Insulin Glargine Has Neutral Effect on CV Outcomes and Cancers

Philadelphia—After >6 years of follow-up, a large, international, randomized trial found that daily injections of insulin glargine in patients with type 2 diabetes, or with a high risk of the disease, had a neutral effect on cancers, serious cardiovascular outcomes, and death compared with standard care. The drug also reduced the progression of diabetes.

Hertzel Gerstein, MD, the study’s principal investigator and a professor of medicine at McMaster University in Ontario, Canada, said the researchers found no new side effects with insulin glargine. Common side effects are hypoglycemia and weight gain, both of which were cited in this study.

Results were presented during a symposium at the ADA meeting. The findings were simultaneously published online in the New England Journal of Medicine [10.156/NEJMoa1203858 and 10.1056/NEJMoa1203859].

Sanofi, the drug’s manufacturer, sponsored the study. Dr. Gerstein said the academic steering committee first analyzed the data and then shared the findings with the company.

“It is very unlikely that the drug is either causing harm or benefit in these individuals,” Dr. Gerstein said. “There is a very clear neutral effect, which is important for patients to know.”

The ORIGIN (Outcome Reduction with an Initial Glargine Intervention) trial had 2 main objectives for high cardiovascular risk patients: (1) determining if administering insulin glargine once daily and adjusting the dose to target a normal fasting glucose level
(≤95 mg/dL) reduces cardiovascular outcomes more than standard care, and (2) if adding omega-3 fatty acids to the regimen reduces cardiovascular death.

The trial included 12,537 patients who had new or recently diagnosed diabetes or impaired fasting glucose/impaired glucose tolerance plus additional risk factors for cardiovascular disease. They were recruited from 573 sites in 40 countries, representing every continent with the exception of Antarctica. Mean age was 63.5 years, and 35% of patients were females. Of the patients, 82% had prior diabetes for a mean of 5.4 years and 6% had new diabetes detected when they were randomized.

The rates of the composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes in the 2 groups were similar: 2.94 per 100 person-years in the insulin glargine group compared with 2.85 per 100 person-years in the standard care group (hazard ratio [HR], 1.02; 95% confidence interval [CI], 0.94-1.11; P=.63). There was also no statistically significant difference in the rates of those 3 events plus revascularization or hospitalization for heart failure: 5.52 per 100 person-years compared with 5.28 per 100 person-years (HR, 1.04; 95% CI, 0.97-1.11; P=.27).

In addition, there was no difference in mortality (HR, 0.98; 95% CI, 0.90-1.08; P=.70) or cancer (HR, 1.00; 95% CI, 0.88-1.13; P=.97).

The authors also noted side effects associated with the drug. In the insulin glargine group, 57% of patients had at least 1 episode of hypoglycemia compared with 25% in the standard group (P<.001). In addition, 6% of patients in the insulin glargine group had at least 1 episode of severe hypoglycemia compared with 2% in the standard group (P<.001). The insulin glargine group gained a median of 3.5 pounds during the trial compared with a loss of 1 pound for the standard group (P<.001).

Jackie Bosch, MSc, associate professor at McMaster University, presented the analysis of the same patient population who received a 1 g capsule of omega-3 fatty acids or placebo on a daily basis for >6 years. She said that adding the omega-3 fatty acids did not reduce cardiovascular outcomes in people with disglycemia and other cardiovascular risk factors.

The study found that compared with placebo, omega-3 fatty acids had a neutral effect on cardiovascular death and other serious outcomes, but they lowered triglyceride levels. Patients who took omega-3 fatty acids tolerated them well, and 88% adhered to the treatment until the study’s completion.