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Parameters influencing renal response to SGLT2 inhibitors and GLP1 receptor agonists in type 2 diabetes patients with
E Biancalana1, G Petralli1, F Raggi2
1Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Purpose:
SGLT2 inhibitors (SGLT2i) and GLP1 receptor agonists (GLP1-RA) protect the kidney in type 2 diabetes (T2DM) subjects. The role of patient's phenotype years before starting the treatment in determining the kidney response to these drugs has never been evaluated.
Subjects And Methods:
Clinical and biochemical parameters were collected in 92 T2DM patients with preserved kidney function from year -4 (T-4) to year +3 (T+3) from the introduction of semaglutide or empagliflozin (T0). Glomerular filtration rate (eGFR) slopes were evaluated to identify eGFR changes (ΔGFR) and predictors of treatment response. Urinary markers of kidney impairment were measured at T0, including KIM-1, TNFR1 and L-FABP.
Results:
Characteristics of patients on semaglutide (n = 46) or empagliflozin (n = 37) were similar at T-4 and T0. ΔGFR from T0 to T+3 was -5.5 [-10.0; -0.7] vs -2.6 [-102.4] ml/min/1.73 m2 for GLP1-RA and SGLT2i, respectively (p = ns). Compared with patients with a slower eGFR decline, those with ΔGFR > 5 ml/min/1.73 m2 from T0 to T+3 (49%) or ΔGFR > 10 ml/min/1.73 m2 from T-4 to T+3 (25%) had similar characteristics and urinary markers at T-4 and T0. The latter group showed greater eGFR decline from T-3 to T0, which tended to be delayed more by SGLT2i than GLP1-RA (p = 0.09).
Conclusion:
In our cohort, subjects with T2DM and preserved renal function show similar eGFR response to treatment with GLP1-RA or SGLT2i. Baseline urinary biomarkers or prior phenotyping do not predict treatment response. An early eGFR decline identifies patients prone to lose more eGFR over time, who may benefit more from SGLT2i treatment.
Insights
Type 2 diabetes patients showed similar kidney function response to SGLT2 inhibitors and GLP1 receptor agonists. Early eGFR decline predicts future loss, suggesting SGLT2 inhibitors may offer greater benefit in these cases.
Area of Science:
- Nephrology
- Endocrinology
- Pharmacology
Background:
- Type 2 diabetes (T2DM) patients are at high risk for kidney disease.
- SGLT2 inhibitors (SGLT2i) and GLP1 receptor agonists (GLP1-RA) are known to offer kidney protection in T2DM.
- The influence of pre-treatment patient phenotype on kidney response to these therapies remains unclear.
Purpose of the Study:
- To evaluate the role of patient phenotype years before treatment in determining kidney response to SGLT2i and GLP1-RA in T2DM.
- To compare the kidney protective effects of SGLT2i and GLP1-RA in T2DM patients with preserved kidney function.
Main Methods:
- A cohort of 92 T2DM patients with preserved kidney function were monitored from 4 years prior to 3 years after initiating semaglutide (GLP1-RA) or empagliflozin (SGLT2i).
- Estimated glomerular filtration rate (eGFR) slopes were analyzed to assess changes (ΔGFR) and identify predictors of response.
- Urinary markers of kidney impairment (KIM-1, TNFR1, L-FABP) were measured at baseline.
Main Results:
- Both semaglutide and empagliflozin showed comparable effects on ΔGFR from baseline to 3 years post-treatment (p=ns).
- Patients experiencing a greater eGFR decline (ΔGFR > 5 ml/min/1.73 m²/year) prior to treatment showed a tendency for greater eGFR loss, which was more delayed by SGLT2i (p=0.09).
- Baseline characteristics and urinary markers did not predict treatment response.
Conclusions:
- In T2DM patients with preserved renal function, SGLT2i and GLP1-RA demonstrate similar effects on eGFR over a 3-year period.
- Pre-treatment urinary biomarkers and patient phenotyping do not reliably predict kidney response to these agents.
- An early decline in eGFR identifies patients at higher risk of future kidney function loss, potentially benefiting more from SGLT2 inhibitor therapy.
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