As of 04/21/23 1

A Comparison of Select Cardiovascular Outcomes by Anti-Diabetic Prescription Drug Classes

Used to Treat Type 2 Diabetes among Military Health System (MHS) Beneficiaries, Fiscal Year 2003-2006

Office of the Assistant Secretary of Defense for Health Affairs/TRICARE Management ActivityMichael R. Peterson, DVM, MPH, DrPH

Director, Health Program Analysis and EvaluationThomas Bacon, PharmD, MS

LtCol, USAF, BSCDirector, Pharmacy Utilization Management

As of 04/21/23 2

Background• May 2007 article in NEJM by Nissen and

Wolski reporting on association of Avandia use and risk of MI and death from cardiovascular causes

• DoD interested in determining very quickly if our beneficiaries were at similar risk

• Is there an increased incidence of select cardiovascular events (acute MI and CHF) among MHS beneficiaries who filled a script for Avandia compared to those who filled scripts for other anti-diabetic medications?

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Methods

• MHS has 9.1M beneficiaries• TRICARE Prime is an HMO-like benefit

(65+ not eligible) – study limited to these beneficiaries

• Cross-sectional analyses of data from fiscal years 2003-2006

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Methods (cont.)

• Data sources:– Defense Eligibility Enrollment System

(DEERS) – gender/age/bencat/location– Inpatient/outpatient encounter claims –

not clinical data – date of service/source of service/diagnoses (ICD-9)/procedure codes (DRG)

– Pharmacy Data Transaction Service (PDTS) – real-time pharmacy fill record regardless of source of fill (military, mail order, civilian)

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Methods (cont.)• Data sources linked by identifiers• Case definition for type 2 diabetics based on

ICD-9 codes• Individual drugs grouped into therapeutic

classes of anti-diabetic drugs• Drug categories not mutually exclusive

(therefore unable to perform statistical comparisons)

• Date of earliest diagnosis used to identify incident cases

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Table 1. Demographics of Military Health System (MHS) TRICARE Prime Beneficiaries with a Diagnosis of Type 2 Diabetes, Fiscal Year 2003-2006 *

N %

Total N 231,962

Gender

Male 105,660 45.55

Female 126,302 54.45

Age Category

0-24 16,111 6.95

25 to 34 17,777 7.66

35 to 44 35,517 15.31

45 to 64 161,329 69.55

65 and over 1,228 0.53

Beneficiary Category †

Active Duty 17,763 7.66

Dependent of Active Duty 35,629 15.36

Retired & Dependent of Retired 124,949 53.87

Other 5,753 2.48

Missing Beneficiary Category Info 47,868 20.64

* Data sources: SIDR, SADR, TED-I, TED-N, DEERS. ICD9 = 250.X0 or 250.X2 was used to identify individuals with type 2 diabetes;

TRICARE Prime is the HMO-like option for MHS beneficiaries.

† Active Duty includes Guard/Reserve personnel enrolled in TRICARE Prime; Dependent of Active Duty includes dependents of Guard/Reserve personnel enrolled in TRICARE Prime; Beneficiaries with "other" as the beneficary category include Presidential Appointees, DoD civil service, DoD Contractors, Disabled Veterans, former service members who were eligible to retire but chose to discharge, Medal of Honor persons, Transitional Assistance Management Program, Foreign Military, and Foreign national employees.

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Table 2: Cardiovascular Outcomes (AMI and CHF) by Anti-Diabetic Prescription Drug Class among MHS TRICARE Prime Enrollees with a Diagnosis of Type 2 Diabetes, Fiscal Year 2003-2006 *

AMI CHF

Prescription DrugN Dispensed

Drug N

Average Annual Incidence per

10,000 N

Average Annual

Incidence per 10,000

TZD 20002 299 37.37 721 90.12

Avandia 13400 202 37.69 463 86.38

Actos 7831 111 35.44 291 92.90

Biguanides 58091 769 33.09 1576 67.82

Sulfonylureas 23520 457 48.58 984 104.59

Insulin 11854 245 51.67 541 114.10

Meglitinides (Prandin & Starlix) 1009

† †Amylin Analogs (Byetta & Symlin)

1310

Alpha-Glucosidase Inhibitors (Glyset & Precose)

299

* Data source: PDTS. Therapeutic Class Code= 6820XX for antidiabetic drugs; SIDR, SADR, TED-I, TED-N. ICD9 = 250.X0 or 250.X2 for Diabetes Type II. ICD9 = 410.XX for AMI. ICD9 = 428.XX for CHF; Data are presented at patient level;

TRICARE Prime is the HMO-like option for MHS beneficiaries; Drug Categories are not Mutually Exclusive; Combination drugs are assigned to each drug group within the combination.

† Data suppressed due to small N

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Results

• Table 1– 232,000 Prime enrollees with dx of

type 2 diabetes between fiscal year 2003 – 2006• 54% female; 70% 45 – 64 years old; 8%

active duty; 15% dependents of active duty; 54% retirees and their dependents; 21% missing beneficiary information

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Results (cont.)

• Table 2• Annual incidence rates averaged

over 4 years • AMI: range from 33/10,000

(biguanides) to 52/10,000 (insulin); 38/10,000 for Avandia, 35/10,000 for Actos, 37/10,000 for any TZD class of drugs, 49/10,000 for sulfonylureas

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Results (cont.)

• CHF: range from 68/10,000 (biguanides) to 114/10,000 (insulin); 86/10,000 for Avandia, 93/10,000 for Actos, 90/10,000 for any TZD class of drugs, 105/10,000 for sulfonylureas

• Bottom line: No increased incidence of select cardiovascular events (acute MI and CHF) among MHS Prime beneficiaries who filled a script for Avandia compared to those who filled scripts for other anti-diabetic medications

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Limitations• Cannot determine from these data if differences

in average annual incidence rates of outcomes are due to anti-diabetic drug; disease progression; number, types and severity of comorbidities; or, other risk factors such as age

• Study did not include those 65 and older• Claims data do not include socioeconomic

status, comorbid conditions, current health status, medical history, drug dose, time on drug, concurrent medications, individual characteristics (e.g. BMI)

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Limitations (cont.)

• AMI/CHF attributed to anti-diabetic class if script filled any time prior to event (assumes cause-effect relationship)

• Because drug categories were not mutually exclusive, unable to make statistical comparisons for significance

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Future Efforts• Possible studies

– Retrospective cohort study to include medical record review/time to event analysis

– Prospective study of cohort of type 2 diabetics with reference cohort and appropriate uniform medical evaluation

• DoD/FDA working on an MOU to permit surveillance of DoD pharmacy data to track sentinel events