title: Effect of Sitagliptin on Kidney Function and Respective Cardiovascular Outcomes in Type 2 Diabetes: Outcomes From TECOS.
abstract: To evaluate chronic kidney disease (CKD) and cardiovascular outcomes in TECOS (Clinical trial reg. no. NCT00790205, clinicaltrials.gov) participants with type 2 diabetes and cardiovascular disease treated with sitagliptin, a dipeptidyl peptidase 4 inhibitor, according to baseline estimated glomerular filtration rate (eGFR).
  
  
  
  We used data from 14,671 TECOS participants assigned in a double-blind design to receive sitagliptin or placebo added to existing therapy, while aiming for glycemic equipoise between groups. Cardiovascular and CKD outcomes were evaluated over a median period of 3 years, with participants categorized at baseline into eGFR stages 1, 2, 3a, and 3b (≥90, 60-89, 45-59, or 30-44 mL/min/1.73 m2, respectively).
  
  
  
  Participants with eGFR stage 3b were older, were more often female, and had a longer duration of diabetes. Four-point major adverse cardiovascular event rates increased with lower baseline eGFR (3.52, 3.55, 5.74, and 7.34 events/100 patient-years for stages 1-3b, respectively). Corresponding adjusted hazard ratios for stages 2, 3a, and 3b versus stage 1 were 0.93 (95% CI 0.82-1.06), 1.28 (1.10-1.49), and 1.39 (1.13-1.72), respectively. Sitagliptin therapy was not associated with cardiovascular outcomes for any eGFR stage (interaction P values were all >0.44). Kidney function declined at the same rate in both treatment groups, with a marginally lower but constant eGFR difference (-1.3 mL/min/1.73 m2) in those participants who were assigned to sitagliptin. Treatment differences in these eGFR values remained after adjustment for region, baseline eGFR, baseline HbA1c, time of assessment, and within-study HbA1clevels.
  
  
  
  Impaired kidney function is associated with worse cardiovascular outcomes. Sitagliptin has no clinically significant impact on cardiovascular or CKD outcomes, irrespective of baseline eGFR.
authors.affiliation: Noordwest Ziekenhuisgroep, Alkmaar, the Netherlands.
authors.forename: Jan H
authors.initials: JH
authors.lastname: Cornel
authors.affiliation: University of Chicago Medicine, Chicago, IL.
authors.forename: George L
authors.initials: GL
authors.lastname: Bakris
authors.affiliation: Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC.
authors.forename: Susanna R
authors.initials: SR
authors.lastname: Stevens
authors.affiliation: Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Solna, Stockholm, Sweden.
authors.forename: Michael
authors.initials: M
authors.lastname: Alvarsson
authors.affiliation: Noordwest Ziekenhuisgroep, Alkmaar, the Netherlands.
authors.forename: Willem A
authors.initials: WA
authors.lastname: Bax
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Lee-Ming
authors.identifier: 0000-0003-0978-2662
authors.initials: LM
authors.lastname: Chuang
authors.affiliation: Merck and Co., Inc., Kenilworth, NJ.
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Engel
authors.affiliation: Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC.
authors.forename: Renato D
authors.initials: RD
authors.lastname: Lopes
authors.affiliation: Department of Medicine, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Darren K
authors.initials: DK
authors.lastname: McGuire
authors.affiliation: GMP, Husby, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Riefflin
authors.affiliation: Endocrine and Metabolic Consultants, Rockville, MD.
authors.forename: Helena Wachslicht
authors.initials: HW
authors.lastname: Rodbard
authors.affiliation: Unit of Diabetes, Instituto Cardiovascular de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Isaac
authors.initials: I
authors.lastname: Sinay
authors.affiliation: Clinical Center of Endocrinology, Medical University, Sofia, Bulgaria.
authors.forename: Tsvetalina
authors.initials: T
authors.lastname: Tankova
authors.affiliation: E. Wolfson Medical Center, Holon, Israel.
authors.forename: Julio
authors.initials: J
authors.lastname: Wainstein
authors.affiliation: Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Peterson
authors.affiliation: Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, U.K. rury.holman@dtu.ox.ac.uk.
authors.forename: Rury R
authors.initials: RR
authors.lastname: Holman
mesh_terms: D000368:Aged; D002318:Cardiovascular Diseases / Q000150:complications / Q000453:epidemiology* / Q000517:prevention & control; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology* / Q000503:physiopathology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000453:epidemiology / Q000503:physiopathology / Q000517:prevention & control; D000068900:Sitagliptin Phosphate / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D000068900:Sitagliptin Phosphate