Basal Insulin and Cardiovascular and Other Outcomes in Dysglycemia

Study Questions:

What is the effect of using sufficient basal insulin to normalize fasting plasma glucose levels on cardiovascular events?


The ORIGIN Basal Insulin trial investigators 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/dl [5.3 mmol/L]) or standard care, and to receive n–3 fatty acids or placebo with the use of a 2 x 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.


The median follow-up was 6.2 years (interquartile range, 5.8-6.7). 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 [HR], 1.02; 95% confidence interval [CI], 0.94-1.11; p = 0.63) and 5.52 and 5.28 per 100 person-years, respectively, for the second coprimary outcome (HR, 1.04; 95% CI, 0.97-1.11; p = 0.27). New diabetes was diagnosed approximately 3 months after therapy was stopped among 30% versus 35% of 1,456 participants without baseline diabetes (odds ratio, 0.80; 95% CI, 0.64-1.00; 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 (HR, 1.00; 95% CI, 0.88-1.13; p = 0.97).


The authors concluded that 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.


The study shows that the early use of basal insulin to target normal fasting plasma glucose levels neither reduced nor increased cardiovascular outcomes as compared with guideline-suggested glycemic control. Moreover, this intervention reduced incident diabetes in participants with impaired fasting glucose or impaired glucose tolerance, although it was associated with modest weight gain and more episodes of hypoglycemia. The impact of the glycemic benefit on future microvascular or other outcomes needs further study. For now, these findings support standard therapies as recommended in current guidelines for early dysglycemia.

Clinical Topics: Dyslipidemia, Prevention, Lipid Metabolism, Nonstatins, Diet

Keywords: Insulin, Fish Oils, Health Resources, Blood Glucose, Transcription Factors, Fasting, Diabetes Mellitus

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