Basal insulin and cardiovascular and other outcomes in dysglycemia.
By H. Gerstein, J. Bosch, G. Dagenais, Rafael Díaz, Hyejung Jung, A. P. Maggioni, Janice Pogue, J. Probstfield, A. Ramachandran, M. C. Riddle and 2 more. New England Journal of Medicine, 2012
1,065 citations recorded by the source corpus.
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. (Funded by Sanofi; ORIGIN ClinicalTrials.gov number, NCT00069784.).
Subfields: Endocrinology, Diabetes and Metabolism
View Paper: https://www.semanticscholar.org/paper/695c6a8e398d66ae418b143a3491ad91d28443bb
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Endocrinology, Diabetes and Metabolism
Citations in the corpus
- Atherosclerotic Cardiovascular Disease and Heart Failure in Type 2 Diabetes – Mechanisms, Management, and Clinical Considerations (2016, positive): “Structural Changes Cardiomyocyte hypertrophy is common in diabetic cardiomyopathy and may result from insulin resistance and cell growth in response to hyperinsulinemia, as occurs in type 2 diabetes mellitus.(104,347,431) This observation has led to concern about the use of insulin but has not been ”
- Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) (2018, neutral): “While the medication was safe (non-inferior), the HR for MACE in the entire trial was 0.91 (95% CI 0.83, 1.0; p = 0.06) not reaching the threshold for demonstrated superiority vs placebo; ARR was 0.8% [49].”
- Management of hyperglycaemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) (2022, positive): “Of note, the level of certainty in this recommendation is higher for the former subgroup, because some CVOTs recruited exclusively people with established CVD, while fewer events were recorded for participants with cardiovascular risk factors only in CVOTs that recruited both subgroup populations.”
- Canadian Diabetes Association Clinical Practice Guidelines Expert Committee (2013, positive): “Epidemiological evidence suggesting a possible link between insulin glargine and cancer has not been substantiated in review of clinical trial data for either glargine or detemir (60,68,69).”