Beginning Long-Acting Insulin Analog Resulted in Fewer Instances of Severe Hypoglycemia Than NPH Insulin

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Study authors examined the risk of ED visits or hospitalizations for hypoglycemia among patients older than 65 who were initiated on glargine, detemir, or NPH insulin.

Among older individuals with type 2 diabetes (T2D), fewer patients on long-acting insulin analog therapy were admitted to the emergency department (ED) or hospital for hypoglycemia compared with those who used neutral protamine Hagedorn (NPH) insulin. These findings, from researchers at the Food and Drug Administration, were published in JAMA Internal Medicine.

Patients (aged ³65 years; N=575,008) who were enrolled in Medicare fee-for-service Parts A, B, and D and initiated using glargine (n=407,018), detemir (n=141,588), or NPH insulin (n=26,402) between 2007 and 2019 were included in this analysis. Healthcare utilization for hypoglycemic events were assessed.

Patients were aged a mean of 74.9 years (standard deviation [SD], 6.7) and 53% were women. Patients who used NPH insulin were more likely to be Black, less likely to use oral diabetes medications and statins, and were assessed fewer times for glycated hemoglobin status. To balance these differences, the investigators applied propensity matching scores and calculated inverse probability of treatment weights.

Hospitalization or ED visits for hypoglycemia occurred 7347 times (glargine, n=5194; detemir, n=1693; NPH, n=460). These visits corresponded with incidence rates of 17.37 (95% CI, 16.89-17.84) and 26.64 (95% CI, 26.01-27.3) per 1000 person-years (PY) for glargine and NPH insulin, respectively. The comparison between detemir and NPH insulin had a similar pattern (16.69; 95% CI, 15.92-17.51 vs 25.04; 95% CI, 24.01-26.11 per 1000 PY, respectively).

Compared with NPH insulin, the hazards ratio [HR] for hypoglycemia requiring a ED or hospital visit for hypoglycemia was 0.99 (95% CI, 0.90-1,09; P =.85) for patients on glargine taking prandial insulin and 0.78 (95% CI, 0.67-0.87; P <.001) for patients not taking concomitant prandial insulin. Among patients who initiated detemir and were taking prandial insulin, HR was 0.96 (95% CI, 0.86-1.08; P =.53) compared to HR of 0.78 (95% CI, 0.68-0.89; P <.001) in patients not taking concomitant prandial insulin.

Among patients who had recurrent hypoglycemic events, those who were taking glargine (HR, 0.70; 95% CI, 0.63-0.79; P <.001) or detemir (HR, 0.74; 95% CI, 0.65-0.84; P <.001) were at reduced risk for ED or hospital visit.

The observed protective effect of long-acting analogs was age dependent, in which individuals aged 69-87 years had a stronger effect than other ages.

Similar patterns were observed between patients receiving low-income subsidies or not, indicating there was little evidence of socioeconomic status influencing these observations.

This study was unable to assess for mild hypoglycemic events which did not result in increased healthcare utilization. It remains unclear whether mild events differed on the basis of drug use.

These data indicated hospitalizations and ED visits for hypoglycemia were reduced among new users of long-acting insulin analogs than new users of NPH insulin.


Bradley M C, Chillarige Y, Lee H, et al. Severe hypoglycemia risk with long-acting insulin analogs vs neutral protamine hagedorn insulin. JAMA Intern Med. Published online March 1, 2021. doi:10.1001/jamainternmed.2020.9176.