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Sitagliptin, liraglutide do not affect kidney function

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September 7, 2016

Renal hemodynamics were not substantially changed with treatment with sitagliptin or liraglutide in adults with type 2 diabetes.

Further, no changes were observed in tubular functions or renal damage markers with either agent, according to researchers.

Lennart Tonneijck, MD, of the diabetes center/department of internal medicine at VU University Medical Center in Amsterdam, and colleagues evaluated 55 adults (mean age, 63 years) with type 2 diabetes who were insulin-naive and screened between July 2013 and March 2015 to determine the effect of the DPP-IV inhibitor sitagliptin (Januvia, Merck) and the glucagon-like peptide-1 receptor agonist liraglutide (Victoza, Novo Nordisk) on renal hemodynamics, tubular functions and markers of renal damage. Participants were randomly assigned to placebo (n = 17), sitagliptin (n = 19) or liraglutide (n = 19) for 12 weeks. Estimated glomerular filtration rate and fractional electrolyte excretions were determined at 2 and 6 weeks.

GFR was not affected by either treatment.

After 12 weeks, effective renal plasma flow was decreased with sitagliptin (P = .053) but did not change with liraglutide. Similarly, sitagliptin was the only treatment that resulted in reduced estimated glomerular hydraulic pressure (P = .043) and fractional excretions of urea (P = .017). Neither treatment resulted in changes in other intrarenal hemodynamic variables, tubular functions, albumin-to-creatinine ratio, neutrophil gelatinase-associated lipocalin or kidney injury molecule-1. Treatment with sitagliptin resulted in increased creatinine-based fractional excretions of sodium (P = .005) and fractional excretions of urea (P = .025) after 2 weeks; however, the levels returned to those of baseline after 12 weeks.

Systolic blood pressure was similarly reduced with treatment with sitagliptin and liraglutide compared with placebo.

HbA1c was reduced by 0.8% with sitagliptin treatment (P = .001) and 1.3% with liraglutide treatment (P < .001) compared with placebo.

“Our results indicate that the potential glucose-independent renoprotective effects of GLP-1-based therapy may not be explained by (intra)renal hemodynamic improvements, but likely relate to benefits on other renal risk factors, such as [BP] and body weight,” the researchers wrote. “Clinical trials with predefined (hard) renal endpoints are needed to determine whether GLP-1–based therapies confer renoprotection in patients with type 2 diabetes, and the use of active comparators in such studies (NCT01243424) may establish effects beyond glucose lowering.” – by Amber Cox

Disclosure: Novo Nordisk provided liraglutide and liraglutide-placebo pens. Two of the researchers report receiving research grants from AstraZeneca, Boehringer Ingelheim, Novo Nordisk and Sanofi.