between healthy participants and participants with T2D and normal renal function. A single 20‐mg oral dose of danuglipron was generally safe and well tolerated in all participant groups. In participants with T2D, renal impairment had no clinically meaningful effect on the pharmacokinetic, safety, and tolerability profiles of danuglipron, indicating that dose adjustment of danuglipron will not be required when administered to patients with T2D and reduced renal function.This article is protected by copyright. All rights reserved

SpaceGrow: efficient shape-based virtual screening of billion-sized combinatorial fragment spaces

“…[65,66] Danuglipron is of current interest, since it is under investigation in clinical trial for the treatment of type 2 diabetes and obesity. [67][68][69][70][71][72][73] Fig. 12 shows Danuglipron within the binding site of GLP-1R (a) and the overlay with three retrieved results (b-d), together with the estimated affinity and the respective Tanimoto similarity calculated using the Morgan Fingerprint implementation with radius four from RDKit.…”