Jan H Cornel1, George L Bakris2, Susanna R Stevens3, Michael Alvarsson4, Willem A Bax1, Lee-Ming Chuang5, Samuel S Engel6, Renato D Lopes3, Darren K McGuire7, Axel Riefflin8, Helena Wachslicht Rodbard9, Isaac Sinay10, Tsvetalina Tankova11, Julio Wainstein12, Eric D Peterson3, Rury R Holman13. 1. Noordwest Ziekenhuisgroep, Alkmaar, the Netherlands. 2. University of Chicago Medicine, Chicago, IL. 3. Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC. 4. Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Solna, Stockholm, Sweden. 5. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. 6. Merck and Co., Inc., Kenilworth, NJ. 7. Department of Medicine, University of Texas Southwestern Medical Center, Dallas, TX. 8. GMP, Husby, Germany. 9. Endocrine and Metabolic Consultants, Rockville, MD. 10. Unit of Diabetes, Instituto Cardiovascular de Buenos Aires, Buenos Aires, Argentina. 11. Clinical Center of Endocrinology, Medical University, Sofia, Bulgaria. 12. E. Wolfson Medical Center, Holon, Israel. 13. Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, U.K. rury.holman@dtu.ox.ac.uk.
Abstract
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.
RCT Entities:
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.
Authors: David León Jiménez; David Z I Cherney; Petter Bjornstad; Luis Castilla-Guerra; José Pablo Miramontes González Journal: Am J Physiol Renal Physiol Date: 2018-08-01
Authors: Stacey A Seggelke; Mark C Lindsay; Ingrid Hazlett; Rebecca Sanagorski; Robert H Eckel; Cecilia C Low Wang Journal: Curr Diab Rep Date: 2017-08 Impact factor: 4.810