Combined empagliflozin and liraglutide therapy protects against tacrolimus-induced pancreatic and renal injury associated with oxidative stress reduction
- Design
- Animal study · Mixed outcome
- Match to healthy normal-weight adults aged 55–75
- Not human evidenceVERY_INDIRECT: male rats with tacrolimus-induced injury and kidney and pancreatic cell lines; no human participants.
- Could weight loss explain it?
- PossiblyNo weight, HbA1c or mediation analysis is reported; tacrolimus raised blood glucose and the treatments gave metabolic protection, so organ protection is not separated from glycaemic improvement.
- Study tier
- Study tier 4VERY_LOW: preclinical rat and cell-line study with no group sizes or statistics in the abstract.
- Assessment
- Version 2 · Two independent AI reviews agreed · 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 given the transplant drug tacrolimus for 4 weeks, liraglutide alone partly reduced the damage to the pancreas and kidneys, and liraglutide combined with empagliflozin protected more; cell experiments pointed the same way. The abstract gives no group sizes or numerical results. This is animal and cell work and does not show the same effect in people.
01Findings
What the study reported
- Drugs
- Liraglutide
- Treatment duration
- 4 weeks
- Comparator
- tacrolimus alone (empagliflozin alone and liraglutide plus empagliflozin were the other arms)
- Primary outcome
- protection against tacrolimus-induced pancreatic and renal injury
- Effect
- Liraglutide or empagliflozin alone partially attenuated tacrolimus-induced injury; the combination gave enhanced protection (better kidney function, preserved islets, less fibrosis and cell death); no numbers reported
- 95% confidence interval
- Not extracted
- Follow-up
- Not stated
- Adverse events
- not reported in abstract
- Limitations
- Preclinical rat and cell-line study with no group sizes or numerical results in the abstract; the main exposure combines liraglutide with an SGLT2 inhibitor, so only the liraglutide-alone arm isolates its effect, and the authors call for further investigation.
Who was studied
- Sex distribution
- male rats only
- Obesity status
- not reported in abstract
- Diabetes status
- not reported in abstract (tacrolimus caused hyperglycaemia in the rats)
- Cvd status
- not reported in abstract
- Ckd status
- not reported in abstract
- Baseline condition
- tacrolimus-induced pancreatic and renal injury (rat model)
Study quality details
- Study design
- Preclinical (animal)
- Sample size
- not extracted
- Randomization
- n/a
- Blinding
- not stated
- Comparator
- tacrolimus alone (empagliflozin alone and liraglutide plus empagliflozin were the other arms)
- 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; no p values or group sizes reported
- 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
- not reported in abstract
- Independent replication
- unknown
Funding is shown on every study and never used to score it.
04Source
The source, as retrieved
Abstract
[BACKGROUND] Sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used in type 2 diabetes mellitus for glycemic control and organ protection. This study investigated whether the combined use of empagliflozin (EMPA) and liraglutide (LIRA) could protect against pancreatic and renal damage caused by tacrolimus (TAC). [METHODS] Male Sprague-Dawley rats received TAC for 4 weeks, either alone, or in combination with EMPA, LIRA, or both. Metabolic, histologic, and molecular parameters were assessed in vivo and in vitro. TAC caused hyperglycemia, reduced creatinine clearance, pancreatic β-cell loss, renal tubulointerstitial fibrosis, and increased oxidative stress and apoptosis. [RESULTS] Either EMPA or LIRA alone partially attenuated these changes, whereas their combination provided enhanced protection- improving kidney function, preserving islet integrity, and reducing fibrosis and cell death. In the kidney and pancreas, dual therapy restored antiapoptotic and antioxidant signaling while suppressing profibrotic pathways, thereby mitigating oxidative stress and injury. Cell-based experiments further confirmed that EMPA plus LIRA enhanced cell viability and reduced reactive oxygen species generation in TAC-injured HK-2 and INS-1 cells. [CONCLUSION] These findings indicate that combined SGLT2i and GLP-1RA therapy confers additive metabolic protection associated with attenuation of oxidative stress in tacrolimus-induced pancreatic and renal damage in this preclinical model, warranting further investigation of its potential as an adjunct strategy for posttransplant diabetes mellitus and nephrotoxicity.