DeDPP4

leptin receptor-deficient (db/db) (10-week-old, male)^[1]

5 mg/kg (4-week study); 10 mg/kg (single-dose efficacy study; 4-week study)

i.v.; every 2 days; 4 weeks (5 mg/kg, 10 mg/kg 4-week study); i.v.; single dose (10 mg/kg efficacy longevity study)

Maintained reduced blood glucose levels for over 60 h, with sustained hypoglycemia observed for up to 48 h (10 mg/kg single dose).
Reduced fasting blood glucose levels more effectively than 5 mg/kg DeDPP4, and lowered hemoglobin A1c (HbA1c) levels to ~7% after 4 weeks of treatment (10 mg/kg).
Reduced blood glucose to 10.6 mmol/L within 60 min during OGTT, with a significantly lower area under the blood glucose curve (AUC) than the model group (10 mg/kg).
Reduced the homeostasis model assessment of insulin resistance (HOMA-IR) more effectively than alogliptin, and preserved pancreatic β-cell function (HOMA-β) (10 mg/kg).
Significantly increased serum glucagon-like peptide-1 (GLP-1) levels compared to alogliptin (10 mg/kg).
Reduced serum levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and free fatty acids (FFA) more effectively than 5 mg/kg DeDPP4 or alogliptin, while increasing high-density lipoprotein cholesterol (HDL-C) (10 mg/kg).
Significantly reduced serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine (CREA) levels (10 mg/kg).
Preserved pancreatic islet morphology with increased β-cell mass and reduced α/β cell ratio (10 mg/kg).
Induced a greater reduction in hepatic DPP-4 protein levels than 5 mg/kg DeDPP4 (10 mg/kg).