Effects of intensive glucose lowering in type 2 diabetes

Hertzel C. Gerstein, Michael E. Miller, Robert P. Byington, David C. Goff, J. Thomas Bigger, John B. Buse, William C. Cushman, Saul Genuth, Faramarz Ismail-Beigi, Richard H. Grimm, Jeffrey L. Probstfield, Denise G. Simons-Morton, William T. Friedewald, A. M. Gotto, K. Bailey, D. Gohdes, S. Haffner, R. Hiss, K. Jamerson, K. Lee & 31 others D. Nathan, J. Sowers, L. Walters, W. T. Friedewald, J. B. Buse, J. T. Bigger, R. P. Byington, W. C. Cushman, H. C. Gerstein, H. N. Ginsberg, D. C. Goff, J. L. Probstfield, D. G. Simons-Morton, H. C. Gerstein, S. Yusuf, Z. Punthakee, R. Russo, S. Anand, B. Cracknell, T. Cukierman-Yaffe, A. Gafni, G. Guyatt, S. Hall, J. Kaszyca, E. Lonn, E. R. Seaquist, J. B. Redmon, K. Peterson, J. L. Feldman, T. J. Mendenhall, The Action to Control Cardiovascular Risk in Diabetes Study Group

Research output: Contribution to journalArticle

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Abstract

Background Epidemiologic studies have shown a relationship between glycated hemoglobin levels and cardiovascular events in patients with type 2 diabetes. We investigated whether intensive therapy to target normal glycated hemoglobin levels would reduce cardiovascular events in patients with type 2 diabetes who had either established cardiovascular disease or additional cardiovascular risk factors. Methods In this randomized study, 10,250 patients (mean age, 60.2 years) with a median glycated hemoglobin level of 8.1% were assigned to receive intensive therapy (targeting a glycated hemoglobin level below 6.0%) or standard therapy (targeting a level from 7.0 to 7.9%). Of these patients, 37% were women, and 7% had had a previous cardiovascular event. The primary outcome was a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The finding of higher mortality in the intensive-therapy group led to a discontinuation of intensive therapy after a mean of 3.5 years of follow-up. Results At 1 year, stable median glycated hemoglobin levels of 6.4% and 7.5% were achieved in the intensive-therapy group and the standard-therapy group, respectively. During follow-up, the primary outcome occurred in 70 patients in the intensive-therapy group, as compared with 359 in the standard-therapy group (hazard ratio, 0.88; 92% confidence interval [CI], 0.76 to 1.04; P = 0.16). At the same time, 255 patients in the intensive-therapy group died, as compared with 203 patients in the standardtherapy group (hazard ratio, 1.22; 92% CI, 1.01 to 1.45; P = 0.04). Hypoglycemia requiring assistance and weight gain of more than 10 kg were more frequent in the intensive-therapy group (P<0.001). Conclusions As compared with standard therapy, the use of intensive therapy to target normal glycated hemoglobin levels for 3.5 years increased mortality and did not significantly reduce major cardiovascular events. These findings identify a previously unrecognized harm of intensive glucose lowering in high-risk patients with type 2 diabetes. (ClinicalTrials.gov number, NCT00000600.).

Original languageEnglish (US)
Pages (from-to)2545-2559
Number of pages15
JournalNew England Journal of Medicine
Volume358
Issue number24
DOIs
StatePublished - Jun 12 2008

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Type 2 Diabetes Mellitus
Group Psychotherapy
Glycosylated Hemoglobin A
Glucose
Therapeutics
Confidence Intervals
Mortality
Hypoglycemia
Weight Gain
Epidemiologic Studies
Cause of Death
Cardiovascular Diseases
Stroke
Myocardial Infarction

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Gerstein, H. C., Miller, M. E., Byington, R. P., Goff, D. C., Bigger, J. T., Buse, J. B., ... The Action to Control Cardiovascular Risk in Diabetes Study Group (2008). Effects of intensive glucose lowering in type 2 diabetes. New England Journal of Medicine, 358(24), 2545-2559. https://doi.org/10.1056/NEJMoa0802743

Effects of intensive glucose lowering in type 2 diabetes. / Gerstein, Hertzel C.; Miller, Michael E.; Byington, Robert P.; Goff, David C.; Bigger, J. Thomas; Buse, John B.; Cushman, William C.; Genuth, Saul; Ismail-Beigi, Faramarz; Grimm, Richard H.; Probstfield, Jeffrey L.; Simons-Morton, Denise G.; Friedewald, William T.; Gotto, A. M.; Bailey, K.; Gohdes, D.; Haffner, S.; Hiss, R.; Jamerson, K.; Lee, K.; Nathan, D.; Sowers, J.; Walters, L.; Friedewald, W. T.; Buse, J. B.; Bigger, J. T.; Byington, R. P.; Cushman, W. C.; Gerstein, H. C.; Ginsberg, H. N.; Goff, D. C.; Probstfield, J. L.; Simons-Morton, D. G.; Gerstein, H. C.; Yusuf, S.; Punthakee, Z.; Russo, R.; Anand, S.; Cracknell, B.; Cukierman-Yaffe, T.; Gafni, A.; Guyatt, G.; Hall, S.; Kaszyca, J.; Lonn, E.; Seaquist, E. R.; Redmon, J. B.; Peterson, K.; Feldman, J. L.; Mendenhall, T. J.; The Action to Control Cardiovascular Risk in Diabetes Study Group.

In: New England Journal of Medicine, Vol. 358, No. 24, 12.06.2008, p. 2545-2559.

Research output: Contribution to journalArticle

Gerstein, HC, Miller, ME, Byington, RP, Goff, DC, Bigger, JT, Buse, JB, Cushman, WC, Genuth, S, Ismail-Beigi, F, Grimm, RH, Probstfield, JL, Simons-Morton, DG, Friedewald, WT, Gotto, AM, Bailey, K, Gohdes, D, Haffner, S, Hiss, R, Jamerson, K, Lee, K, Nathan, D, Sowers, J, Walters, L, Friedewald, WT, Buse, JB, Bigger, JT, Byington, RP, Cushman, WC, Gerstein, HC, Ginsberg, HN, Goff, DC, Probstfield, JL, Simons-Morton, DG, Gerstein, HC, Yusuf, S, Punthakee, Z, Russo, R, Anand, S, Cracknell, B, Cukierman-Yaffe, T, Gafni, A, Guyatt, G, Hall, S, Kaszyca, J, Lonn, E, Seaquist, ER, Redmon, JB, Peterson, K, Feldman, JL, Mendenhall, TJ & The Action to Control Cardiovascular Risk in Diabetes Study Group 2008, 'Effects of intensive glucose lowering in type 2 diabetes', New England Journal of Medicine, vol. 358, no. 24, pp. 2545-2559. https://doi.org/10.1056/NEJMoa0802743
Gerstein HC, Miller ME, Byington RP, Goff DC, Bigger JT, Buse JB et al. Effects of intensive glucose lowering in type 2 diabetes. New England Journal of Medicine. 2008 Jun 12;358(24):2545-2559. https://doi.org/10.1056/NEJMoa0802743
Gerstein, Hertzel C. ; Miller, Michael E. ; Byington, Robert P. ; Goff, David C. ; Bigger, J. Thomas ; Buse, John B. ; Cushman, William C. ; Genuth, Saul ; Ismail-Beigi, Faramarz ; Grimm, Richard H. ; Probstfield, Jeffrey L. ; Simons-Morton, Denise G. ; Friedewald, William T. ; Gotto, A. M. ; Bailey, K. ; Gohdes, D. ; Haffner, S. ; Hiss, R. ; Jamerson, K. ; Lee, K. ; Nathan, D. ; Sowers, J. ; Walters, L. ; Friedewald, W. T. ; Buse, J. B. ; Bigger, J. T. ; Byington, R. P. ; Cushman, W. C. ; Gerstein, H. C. ; Ginsberg, H. N. ; Goff, D. C. ; Probstfield, J. L. ; Simons-Morton, D. G. ; Gerstein, H. C. ; Yusuf, S. ; Punthakee, Z. ; Russo, R. ; Anand, S. ; Cracknell, B. ; Cukierman-Yaffe, T. ; Gafni, A. ; Guyatt, G. ; Hall, S. ; Kaszyca, J. ; Lonn, E. ; Seaquist, E. R. ; Redmon, J. B. ; Peterson, K. ; Feldman, J. L. ; Mendenhall, T. J. ; The Action to Control Cardiovascular Risk in Diabetes Study Group. / Effects of intensive glucose lowering in type 2 diabetes. In: New England Journal of Medicine. 2008 ; Vol. 358, No. 24. pp. 2545-2559.
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title = "Effects of intensive glucose lowering in type 2 diabetes",
abstract = "Background Epidemiologic studies have shown a relationship between glycated hemoglobin levels and cardiovascular events in patients with type 2 diabetes. We investigated whether intensive therapy to target normal glycated hemoglobin levels would reduce cardiovascular events in patients with type 2 diabetes who had either established cardiovascular disease or additional cardiovascular risk factors. Methods In this randomized study, 10,250 patients (mean age, 60.2 years) with a median glycated hemoglobin level of 8.1{\%} were assigned to receive intensive therapy (targeting a glycated hemoglobin level below 6.0{\%}) or standard therapy (targeting a level from 7.0 to 7.9{\%}). Of these patients, 37{\%} were women, and 7{\%} had had a previous cardiovascular event. The primary outcome was a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The finding of higher mortality in the intensive-therapy group led to a discontinuation of intensive therapy after a mean of 3.5 years of follow-up. Results At 1 year, stable median glycated hemoglobin levels of 6.4{\%} and 7.5{\%} were achieved in the intensive-therapy group and the standard-therapy group, respectively. During follow-up, the primary outcome occurred in 70 patients in the intensive-therapy group, as compared with 359 in the standard-therapy group (hazard ratio, 0.88; 92{\%} confidence interval [CI], 0.76 to 1.04; P = 0.16). At the same time, 255 patients in the intensive-therapy group died, as compared with 203 patients in the standardtherapy group (hazard ratio, 1.22; 92{\%} CI, 1.01 to 1.45; P = 0.04). Hypoglycemia requiring assistance and weight gain of more than 10 kg were more frequent in the intensive-therapy group (P<0.001). Conclusions As compared with standard therapy, the use of intensive therapy to target normal glycated hemoglobin levels for 3.5 years increased mortality and did not significantly reduce major cardiovascular events. These findings identify a previously unrecognized harm of intensive glucose lowering in high-risk patients with type 2 diabetes. (ClinicalTrials.gov number, NCT00000600.).",
author = "Gerstein, {Hertzel C.} and Miller, {Michael E.} and Byington, {Robert P.} and Goff, {David C.} and Bigger, {J. Thomas} and Buse, {John B.} and Cushman, {William C.} and Saul Genuth and Faramarz Ismail-Beigi and Grimm, {Richard H.} and Probstfield, {Jeffrey L.} and Simons-Morton, {Denise G.} and Friedewald, {William T.} and Gotto, {A. M.} and K. Bailey and D. Gohdes and S. Haffner and R. Hiss and K. Jamerson and K. Lee and D. Nathan and J. Sowers and L. Walters and Friedewald, {W. T.} and Buse, {J. B.} and Bigger, {J. T.} and Byington, {R. P.} and Cushman, {W. C.} and Gerstein, {H. C.} and Ginsberg, {H. N.} and Goff, {D. C.} and Probstfield, {J. L.} and Simons-Morton, {D. G.} and Gerstein, {H. C.} and S. Yusuf and Z. Punthakee and R. Russo and S. Anand and B. Cracknell and T. Cukierman-Yaffe and A. Gafni and G. Guyatt and S. Hall and J. Kaszyca and E. Lonn and Seaquist, {E. R.} and Redmon, {J. B.} and K. Peterson and Feldman, {J. L.} and Mendenhall, {T. J.} and {The Action to Control Cardiovascular Risk in Diabetes Study Group}",
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month = "6",
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doi = "10.1056/NEJMoa0802743",
language = "English (US)",
volume = "358",
pages = "2545--2559",
journal = "New England Journal of Medicine",
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TY - JOUR

T1 - Effects of intensive glucose lowering in type 2 diabetes

AU - Gerstein, Hertzel C.

AU - Miller, Michael E.

AU - Byington, Robert P.

AU - Goff, David C.

AU - Bigger, J. Thomas

AU - Buse, John B.

AU - Cushman, William C.

AU - Genuth, Saul

AU - Ismail-Beigi, Faramarz

AU - Grimm, Richard H.

AU - Probstfield, Jeffrey L.

AU - Simons-Morton, Denise G.

AU - Friedewald, William T.

AU - Gotto, A. M.

AU - Bailey, K.

AU - Gohdes, D.

AU - Haffner, S.

AU - Hiss, R.

AU - Jamerson, K.

AU - Lee, K.

AU - Nathan, D.

AU - Sowers, J.

AU - Walters, L.

AU - Friedewald, W. T.

AU - Buse, J. B.

AU - Bigger, J. T.

AU - Byington, R. P.

AU - Cushman, W. C.

AU - Gerstein, H. C.

AU - Ginsberg, H. N.

AU - Goff, D. C.

AU - Probstfield, J. L.

AU - Simons-Morton, D. G.

AU - Gerstein, H. C.

AU - Yusuf, S.

AU - Punthakee, Z.

AU - Russo, R.

AU - Anand, S.

AU - Cracknell, B.

AU - Cukierman-Yaffe, T.

AU - Gafni, A.

AU - Guyatt, G.

AU - Hall, S.

AU - Kaszyca, J.

AU - Lonn, E.

AU - Seaquist, E. R.

AU - Redmon, J. B.

AU - Peterson, K.

AU - Feldman, J. L.

AU - Mendenhall, T. J.

AU - The Action to Control Cardiovascular Risk in Diabetes Study Group

PY - 2008/6/12

Y1 - 2008/6/12

N2 - Background Epidemiologic studies have shown a relationship between glycated hemoglobin levels and cardiovascular events in patients with type 2 diabetes. We investigated whether intensive therapy to target normal glycated hemoglobin levels would reduce cardiovascular events in patients with type 2 diabetes who had either established cardiovascular disease or additional cardiovascular risk factors. Methods In this randomized study, 10,250 patients (mean age, 60.2 years) with a median glycated hemoglobin level of 8.1% were assigned to receive intensive therapy (targeting a glycated hemoglobin level below 6.0%) or standard therapy (targeting a level from 7.0 to 7.9%). Of these patients, 37% were women, and 7% had had a previous cardiovascular event. The primary outcome was a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The finding of higher mortality in the intensive-therapy group led to a discontinuation of intensive therapy after a mean of 3.5 years of follow-up. Results At 1 year, stable median glycated hemoglobin levels of 6.4% and 7.5% were achieved in the intensive-therapy group and the standard-therapy group, respectively. During follow-up, the primary outcome occurred in 70 patients in the intensive-therapy group, as compared with 359 in the standard-therapy group (hazard ratio, 0.88; 92% confidence interval [CI], 0.76 to 1.04; P = 0.16). At the same time, 255 patients in the intensive-therapy group died, as compared with 203 patients in the standardtherapy group (hazard ratio, 1.22; 92% CI, 1.01 to 1.45; P = 0.04). Hypoglycemia requiring assistance and weight gain of more than 10 kg were more frequent in the intensive-therapy group (P<0.001). Conclusions As compared with standard therapy, the use of intensive therapy to target normal glycated hemoglobin levels for 3.5 years increased mortality and did not significantly reduce major cardiovascular events. These findings identify a previously unrecognized harm of intensive glucose lowering in high-risk patients with type 2 diabetes. (ClinicalTrials.gov number, NCT00000600.).

AB - Background Epidemiologic studies have shown a relationship between glycated hemoglobin levels and cardiovascular events in patients with type 2 diabetes. We investigated whether intensive therapy to target normal glycated hemoglobin levels would reduce cardiovascular events in patients with type 2 diabetes who had either established cardiovascular disease or additional cardiovascular risk factors. Methods In this randomized study, 10,250 patients (mean age, 60.2 years) with a median glycated hemoglobin level of 8.1% were assigned to receive intensive therapy (targeting a glycated hemoglobin level below 6.0%) or standard therapy (targeting a level from 7.0 to 7.9%). Of these patients, 37% were women, and 7% had had a previous cardiovascular event. The primary outcome was a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The finding of higher mortality in the intensive-therapy group led to a discontinuation of intensive therapy after a mean of 3.5 years of follow-up. Results At 1 year, stable median glycated hemoglobin levels of 6.4% and 7.5% were achieved in the intensive-therapy group and the standard-therapy group, respectively. During follow-up, the primary outcome occurred in 70 patients in the intensive-therapy group, as compared with 359 in the standard-therapy group (hazard ratio, 0.88; 92% confidence interval [CI], 0.76 to 1.04; P = 0.16). At the same time, 255 patients in the intensive-therapy group died, as compared with 203 patients in the standardtherapy group (hazard ratio, 1.22; 92% CI, 1.01 to 1.45; P = 0.04). Hypoglycemia requiring assistance and weight gain of more than 10 kg were more frequent in the intensive-therapy group (P<0.001). Conclusions As compared with standard therapy, the use of intensive therapy to target normal glycated hemoglobin levels for 3.5 years increased mortality and did not significantly reduce major cardiovascular events. These findings identify a previously unrecognized harm of intensive glucose lowering in high-risk patients with type 2 diabetes. (ClinicalTrials.gov number, NCT00000600.).

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DO - 10.1056/NEJMoa0802743

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