Reference: JAMA Intern Med. 2021 Mar 1
Switching from long-acting insulins (LAIs) such as detemir or glargine to intermediate-acting isophane (NPH) insulin could save the average older patient in the United States using one vial/month over $2000 annually with no loss in glycemic control. So why not switch? The LAI preparations have been pushed as having less hypoglycemic side effects. Recently, researchers at the FDA analyzed Medicare claims data to show that there certainly is a difference between the rate of hypoglycemia in people who initiate LAIs and those who initiate therapy with NPH—but how meaningful is this difference?
Researchers examined Medicare insurance claims for those 65 or older with diabetes but without end-stage renal failure who initiated either an LAI or NPH insulin (but not combination NPH/prandial insulin products) between 2007 and 2019. Over 558,000 patients were initiated on LAI and during that time about 26,000 were started on NPH. At baseline, those receiving their first NPH prescription were more likely to have lower socioeconomic status, less likely to be prescribed statins, and had fewer visits prior to insulin initiation than those started on LAI. The investigators propensity matched patients based on income and other potential confounders and followed patients to examine subsequent rates of emergency room visits or hospitalizations for hypoglycemia. They also looked at prescription discontinuation as well as the addition of short-acting (prandial) insulin either at initiation or later. Treatment with glargine or detemir was associated with decreased risk of hypoglycemia compared with NPH alone (hazard ratio 0.7, 95% CI 0.6-0.8). On the other hand, when short-acting insulin was prescribed along with the NPH or LAI, and when people had been maintained on the insulins after the initiation period, the rates of hypoglycemia equalized.
This study builds on recent research indicating that we should feel comfortable prescribing NPH insulin for older patients, particularly when we use it in combination with prandial insulin. The authors calculated that over 150 NPH prescriptions would need to be written to cause a single additional episode of hypoglycemia per year compared with writing for an LAI. The apparent advantage of the LAIs goes away completely when prandial insulin is added or if NPH is used for maintenance after the initial period. The claims data show that over twenty times as many prescriptions are being written for LAIs as for NPH: this seems to be based more on advertising than evidence. If LAIs were reasonably priced, this wouldn’t be an issue.
For more information, see the topic Insulin Management in DynaMed.
DynaMed EBM Focus Editorial Team
This EBM Focus was written by Dan Randall, MD, Deputy Editor for Internal Medicine at DynaMed. Edited by Alan Ehrlich, MD, Executive Editor at DynaMed and Associate Professor in Family Medicine at the University of Massachusetts Medical School, Carina Brown, MD, Assistant Professor at Cone Health Family Medicine Residency, and Katharine DeGeorge, MD, MS, Associate Professor of Family Medicine at the University of Virginia and Clinical Editor at DynaMed.