In clinical trial populations, long-acting insulin analogs modestly reduce the risk of nocturnal hypoglycemia compared with neutral protamine Hagedorn (NPH) in type 2 diabetes, but cost 2-4 times more. In real-world clinical practice, insulin performance may vary due to greater heterogeneity of patient characteristics and behaviors.

To compare rates of severe hypoglycemia and changes in glycemic control associated with insulin analogs vs. NPH, we conducted a propensity-score matched cohort analysis using data from Kaiser Permanente Northern California (20to 2015). We included patients with type 2 diabetes if they started a long-acting insulin analog or NPH, and we censored follow-up at death, loss of health plan coverage, change in type of insulin used, change in sulfonylurea treatment, or end of follow-up. Main outcomes were time to hypoglycemia-related utilization (emergency department visit or hospitalization with a primary or principal discharge diagnosis of hypoglycemia) and change in hemoglobin A1c within 1 year of insulin initiation.

Among 1,928 patients with type 2 diabetes who started insulin analogs and 23,561 who started NPH, there were 31 and 319 hypoglycemic events, respectively. After propensity score matching, the hazard ratio for severe hypoglycemia associated with insulin analog use was 0.95 (95% CI, 0.57, 1.46) and did not change significantly after additional adjustment for prior severe hypoglycemia and time-dependent diabetes medication use (HR 0.97, 95% CI 0.58, 1.54). Hemoglobin A1c decreased from 9.4% to 8.1% after initiation of insulin analogs and from 9.4% to 7.9% after initiation of NPH (difference-in-difference -0.19% (95% CI, -0.06, -0.34)).

In real-world clinical practice, the use of basal insulin analogs is not associated with a substantial reduction in hypoglycemia-related utilization or improvement in glycemic control compared with NPH insulin.


K.J. Lipska: Other Relationship; Self; Centers for Medicare and Medicaid Services. Research Support; Self; National Institutes of Health. M.M. Parker: Research Support; Self; Eli Lilly and Company. H.H. Moffet: Research Support; Self; Regeneron Pharmaceuticals, Inc., AstraZeneca. E. Huang: None. A.J. Karter: None.

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