@article{21601,
  author = {Cooper M. and Wanner C. and Groop P. and Woerle H. and von Eynatten M. and McGill J. and Rosenstock J. and Hehnke U. and Perkovic Vlado},
  title = {Kidney Disease End Points in a Pooled Analysis of Individual Patient-Level Data From a Large Clinical Trials Program of the Dipeptidyl Peptidase 4 Inhibitor Linagliptin in Type 2 Diabetes},
  abstract = {<p>
BACKGROUND: Although assessment of cardiovascular safety is mandated by regulatory agencies for the development of new drugs to treat type 2 diabetes, evaluation of their renal safety has been relatively neglected. STUDY DESIGN: Individual patient-level data pooled analysis of 13 phase 2 or 3 randomized, double-blind, placebo-controlled, clinical trials of the dipeptidyl peptidase 4 inhibitor linagliptin. SETTING &amp; PARTICIPANTS: Participants who participated in any of 13 randomized clinical trials and fulfilled predefined inclusion/exclusion criteria, such as being drug-naive (hemoglobin A1c, 7.0%-11.0% [53-97mmol/mol]) or being on background glucose-lowering therapy (hemoglobin A1c, 6.5%-10.5% [48-91mmol/mol]). INTERVENTION: Of 5,466 consenting individuals with inadequately controlled type 2 diabetes, 3,505 received linagliptin, 5mg/d, and 1,961 received placebo. OUTCOMES: The primary kidney disease outcome was defined as first occurrence during the study of 6 predefined safety end points: new onset of moderate elevation of albuminuria (urinary albumin-creatinine ratio [ACR] &gt;30mg/g with baseline values <!--= 30mg/g), new onset of severe elevation of albuminuria (ACR --> 300mg/g with baseline values <!--= 300mg/g), reduction in kidney function (serum creatinine increase to -->/=250mumol/L from a baseline value &lt;250mumol/L), halving of estimated glomerular filtration rate (loss of baseline eGFR &gt;50%), acute renal failure (ascertained from diagnostic codes), or death from any cause. MEASUREMENTS: Albuminuria was assessed using ACR. GFR was estimated using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation. RESULTS: Cumulative exposure (person-years) was 1,751 for linagliptin and 1,055 for placebo. The primary composite outcome occurred in 448 (12.8%) and 306 (15.6%) participants in the linagliptin and placebo groups, respectively. Linagliptin treatment significantly reduced the hazard of kidney disease events by 16% compared with placebo (HR, 0.84; 95% CI, 0.72-0.97; P=0.02). LIMITATIONS: Retrospective and hypothesis-generating study involving short- to midterm clinical trials. CONCLUSIONS: Linagliptin was not associated with increased kidney disease risk in patients with type 2 diabetes. The potential of this drug to improve kidney disease outcomes warrants further investigation.
</p>
},
  year = {2015},
  journal = {American Journal of Kidney Diseases},
  volume = {66},
  edition = {2015/05/12},
  number = {3},
  pages = {441-9},
  isbn = {1523-6838 (Electronic)<br/>0272-6386 (Linking)},
  note = {Cooper, Mark E<br/>Perkovic, Vlado<br/>McGill, Janet B<br/>Groop, Per-Henrik<br/>Wanner, Christoph<br/>Rosenstock, Julio<br/>Hehnke, Uwe<br/>Woerle, Hans-Juergen<br/>von Eynatten, Maximilian<br/>Am J Kidney Dis. 2015 May 7. pii: S0272-6386(15)00604-6. doi: 10.1053/j.ajkd.2015.03.024.},
  language = {Eng},
}