VIENNA – There is no increased risk for myocardial infarction or other vascular events from prolonged use of insulin in people with pre- or type 2 diabetes who are already at high risk for cardiovascular disease, according to additional follow-up data from the ORIGIN study.
The ORIGINALE (Origin and Legacy Effects) study provides an additional 2.5 years of observational follow-up of more than 8,000 of the 12,000-plus individuals who participated in the ORIGIN (Outcome Reduction with an Initial Glargine Intervention) study.
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Long-term insulin use had no effect on cardiovascular disease in patients with dysglycemia or type 2 diabetes.
The results of the ORIGIN trial were that 6.2 years of treatment with insulin glargine (Sanofi’s Lantus) had a neutral effect on cardiovascular events and other serious health outcomes such as cancer, and possibly slowed diabetes progression (N. Engl. J. Med. 2012;367:319-28). In addition, omega-3 fatty acid supplementation was found to offer no benefit over placebo.
The results of the ORIGINALE study continue to support these findings, Dr. Hertzel C. Gerstein reported at the annual meeting of the European Society for the Study of Diabetes.
The key conclusion of ORIGIN and ORIGINALE with regard to insulin use is that “targeting a normal fasting plasma glucose with basal insulin glargine for more than 6 years improves metabolic status and has a neutral effect on serious health outcomes,” Dr. Gerstein of McMaster University, Hamilton, Ont., observed.
Two coprimary composite cardiovascular outcomes were assessed, neither of which showed any advantage or disadvantage of using insulin glargine versus standard care.
The hazard ratio for the first coprimary outcome of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke in ORIGINALE was 1.01, and the HR for the second coprimary endpoint of any cardiovascular event, a revascularization procedure, or hospitalization for heart failure was 1.03.
There was also a “neutral effect” on the individual components of these composite endpoints, with HRs of 1.02, 1.05, 1.00, 0.90, and 1.04 for myocardial infarction, stroke, cardiovascular death, heart failure hospitalization, and revascularization, respectively.
Median hemoglobin A1c values at the end of ORIGIN and at the end of ORIGINALE were 6.3% and 6.6%, respectively, in the 2,351 patients treated with insulin glargine, and 6.52% and 6.70% in the 3,267 patients in the standard-care arm.
Likewise, analysis showed a neutral effect on cancer incidence and cancer death between the insulin and standard-care groups.
There was a trend toward fewer new cases of diabetes among insulin-treated patients than in the standard-care group (37.7% vs. 41.7%; P = .12), with fewer new and possible diabetes cases if insulin was received (41.2% vs. 47.7%; P = .014). The latter included patients who could not be confirmed as having diabetes by adjudication criteria.
In an interview, Dr. Gerstein commented that the findings are reassuring for people at high cardiovascular risk with impaired fasting glucose, impaired glucose tolerance, or early type 2 diabetes who are in need of insulin therapy.
“Insulin is a safe and effective drug, we can use it to lower patients’ glucose levels, and it’s not going to do anything else,” he said. “We have to make sure we use it correctly to avoid hypoglycemia, but there are no hidden perils, at least based on what we know now, and close to 10 years of follow-up.”
Regarding the value of omega-3 fatty acid supplementation, also studied in ORIGIN, the results of ORIGINALE showed no effect on any outcome. “All of the evidence around the world shows that if you take an omega-3 fatty acid capsule, you have no difference in your health outcomes than if you do not,” he said. “All you do is create expensive urine. You do not do anything else with respect to your health.”
Sanofi provided funding for the study, which was coordinated by the Population Health Research Institute in Hamilton. Dr. Gerstein has received research support and adviser fees from Sanofi, Novartis, and other companies.