Oral Presentation Australian and New Zealand Obesity Society Annual Scientific Conference 2026

Tirzepatide attenuates renal injury in a mouse model of insulin-deficient diabetes with obesity (144782)

Amanda R Purcell 1 2 3 , Natassia Rodrigo 1 2 4 , Matilda SG Longfield 1 2 3 , Sonia Saad 1 3 , Carol Pollock 1 4 5 , Sarah J Glastras 1 2 4
  1. The Kolling Institute, St Leonards, New South Wales, Australia
  2. Department of Diabetes, Endocrinology and Metabolism, Royal North Shore Hospital, St Leonards, NSW, Australia
  3. Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
  4. Northern Precinct, Sydney Medical School, University of Sydney, Sydney, NSW, Australia
  5. Department of Renal Medicine, Royal North Shore Hospital, St Leonards, NSW, Australia

The growing prevalence of obesity and insulin resistance in people with type 1 diabetes (T1D) may compound the risk of diabetes-related kidney disease. Tirzepatide improves metabolic outcomes and may confer kidney benefits in type 2 diabetes, although its renal effects in T1D remain unclear. We investigated whether tirzepatide improved renal outcomes in a mouse model of insulin-deficient diabetes with obesity when initiated at diabetes onset or after established disease.

Eight-week-old male C57BL/6 mice were allocated to four groups (n=8/group). Controls without diabetes received standard chow (CON). Insulin-deficient diabetes was induced using streptozotocin (55mg/kg/day for five consecutive days) alongside high-fat diet feeding (HFD, 20kJ/g, 43.5% fat). Mice received saline (DD), tirzepatide from diabetes onset (DD-eTZP), or tirzepatide after 12 weeks of HFD (DD-lTZP). Tirzepatide was dose-escalated to 40 nmol/kg and administered subcutaneously three times weekly. Metabolic outcomes, relative kidney weight, urinary albumin-to-creatinine ratio and renal histopathology were assessed after 24 weeks of treatment. Data is presented as mean±SEM and was analysed using one-way ANOVA with Bonferroni-adjusted comparisons.

At study completion, body weight was lower in DD-eTZP and DD-lTZP groups compared to DD (27.7±0.4 and 26.8±0.5 vs 32.5±0.4g; p<0.0001). Blood glucose was also lowered (10.3±0.4 and 14.2±1.8 vs 31.4±0.9mmol/L; p<0.0001). Both regimens reduced relative kidney weight by 22–34% and decreased tubular vacuolation, casts and glycogenated nuclei (p<0.05 vs DD). Only early treatment (DD-eTZP) reduced tubular dilation and urinary albumin-to-creatinine ratio (p<0.05 vs DD).

Tirzepatide improved metabolic parameters and attenuated renal injury in a mouse model of insulin-deficient diabetes with obesity, irrespective of whether treatment began at disease onset or after established disease. Early initiation conferred additional renoprotective benefits highlighting the importance of timely intervention. These data provide strong preclinical evidence that tirzepatide may offer renoprotective effects in T1D and warrant urgent evaluation in translational and clinical studies.