Differential glycemic effects of DWP16001 in diabetic dogs according to baseline glycemic status: a multicenter randomized controlled trial

Abstract

Background: Sodium-glucose cotransporter 2 inhibitors are widely used in human medicine for their insulin-independent glucose-lowering effects. However, their clinical efficacy and safety for managing diabetes mellitus in dogs have not been established. This study aimed to evaluate the efficacy and safety of DWP16001, a selective sodium-glucose cotransporter 2 inhibitor, as an adjunct to insulin therapy for client-owned dogs with diabetes mellitus. Methods: This multicenter, randomized, double-blind, placebo-controlled clinical trial involved 61 dogs receiving stable insulin therapy. They were randomly assigned to receive DWP16001 (0.025 mg/kg PO q24h) or placebo for 8 weeks. The changes in the serum fructosamine (weeks 0, 1, 4, and 8) and HbA1c (weeks 0, 4 and 8) concentrations and daily insulin dose were assessed. Safety evaluations included adverse event monitoring, physical examination, body weight measurement, blood gas and ketone analyses, urinalysis, and hematologic and biochemical profiling. Hypoglycemia was detected via blood glucose curve. Results: DWP16001 significantly reduced fructosamine and HbA1c concentrations in the dogs, especially in those with poor baseline glycemic control (fructosamine ≥ 500 µmol/L, HbA1c ≥ 6%). A trend toward reduced insulin requirements was observed in the treatment group without significant weight loss or clinically relevant changes in systolic blood pressure or signs of volume depletion. Asymptomatic hypoglycemia was detected in four dogs receiving DWP16001, but it resolved following insulin dose adjustment. No episodes of diabetic ketoacidosis were recorded, and laboratory parameters remained stable throughout the study. Conclusions: DWP16001 is a safe and effective adjunct to insulin therapy for diabetic dogs, especially those with suboptimal glycemic control. It demonstrated insulin-sparing effects and favorable metabolic safety, necessitating further evaluation in long-term clinical studies.