Less Risk of Severe Hypoglycemia With Long-Acting Insulin Analogs in Elderly

By Reuters Staff

March 02, 2021

NEW YORK (Reuters Health) - Long-acting insulin analogs may be a safer option than neutral protamine Hagedorn (NPH, also known as isophane insulin) in elderly patients with type 2 diabetes initiating insulin therapy, according to a large observational study.

The study, in JAMA Internal Medicine, found that the long-acting insulin analogs glargine and detemir were associated with a reduced risk of severe hypoglycemia compared with NPH insulin.

The study team analyzed Medicare data on 575,008 patients to gauge the risk of ED visits or hospitalizations for hypoglycemia among older patients with type 2 diabetes (mean age, 74.9 years, 53% women) who initiated glargine or detemir compared with NPH insulin in real-world settings.

Overall, 407,018 patients initiated glargine, 141,588 started detemir, and 26,402 used NPH insulin. During a median follow-up of 0.37 years, there were 7,347 ED visits or hospitalizations for hypoglycemia (5,194 for glargine, 1,693 for detemir, and 460 for NPH insulin).

A propensity score-weighted Cox proportional hazards regression model showed that patients taking long-acting insulin analogs had fewer ED visits or hospital admissions for hypoglycemia compared with patients taking NPH (hazard ratio of 0.7 for both glargine and detemir).

Compared with initiating NPH, initiating glargine or detemir was associated with a nearly 30% lower risk of ED visits or hospitalizations for hypoglycemia, "which translated to 9.3 fewer hypoglycemia events with glargine and 8.4 fewer with detemir per 1000 patient-years of treatment," report Dr. Marie Bradley with the U.S. Food and Drug Administration Center for Drug Evaluation and Research and colleagues.

"In terms of number needed to harm, one would need to treat 154 patients with glargine or 167 with detemir rather than with NPH insulin for a year to prevent one excess case of severe hypoglycemia. However, this protective association was no longer seen when insulin analogs were used concomitantly with prandial insulin," they note in their article.

The overall findings were similar in post hoc subgroup analyses by low-income subsidy, a proxy measure for low-income status, "which provides some assurance that confounding by socioeconomic status is not at play," say the co-authors of a linked editorial.

However, an important limitation of the study is the lack of laboratory data, note Dr. Elbert Huang with University of Chicago, Illinois, and Dr. Kasia Lipska with Yale University, New Haven, Connecticut.

"Without this, the authors could not adjust for baseline glycemic control. Adjusting for the baseline glycemic control would help to account for some of the practice variation related to initiation of insulin use. Having the laboratory data would also allow for an assessment of the appropriateness of the decision to initiate insulin treatment," Drs. Huang and Lipska write.

Despite these concerns, they say the findings of this study suggest that when clinicians and patients are faced with a choice between insulin isophane suspension and basal insulin analog, the insulin analog may reduce the risk of dangerous low blood sugar.

"Put another way, the findings suggest a need for caution for the use of insulin isophane suspension among Medicare beneficiaries, particularly those who may be at greatest risk for hypoglycemia," they write.

"For the individual older patient, the decision to initiate insulin use has to be made with an open discussion of the risks and benefits, taking into account the overall goals of care, the capacity of the patient to perform the treatment plan safely, and practical considerations, such as out-of-pocket costs and type of delivery (pen vs vial)," Dr. Huang and Dr. Lipska advise.

This study was supported by the U.S. Food and Drug Administration through an interagency agreement with the Centers for Medicare & Medicaid Services.

SOURCE: https://bit.ly/302fQ2B JAMA Internal Medicine, online March 1, 2021.

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