February 20, 2013
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Exogenous insulin increased risk for complications, mortality in type 2 diabetes

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According to results of a retrospective cohort study, exogenous insulin therapy was associated with an increased risk for diabetes-related complications, cancer and all-cause mortality among patients with type 2 diabetes.

Using data from the UK General Practice Research Database, 2000-2010, researchers from Cardiff University and the University Hospital of Wales in the United Kingdom compared outcomes among 84,622 patients with type 2 diabetes assigned to one of five glucose-lowering therapies: metformin monotherapy; sulfonylurea monotherapy; insulin monotherapy; metformin plus sulfonylurea; and insulin plus metformin.

The primary endpoint was risk for the first major adverse cardiac event, first cancer or mortality. Secondary endpoints included any of the individual primary endpoints plus microvascular complications.

When compared with metformin alone, the adjusted hazard ratio (aHR) for the primary endpoint was significantly higher for sulfonylurea monotherapy (aHR=1.436; 95% CI, 1.354-1.523); insulin monotherapy (aHR=1.808; 95% CI, 1.630-2.005); and insulin plus metformin (aHR=1.309; 95% CI, 1.150-1.491).

Among subgroups of patients with glycosylated hemoglobin/morbidity, those treated with insulin monotherapy had aHRs for the primary endpoint ranging from 1.469 (95% CI, 0.978-2.206) to 2.644 (95% CI, 1.896-3.687), according to the researchers.

Insulin monotherapy was associated with increased aHRs for secondary endpoints, including myocardial infarction (aHR=1.954; 95% CI, 1.479-2.583); major adverse cardiac events (aHR=1.736; 95% CI, 1.441-2.092); stroke (aHR=1.432; 95% CI, 1.159-1.771); renal complications (aHR=3.504; 95% CI, 2.718-4.518); neuropathy (aHR=2.146; 95% CI, 1.832-2.514); eye complications (aHR=1.171; 95% CI, 1.057-1.298); cancer (aHR=1.437; 95% CI, 1.234-1.674); or all-cause mortality (aHR=2.197; 95% CI, 1.983-2.434).

Adjusted HRs were higher for insulin monotherapy vs. all other treatments for the primary endpoint and all-cause mortality, when compared directly, the researchers wrote.

Though exogenous insulin provides benefits in patients with type 1 diabetes, the researchers said “… There is a clear need to review the way in which exogenous insulin is used in people with type 2 diabetes and to establish in detail the risk-benefit profile at differing stages of the natural history of the disease and in phenotypically different subgroups.”

Disclosure: See the full study for a complete list of disclosures.