Use of insulin glargine is not associated with increased risk for breast cancer in women over 65 years of age, according to study results published in Diabetes Care.
Studies of insulin glargine in vitro have shown more potent mitogenic properties than regular insulin and higher proliferative effects on breast cancer cells compared with other insulins. Clinical trials exploring the relationship between insulin glargine use and breast cancer incidence have been inconsistent and few have examined the effects of long-term use. Given that insulin glargine is widely used in the United States, the researchers used Medicare data to assess whether long-term use of glargine was associated with an increased risk for breast cancer compared with the use of insulin detemir or neutral protamine Hagedorn (NPH).
Older women (aged ≥65 years) who had initiated glargine (n=203,159), detemir (n=67,012), or NPH insulin (n=47,388) contributed >1 million person-years of cumulative follow-up. The researchers considered ever use of each drug as well as duration of use (0 to <3, 3 to <5, and ≥5 years). The cumulative insulin dose dispensed (0-20,000, 20,000-60,000, and ≥60,000 units), length of follow-up (0 to <3, 3 to <5, and ≥5 years), and a combination of dose and follow-up time were also examined. Patients were followed until the end of the study (maximum, 10.7 years) or until unenrollment from Medicare, change in insulin type, diagnosis of breast cancer, or death.
Over the course of follow-up, there were 6267 cases of breast cancer identified, including 4170 (66%) in glargine users, 864 (14%) in NPH users, and 1233 (20%) in detemir users. The breast cancer incidence rate was similar across all 3 groups (range, 6.02 to 6.20 cases per 1000 person-years). Ever use of glargine was not associated with an increased risk for breast cancer compared with ever use of NPH (hazard ratio [HR], 0.97; 95% CI, 0.88-1.06) or detemir (HR, 0.98; 95% CI, 0.92-1.05), and there was no difference when stratified by duration of use, length of follow-up, or cumulative insulin dose.
In glargine users, the only group for which breast cancer risk was found to be increased was individuals using insulin for 3 to 5 years with a cumulative dose ≥60,000 units. In this group, the risk for breast cancer was higher in glargine users than in NPH insulin users (HR, 1.62; 95% CI, 1.02-2.58) and detemir users (HR, 1.53; 95% CI, 0.99-2.36). However, no difference in breast cancer risk was observed in women with the longest follow-up time (≥5 years) and highest cumulative dose (≥60,000 units) between glargine users and users of NPH (HR, 0.99; 95% CI, 0.63-1.57) or detemir insulin (HR, 0.89; 95% CI, 0.65-1.21).
The researchers noted that the observational nature of the study limited the exploration of potential confounding factors not adjusted for in the analyses. In addition, the results of the study may not be generalizable to women outside of the examined age group. However, they also noted that the study was “the largest study to date to examine the association between glargine use and breast cancer risk and had almost five times as many glargine users as the next-largest study that examined this question.”
“In summary, insulin glargine use was not associated with an increased risk of breast cancer compared with NPH or detemir use, in female Medicare beneficiaries with diabetes, irrespective of dose, duration of use, or length of follow-up,” the researchers concluded.
Bradley MC, Chillarige Y, Lee H, et al. Similar breast cancer risk in women older than 65 years initiating glargine, detemir, and NPH insulins [published online February 19, 2020]. Diabetes Care. doi:10.2337/dc19-0614