Continuation of SGLT2 inhibitors such as empagliflozin may offer kidney-protective effects against AKI in patients with diabetes undergoing cisplatin chemotherapy for solid and haematological cancers.
A US study, published in Kidney International Reports [link here], provides real-world evidence for SGLT2is as a supportive therapy during cisplatin treatment.
“We find our observations promising and worth exploring for the continuation of SGLT2i in patients with cancer having diabetes mellitus who are receiving cisplatin,” the investigator said.
“Nonetheless, there is currently insufficient evidence to recommend initiating SGLT2i in patients with or without diabetes mellitus solely for potential kidney protection. A well-designed randomised clinical trial with a larger sample size is needed to evaluate this potential indication.”
The single-centre retrospective study comprised 288 patients with pre-existing diabetes who had received at least one dose of cisplatin for a cancer including squamous cell carcinoma, genitourinary, hepatobiliary, endometrial and lung cancers.
The cohort was divided into those receiving SGLT2i during cisplatin therapy and those on other diabetes therapy such as GLP-1 RA and/or DPP-4i. SGLT2is were mainly empagliflozin followed by dapagliflozin, canagliflozin and ertugliflozin.
Patients were mostly White (72.9%) males (71.5%) with a mean age of 62.9 years. Median cisplatin dose per infusion was 40 mg/m2 (range: 10–120 mg/m2) and the median number of infusions was five (range 1-30).
The study found the primary outcome of AKI incidence was 13.9% in the SGKLT2i group compared with 28.5% in the control group (OR: 0.42; P = 0.004).
Among patients who developed AKI, the control group had higher AKI rates across all stages of disease – 28.5% v 14.0% for stage ≥1, 12.5% v 8.0% for stage ≥2, and 3.5% v 1.0% for stage 3.
Kidney recovery at 3 months also differed between the two groups with 65% of patients receiving SGLT2i achieving complete kidney recovery compared to 48.8% in the control group.
In secondary outcomes:
- mean eGFR was higher in the SGLT2i group compared with controls (84.4 ± 25.7 vs. 78.3 ± 25.1 ml/min per 1.73 m2; P=0.043)
- patients receiving SGLT2is experienced a significantly lower incidence of hypomagnesemia (23.2% vs. 57.3%; OR: 0.23, P<0.001)
- patients receiving SGLT2is experienced a significantly lower incidence of anemia (83.3% vs. 95.1%; OR: 0.21, P<0.001)
- there was no difference between the groups in genitourinary infections or hyponatremia
- two cases of diabetic ketoacidosis occurred in the group receiving SGLT2is during cisplatin therapy.
The investigators said the 58% reduction in AKI incidence as well as secondary benefits suggested that SGLT2is were associated with better kidney outcomes in this population.
“Despite previous evidence of the nephroprotective effects of SGLT2is in animal studies, there is a paucity of clinical data evaluating those benefits in humans,” they said. “Our study departs from the currently available data by demonstrating kidney-protective effects.”
They called for a larger, well-designed RCT to further evaluate the findings.
They added that beyond the prevention of cisplatin nephrotoxicity and indications for diabetes management, SGLT2is may also have implications for cancer treatment.
“SGLT2 is overexpressed by many types of tumour cells and is believed to be involved in tumourigenesis, tumour progression, and metastasis. Accordingly, large-scale studies have shown that SGLT2i can inhibit tumour growth and improve prognosis through multiple pathways that are independent of the effects of SGLT2i on blood glucose.”