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Glucagon-like peptide 1 receptor agonist (GLP-1 RA): long-term effect on kidney function in patients with type 2
Bernt Johan von Scholten1, Tine Willum Hansen1, Jens Peter Goetze2
1Steno Diabetes Center, Gentofte, Denmark.
Aims:
In a short-term study including 31 patients with type 2 diabetes, glucagon-like peptide 1 receptor agonist (GLP-1 RA) treatment was associated with a significant reversible decline in GFR. Twenty-three patients re-initiated GLP-1 RA treatment after the primary study, and the aim was to investigate the long-term effect on kidney function.
Methods:
We included 30 patients in a one-year extension study, all initially treated with liraglutide for seven weeks. During follow-up 23 were treated with liraglutide and seven untreated. Primary outcome was change in GFR ((51)Cr-EDTA plasma clearance).
Results:
Patients were 61.5 (10.0) years and HbA(1c) 60.1 (13.8) mmol/mol. Baseline GFR was 100.6 (24.9) mL/min/1.73 m(2) and was reduced by 11 (95% CI: 6.6-15.7, p < 0.001) mL/min/1.73 m(2), independent of change in 24-h systolic blood pressure (SBP), weight, UAER or HbA(1c) (p≥0.33). Geometric mean (IQR) of UAER was 25.5 (9.9-50.9) mg/d and was reduced by 27 (95% CI: 5-44; p = 0.020)%, and 24-h SBP was reduced by 8.2 (p = 0.048) mmHg. No changes occurred in untreated patients.
Conclusions:
Long-term treatment with liraglutide was associated with a reduction in measured GFR similar to the effect during short-term treatment, suggesting a metabolic or haemodynamic reversible effect and not structural changes. Moreover, UAER and 24-h SBP were reduced.
Trial Registration:
ClinicalTrials.gov identifier: NCT01499108.
Insights
Long-term liraglutide treatment in type 2 diabetes patients showed a reversible decline in kidney function, similar to short-term use. This study suggests a metabolic or hemodynamic effect, not structural kidney damage, with benefits in albuminuria and blood pressure.
Area of Science:
- Nephrology
- Endocrinology
- Pharmacology
Background:
- Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are used for type 2 diabetes.
- Short-term GLP-1 RA use was linked to reversible GFR decline.
- Long-term effects on kidney function require further investigation.
Purpose of the Study:
- To assess the long-term impact of liraglutide on kidney function in type 2 diabetes patients.
- To determine if the previously observed short-term GFR reduction persists with prolonged treatment.
- To evaluate changes in albuminuria and blood pressure during long-term liraglutide therapy.
Main Methods:
- A one-year extension study included 30 type 2 diabetes patients previously treated with liraglutide.
- Twenty-three patients continued liraglutide, while seven served as untreated controls.
- Glomerular filtration rate (GFR) was measured using (51)Cr-EDTA plasma clearance.
Main Results:
- Long-term liraglutide treatment resulted in an 11 mL/min/1.73 m(2) reduction in GFR (p < 0.001), independent of HbA(1c), weight, or blood pressure.
- Albuminuria (UAER) decreased by 27% (p = 0.020), and 24-h systolic blood pressure (SBP) decreased by 8.2 mmHg (p = 0.048).
- No significant changes in GFR were observed in the untreated group.
Conclusions:
- Long-term liraglutide treatment is associated with a sustained, reversible reduction in GFR in type 2 diabetes patients.
- The observed GFR changes are likely due to metabolic or hemodynamic factors, not structural kidney damage.
- Liraglutide also demonstrated benefits in reducing albuminuria and systolic blood pressure.
