The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.
Basal Insulin and Cardiovascular and Other Outcomes in Dysglycemia
Open accessAbstract
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.).
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In the citing paper
“Both insulin glargine U100 and insulin degludec have demonstrated cardiovascular safety in dedicated CVOTs (207,208).”
From Management of Hyperglycemia 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) · cites this paper as [208]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“There are a number of other trials regarding cardiovascular outcomes in high-risk cohorts of patients with type 2 diabetes in which similar magnitude effects on glycemic control have been shown but without significant benefits with respect to rates of cardiovascular events or death.”
From Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes (2016) · cites this paper as [16]
The cited source says what the claim attributes to it.
In the citing paper
“ORIGIN reported a 1.6 kg gain over 6 years with insulin glargine [46].”
From Precision obesity medicine: A phenotype-guided framework for pharmacologic therapy across the lifespan (2025) · cites this paper as [46]
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In the citing paper
“Modest survival benefits also have been reported for breast, ovarian, endometrial, prostate, lung, kidney, liver, and earlier stage pancreatic cancers.1791–1800”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [1800]
Experimental — accuracy not yet measuredIn the citing paper
“The following drug classes were excluded due to lack of current evidence of efficacy in cardiovascular outcome trials: dipeptidyl peptidase-4 inhibitors,19 sulfonylureas,20 and insulin.21,22”
From Cardioprotective Glucose-Lowering Agents and Dementia Risk: A Systematic Review and Meta-Analysis (2025) · cites this paper as [21]
In the citing paper
“It is associated with a lower risk of death and HF hospitalization compared with insulin and sulphonylureas in observational studies, though dedicated randomized, controlled, CVOTs evaluating safety and efficacy of metformin have not been conducted.[555][556][557]”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [555]
In the citing paper
“It is associated with a lower risk of death and HF hospitalization compared with insulin and sulphonylureas in observational studies, though dedicated randomized, controlled, CVOTs evaluating safety and efficacy of metformin have not been conducted.[555][556][557]”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [555]
In the citing paper
“These trials have more or less uniformly demonstrated a benefit, with lifestyle more efficacious than all medications with the exception of the thiazolidinediones140–152.”
From Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future (2014) · cites this paper as [146]
In the citing paper
“In the only RCT of insulin vs. placebo [ORIGIN, 12 537 people with CV risk factors plus impaired fasting glucose, impaired glucose tolerance, or T2DM (i.e.not in patients with HF)], insulin was not associated with higher rates of HF hospitalization than placebo.187”
From Type 2 diabetes mellitus and heart failure: A position statement from the Heart Failure Association of the European Society of Cardiology (2018) · cites this paper as [187]
In the citing paper
“Lowering glucose without addressing the vascular effects of insulin resistance may be insufficient to reduce risk of cardiovascular events.”
From The Vasculature in Prediabetes (2018) · cites this paper as [27]
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Citations
Cites
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Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes
Marso, S. P., Daniels, G. H., Brown-Frandsen, K., Kristensen, P., Mann, J. F. E., Nauck, M. A., Nissen, S. E., Pocock, S., Poulter, N. R., Ravn, L. S., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1603827 · Cited by 7,629
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Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus
Scirica, B. M., Bhatt, D. L., Braunwald, E., Steg, P. G., Davidson, J., Hirshberg, B., Ohman, P., Frederich, R., Wiviott, S. D., Hoffman, E. B., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1307684 · Cited by 3,470
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Metadata
- Authors
- The ORIGIN Trial Investigators
- Affiliations
- Population Health Research Institute (CA)
- Corresponding author
- The ORIGIN Trial Investigators
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2012-07-26
- Volume
- 367
- Issue
- 4
- Pages
- 319-328
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W1975663485
- Semantic Scholar
- 695c6a8e398d66ae418b143a3491ad91d28443bb
- Cited by
- 1,636
- References
- 29
- Citations by year
- 2026: 34 · 2025: 41 · 2024: 76 · 2023: 86 · 2022: 82 · 2021: 108 · 2020: 101 · 2019: 139 · 2018: 155 · 2017: 152 · 2016: 155 · 2015: 132 · 2014: 168 · 2013: 147 · 2012: 53
- FWCI
- 128.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Monash University Research Portal (Monash University) (acceptedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- HAL (submittedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- IRIS (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- Amgen
- Bristol-Myers Squibb
- Eli Lilly and Company
- AstraZeneca
- GlaxoSmithKline
- Sanofi
- University of Oxford
- AFA Försäkring
- Hjärt-Lungfonden
- Novo Nordisk
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- basal insulin, insulin glargine, impaired fasting glucose, impaired glucose tolerance, type 2 diabetes, cardiovascular outcomes, myocardial infarction, stroke, heart failure, omega-3 fatty acids, hypoglycemia, weight gain, cancer risk, microvascular outcomes, cardiovascular risk factors, revascularization, hospitalization, new-onset diabetes
- MeSH terms
- Insulin Glargine, Aged, Blood Glucose, Cardiovascular Diseases, Cholesterol, Diabetes Mellitus, Type 2, Double-Blind Method, Drug Therapy, Combination, Fasting, Female, Follow-Up Studies, Hospitalization, Humans, Hypoglycemia, Hypoglycemic Agents, Male, Middle Aged, Triglycerides, Fatty Acids, Omega-3, Incidence, Proportional Hazards Models, Glucose Intolerance, Insulin, Long-Acting, Intention to Treat Analysis
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