Diabetes

Streptozotocin (STZ) administration induced robust and sustained hyperglycemia in mice, characterized by markedly elevated postprandial and fasting blood glucose levels and a profound reduction in plasma insulin. Diabetic mice maintained blood glucose levels above 30 mmol/L for up to 112 days and exhibited significantly reduced body weight gain, demonstrating successful establishment of a stable insulin-deficient diabetes model.

(A) Postprandial blood glucose levels 14 days after the first STZ injection; (B) 5–6 h fasting blood glucose levels 14 days after the first STZ injection; (C) plasma insulin levels 14 days after the first STZ injection; (D) longitudinal postprandial blood glucose levels over the 112-day study period; and (E) body weight changes during the study period. Groups were defined as follows: G1, Vehicle; and G2, STZ (50 mpk, QD × 5, i.p.). Data are presented as mean ± SD. Statistical significance is indicated in the figure. ***, p < 0.001; and ****, p < 0.0001 by one-way ANOVA.

db/db mice developed progressive obesity and severe type 2 diabetes, characterized by marked body weight gain, persistent hyperglycemia, elevated HbA1c, and dynamic changes in plasma insulin levels. Treatment with Tirzepatide, Retatrutide, and Empagliflozin significantly improved glycemic control, while Tirzepatide and Retatrutide also enhanced glucose tolerance and reduced urinary albumin-to-creatinine ratio (UACR), demonstrating pronounced metabolic and renoprotective benefits.

(A) Body weight progression from baseline to 20 weeks of age; (B) postprandial blood glucose levels during model development; (C) HbA1c levels during model development; (D) plasma insulin levels during model development; (E) HbA1c levels after 4 weeks of treatment; (F) oral glucose tolerance test (OGTT) results following treatment; and (G) urinary albumin-to-creatinine ratio (UACR) after treatment. Groups were defined as follows: BKS-Lepr-/- mice treated with Vehicle, Tirzepatide, Retatrutide, or Empagliflozin, as indicated in the figure. Data are presented as mean ± SD. Statistical significance is indicated in the figure. *, p < 0.05; **, p < 0.01; ***, p < 0.001; and ****, p < 0.0001 vs. (BKS-Lepr-/-, Vehicle) by one-way ANOVA with Dunnett’s post-hoc test.

High-fat high-sucrose diet (HFHSD) combined with streptozotocin (STZ) successfully induced type 2 diabetes in mice, as evidenced by elevated fasting blood glucose, increased HbA1c, and impaired glucose tolerance. Treatment with the SGLT2i significantly reduced fasting blood glucose and HbA1c levels, improved glucose clearance during the oral glucose tolerance test (OGTT), and decreased glucose AUC, demonstrating robust antihyperglycemic efficacy.

(A) Six-hour fasting blood glucose levels; (B) HbA1c levels; (C) oral glucose tolerance test (OGTT) profiles; and (D) glucose AUC (0–120 min) during OGTT. Groups were defined as follows: G1, Control; G2, HFHSD + STZ + Vehicle; and G3, HFHSD + STZ + SGLT2i, as indicated in the figure. Data are presented as mean ± SD. Statistical significance is indicated in the figure. ****, p < 0.0001 vs. Control or HFHSD + STZ + Vehicle by one-way ANOVA with appropriate post-hoc comparisons.