03060nas a2200229   4500000000100000008004100001100001400042700001400056700001300070700001400083700002000097700001400117700001800131700001400149700001900163245019200182250001500374300001000389490000700399520237300406020005102779       2015                            d1 aCooper M.1 aWanner C.1 aGroop P.1 aWoerle H.1 avon Eynatten M.1 aMcGill J.1 aRosenstock J.1 aHehnke U.1 aPerkovic Vlado00aKidney 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  a2015/05/12  a441-90 v663 a<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.
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