Insulin’s Place In Treatment of Type 2 Diabetes

Insulin associated with increased risk for major adverse cardiac events, first cancer, or mortality….

A recent study conducted in the United Kingdom set out to characterize the risk of adverse events associated with the use of variable glucose-lowering agents in people with type 2 diabetes (T2DM). The study was a retrospective cohort using data from the UK General Practice Research Database (GPRD) between 2000 and 2010, which is derived from nearly 600 primary care practices across the UK. Primary outcomes were risk for a first major adverse cardiac event, first cancer, or mortality among 84,622 primary care patients with T2DM.

Patients were treated with 1 of 5 glucose-lowering therapeutic regimens, including: metformin monotherapy, sulfonylurea monotherapy, insulin monotherapy, metformin plus sulfonylurea combination therapy, and insulin plus metformin combination therapy. This study did allow for patients to switch regimens, leaving a total of 105,123 exposure periods to be included in analysis.

Using metformin therapy as the referent, the adjusted hazard ratio (aHR) for the primary end point was significantly increased for the following:

• sulfonylurea monotherapy – 1.436          
• insulin monotherapy – 1.808
• insulin + metformin – 1.309

In the glycosylated hemoglobin and morbidity subgroups, patients who were treated with insulin monotherapy had aHRs for the primary outcome ranging from 1.47 to 2.64.

All aHRs were increased for insulin monotherapy in regards to individual secondary outcomes (myocardial infarction, major adverse cardiac events, stroke, renal complications, neuropathy, eye complications, cancer, and all-cause mortality). A statistical significance did exist for higher aHRs in the insulin plus metformin group, but these values were substantially lower than those for insulin monotherapy.

Authors argue that the increased risk for the outcomes aforementioned is seemingly precipitated by insulin use. Previous studies have also shown increased risk for cardiovascular disease, heart failure, and some cancers.

Practice Pearls:

• This study does not suggest stopping insulin, however caution is warranted with its use pending further investigation.
• Consideration should be given to the addition of metformin with insulin, as this study suggests an ability of metformin to mitigate the increased risks seen with insulin monotherapy.

Mortality and Other Important Diabetes-Related Outcomes With Insulin vs Other Antihyperglycemic Therapies in Type 2 Diabetes. Currie CJ, Poole CD, Evans M, Peters JR, Morgan CLJ Clin Endocrinol Metab. 2013;98:668-677