Long term use of insulin does not put people with diabetes or pre-diabetes at higher risk for heart attack, stroke or cancer, according to a large international study that followed more than 12,500 people in 40 countries over 6 years.
One of the study's two principal investigators, Dr Hertzel Gerstein, of McMaster University in Canada, presented the findings on Monday at the 72nd scientific sessions of the American Diabetes Association in Philadelphia, USA.
Gerstein is professor of medicine at McMaster's Michael G DeGroote School of Medicine and deputy director of the Population Health Research Institute at McMaster University and Hamilton Health Sciences.
He said the results run counter to concerns that long-term use of insulin may lead to heart disease.
"People have been debating the question of whether there are adverse consequences to long-term insulin use for years. This study provides the clearest answer yet to that question: No, there are not," said Gerstein in a statement.
The results of the study, called ORIGIN (Outcome Reduction with an Initial Glargine Intervention study), are due to be published this week in the New England Journal of Medicine (NEJM).
Another important finding from the ORIGIN study is that people with pre-diabetes who had daily insulin injections had a 28% lower risk of developing type 2 diabetes. The effect was still there after the daily basal injections with insulin glargine had stopped.
For the study, Gerstein and colleagues examined data on more than 12,500 people of average age 64 from 537 sites in 40 countries, who were either at high risk for type 2 diabetes or were in the early stages of the disease and had a high risk for cardiovascular (CV) problems.
The participants were randomly assigned to receive either standard care (no insulin) or one daily injection of insulin (glargine) for an average of six years.
The researchers measured a number of outcomes, including deaths due to cardiovascular events, and non-fatal cardiovascular events, such as heart attack (myocardial infarction), stroke, heart failure, and heart-related surgery such as revascularization procedures.
They also measured cancer incidence: all cancers combined and organ-specific cancers.
When they analyzed the results, the researchers found no difference between the two groups in cardiovascular outcomes or cancer (either combined or of any type).
They suggest this means there is no long term harm from having daily insulin injections (with insulin glargine) to control glucose.
Through most of the study, the participants who took insulin managed to keep their normal fasting glucose under control (levels were under 6 mmol/l).
The results did, however, confirm two already-known, minor medical effects of daily insulin use: low blood sugar (hypoglycemia) and a slight gain in weight. On average, participants using insulin gained 3.5 lbs (1.6 kg) over the six years and experienced 0.7% higher risk of severe hypoglycemia per year, compared to those who did not use insulin.
"We now know what the risks are of taking insulin on a long-term basis, and they are low."
Another finding was that taking omega-3 fatty acid supplements (in the form of 1 gm daily capsules) did not reduce heart-related deaths in people with type 2 diabetes or pre-diabetes. But the researchers couldn't say if this was also true of a diet rich in omega-3 fatty acids, since they did not study this effect.
A key feature of the ORIGIN trial is that it investigated the use of insulin glargine in a population in which insulins are not typically used. Thus it provides new data on the benefits and risks of starting insulin therapy earlier in the course of the disease.
Sanofi Inc, who market Lantus (a brand name for insulin glargine in injection form) funded the study and the Norwegian company Pronova Biocare AS provided the omega-3 supplements.
Gerstein described the trial as an "excellent example of collaboration between industry and academia".
Riccardo Perfetti, MD, Vice President Medical Affairs, Global Diabetes, Sanofi, told the press:
"In patients with pre-diabetes or early type 2 diabetes and high CV risk, ORIGIN shows that it is possible to maintain low and stable HbA1c levels that are close to normal over a long time, and to potentially delay the progression from pre-diabetes to diabetes."
Diabetes is a chronic, often debilitating, and sometimes fatal disease. It occurs when the body either can't make the insulin required to keep blood sugar (glucose) under control, or when it can't use the insulin it produces. Glucose is an essential source of energy, which the body controls with insulin. Without this control, blood glucose levels remain high, eventually damaging organs, blood vessels and nerves.
There are currently over 9 million people in Canada living with diabetes or pre-diabetes, a condition where blood sugar is above normal, but not yet developed into full-blown diabetes. People with pre-diabetes are at a high risk for developing type 2 diabetes.