Patient-Oriented Evidence That Matters

NPH Insulin: Fewer Episodes of Severe Hypoglycemia Than Analogs and Less Than One-Half the Cost


Am Fam Physician. 2019 Jan 1;99(1):53-54.

Clinical Question

Do long-acting insulin analogs, such as glargine (Lantus) or detemir (Levemir), reduce the risk of clinically significant hypoglycemia compared with neutral protamine Hagedorn (NPH) insulin?

Bottom Line

This study found that compared with expensive long-acting insulin analogs costing two to 10 times as much, NPH insulin results in a similar number of episodes of severe hypoglycemia (if not fewer) that result in emergency department visits and hospitalizations. NPH insulin also improves glycemic control as well as, if not better than, insulin analogs. In a previous report (Singh SR, et al. CMAJ. 2009;180(4):385–397), overall quality of life was also similar with NPH insulin or insulin analogs. Compared with long-acting insulin analogs, NPH insulin is as safe, if not safer, equally tolerated, equally or more effective, and at a much lower price. One in four adults with diabetes mellitus either stops or cuts back significantly on their insulin because they cannot afford it. (Level of Evidence = 2b–)


Marketing efforts have convinced most clinicians that long-acting insulin analogs, such as glargine and detemir, reduce the risk of hypoglycemia and are thus safer than traditional NPH insulin. These investigators analyzed data from 2006 and 2015 from multiple patient and prescription registries with Kaiser Permanente of Northern California. Outcomes of interest included pharmacy use; laboratory results; and outpatient, emergency department, and hospitalization diagnoses of diabetes and related complications. The inception cohort comprised 25,489 adults, 19 years or older, with type 2 diabetes who were initiating basal insulin therapy without any insulin prescription fills during the prior 12 months. Results were analyzed after controlling for multiple potential confounders, including demographics, index year, clinician specialty, comorbidity index, chronic kidney and/or liver disease, visual impairment, history of depression, glycemic control, history of severe hypoglycemia episodes requiring third-party intervention, and medication nonadherence. The risk of a subsequent severe hypoglycemic episode resulting in an emergency department visit or hospital admission was not significantly lower in patients who initiated NPH insulin at baseline compared with those initiating insulin analogs (8.8 vs. 11.9 events per 1,000 person-years, respectively). In addition, glycemic control was significantly improved in patients using NPH insulin vs. insulin analogs (difference in A1C, −0.22%; 95% confidence interval, −0.09% to −0.37%).

Study design: Cohort (retrospective)

Funding source: Government

Setting: Population-based

Reference: Lipska KJ, Parker MM, Moffet HH, Huang ES, Karter AJ. 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. JAMA. 2018;320(1):53–62.

POEMs (patient-oriented evidence that matters) are provided by EssentialEvidence Plus, a point-of-care clinical decision support system published by Wiley-Blackwell. For more information, please see http://www.essentialevidenceplus.com. Copyright Wiley-Blackwell. Used with permission.

For definitions of levels of evidence used in POEMs, see https://www.essentialevidenceplus.com/product/ebm_loe.cfm?show=oxford.

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This series is coordinated by Sumi Sexton, MD, Editor-in-Chief.

A collection of POEMs published in AFP is available at https://www.aafp.org/afp/poems.



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