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Features That Predispose Patients with T2DM To Severe Hypoglycemia

Jun 23, 2018

Study describes patient characteristics that place patients with type 2 diabetes at increased risk for severe hypoglycemia.

A major concern in those receiving diabetes treatment is hypoglycemia. This condition leads to significant physical and economic burden in those with diabetes, ultimately leading to loss of productivity, adherence concerns, and hospitalizations. While non-severe hypoglycemia is generally more common, severe varieties of this condition remain significant. Severe occurrences of hypoglycemia have been defined by the American Diabetes Association as a “severe cognitive impairment requiring external assistance for recovery.”

Recent rates of emergency department visits and hospitalizations are elevated, as many as 1.4-1.6 events per 100 person-years, indicating a strong need to identify characteristics predisposing patients to severe hypoglycemia. The objective of this retrospective study was the following: 1) identify patients with type 2 diabetes who received treatment at the Cleveland Clinic Health System for severe hypoglycemia from January 2006 – December 2015, 2) identify patient characteristics associated with the hypoglycemic event, and 3) determine which antidiabetic medications cause hypoglycemia.

Using ICD-9/-10 codes, patients (N = 50,439) meeting study criteria, severe hypoglycemic events, and comorbidities were identified. Demographic (i.e. age, sex, race, etc.), income, BMI, HbA1c within past 12 months, and medication data were also obtained.

From 2006 to 2015, emergency department visits/hospitalizations increased from 0.12% to 0.31% (p = 0.01). Moreover, most hypoglycemic events resulted in hospitalizations and were identified as the patients’ first episode of severe hypoglycemia.

Analysis revealed patients who experienced severe hypoglycemia, were often older (71.9 years, p <0.001) and had a low BMI (31.7 kg/m2, p < 0.001). Incidents of severe hypoglycemia were seen in patients treated with insulin or sulfonylurea monotherapy, combination therapy that included insulin, sulfonylurea, and other diabetes medication, and lastly a sulfonylurea with other non-insulin diabetes medications. Additionally, patients treated with ≥3 medications were more likely to experience an event (18.5%, p < 0.001).

Comorbidities associated with severe hypoglycemia included dementia, cognitive impairment, cardiovascular disease, congestive heart failure, and chronic kidney disease. Patients with prior history of non-severe hypoglycemia were more likely to experience a more severe event (9%, p<0.001). Moreover, 16.1% of patients with an HbA1c < 6% experienced a severe event compared to the 12% of those without a severe event.

Finally, multivariable logistic regression analysis showed significant and increased odds results for severe events in the following: 1) insulin treatment (2.77 OR, p < 0.001), 2) sulfonylurea treatment (2.49 OR, p < 0.001), 3) increased number of antidiabetic medications (1.56 OR, p < 0.001), 4) history of non-severe events (3.01 OR, p <0.001), 5) HbA1c < 6% (1.95 OR, p , 0.001), 6) black race (2.55 OR, p < 0.001), 7) cardiovascular disease (1.68 OR, p = 0.001), and 8) congestive heart failure (1.33 OR, p = 0.04).

Despite the strengths of this study, some limitations were noted. The use of ICD-9/-10 codes relies heavily on providers use of them. Possible increased use of hypoglycemia codes at the time of the study could contribute to the rate of severe hypoglycemia cases. Although non-severe hypoglycemia events were considered significant and could place a patient at risk for severe hypoglycemia, it is possible that current coding practices underestimated the number of non-severe episodes. Finally, some severe events may have been missed due to patient improvement at home or treatment at an alternate health system.

All in all, this real-world example utilizing electronic medical record information has uncovered a wealth of information. Although the severity of hypoglycemia can vary, severe instances warranting hospitalizations or emergency department visits are a major concern. Still, opportunities to prevent this unwanted consequence exist. Identification of patients with risk factors for hypoglycemia is crucial as it allows for modifications to treatment regimens with the intention of reducing hypoglycemic events. By preventing these severe episodes, medical costs are reduced, adherence to medications is improved, hospitalizations are prevented, and glycemic control is achieved.

Practice Pearls:

  • History of non-severe hypoglycemic events places a patient with diabetes at higher risk for severe hypoglycemia.
  • Treatment regimens, including insulin, sulfonylurea, combinations with either medication, or ≥3 medications predisposes an individual to severe bouts of hypoglycemia.
  • Other patient characteristics that increase their risk for severe hypoglycemia include older age, lower BMI, and comorbidities (i.e. dementia, cognitive impairment, cardiovascular disease, etc.)


Misra-Hebert, A., Pantalone, K., Ji, X., Milinovich, A., Dey, T., Chagin, K.M., Bauman, J.M., Kattan, M., and Zimmerman, R.S. Patient Characteristics Associated With Severe Hypoglycemia in a Type 2 Diabetes Cohort in a Large, Integrated Health Care System From 2006 to 2015. Diabetes Care. 2018. https://doi.org/10.2337/dc17-1834

Kaytie A. Weierstahl, Pharm.D. Candidate, LECOM School of Pharmacy