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Study questions use of insulin as primary diabetes add-on therapy

Type 2 diabetes patients taking metformin and insulin are at increased risk of death compared to those who take metformin and a sulfonylurea, according to latest research.

The authors, from Vanderbilt University in Tennessee, said there was a “lack of consensus” over what add-on treatment to choose for diabetes patients that had failed to reach blood glucose targets with metformin and lifestyle changes.

“These findings… call into question recommendations that insulin is equivalent to sulfonylureas for patients who may be able to receive an oral agent”

Study authors

They said promising results from a few trials had led to an increase in early initiation of insulin and its use as an add-on therapy to metformin.

Their study concentrated on insulin and sulfonylureas, though they noted that other choices could include thiazolidinediones, glucagon-like peptide 1 receptor agonists, or dipeptidyl peptidase 4 inhibitors.

The study looked at data on nearly 15,000 patients with diabetes initially treated with metformin who subsequently added either insulin or sulfonylurea. Patients had received metformin for a median of 14 months before adding another therapy.

The researchers compared the risk between therapies of heart attack, stroke, or all-cause death. Analysis indicated that heart attack and stroke rates were statistically similar, whereas there was a higher rate of all-cause death among patients who received insulin.

Cardiovascular disease − acute myocardial infarction and stroke − events were 41 and 229 among patients who added insulin or sulfonylurea, respectively (10.2 and 11.9 per 1,000 person-years). All-cause deaths were 137 versus 444, respectively (33.7 and 22.7 per 1,000 person-years).

Writing in the Journal of the American Medical Association, the authors said their findings “called into question” recommendations that insulin was equivalent to sulfonylureas for patients able to receive an oral treatment.

“Although insulin remains a reasonable option for patients who have very high glucose levels or who desire flexible and fast glucose reduction, most patients prefer to delay insulin initiation,” they said.

“Our study suggests that intensification of metformin with insulin among patients who could add a sulfonylurea (HbA1c level less than 10%) offers no advantage in regard to risk of cardiovascular events and is associated with some risk,” they added.

“These findings require further investigation to understand risks associated with insulin use in these patients and call into question recommendations that insulin is equivalent to sulfonylureas for patients who may be able to receive an oral agent,” the authors concluded.

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