Samuel S Engel1, Shailaja Suryawanshi1, Susanna R Stevens2, Robert G Josse3, Jan H Cornel4,5, Neli Jakuboniene6, Axel Riefflin7, Tsvetalina Tankova8, Julio Wainstein9, Eric D Peterson2, Rury R Holman10. 1. Merck & Co., Inc., Kenilworth, New Jersey. 2. Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina. 3. St. Michael's Hospital, University of Toronto, Toronto, Canada. 4. Department of Cardiology, Noordwest Ziekenhuisgroep, Alkmaar, the Netherlands. 5. Working group on Cardiovascular Research the Netherlands (WCN), Utrecht, the Netherlands. 6. Department of Endocrinology, Lithuanian University of Health Sciences, Kaunas, Lithuania. 7. GMP Husby, Husby, Germany. 8. Clinical Center of Endocrinology, Medical University, Sofia, Bulgaria. 9. Wolfson Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel. 10. Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
Abstract
AIMS: To characterize the incidence of diabetes-associated complications and assess the safety of sitagliptin in participants with chronic kidney disease (CKD) in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). MATERIALS AND METHODS: For participants with baseline eGFR measurements (n = 14 528), baseline characteristics and safety outcomes were compared for the CKD cohort (eGFR < 60 mL/min per 1.73 m2 ) vs those without CKD. Within the CKD cohort, the same analyses were performed, comparing sitagliptin- and placebo-assigned participants. Baseline characteristics were summarized for all participants, and serious adverse events were analysed in those who received at least 1 dose of study medication. Adverse events of interest and diabetes complications were summarized for the intention-to-treat population. RESULTS:CKD was present in 3324 (23%) participants at entry into TECOS. The mean (SD) age for this CKD cohort was 68.8 (7.9) years, mean diabetes duration was 13.7 (9.0) years, and 62% were men. Incidences of serious adverse events, malignancy, bone fracture, severe hypoglycaemia and most categories of diabetes complications were higher in the CKD cohort compared with those without CKD. Over ~2.8 median years of follow-up, CKD participants assigned to sitagliptin had rates of diabetic eye disease, diabetic neuropathy, renal failure, malignancy, bone fracture, pancreatitis and severe hypoglycaemia similar to those of placebo-assigned participants. CONCLUSIONS: Participants in TECOS with CKD had higher incidences of serious adverse events and diabetes complications than those without CKD. Treatment with sitagliptin was generally well tolerated, with no meaningful differences in safety outcomes observed between those with CKD assigned to sitagliptin or placebo.
RCT Entities:
AIMS: To characterize the incidence of diabetes-associated complications and assess the safety of sitagliptin in participants with chronic kidney disease (CKD) in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). MATERIALS AND METHODS: For participants with baseline eGFR measurements (n = 14 528), baseline characteristics and safety outcomes were compared for the CKD cohort (eGFR < 60 mL/min per 1.73 m2 ) vs those without CKD. Within the CKD cohort, the same analyses were performed, comparing sitagliptin- and placebo-assigned participants. Baseline characteristics were summarized for all participants, and serious adverse events were analysed in those who received at least 1 dose of study medication. Adverse events of interest and diabetes complications were summarized for the intention-to-treat population. RESULTS: CKD was present in 3324 (23%) participants at entry into TECOS. The mean (SD) age for this CKD cohort was 68.8 (7.9) years, mean diabetes duration was 13.7 (9.0) years, and 62% were men. Incidences of serious adverse events, malignancy, bone fracture, severe hypoglycaemia and most categories of diabetes complications were higher in the CKD cohort compared with those without CKD. Over ~2.8 median years of follow-up, CKD participants assigned to sitagliptin had rates of diabetic eye disease, diabetic neuropathy, renal failure, malignancy, bone fracture, pancreatitis and severe hypoglycaemia similar to those of placebo-assigned participants. CONCLUSIONS:Participants in TECOS with CKD had higher incidences of serious adverse events and diabetes complications than those without CKD. Treatment with sitagliptin was generally well tolerated, with no meaningful differences in safety outcomes observed between those with CKD assigned to sitagliptin or placebo.
Authors: Flory T Muanda; Matthew A Weir; Lavanya Bathini; Kristin K Clemens; Vlado Perkovic; Manish M Sood; Eric McArthur; Jessica M Sontrop; Richard B Kim; Amit X Garg Journal: Clin J Am Soc Nephrol Date: 2020-11-25 Impact factor: 8.237