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insulinMay 11 2016

Serious health risks in type 2 diabetes may be reduced more effectively with insulin and metformin than insulin on its own, researchers have suggested.

Combination therapy resulted in a lower risk of death and major adverse cardiac events (MACE) than insulin monotherapy, the retrospective cohort study found. However, any impact on cancer was less pronounced.

The study by researchers from The Institute of Primary Care and Public Health at Cardiff University has been published on PLoS One. They analysed data from 12,020 patients, among whom 6,484 were treated with insulin monotherapy and 5,536 were prescribed insulin plus metformin. Subjects were followed for an average of 3.5 years.

Overall, there were 1,486 deaths, 579 MACE and 680 cancer events, and the corresponding event rates per 1,000 person years were 41.5 deaths, 20.8 MACE and 21.6 cancer events.

When the different cohorts were compared, the adjusted hazard ratios (aHRs) for people using combination therapy compared to insulin monotherapy were 0.60 for all cause mortality, 0.75 for MAC and 0.96 for cancer. When patients were compared in terms of event propensity, the aHRs were 0.62 for deaths, and 0.99 for cancer. For MACE, the propensity aHRs changed with time, being 1.06 before 3.5 years and 1.87 after 3.5 years.

Although the data looked specifically for patients with type 2 diabetes who had either started therapy with insulin either on its own or in combination with metformin, all patients were prescribed at least two different classes of glucose-lowering medication other than insulin. Other exclusion criteria included people who had a yearly average insulin dose greater than 4 units/kg/day, and patients with an existing history of cancer or large vessel disease, such as myocardial infarction, stroke, or angina.

Among the findings of the study were that those prescribed higher dose insulin monotherapy had the highest MACE risk, with an aHR of 1.46 compared to the lowest risk category of low-dose insulin plus metformin. The researchers noted that high-dose insulin was associated with a higher risk of cancer, but the results were not statistically significant.

Discussing the findings, the researchers say: “Among its purported benefits, metformin may be cardioprotective, an effect that cannot be solely explained by its ability to lower blood glucose. Systematic reviews have reported that insulin plus metformin cause improved glycaemic control, less weight gain, and reduced insulin requirements when compared with insulin monotherapy.”

However, the researchers acknowledge that in selecting data from patients who had been initiated on insulin and the fact that metformin may not always be indicated due to other conditions a patient may have, “the population of people receiving insulin in combination with metformin may be healthier than the monotherapy group.”

Link:

SE Holden at al. ‘Association between Insulin Monotherapy versus Insulin plus Metformin and the Risk of All-Cause Mortality and Other Serious Outcomes: A Retrospective Cohort Study’. PLoS One. Published online May 6 2016

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