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Original Investigation
July 3, 2018

Association of Initiation of Basal Insulin Analogs vs Neutral Protamine Hagedorn Insulin With Hypoglycemia-Related Emergency Department Visits or Hospital Admissions and With Glycemic Control in Patients With Type 2 Diabetes

Author Affiliations
  • 1Section of Endocrinology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut
  • 2Division of Research, Kaiser Permanente of Northern California, Oakland
  • 3Department of Medicine, University of Chicago, Chicago, Illinois
  • 4Department of General Internal Medicine, University of California, San Francisco
  • 5Department of Epidemiology, University of Washington, Seattle
  • 6Department of Health Services, University of Washington, Seattle
JAMA. 2018;320(1):53-62. doi:10.1001/jama.2018.7993
Key Points

Question  Is initiation of a basal insulin analog compared with human neutral protamine Hagedorn (NPH) insulin associated with a reduced risk of hypoglycemia-related emergency department (ED) visits or hospital admissions in patients with type 2 diabetes?

Findings  In this retrospective observational study of 25 489 patients with type 2 diabetes, initiation of basal insulin analogs compared with NPH insulin was not associated with a significant difference in hypoglycemia-related ED visits or hospital admissions among a propensity-score matched cohort of 4428 patients (hazard ratio, 1.16).

Meaning  Among patients with type 2 diabetes, the use of basal insulin analogs compared with NPH insulin was not associated with a reduced risk of hypoglycemia-related ED visits or hospital admissions.

Abstract

Importance  In clinical trials of patients with type 2 diabetes, long-acting insulin analogs modestly reduced the risk of nocturnal hypoglycemia compared with human neutral protamine Hagedorn (NPH) insulin, but cost 2 to 10 times more. Outcomes in clinical practice may differ from trial results.

Objective  To compare the rates of hypoglycemia-related emergency department (ED) visits or hospital admissions associated with initiation of long-acting insulin analogs vs human NPH insulin in patients with type 2 diabetes.

Design, Setting, and Participants  A retrospective observational study using data from Kaiser Permanente of Northern California from January 1, 2006, through September 30, 2015. Patients with type 2 diabetes who initiated a long-acting insulin analog or NPH insulin were included and censored at death, loss of health plan coverage, change in insulin treatment, or study end on September 30, 2015.

Exposure  Initiation of basal insulin analogs (glargine or detemir) vs NPH insulin.

Main Outcomes and Measures  The primary outcome was the time to a hypoglycemia-related ED visit or hospital admission and the secondary outcome was the change in hemoglobin A1c level within 1 year of insulin initiation.

Results  There were 25 489 patients with type 2 diabetes who initiated basal insulin therapy (mean age, 60.2 [SD, 11.8] years; 51.9% white; 46.8% female). During a mean follow-up of 1.7 years, there were 39 hypoglycemia-related ED visits or hospital admissions among 1928 patients who initiated insulin analogs (11.9 events [95% CI, 8.1 to 15.6] per 1000 person-years) compared with 354 hypoglycemia-related ED visits or hospital admissions among 23 561 patients who initiated NPH insulin (8.8 events [95% CI, 7.9 to 9.8] per 1000 person-years) (between-group difference, 3.1 events [95% CI, −1.5 to 7.7] per 1000 person-years; P = .07). Among 4428 patients matched by propensity score, the adjusted hazard ratio was 1.16 (95% CI, 0.71 to 1.78) for hypoglycemia-related ED visits or hospital admissions associated with insulin analog use. Within 1 year of insulin initiation, hemoglobin A1c level decreased from 9.4% (95% CI, 9.3% to 9.5%) to 8.2% (95% CI, 8.1% to 8.2%) after initiation of insulin analogs and from 9.4% (95% CI, 9.3% to 9.5%) to 7.9% (95% CI, 7.9% to 8.0%) after initiation of NPH insulin (adjusted difference-in-differences for glycemic control, −0.22% [95% CI, −0.09% to −0.37%]).

Conclusions and Relevance  Among patients with type 2 diabetes, initiation of a basal insulin analog compared with NPH insulin was not associated with a reduced risk of hypoglycemia-related ED visits or hospital admissions or with improved glycemic control. These findings suggest that the use of basal insulin analogs in usual practice settings may not be associated with clinical advantages for these outcomes.

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