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
Open accessAbstract
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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Basal insulin analogs reduce hypoglycemia risk compared with NPH insulin.
“Basal insulin analogs are preferred over NPH insulin because of a reduced risk of hypoglycemia.1066–1071”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [1066]
The Results and Conclusions report that, among patients with type 2 diabetes, starting a basal insulin analog rather than NPH insulin was not associated with fewer hypoglycemia-related emergency visits or hospital admissions. The Discussion notes that earlier trials found modest reductions in overall or nocturnal hypoglycemia, but that is distinct from this paper’s finding in usual practice. (LLM, conf=0.87)
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- Authors
- Lipska, K. J., Parker, M. M., Moffet, H. H., Huang, E. S., & Karter, A. J.
- Affiliations
- Yale University (US)
- Kaiser Permanente (US)
- University of Chicago (US)
- Corresponding author
- Lipska, Kasia J.
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2018-07-03
- Volume
- 320
- Issue
- 1
- Pages
- 53
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC6134432
- OpenAlex
- W2808944450
- Cited by
- 76
- References
- 43
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 1 · 2023: 7 · 2022: 10 · 2021: 19 · 2020: 13 · 2019: 17 · 2018: 3
- FWCI
- 10.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eli Lilly and Company
- AstraZeneca
- Sanofi
- Yale University (P30AG021342)
- Regeneron Pharmaceuticals
- National Institutes of Health (DK092924)
- National Institute on Aging (R56AG051683, K23AG048359, P30AG021342)
- National Institute of Diabetes and Digestive and Kidney Diseases (K24DK105340, DK092949, R01DK103721, R01DK081796, P30DK092949, P30DK092924)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Health Professions › Emergency Medical Services › Patient Safety and Medication Errors
- Keywords
- type 2 diabetes, basal insulin analogues, NPH insulin, long-acting insulin, hypoglycemia, emergency department visits, hospitalization, glycemic control, HbA1c, glargine, detemir, insulin initiation, real-world outcomes, cost-effectiveness, Kaiser Permanente
- MeSH terms
- Insulin Glargine, Insulin Detemir, Adult, Aged, Blood Glucose, Diabetes Mellitus, Type 2, Emergency Service, Hospital, Female, Hospitalization, Humans, Hypoglycemia, Hypoglycemic Agents, Insulin, Isophane, Male, Middle Aged, Retrospective Studies
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