Singh G, Mithal A, Mannalithara A, Sehgal A, Bron M, Dabbous O, Peng X ICORE

1. Hospitalizations Due to Severe Hypoglycemia in Patients with Type 1 Diabetes Mellitus: US National Perspective Singh G, Mithal A, Mannalithara A, Sehgal A, Bron M, Dabbous O, Peng X ICORE Stanford University Takeda Pharmaceuticals

2. Disclosures • Supported by a grant from Takeda Pharmaceuticals • Drs. Bron and Peng are employees of Takeda Pharmaceuticals • Dr. Dabbous is a former employee of Takeda Pharmaceuticals

3. Type 1 Diabetes Mellitus in US • Type 1 Diabetes Mellitus (T1DM) affects >1 million Americans • In adults, T1DM constitutes approximately 5% of all diagnosed cases of diabetes • Tight glycemic control using intensive insulin therapy significantly reduces long-term microvascular and macrovascular complications in T1DM (The Diabetes Control and Complications Trial (DCCT)) U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, 2011. National diabetes fact sheet: national estimates and general information on diabetes and prediabetes in the United States, 2011. Available at http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2011.pdf. Accessed August 29,2012.

4. Objective • To examine the prevalence and costs and payer status of severe hypoglycemia hospitalizations in T1DM patients in the US

5. Methods and DataNationwide Inpatient Sample (NIS) • Largest publicly available all-payer inpatient care database • 20% stratified sample of all U.S. hospitalizations (1988 – 2011) • ~5 to 8 million records of inpatient stays per year from about 1,000 hospitals representing ~85 – 96 % of all non–federal hospitals • Complex survey design with multistage strata and clustering • Strict quality-control and extensive validation

6. 2009 NIS: Represents 96% of US Population NIS 2009

7. NIS: Data Characteristics • Over 100 clinical and non-clinical variables for each hospital stay, for example: • Primary and secondary diagnoses • Primary and secondary procedures. • Admission and discharge status • Patient demographics (e.g., gender, age, race, median income for ZIP Code). • Expected payment source • Length of stay and total charges • Hospital characteristics (e.g., ownership, size, teaching status)

8. Study Cohort • All inpatient hospitalizations in 2009 with primary or secondary diagnosis of: • T1DM (ICD9 codes 250.x1, 250.x3), and • Hypoglycemia (ICD9 codes 250.8x, 251.0x, 251.1x, 251.2x) in patients aged ≥18 years. • Denominator: 2009 US resident population (over 18 years): 232,637,3621 1Estimated from US Census Bureau Data, 2010 census

9. Statistics • SAS ( Statistical Analysis System) version 9.3 procedure PROC SURVEYMEANS used for calculating sample statistics and appropriate variances based on data from complex sampling designs • All estimates reported with 95% Confidence Intervals (CI)

10. Results

13. Hypoglycemia Hospitalizations as % of All-Cause T1DM and T2DM Hospitalizations

14. Hypoglycemia Hospitalizations as a % of All-Cause T1DM hospitalizations by Gender

15. Mean Age at Admission with Diagnosis of Hypoglycemia with T1DM

16. Hospitalization Type in T1DM HypoglycemiaMost Hospitalizations are Non-Elective

17. Length of StayT1DM patients with hypoglycemia stayed longer compared to those with all-cause hospitalizations

18. Charges for Hospitalizations with Hypoglycemia in T1DM (US$ per admission)

19. National Bill : Total Charges for Hypoglycemia Hospitalizations in T1DM • Total hospitalizations = 20,839(95% CI = 19,233 - 22,445) • Charge per hospitalization = $46,039 (CI = $42,144-$49,934) • Total charges = $ 959,406,721 • As a comparison, hypoglycemia hospitalizations in T2DM : • Total hospitalizations = 248,422 (CI = 234,321-262,523) • Charges per hospitalization = $48,569 (CI = $45,781-$51,357) • Total charges = $ 12.07 billion • Average Charge of US All-Cause Hospitalization: $33,232

20. Who is paying for T1DM Hypoglycemia Hospitalizations ?Medicare and Medicaid are responsible for 64% of Payment

21. Inpatient Case Fatality Rate in T1DM Hypoglycemia Hospitalizations • Case-fatality in T1DM Hypoglycemia • 284 deaths • Case-fatality = 1.36% (CI = 0.98-1.74%) • Case Fatality rate for all-cause T1DM hospitalizations • 1.4% (CI = 1.3-1.51%) • Case Fatality rate for all-cause hospitalizations • 2.2%

22. Limitations and Strengths • No unique patient identifiers. • Dependence on ICD9 codes. • No information on lifestyle factors or medications. • Charges vs. Costs • Study limited to adults 18 years or older • Nationwide sample of over 96% of all US population – robust data. • Stratified, randomized sample from US hospitals - not a “convenience” sample.

23. Future Work Can we predict hypoglycemia?

24. Conclusions • Hypoglycemia in T1DM was associated with 20,839 hospitalizations and 284 deaths in 2009, and a total cost of about $1 billion, most of which is paid by Medicare and Medicaid. • While aggressive glycemic control remains important for patients, the significant clinical and financial implications of severe hypoglycemia should also be noted. • Careful selection of anti-diabetic drugs and close monitoring should be considered to reduce the risk of severe hypoglycemia. • Development of novel anti-diabetics to reduce hypoglycemia while maintaining glycemic control would be highly desirable.