Maenne OkunolaPharm D Candidate: University of GeorgiaJune 3, 2012Preceptor Dr. Ali Rahimi

Level of Evidence

Intervention to Decrease Glyburide Use in Elderly Patients With Renal Insufficiency

Authors: Aspinall, Zhao, Good, Stone, Boresi, Cox, Bartholomew, Jansen, Guterman, Patino, Rivera-Miranda, Burlingame, Frazer, Sellers, Steele, Witt, Cunningham

The American Journal of Geriatric Pharmacotherapy 2011; 9:58-68

This study examines the changes in prescribing of glyburide in elderly patients with decreased renal function and the adverse effects of discontinuing therapy

Background Information Sulfonylureas have an increased rate of

hypoglycemia Predisposing factors include renal insufficiency,

advanced age, dose, concomitant medications, and beginning new therapy

Glyburide is not recommended in patients with CrCl less than 50ml/min

Reason for study: Veterans Affairs Center for Medication Safety received a report of severe hypoglycemia associated with glyburide use and the majority of the patients were elderly and renally impaired

Design Uncontrolled observational study 4368 targeted outpatient Veterans and 1886

non-targeted Veterans in the comparison group

Targeted Veteran Cohort: SrCr ≥ 2 and age ≥ 65 with prescription of glyburide during April 1- June 30

Non-targeted Veteran Cohort: SrCr ≥ 2 and age ≥ 65 with prescription of glyburide during July 1 to September 3

Duration of study: The date they met requirements of the study to March 31, 2008. (longest duration April 1,2007-March 3,2008)

Patient Demographics Targeted group: 77

years, male, Caucasian, 2.5 SrCr, 3.8 Charlson comorbidity index score

Non-targeted group: 77 years, male, Caucasian, 2.3 SrCr, 3.5 Charlson comorbidity score

Design Information given to Pharmacy Executives in

21 VA geographic areas on September 4,2007: Compiled collected data from April 1, 2007- June 30

of patients age over 65 and SCr of >2 (targeted Veterans)

Data on the risk of risk of hypoglycemia of glyburide compared to other sulfonylureas

Data on the risk of hypoglycemia of glyburide in patients with renal failure

Dosing and monitoring suggestions for patients converted to glipizide

Instructions to pharmacy executives to contact providers and inform them of the risk with glyburide and encourage a change in therapy

Data Evaluated Monthly glyburide incidence rate ratios

of discontinuation in targeted versus nontargeted groups

Variability of glyburide discontinuation rates by geographic area

Medication to replace glyburide Patient specific factors associated with

stopping glyburide Comparisons of hypoglycemia in

patients with and without more severe renal insufficiency

Clinical Endpoints Primary endpoint

Changes in glyburide prescribing comparing targeted groups to non-targeted groups

A new prescription for a sulfonylurea or no new prescriptions for glyburide 135 days after the prescription date

Secondary endpoint: Change in HbA1c after stopping glyburide Comparison of of hypoglycemia before and

after discontinuing glyburide Hospitalization or ER visit

Results- Primary Endpoints

- Incidence rate ratios (IRR) for discontinuing glyburide was statistically significantly elevated in the months of September, October, and November for the targeted group compared with the non-targeted group

- Remainder of the study the discontinuation rates were not significant

IRR 95% CI

Sep. 2.1 1.7-2.5

Oct. 1.3 1.1-1.6

Nov. 1.4 1.1-1.7

Results Overall glyburide discontinued in 71.5%

of targeted cohort and 56% of the non-targeted cohort

Glyburide most commonly switched to glipizide

African-American race, SCr, Charlson comorbity score, new glyburide use and the VA regions were all associated with physician discontinuation

Results Secondary endpoints

For patients in the targeted group who discontinued glyburide

Baseline HbA1c: 7.17% Baseline - most recent value within 3 months of index

date After discontinuation HbA1c: 7.22%

Value 3-9 months after discontinuing glyburide Baseline hypoglycemia rates/1000 person-days:

0.093 (p-value 0.36) After discontinuation Hpoglycemia: 0.070 (p-value

0.10)

Results- Renal Comparison

SCr ≥ 3mg/dL

SrCr 2-3 3mg/dL

Pre -intervention hypoglycemi

a rate

0.169/1000 person days

0.081/1000 person days

Post-intervention hypoglycemi

a rate

0.039/1000 person days

0.075/1000 person days

Conclusion

This intervention to target elderly patients with proposed renal insufficiency decreased glyburide use over 3 months without compromising glucose control and without major detrimental effects

Limitations Uncontrolled observational study SrCr was the marker for renal function instead

of creatinine clearance Information sent to the targeted group could

have had profound effects on the prescribing for the non-targeted group because information could have spread

Only looked at the first time glyburide was discontinued although it might have been re-started

Hypoglycemia codes may be more strict within the VA versus outside the VA

Importance to Health Care Professionals

Continued research to decrease glyburide use in elderly patients with renal insufficiency

Risk of hypoglycemia more prevalent in the elderly taking sulfonylurea