The influence of pharmaceutically induced weight changes on estimates of renal function: A patient-level pooled analysis of seven randomised controlled trials of glucose lowering medication.
BACKGROUND
Estimation of kidney function (eGFR) is essential in monitoring of patients with kidney disease. Estimates of kidney function based on serum creatinine are derived from cross-sectional studies. If body weight (BW) changes, this might affect creatinine and eGFR. The Cockcroft-Gault (CG) equation includes creatinine and BW, whereas the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations only include creatinine.


METHODS
Data were pooled from the six LEAD (Liraglutide Effect and Action in Diabetes) trials and the LIRA-DPP4 trial. The trials were conducted in patients with type 2 diabetes and of 26weeks duration. We investigated changes in eGFR for patients treated with liraglutide, and for patients treated with glucose-lowering medications with less weight-reducing effects (insulin glargine, glimepiride, exenatide and rosiglitazone).


RESULTS
We included 5100 patients (liraglutide n=3173, comparator n=1927). Mean (SD) CKD-EPI eGFR was 81.2 (20.6) ml/min/1.73m(2) for liraglutide and 81.6 (20.3) ml/min/1.73m(2) for comparator. For liraglutide, BW changed -1.9 (95% CI (-2.0; -1.8)) kg, for comparator BW changed 0.2 (95% CI (0.03; 0.3)) kg. Using regression modelling, a 10% BW decrease yielded no change in creatinine, MDRD eGFR or CKD-EPI eGFR for both liraglutide and comparator, but was associated with a 10.2% (-11.3%; -9.1%) decrease in CG eGFR for liraglutide, and a 10.6% (-12.0%; -9.1%) decrease for comparator.


CONCLUSIONS
A liraglutide-induced weight reduction of 1.9kg was not associated with change in creatinine. Accordingly, there was no change in weight-independent estimates of GFR, whereas weight-dependent estimates were changed. The MDRD and CKD-EPI equations can be used in patients experiencing pharmaceutically induced weight reductions.
Steno Diabetes Center, Gentofte, Denmark. Electronic address: bjos@steno.dk.
Bernt Johan
BJ
von Scholten
Novo Nordisk, Denmark.
David Dynnes
DD
Ørsted
Novo Nordisk, Denmark.
Anne Louise
AL
Svendsen
Steno Diabetes Center, Gentofte, Denmark.
Frederik
F
Persson
Steno Diabetes Center, Gentofte, Denmark; Aarhus University, Denmark; University of Copenhagen, Denmark.
Peter
P
Rossing
D000465:Algorithms; D003404:Creatinine / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000139:chemically induced* / Q000175:diagnosis; D016903:Drug Monitoring / Q000379:methods; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D000069450:Liraglutide / Q000009:adverse effects* / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D051437:Renal Insufficiency / Q000139:chemically induced* / Q000150:complications / Q000175:diagnosis; D015431:Weight Loss / Q000187:drug effects
D007004:Hypoglycemic Agents; D000069450:Liraglutide; D003404:Creatinine
GLP-1; creatinine; glomerular filtration rate; liraglutide; type 2 diabetes