Retatrutide treatment in streptozotocin-induced diabetic rats: renal inflammatory cytokines, HIF‑1α expression, and histopathological injury profile
- Design
- Animal study · Mixed outcome
- Match to healthy normal-weight adults aged 55–75
- Not human evidenceVERY_INDIRECT: male rats with streptozotocin-induced diabetes; non-human evidence.
- Could weight loss explain it?
- PossiblyPossibly: the abstract reports no weight or glycaemic data, so metabolic change is not separated from a drug effect (the evidence model's default for GLP-1 effects).
- Study tier
- Study tier 4VERY_LOW: a preclinical rat study with no number of animals given in the abstract.
- Assessment
- Version 3 · Two reviewers differed; settled by a recorded ruling · Oct 19, 2026
Study facts come from the paper. Population match, weight-loss explanation and study tier are our judgments, made against the reference group of healthy normal-weight adults aged 55–75.
In male rats made diabetic with streptozotocin, researchers tested 21 days of subcutaneous retatrutide on early kidney injury. Kidney HIF-1α expression was lower than in untreated diabetic rats (p = 0.020), but kidney damage scores were not significantly better after correction for multiple testing, and TNF-α did not differ significantly. The authors note that this acute model does not resemble type 2 diabetes, and animal results do not show what happens in people.
01Findings
What the study reported
- Drugs
- Retatrutide
- Route
- subcutaneous
- Comparator
- untreated STZ-induced diabetic rats; also healthy control and retatrutide-alone groups
- Treatment duration
- 21 days
- Primary outcome
- renal histopathological injury scores, IL-1β and TNF-α levels, and HIF-1α expression in kidney tissue
- Effect
- No statistically significant histopathological protection (Cliff's δ = 0.90 cortex, 0.85 medulla, not confirmed under family-wise error correction); HIF-1α expression lower with retatrutide in diabetic rats (p = 0.020); TNF-α no significant difference
- 95% confidence interval
- not reported in abstract
- P value
- p = 0.020 (HIF-1α, S vs. SR)
- Follow-up
- Not stated
- Adverse events
- No evidence of intrinsic renal toxicity with retatrutide
- Limitations
- Rat study in an acute insulin-deficient model that the authors call a critical limitation, with 21 days of treatment and no number of animals in the abstract; longer studies in type 2 diabetes models are needed.
Who was studied
- Sex distribution
- male rats only
- Obesity status
- not reported in abstract
- Diabetes status
- STZ-induced diabetic and non-diabetic groups (rat model)
- Cvd status
- not reported in abstract
- Ckd status
- not reported in abstract
- Baseline condition
- streptozotocin-induced diabetes with early renal injury (rat model)
Study quality details
- Study design
- Preclinical (animal)
- Sample size
- not extracted
- Randomization
- not reported in abstract
- Blinding
- not stated
- Comparator
- untreated STZ-induced diabetic rats; also healthy control and retatrutide-alone groups
- Follow up duration
- not stated
- Outcome type
- mixed
- Replication
- not assessed
- Consistency with other evidence
- not assessed
- Population applicability
- VERY_INDIRECT
- Statistical precision
- no CI reported; p-values and Cliff's δ effect sizes; histology effects not confirmed under family-wise error correction
- Risk of bias
- not assessed
- Funding conflicts
- unclear
- Peer review status
- yes
02Funding
Funding and conflicts
- Funding
- not reported in abstract
- Industry funded
- Unclear
- Manufacturer
- not stated in source
- Sponsor role
- not reported in abstract
- Author conflicts
- The authors declare no competing interests.
- Independent replication
- unknown
Funding is shown on every study and never used to score it.
04Source
The source, as retrieved
Abstract
This study investigated whether Retatrutide, a triple incretin agonist, attenuates early diabetes-associated renal injury in a streptozotocin-induced rat model, and whether any protective effect is mediated through modulation of inflammatory cytokines (IL-1β, TNF-α) and HIF-1α gene expression in kidney tissue. Male Sprague-Dawley rats were divided into four groups: control, STZ-induced diabetic, STZ plus Retatrutide, and Retatrutide alone. Diabetes was induced via a single intraperitoneal STZ injection; Retatrutide was administered subcutaneously for 21 days at a dose adapted from prior metabolic studies. Renal tissue underwent ELISA for interleukin-1β (IL-1β) and tumour necrosis factor-α (TNF-α), quantitative real-time PCR for HIF-1α expression, and semi-quantitative histopathological scoring of cortical and medullary parameters including haemorrhage, tubular dilatation, inflammatory cell infiltration, tubular vacuolisation, interstitial fibrosis, and intraluminal debris. STZ-induced rats exhibited significantly elevated cortical and medullary histopathological scores and increased renal IL-1β levels relative to controls, confirming successful early injury induction. Retatrutide did not produce statistically significant histopathological protection, although STZ plus Retatrutide animals showed consistently lower damage scores than STZ-only animals, corresponding to large standardised effects (Cliff's δ = 0.90 in the cortex and 0.85 in the medulla) that could not be confirmed under family-wise error correction. HIF-1α expression was highest in the untreated diabetic group and was significantly lower in Retatrutide-treated diabetic animals (S vs. SR, p = 0.020), whereas Retatrutide alone did not alter expression relative to controls. TNF-α did not differ significantly in any pairwise comparison; levels in Retatrutide-treated diabetic animals were nonetheless comparable to controls (g* = 0.03). Retatrutide selectively modulated HIF-1α transcriptional levels in the acute STZ model without statistically confirmed histopathological renoprotection, and without evidence of intrinsic renal toxicity. Because the acute STZ model reflects insulin-deficient rather than T2DM-like disease, the model itself is a critical limitation; chronic type 2 diabetes models, together with longer treatment durations and refined dosing regimens, are required to determine whether the observed early molecular effects translate into structural renal benefit.