title: Risk of severe hypoglycemia in sulfonylurea-treated patients from diabetes centers in Germany/Austria: How big is the problem? Which patients are at risk?
abstract: BACKGROUND
  We investigated the rate of severe hypoglycemic events and confounding factors in patients with type 2 diabetes treated with sulfonylurea at specialized diabetes centers, documented in the German/Austrian DPV-Wiss database.
  
  
  METHODS
  Data from 29 485 sulfonylurea-treated patients were analyzed (median[IQR] age 70.8[62.2-77.8] years, diabetes duration 8.2[4.3-12.8] years). The primary objective was to estimate the event rate of severe hypoglycemia (requiring external help, causing unconsciousness/coma/convulsion and/or emergency hospitalization). Secondary objectives included exploration of confounding risk factors through group comparison and Poisson regression.
  
  
  RESULTS
  Severe hypoglycemic events were reported in 826(2.8%) of all patients during their most recent year of sulfonylurea treatment. Of these, n = 531(1.8%) had coma, n = 501(1.7%) were hospitalized at least once. The adjusted event rate of severe hypoglycemia [95%CI] was 3.9[3.7-4.2] events/100 patient-years (coma: 1.9[1.8-2.1]; hospitalization: 1.6[1.5-1.8]). Adjusted event rates by diabetes treatment were 6.7 (sulfonylurea + insulin), 4.9 (sulfonylurea + insulin + other OAD), 3.1 (sulfonylurea + other OAD) and 3.8 (sulfonylurea only). Patients with ≥1 severe event were older (p < 0.001) and had longer diabetes duration (p = 0.020) than patients without severe events. Participation in educational diabetes-programs and indirect measures of insulin-resistance (increased BMI, plasma-triglycerides) were associated with fewer events (all p < 0.001). Impaired renal function was common (n = 3113 eGFR; ≤30 mL/min) and associated with an increased rate of severe events (≤30 mL/min: 7.7; 30-60 mL/min: 4.8; >60 mL/min: 3.9).
  
  
  CONCLUSIONS
  These real-life data showed a rate of severe hypoglycemia of 3.9/100 patient-years in sulfonylurea-treated patients from specialized diabetes centers. Higher risk was associated with known risk factors including lack of diabetes education, older age and decreased eGFR but also with lower BMI and lower triglyceride levels, suggesting that sulfonylurea treatment in those patients should be considered with caution.
authors.affiliation: Medical BU Diabetes, Lilly Deutschland GmbH, Bad Homburg, Bad Homburg, Germany.|Institute for Clinical Diabetology, German Diabetes Center, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Nanette C
authors.initials: NC
authors.lastname: Schloot
authors.affiliation: Medical BU Diabetes, Lilly Deutschland GmbH, Bad Homburg, Bad Homburg, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Haupt
authors.affiliation: Department of Internal Medicine I, University of Lübeck, Lübeck, Germany.
authors.forename: Morten
authors.initials: M
authors.lastname: Schütt
authors.affiliation: Department of Internal Medicine I, Division of Endocrinology and Metabolism, Goethe University Hospital, Frankfurt am Main, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Badenhoop
authors.affiliation: Department of Internal Medicine I, Medical University of Innsbruck, Innsbruck, Austria.|Division of Endocrinology, Diabetes & Clinical Nutrition, Inselspital, Bern University Hospital, and University of Bern, Bern, Switzerland.
authors.forename: Markus
authors.initials: M
authors.lastname: Laimer
authors.affiliation: European Statistics, Diabetes (HTA/Medical Affairs), Lilly Deutschland GmbH, Bad Homburg, Bad Homburg, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Nicolay
authors.affiliation: eResearchTechnology Limited (ERT), Peterborough, United Kingdom.
authors.forename: Matthew
authors.initials: M
authors.lastname: Reaney
authors.affiliation: Institute for Epidemiology and Medical Biometry (ZIBMT), German Center for Diabetes Research (DZD), University Ulm, Ulm, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Fink
authors.affiliation: Institute for Epidemiology and Medical Biometry (ZIBMT), German Center for Diabetes Research (DZD), University Ulm, Ulm, Germany.
authors.forename: Reinhard W
authors.initials: RW
authors.lastname: Holl
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001317:Austria / Q000453:epidemiology; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005260:Female; D005858:Germany / Q000453:epidemiology; D006442:Glycated Hemoglobin / Q000378:metabolism; D006760:Hospitalization; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000453:epidemiology* / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D013453:Sulfonylurea Compounds / Q000009:adverse effects*
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds
keywords: DPV-Wiss; hypoglycemia; real-life data; sulfonylurea; type 2 diabetes