Effect of Sitagliptin on Kidney Function and Respective Cardiovascular Outcomes in Type 2 Diabetes: Outcomes From TECOS

Diabetes Care. 2016 Dec;39(12):2304-2310. doi: 10.2337/dc16-1415. Epub 2016 Oct 14.


Objective: 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).

Research design and methods: 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).

Results: 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 HbA1c levels.

Conclusions: Impaired kidney function is associated with worse cardiovascular outcomes. Sitagliptin has no clinically significant impact on cardiovascular or CKD outcomes, irrespective of baseline eGFR.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Cardiovascular Diseases / complications
  • Cardiovascular Diseases / epidemiology*
  • Cardiovascular Diseases / prevention & control
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / epidemiology*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use
  • Double-Blind Method
  • Female
  • Glomerular Filtration Rate / drug effects*
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use*
  • Kidney / drug effects*
  • Kidney / physiopathology
  • Male
  • Middle Aged
  • Renal Insufficiency, Chronic / complications
  • Renal Insufficiency, Chronic / epidemiology
  • Renal Insufficiency, Chronic / physiopathology
  • Renal Insufficiency, Chronic / prevention & control
  • Sitagliptin Phosphate / pharmacology
  • Sitagliptin Phosphate / therapeutic use*
  • Treatment Outcome


  • Dipeptidyl-Peptidase IV Inhibitors
  • Hypoglycemic Agents
  • Sitagliptin Phosphate

Associated data

  • ClinicalTrials.gov/NCT00790205