Basal insulin and cardiovascular and other outcomes in dysglycemia.
Level 2 - randomized trial
Individual randomized controlled trial
PubMed 22686416 · doi:10.1056/NEJMoa1203858
What was done
A multicenter randomized controlled trial (ORIGIN) evaluated 12,537 participants (mean age 63.5 years) with cardiovascular risk factors and dysglycemia (impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes). Using a 2-by-2 factorial design, participants were randomized to receive insulin glargine (titrated to target fasting blood glucose ≤95 mg/dL [5.3 mmol/L]) or standard care, alongside n-3 fatty acids or placebo. Median follow-up was 6.2 years. Coprimary outcomes were: 1) nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death; and 2) the first coprimary outcome plus revascularization or hospitalization for heart failure. Secondary outcomes included incident diabetes, microvascular outcomes, severe hypoglycemia, weight change, and cancers.
What was found
Cardiovascular event rates were similar between the insulin glargine and standard-care groups for the first coprimary outcome (2.94 vs. 2.85 per 100 person-years; HR 1.02, 95% CI 0.94–1.11, P=0.63) and the second coprimary outcome (5.52 vs. 5.28 per 100 person-years; HR 1.04, 95% CI 0.97–1.11, P=0.27). In participants without baseline diabetes (n=1,456), new diabetes diagnosed ~3 months post-therapy cessation was lower with glargine (30% vs. 35%; OR 0.80, 95% CI 0.64–1.00, P=0.05). Severe hypoglycemia was higher with glargine (1.00 vs. 0.31 per 100 person-years). Median weight increased by 1.6 kg with glargine versus a 0.5 kg loss with standard care. Cancer incidence did not differ (HR 1.00, 95% CI 0.88–1.13, P=0.97).
Why it matters
This trial established that long-term normalization of fasting plasma glucose with basal insulin glargine in people with early dysglycemia or diabetes neither increases nor decreases major cardiovascular events or cancer incidence, clarifying both its cardiovascular safety and lack of macrovascular protection.
Limits
The study evaluated individuals at high cardiovascular risk with early dysglycemia or established type 2 diabetes, limiting generalizability to younger or lower-risk cohorts. A median follow-up of 6.2 years may remain insufficient to detect very delayed macrovascular benefits or rare long-term adverse effects. Specific microvascular outcome rates were not detailed in the abstract.
Cited by
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