Glucagon-like peptide 1 receptor agonist (GLP-1 RA): long-term effect on kidney function in patients with type 2 diabetes.
OBJECTIVE
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.


BACKGROUND
ClinicalTrials.gov identifier: NCT01499108.
Steno Diabetes Center, Gentofte, Denmark. Electronic address: bjos@steno.dk.
Bernt Johan
BJ
von Scholten
Steno Diabetes Center, Gentofte, Denmark.
Tine Willum
TW
Hansen
Rigshospitalet, Copenhagen, Denmark; Aarhus University, Denmark.
Jens Peter
JP
Goetze
Steno Diabetes Center, Gentofte, Denmark.
Frederik
F
Persson
Steno Diabetes Center, Gentofte, Denmark; Aarhus University, Denmark; University of Copenhagen, Denmark.
Peter
P
Rossing
D000368:Aged; D000419:Albuminuria / Q000209:etiology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000503:physiopathology / Q000517:prevention & control*; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000187:drug effects; D000067757:Glucagon-Like Peptide-1 Receptor / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D000069450:Liraglutide / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D051437:Renal Insufficiency / Q000503:physiopathology / Q000517:prevention & control*; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
D000067757:Glucagon-Like Peptide-1 Receptor; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069450:Liraglutide; D000097789:Glucagon-Like Peptide-1 Receptor Agonists; C000593833:GLP1R protein, human; C517652:hemoglobin A1c protein, human
GLP-1; Glomerular filtration rate; Kidney function; Liraglutide; MR-proANP; Urinary albumin excretion rate