ADA: Aggressive Treatment with Insulin for Pre-Diabetes

It found that those who had impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and were randomized to receive daily insulin injections had a 28 percent lower chance of developing type 2 diabetes over more than 6 years even after the injections were stopped, compared to those who were not given insulin.

Principal Investigator Hertzel Gerstein, MD, McMaster University Department of Medicine in Ontario, stated that, "We believe this is because giving insulin to those with somewhat elevated glucose levels allows the pancreas to rest during this period, essentially helping it to work longer." However, he added, the durability of this effect for more than 3 months after stopping insulin remains unknown.

In particular, the glycated hemoglobin A1c levels for the two arms were similar throughout the trial. At baseline, they were 6.4% for each group. At 4 years, they were 6.1% and 6.4% for the glargine and standard care arms, respectively, and at the conclusion of the study they were 6.2% and 6.5%, respectively.

At 2 years, 90% of those in the glargine arm were compliant; that dropped to 85% at 5 years.

Of those without diabetes at baseline, those assigned to insulin glargine were 28% less likely to develop diabetes at the time of the first oral glucose tolerance test. At this point, they were taken off glargine and by the next glucose tolerance test (median 100 days), they were 20% less likely to develop diabetes compared with standard care participants.

"Our trial showed that near-normal fasting plasma glucose and glycated hemoglobin levels can be achieved and maintained for more than 6 years with a daily injection of basal insulin with or without an oral agent when self-monitored fasting glucose levels are used by high-risk patients to adjust the dose of insulin glargine," researchers noted.

More than half of the participants in the glargine arm were able to maintain a fasting plasma glucose level of 95 mg/dL for at least 5 years compared with a median fasting glucose level of 123 mg/dL of those in the standard care group who were taking oral agents.

The study is limited because nearly 50% of those in the glargine arm ultimately used metformin, which could have contributed to the cardioprotective benefit, researchers said.

"ORIGIN's findings should reassure patients and clinicians regarding the long-term health impact of using basal insulin therapy to target normoglycemia," he said. "Ninety years after it was first used to treat diabetes we can say that when you need an effective glucose lowering drug, there is no reason to be concerned about undiscovered long-term risks of using basal insulin early in the course of diabetes."

Sturmer T, et al "Risk for cancer after initiation of insulin glargine versus NPH -- A new user comparator drug cohort study" ADA2012.