Effects of Extended-Release Niacin Added to Simvastatin/Ezetimibe on Glucose and Insulin Values in AIM-HIGH

Ronald B Goldberg, Vera A. Bittner, Richard L. Dunbar, Jerome L. Fleg, George Grunberger, John R. Guyton, Lawrence A. Leiter, Ruth McBride, Jennifer G. Robinson, Debra L. Simmons, Carol Wysham, Ping Xu, William E. Boden

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background: Niacin is an antidyslipidemic agent that may cause blood sugar elevation in patients with diabetes, but its effects on glucose and insulin values in nondiabetic statin-treated subjects with cardiovascular disease and at high risk for diabetes are less well known. Methods: This was a prespecified, intent-to-treat analysis of the Atherothrombosis Intervention in Metabolic syndrome with low high-density lipoprotein/high triglycerides: Impact on Global Health outcomes trial which randomized 3,414 participants at 92 centers in the US and Canada to extended-release niacin (ERN) plus simvastatin/ezetimibe (ERN) or simvastatin/ezetimibe plus placebo (Placebo). Baseline and annual fasting glucose and insulin values were measured. Those experiencing an adverse event indicative of diabetes or starting medications for diabetes were considered to have confirmed diabetes. In addition, nondiabetic subjects with 2 annual follow-up glucose measurements were categorized into normal, impaired fasting glucose or newly diagnosed diabetes (presumed or confirmed) states. Results: Compared with placebo, ERN increased annual fasting glucose from baseline to 1 year in both those with normal (7.9 ± 15.8 vs 4.3 ± 10.3 mg/dL; P <.001) and impaired fasting glucose (4.1 ± 18.7 vs 1.4 ± 14.9; P <.02) and increased insulin levels. Both effects waned over the next 2 years. There were less consistent effects in those with baseline diabetes. There was an increased risk of progressing from normal to presumed or confirmed impaired fasting glucose (ERN 197/336) cases (58.6%) vs placebo 135/325 cases (41.5%; P <.001) over time, but no difference in diabetes development in the 2 treatment groups except in those with normal fasting glucose at baseline. Conclusions: The addition of ERN to simvastatin/ezetimibe had marginal effects on glycemia in those with diabetes at baseline, and there was a trend toward increased development of new-onset diabetes. In addition, ERN increased the risk of developing impaired fasting glucose, which may have deleterious consequences over time and warrants further study.

Original languageEnglish (US)
JournalAmerican Journal of Medicine
DOIs
StateAccepted/In press - 2016

Fingerprint

Simvastatin
Niacin
Insulin
Fasting
Glucose
Placebos
Ezetimibe
Hydroxymethylglutaryl-CoA Reductase Inhibitors
HDL Lipoproteins
LDL Lipoproteins
Canada
Blood Glucose
Triglycerides
Cardiovascular Diseases

Keywords

  • Clinical trial
  • Diabetes
  • Extended release niacin
  • Glucose and insulin
  • Heart disease
  • Impaired fasting glucoses

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Effects of Extended-Release Niacin Added to Simvastatin/Ezetimibe on Glucose and Insulin Values in AIM-HIGH. / Goldberg, Ronald B; Bittner, Vera A.; Dunbar, Richard L.; Fleg, Jerome L.; Grunberger, George; Guyton, John R.; Leiter, Lawrence A.; McBride, Ruth; Robinson, Jennifer G.; Simmons, Debra L.; Wysham, Carol; Xu, Ping; Boden, William E.

In: American Journal of Medicine, 2016.

Research output: Contribution to journalArticle

Goldberg, RB, Bittner, VA, Dunbar, RL, Fleg, JL, Grunberger, G, Guyton, JR, Leiter, LA, McBride, R, Robinson, JG, Simmons, DL, Wysham, C, Xu, P & Boden, WE 2016, 'Effects of Extended-Release Niacin Added to Simvastatin/Ezetimibe on Glucose and Insulin Values in AIM-HIGH', American Journal of Medicine. https://doi.org/10.1016/j.amjmed.2016.02.039
Goldberg, Ronald B ; Bittner, Vera A. ; Dunbar, Richard L. ; Fleg, Jerome L. ; Grunberger, George ; Guyton, John R. ; Leiter, Lawrence A. ; McBride, Ruth ; Robinson, Jennifer G. ; Simmons, Debra L. ; Wysham, Carol ; Xu, Ping ; Boden, William E. / Effects of Extended-Release Niacin Added to Simvastatin/Ezetimibe on Glucose and Insulin Values in AIM-HIGH. In: American Journal of Medicine. 2016.
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abstract = "Background: Niacin is an antidyslipidemic agent that may cause blood sugar elevation in patients with diabetes, but its effects on glucose and insulin values in nondiabetic statin-treated subjects with cardiovascular disease and at high risk for diabetes are less well known. Methods: This was a prespecified, intent-to-treat analysis of the Atherothrombosis Intervention in Metabolic syndrome with low high-density lipoprotein/high triglycerides: Impact on Global Health outcomes trial which randomized 3,414 participants at 92 centers in the US and Canada to extended-release niacin (ERN) plus simvastatin/ezetimibe (ERN) or simvastatin/ezetimibe plus placebo (Placebo). Baseline and annual fasting glucose and insulin values were measured. Those experiencing an adverse event indicative of diabetes or starting medications for diabetes were considered to have confirmed diabetes. In addition, nondiabetic subjects with 2 annual follow-up glucose measurements were categorized into normal, impaired fasting glucose or newly diagnosed diabetes (presumed or confirmed) states. Results: Compared with placebo, ERN increased annual fasting glucose from baseline to 1 year in both those with normal (7.9 ± 15.8 vs 4.3 ± 10.3 mg/dL; P <.001) and impaired fasting glucose (4.1 ± 18.7 vs 1.4 ± 14.9; P <.02) and increased insulin levels. Both effects waned over the next 2 years. There were less consistent effects in those with baseline diabetes. There was an increased risk of progressing from normal to presumed or confirmed impaired fasting glucose (ERN 197/336) cases (58.6{\%}) vs placebo 135/325 cases (41.5{\%}; P <.001) over time, but no difference in diabetes development in the 2 treatment groups except in those with normal fasting glucose at baseline. Conclusions: The addition of ERN to simvastatin/ezetimibe had marginal effects on glycemia in those with diabetes at baseline, and there was a trend toward increased development of new-onset diabetes. In addition, ERN increased the risk of developing impaired fasting glucose, which may have deleterious consequences over time and warrants further study.",
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author = "Goldberg, {Ronald B} and Bittner, {Vera A.} and Dunbar, {Richard L.} and Fleg, {Jerome L.} and George Grunberger and Guyton, {John R.} and Leiter, {Lawrence A.} and Ruth McBride and Robinson, {Jennifer G.} and Simmons, {Debra L.} and Carol Wysham and Ping Xu and Boden, {William E.}",
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T1 - Effects of Extended-Release Niacin Added to Simvastatin/Ezetimibe on Glucose and Insulin Values in AIM-HIGH

AU - Goldberg, Ronald B

AU - Bittner, Vera A.

AU - Dunbar, Richard L.

AU - Fleg, Jerome L.

AU - Grunberger, George

AU - Guyton, John R.

AU - Leiter, Lawrence A.

AU - McBride, Ruth

AU - Robinson, Jennifer G.

AU - Simmons, Debra L.

AU - Wysham, Carol

AU - Xu, Ping

AU - Boden, William E.

PY - 2016

Y1 - 2016

N2 - Background: Niacin is an antidyslipidemic agent that may cause blood sugar elevation in patients with diabetes, but its effects on glucose and insulin values in nondiabetic statin-treated subjects with cardiovascular disease and at high risk for diabetes are less well known. Methods: This was a prespecified, intent-to-treat analysis of the Atherothrombosis Intervention in Metabolic syndrome with low high-density lipoprotein/high triglycerides: Impact on Global Health outcomes trial which randomized 3,414 participants at 92 centers in the US and Canada to extended-release niacin (ERN) plus simvastatin/ezetimibe (ERN) or simvastatin/ezetimibe plus placebo (Placebo). Baseline and annual fasting glucose and insulin values were measured. Those experiencing an adverse event indicative of diabetes or starting medications for diabetes were considered to have confirmed diabetes. In addition, nondiabetic subjects with 2 annual follow-up glucose measurements were categorized into normal, impaired fasting glucose or newly diagnosed diabetes (presumed or confirmed) states. Results: Compared with placebo, ERN increased annual fasting glucose from baseline to 1 year in both those with normal (7.9 ± 15.8 vs 4.3 ± 10.3 mg/dL; P <.001) and impaired fasting glucose (4.1 ± 18.7 vs 1.4 ± 14.9; P <.02) and increased insulin levels. Both effects waned over the next 2 years. There were less consistent effects in those with baseline diabetes. There was an increased risk of progressing from normal to presumed or confirmed impaired fasting glucose (ERN 197/336) cases (58.6%) vs placebo 135/325 cases (41.5%; P <.001) over time, but no difference in diabetes development in the 2 treatment groups except in those with normal fasting glucose at baseline. Conclusions: The addition of ERN to simvastatin/ezetimibe had marginal effects on glycemia in those with diabetes at baseline, and there was a trend toward increased development of new-onset diabetes. In addition, ERN increased the risk of developing impaired fasting glucose, which may have deleterious consequences over time and warrants further study.

AB - Background: Niacin is an antidyslipidemic agent that may cause blood sugar elevation in patients with diabetes, but its effects on glucose and insulin values in nondiabetic statin-treated subjects with cardiovascular disease and at high risk for diabetes are less well known. Methods: This was a prespecified, intent-to-treat analysis of the Atherothrombosis Intervention in Metabolic syndrome with low high-density lipoprotein/high triglycerides: Impact on Global Health outcomes trial which randomized 3,414 participants at 92 centers in the US and Canada to extended-release niacin (ERN) plus simvastatin/ezetimibe (ERN) or simvastatin/ezetimibe plus placebo (Placebo). Baseline and annual fasting glucose and insulin values were measured. Those experiencing an adverse event indicative of diabetes or starting medications for diabetes were considered to have confirmed diabetes. In addition, nondiabetic subjects with 2 annual follow-up glucose measurements were categorized into normal, impaired fasting glucose or newly diagnosed diabetes (presumed or confirmed) states. Results: Compared with placebo, ERN increased annual fasting glucose from baseline to 1 year in both those with normal (7.9 ± 15.8 vs 4.3 ± 10.3 mg/dL; P <.001) and impaired fasting glucose (4.1 ± 18.7 vs 1.4 ± 14.9; P <.02) and increased insulin levels. Both effects waned over the next 2 years. There were less consistent effects in those with baseline diabetes. There was an increased risk of progressing from normal to presumed or confirmed impaired fasting glucose (ERN 197/336) cases (58.6%) vs placebo 135/325 cases (41.5%; P <.001) over time, but no difference in diabetes development in the 2 treatment groups except in those with normal fasting glucose at baseline. Conclusions: The addition of ERN to simvastatin/ezetimibe had marginal effects on glycemia in those with diabetes at baseline, and there was a trend toward increased development of new-onset diabetes. In addition, ERN increased the risk of developing impaired fasting glucose, which may have deleterious consequences over time and warrants further study.

KW - Clinical trial

KW - Diabetes

KW - Extended release niacin

KW - Glucose and insulin

KW - Heart disease

KW - Impaired fasting glucoses

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