TY - JOUR
T1 - Glomerular Filtration Rate and Associated Risks of Cardiovascular Events, Mortality, and Severe Hypoglycemia in Patients with Type 2 Diabetes
T2 - Secondary Analysis (DEVOTE 11)
AU - the DEVOTE study group
AU - Amod, Aslam
AU - Buse, John B.
AU - McGuire, Darren K.
AU - Pieber, Thomas R.
AU - Pop-Busui, Rodica
AU - Pratley, Richard E.
AU - Zinman, Bernard
AU - Hansen, Marco Bo
AU - Jia, Ting
AU - Mark, Thomas
AU - Poulter, Neil R.
N1 - Funding Information:
Aslam Amod has received personal fees related to advisory boards and lectures from Novo Nordisk, Sanofi (South Africa), AstraZeneca, Merck Sharp and Dohme Corp., Lilly South Africa, Boehringer Ingelheim, Merck Biopharma, and Novartis South Africa. John B. Buse’s contracted consulting fees are paid to the University of North Carolina by Adocia, AstraZeneca, Dance Biopharm, Eli Lilly, MannKind, NovaTarg, Novo Nordisk, Senseonics, vTv Therapeutics, and Zafgen; he has received grant support from Novo Nordisk, Sanofi, and vTv Therapeutics. He is a consultant to Cirius Therapeutics Inc., CSL Behring, Neurimmune AG, and Pendulum Therapeutics. He holds stock options in Mellitus Health, Pendulum Therapeutics, PhaseBio, and Stability Health. He is supported by a grant from the National Institutes of Health (UL1TR002489). Darren K. McGuire has received personal fees from Boehringer Ingelheim, Janssen Research and Development LLC, Sanofi US, Merck Sharp and Dohme Corp., Eli Lilly USA, Novo Nordisk, GlaxoSmithKline, AstraZeneca, Lexicon Pharmaceuticals, Eisai, Pfizer, Metavant, Applied Therapeutics, and Esperion. Thomas R. Pieber has received research support from Novo Nordisk and AstraZeneca (paid directly to the Medical University of Graz) and personal fees as a consultant from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Novo Nordisk, and Roche Diabetes Care. TRP is also the Chief Scientific Officer of CBmed (Center for Biomarker Research in Medicine), a public-funded biomarker research company. Rodica Pop-Busui has received research support (to the University of Michigan) from AstraZeneca, and is supported by grants from the National Institutes of Health (NIDDK-1-R01-DK-107956-01, UC4 DK101108). Payment for Richard E. Pratley’s services were directed to AdventHealth (formerly Florida Hospital), a non-profit organization; he also received consultancy and speaker fees from AstraZeneca, Takeda, and Novo Nordisk; consultancy fees from Boehringer Ingelheim, GlaxoSmithKline, Hanmi Pharmaceutical Co. Ltd., Janssen Scientific Affairs LLC, Ligand Pharmaceuticals, Inc., Eli Lilly, Merck, Pfizer, and Eisai, Inc.; and research grants from Gilead Sciences, Lexicon Pharmaceuticals, Ligand Pharmaceuticals, Inc., Eli Lilly, Merck, Sanofi US LLC, and Takeda. Bernard Zinman has received grant support from Boehringer Ingelheim, AstraZeneca, and Novo Nordisk and consulting fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk, and Sanofi. Ting Jia is a full-time employee of and holds stock in Novo Nordisk A/S. Marco Bo Hansen is a full-time employee of and holds stock in Novo Nordisk A/S. Thomas Mark is a full-time employee of and holds stock in Novo Nordisk A/S. Neil R. Poulter has received personal fees from Servier, Takeda, Novo Nordisk, and AstraZeneca in relation to speakers’ fees and advisory board activities (concerning diabetes mellitus); and research grants for his research group (relating to type 2 diabetes mellitus) from Diabetes UK, National Institute for Health Research Efficacy and Mechanism Evaluation (NIHR EME), Julius Clinical, and the British Heart Foundation.
Funding Information:
The trial, these secondary analyses and the Rapid Service Fee were funded by Novo Nordisk. The sponsor contributed to data collection and statistical analyses. Novo Nordisk was involved in obtaining the data and designing these secondary analyses, provided logistical support, and ran all the statistical analyses, the results of which were evaluated jointly by the authors and the sponsor. DEVOTE research activities were supported at numerous US centers by Clinical and Translational Science Awards from the National Institutes of Health’s National Center for Advancing Translational Science.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - Introduction: The associations of chronic kidney disease (CKD) severity, cardiovascular disease (CVD), and insulin with the risks of major adverse cardiovascular events (MACE), mortality, and severe hypoglycemia in patients with type 2 diabetes (T2D) at high cardiovascular (CV) risk are not known. This secondary, pooled analysis of data from the DEVOTE trial examined whether baseline glomerular filtration rate (GFR) categories were associated with a higher risk of these outcomes. Methods: DEVOTE was a treat-to-target, double-blind trial involving 7637 patients with T2D at high CV risk who were randomized to once-daily treatment with either insulin degludec (degludec) or insulin glargine 100 units/mL (glargine U100). Patients with estimated GFR data at baseline (n = 7522) were analyzed following stratification into four GFR categories. Results: The risks of MACE, CV death, and all-cause mortality increased with worsening baseline GFR category (P < 0.05), with a trend towards higher rates of severe hypoglycemia. Patients with prior CVD, CKD (estimated GFR < 60 mL/min/m2), or both were at higher risk of MACE, CV death, and all-cause mortality. Only CKD was associated with a higher rate of severe hypoglycemia, and the risk of MACE was higher in patients with CVD than in those with CKD (P = 0.0003). There were no significant interactions between randomized treatment and GFR category. Conclusion: The risks of MACE, CV death, and all-cause mortality were higher with lower baseline GFR and with prior CVD, CKD, or both. The relative effects of degludec versus glargine U100 on outcomes were consistent across baseline GFR categories, suggesting that the lower rate of severe hypoglycemia associated with degludec use versus glargine U100 use was independent of baseline GFR category. Funding: Novo Nordisk.
AB - Introduction: The associations of chronic kidney disease (CKD) severity, cardiovascular disease (CVD), and insulin with the risks of major adverse cardiovascular events (MACE), mortality, and severe hypoglycemia in patients with type 2 diabetes (T2D) at high cardiovascular (CV) risk are not known. This secondary, pooled analysis of data from the DEVOTE trial examined whether baseline glomerular filtration rate (GFR) categories were associated with a higher risk of these outcomes. Methods: DEVOTE was a treat-to-target, double-blind trial involving 7637 patients with T2D at high CV risk who were randomized to once-daily treatment with either insulin degludec (degludec) or insulin glargine 100 units/mL (glargine U100). Patients with estimated GFR data at baseline (n = 7522) were analyzed following stratification into four GFR categories. Results: The risks of MACE, CV death, and all-cause mortality increased with worsening baseline GFR category (P < 0.05), with a trend towards higher rates of severe hypoglycemia. Patients with prior CVD, CKD (estimated GFR < 60 mL/min/m2), or both were at higher risk of MACE, CV death, and all-cause mortality. Only CKD was associated with a higher rate of severe hypoglycemia, and the risk of MACE was higher in patients with CVD than in those with CKD (P = 0.0003). There were no significant interactions between randomized treatment and GFR category. Conclusion: The risks of MACE, CV death, and all-cause mortality were higher with lower baseline GFR and with prior CVD, CKD, or both. The relative effects of degludec versus glargine U100 on outcomes were consistent across baseline GFR categories, suggesting that the lower rate of severe hypoglycemia associated with degludec use versus glargine U100 use was independent of baseline GFR category. Funding: Novo Nordisk.
KW - Basal insulin analogs
KW - Cardiovascular disease
KW - Chronic kidney disease
KW - Glomerular filtration rate
KW - Insulin degludec
KW - Insulin glargine U100
KW - Severe hypoglycemia
KW - Type 2 diabetes
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U2 - 10.1007/s13300-019-00715-x
DO - 10.1007/s13300-019-00715-x
M3 - Article
C2 - 31667706
AN - SCOPUS:85074718581
VL - 11
SP - 53
EP - 70
JO - Diabetes Therapy
JF - Diabetes Therapy
SN - 1869-6953
IS - 1
ER -