Glomerular Filtration Rate and Associated Risks of Cardiovascular Events, Mortality, and Severe Hypoglycemia in Patients with Type 2 Diabetes: Secondary Analysis (DEVOTE 11)

Aslam Amod, John B. Buse, Darren K. McGuire, Thomas R. Pieber, Rodica Pop-Busui, Richard E. Pratley, Bernard Zinman, Marco Bo Hansen, Ting Jia, Thomas Mark, Neil R. Poulter, DEVOTE Study Group the DEVOTE Study Group

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
JournalDiabetes Therapy
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Glomerular Filtration Rate
Hypoglycemia
Type 2 Diabetes Mellitus
Mortality
Chronic Renal Insufficiency
Cardiovascular Diseases
Cause of Death
Insulin
Insulin Glargine
insulin degludec
Therapeutics

Keywords

  • Basal insulin analogs
  • Cardiovascular disease
  • Chronic kidney disease
  • Glomerular filtration rate
  • Insulin degludec
  • Insulin glargine U100
  • Severe hypoglycemia
  • Type 2 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Glomerular Filtration Rate and Associated Risks of Cardiovascular Events, Mortality, and Severe Hypoglycemia in Patients with Type 2 Diabetes : Secondary Analysis (DEVOTE 11). / Amod, Aslam; Buse, John B.; McGuire, Darren K.; Pieber, Thomas R.; Pop-Busui, Rodica; Pratley, Richard E.; Zinman, Bernard; Hansen, Marco Bo; Jia, Ting; Mark, Thomas; Poulter, Neil R.; the DEVOTE Study Group, DEVOTE Study Group.

In: Diabetes Therapy, 01.01.2019.

Research output: Contribution to journalArticle

Amod, Aslam ; Buse, John B. ; McGuire, Darren K. ; Pieber, Thomas R. ; Pop-Busui, Rodica ; Pratley, Richard E. ; Zinman, Bernard ; Hansen, Marco Bo ; Jia, Ting ; Mark, Thomas ; Poulter, Neil R. ; the DEVOTE Study Group, DEVOTE Study Group. / Glomerular Filtration Rate and Associated Risks of Cardiovascular Events, Mortality, and Severe Hypoglycemia in Patients with Type 2 Diabetes : Secondary Analysis (DEVOTE 11). In: Diabetes Therapy. 2019.
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abstract = "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.",
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author = "Aslam Amod and Buse, {John B.} and McGuire, {Darren K.} and Pieber, {Thomas R.} and Rodica Pop-Busui and Pratley, {Richard E.} and Bernard Zinman and Hansen, {Marco Bo} and Ting Jia and Thomas Mark and Poulter, {Neil R.} and {the DEVOTE Study Group}, {DEVOTE Study Group}",
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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 - 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.

AU - the DEVOTE Study Group, DEVOTE Study Group

PY - 2019/1/1

Y1 - 2019/1/1

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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DO - 10.1007/s13300-019-00715-x

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