Basal insulin and cardiovascular and other outcomes in dysglycemia

Hertzel C Gerstein; Jackie Bosch; Gilles R Dagenais; Rafael Díaz; Hyejung Jung; Aldo P Maggioni; Janice Pogue; Jeffrey Probstfield; Ambady Ramachandran; Matthew C Riddle; Lars E Rydén; Salim Yusuf; ORIGIN Trial Investigators; Thure Krarup; Hans Jørgen Duckert Perrild; Christian Tobias Torp-Pedersen

doi:10.1056/nejmoa1203858

Basal insulin and cardiovascular and other outcomes in dysglycemia

Hertzel C Gerstein, Jackie Bosch, Gilles R Dagenais, Rafael Díaz, Hyejung Jung, Aldo P Maggioni, Janice Pogue, Jeffrey Probstfield, Ambady Ramachandran, Matthew C Riddle, Lars E Rydén, Salim Yusuf, ORIGIN Trial Investigators, Thure Krarup, Hans Jørgen Duckert Perrild, Christian Tobias Torp-Pedersen

1134 Citations (Scopus)

Abstract

Background: The provision of sufficient basal insulin to normalize fasting plasma glucose levels may reduce cardiovascular events, but such a possibility has not been formally tested. Methods: We randomly assigned 12,537 people (mean age, 63.5 years) with cardiovascular risk factors plus impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes to receive insulin glargine (with a target fasting blood glucose level of ≤95 mg per deciliter [5.3 mmol per liter]) or standard care and to receive n-3 fatty acids or placebo with the use of a 2-by-2 factorial design. The results of the comparison between insulin glargine and standard care are reported here. The coprimary outcomes were nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes and these events plus revascularization or hospitalization for heart failure. Microvascular outcomes, incident diabetes, hypoglycemia, weight, and cancers were also compared between groups. Results: The median follow-up was 6.2 years (interquartile range, 5.8 to 6.7). Rates of incident cardiovascular outcomes were similar in the insulin-glargine and standard-care groups: 2.94 and 2.85 per 100 person-years, respectively, for the first coprimary outcome (hazard ratio, 1.02; 95% confidence interval [CI], 0.94 to 1.11; P = 0.63) and 5.52 and 5.28 per 100 person-years, respectively, for the second coprimary outcome (hazard ratio, 1.04; 95% CI, 0.97 to 1.11; P = 0.27). New diabetes was diagnosed approximately 3 months after therapy was stopped among 30% versus 35% of 1456 participants without baseline diabetes (odds ratio, 0.80; 95% CI, 0.64 to 1.00; P = 0.05). Rates of severe hypoglycemia were 1.00 versus 0.31 per 100 person-years. Median weight increased by 1.6 kg in the insulin-glargine group and fell by 0.5 kg in the standard-care group. There was no significant difference in cancers (hazard ratio, 1.00; 95% CI, 0.88 to 1.13; P = 0.97). Conclusions: When used to target normal fasting plasma glucose levels for more than 6 years, insulin glargine had a neutral effect on cardiovascular outcomes and cancers. Although it reduced new-onset diabetes, insulin glargine also increased hypoglycemia and modestly increased weight.

Original language	English
Journal	New England Journal of Medicine
Volume	367
Issue number	4
Pages (from-to)	319-28
Number of pages	10
ISSN	0028-4793
DOIs	https://doi.org/10.1056/nejmoa1203858
Publication status	Published - 26 Jul 2012

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Gerstein, H. C., Bosch, J., Dagenais, G. R., Díaz, R., Jung, H., Maggioni, A. P., Pogue, J., Probstfield, J., Ramachandran, A., Riddle, M. C., Rydén, L. E., Yusuf, S., ORIGIN Trial Investigators, Krarup, T., Perrild, H. J. D., & Torp-Pedersen, C. T. (2012). Basal insulin and cardiovascular and other outcomes in dysglycemia. New England Journal of Medicine, 367(4), 319-28. https://doi.org/10.1056/nejmoa1203858

Gerstein, HC, Bosch, J, Dagenais, GR, Díaz, R, Jung, H, Maggioni, AP, Pogue, J, Probstfield, J, Ramachandran, A, Riddle, MC, Rydén, LE, Yusuf, S, ORIGIN Trial Investigators, Krarup, T, Perrild, HJD & Torp-Pedersen, CT 2012, 'Basal insulin and cardiovascular and other outcomes in dysglycemia', New England Journal of Medicine, vol. 367, no. 4, pp. 319-28. https://doi.org/10.1056/nejmoa1203858

@article{46b6ccc5b8ea4ad9a7b8c35718ffa9ad,

title = "Basal insulin and cardiovascular and other outcomes in dysglycemia",

abstract = "Background: The provision of sufficient basal insulin to normalize fasting plasma glucose levels may reduce cardiovascular events, but such a possibility has not been formally tested. Methods: We randomly assigned 12,537 people (mean age, 63.5 years) with cardiovascular risk factors plus impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes to receive insulin glargine (with a target fasting blood glucose level of ≤95 mg per deciliter [5.3 mmol per liter]) or standard care and to receive n-3 fatty acids or placebo with the use of a 2-by-2 factorial design. The results of the comparison between insulin glargine and standard care are reported here. The coprimary outcomes were nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes and these events plus revascularization or hospitalization for heart failure. Microvascular outcomes, incident diabetes, hypoglycemia, weight, and cancers were also compared between groups. Results: The median follow-up was 6.2 years (interquartile range, 5.8 to 6.7). Rates of incident cardiovascular outcomes were similar in the insulin-glargine and standard-care groups: 2.94 and 2.85 per 100 person-years, respectively, for the first coprimary outcome (hazard ratio, 1.02; 95% confidence interval [CI], 0.94 to 1.11; P = 0.63) and 5.52 and 5.28 per 100 person-years, respectively, for the second coprimary outcome (hazard ratio, 1.04; 95% CI, 0.97 to 1.11; P = 0.27). New diabetes was diagnosed approximately 3 months after therapy was stopped among 30% versus 35% of 1456 participants without baseline diabetes (odds ratio, 0.80; 95% CI, 0.64 to 1.00; P = 0.05). Rates of severe hypoglycemia were 1.00 versus 0.31 per 100 person-years. Median weight increased by 1.6 kg in the insulin-glargine group and fell by 0.5 kg in the standard-care group. There was no significant difference in cancers (hazard ratio, 1.00; 95% CI, 0.88 to 1.13; P = 0.97). Conclusions: When used to target normal fasting plasma glucose levels for more than 6 years, insulin glargine had a neutral effect on cardiovascular outcomes and cancers. Although it reduced new-onset diabetes, insulin glargine also increased hypoglycemia and modestly increased weight.",

author = "Gerstein, {Hertzel C} and Jackie Bosch and Dagenais, {Gilles R} and Rafael D{\'i}az and Hyejung Jung and Maggioni, {Aldo P} and Janice Pogue and Jeffrey Probstfield and Ambady Ramachandran and Riddle, {Matthew C} and Ryd{\'e}n, {Lars E} and Salim Yusuf and Torp-Pedersen, {Christian Tobias} and Thure Krarup and Perrild, {Hans J{\o}rgen Duckert} and Torp-Pedersen, {Christian Tobias}",

year = "2012",

month = jul,

day = "26",

doi = "10.1056/nejmoa1203858",

language = "English",

volume = "367",

pages = "319--28",

journal = "New England Journal of Medicine",

issn = "0028-4793",

publisher = "Massachusetts Medical Society",

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TY - JOUR

T1 - Basal insulin and cardiovascular and other outcomes in dysglycemia

AU - Gerstein, Hertzel C

AU - Bosch, Jackie

AU - Dagenais, Gilles R

AU - Díaz, Rafael

AU - Jung, Hyejung

AU - Maggioni, Aldo P

AU - Pogue, Janice

AU - Probstfield, Jeffrey

AU - Ramachandran, Ambady

AU - Riddle, Matthew C

AU - Rydén, Lars E

AU - Yusuf, Salim

AU - ORIGIN Trial Investigators

AU - Krarup, Thure

AU - Perrild, Hans Jørgen Duckert

AU - Torp-Pedersen, Christian Tobias

PY - 2012/7/26

Y1 - 2012/7/26

N2 - Background: The provision of sufficient basal insulin to normalize fasting plasma glucose levels may reduce cardiovascular events, but such a possibility has not been formally tested. Methods: We randomly assigned 12,537 people (mean age, 63.5 years) with cardiovascular risk factors plus impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes to receive insulin glargine (with a target fasting blood glucose level of ≤95 mg per deciliter [5.3 mmol per liter]) or standard care and to receive n-3 fatty acids or placebo with the use of a 2-by-2 factorial design. The results of the comparison between insulin glargine and standard care are reported here. The coprimary outcomes were nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes and these events plus revascularization or hospitalization for heart failure. Microvascular outcomes, incident diabetes, hypoglycemia, weight, and cancers were also compared between groups. Results: The median follow-up was 6.2 years (interquartile range, 5.8 to 6.7). Rates of incident cardiovascular outcomes were similar in the insulin-glargine and standard-care groups: 2.94 and 2.85 per 100 person-years, respectively, for the first coprimary outcome (hazard ratio, 1.02; 95% confidence interval [CI], 0.94 to 1.11; P = 0.63) and 5.52 and 5.28 per 100 person-years, respectively, for the second coprimary outcome (hazard ratio, 1.04; 95% CI, 0.97 to 1.11; P = 0.27). New diabetes was diagnosed approximately 3 months after therapy was stopped among 30% versus 35% of 1456 participants without baseline diabetes (odds ratio, 0.80; 95% CI, 0.64 to 1.00; P = 0.05). Rates of severe hypoglycemia were 1.00 versus 0.31 per 100 person-years. Median weight increased by 1.6 kg in the insulin-glargine group and fell by 0.5 kg in the standard-care group. There was no significant difference in cancers (hazard ratio, 1.00; 95% CI, 0.88 to 1.13; P = 0.97). Conclusions: When used to target normal fasting plasma glucose levels for more than 6 years, insulin glargine had a neutral effect on cardiovascular outcomes and cancers. Although it reduced new-onset diabetes, insulin glargine also increased hypoglycemia and modestly increased weight.

AB - Background: The provision of sufficient basal insulin to normalize fasting plasma glucose levels may reduce cardiovascular events, but such a possibility has not been formally tested. Methods: We randomly assigned 12,537 people (mean age, 63.5 years) with cardiovascular risk factors plus impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes to receive insulin glargine (with a target fasting blood glucose level of ≤95 mg per deciliter [5.3 mmol per liter]) or standard care and to receive n-3 fatty acids or placebo with the use of a 2-by-2 factorial design. The results of the comparison between insulin glargine and standard care are reported here. The coprimary outcomes were nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes and these events plus revascularization or hospitalization for heart failure. Microvascular outcomes, incident diabetes, hypoglycemia, weight, and cancers were also compared between groups. Results: The median follow-up was 6.2 years (interquartile range, 5.8 to 6.7). Rates of incident cardiovascular outcomes were similar in the insulin-glargine and standard-care groups: 2.94 and 2.85 per 100 person-years, respectively, for the first coprimary outcome (hazard ratio, 1.02; 95% confidence interval [CI], 0.94 to 1.11; P = 0.63) and 5.52 and 5.28 per 100 person-years, respectively, for the second coprimary outcome (hazard ratio, 1.04; 95% CI, 0.97 to 1.11; P = 0.27). New diabetes was diagnosed approximately 3 months after therapy was stopped among 30% versus 35% of 1456 participants without baseline diabetes (odds ratio, 0.80; 95% CI, 0.64 to 1.00; P = 0.05). Rates of severe hypoglycemia were 1.00 versus 0.31 per 100 person-years. Median weight increased by 1.6 kg in the insulin-glargine group and fell by 0.5 kg in the standard-care group. There was no significant difference in cancers (hazard ratio, 1.00; 95% CI, 0.88 to 1.13; P = 0.97). Conclusions: When used to target normal fasting plasma glucose levels for more than 6 years, insulin glargine had a neutral effect on cardiovascular outcomes and cancers. Although it reduced new-onset diabetes, insulin glargine also increased hypoglycemia and modestly increased weight.

U2 - 10.1056/nejmoa1203858

DO - 10.1056/nejmoa1203858

M3 - Journal article

C2 - 22686416

SN - 0028-4793

VL - 367

SP - 319

EP - 328

JO - New England Journal of Medicine

JF - New England Journal of Medicine

IS - 4

ER -

Basal insulin and cardiovascular and other outcomes in dysglycemia

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