Jing Yuan, B.S Pharm; Kevin Lu, Ph.D; Minghui Li, M.S

Department of Clinical Pharmacy and Outcomes Sciences, College of Pharmacy, University of South Carolina

Training Program Components

ISPOR 20th Annual International Meeting

Philadelphia, PA, USA

Pre-program Medication Errors (Jan-Sep 2006;

n=191)

Backgrounds

With the aging of population, Alzheimer

disease (AD) and dementia are becoming

the epidemic in the United States (U.S).1-2

Along with this large and increasing number

of elderly with dementia, a growing body of

evidence suggests that individuals with

diabetes are associated with an elevated risk

of developing cognitive impairment,

including AD, vascular dementia.3-6

Given the increased risk of dementia related

to diabetes, antidiabetic drugs, including

both insulins and oral antidiabetic drugs,

may play a significant role in the altering the

risk of developing dementia, particularly

vascular dementia.

To date, the neuroprotective effects of

antidiabetic drugs are mainly characterized

for metformin from animal and in-vitro

studies.

Methods

Study Design case-control study

Data sources

• Medicare Current Beneficiary Survey

(MCBS) 2002-2010

• nationally representative sample of the

Medicare beneficiaries

• linked with Medicare claims data.

AD and Dementia Cases

• the self/proxy-reported diagnosis by a

positive response to the survey question

“Has a doctor ever told you that you had

Alzheimer’s disease or dementia?”;

• or having at least one International

Classification of Diseases-ninth revision-

Clinical Modification (ICD-9-CM) diagnosis

codes in Medicare claims (AD, 331.0;

dementia, 290 or 331.0);

• or using AD-targeted prescription drugs

identified in the prescription drug event

files.

PDB8

Objectives

The main objective of this study is to explore

the association between use of anti-diabetic

drugs including insulins and oral anti-diabetic

drugs, and risk of dementia among nationally

representative sample of Medicare

beneficiaries.

Adjusted OR of Dementia and Alzheimer’s Disease

Results

A total of 8,741 community-dwelling

Medicare beneficiaries were included in the

analysis. There were no significant

differences observed between two groups in

regarding to mean age, distribution of

gender and race.

Compared to the controls, the proportion of

dementia cases receiving anti-diabetic drugs

was significantly higher over the two-year

period (Insulins 7.1% vs. 3.7%; metformin,

9.1% vs. 8.0%; sulfonylurea, 13.3% vs.

10.8%; thiazolidinedione, 7.1% vs. 4.7%).

Compared to non-users, elderly receiving

anti-diabetics drugs did not have an altering

risk of developing dementia (adjusted OR

[AOR], 0.96; 95% Confidence Interval [CI],

0.70-1.32), and Alzheimer's disease (AOR,

0.93; 95% CI, 0.59-1.47), after controlling

for demographics, socioeconomics, smoking

status, BMI, ADL difficulties, and

comorbidities

Individuals receiving insulins had higher AOR

of having AD and dementia than the non-

users. However, the increased risk of AD and

dementia was not observed among the

elderly using oral anti-diabetic drugs,

suggesting the potential confounder, severity

of diabetes, which was not controlled in the

analysis.

Adjusted OR by Drug Class

Conclusions

This study does not provide enough evidence that use of anti-diabetic drugs, such as metformin, sulfonylurea, thiazolidinedione, are associated with the altering risk of developing AD and related dementia.

Considering the high prevalence of diabetes, future studies are warranted with longer follow-up period and larger sample size, to better understand the effect of anti-diabetic medication therapy on the risk of AD and related dementia.

References

1. Plassman BL, Langa KM, Fisher GG, Heeringa SG, Weir DR, Ofstedal MB, et al. Prevalence of dementia in the United States: the aging, demographics, and memory study. Neuroepidemiology. 2007;29(1-2):125-32.

2. Brookmeyer R, Gray S, Kawas C. Projections of Alzheimer's disease in the United States and the public health impact of delaying disease onset. Am J Public Health. 1998 Sep;88(9):1337-42.

3. Arvanitakis Z, Wilson RS, Bienias JL, Evans DA, Bennett DA. Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function. Arch Neurol. 2004 May;61(5):661-6.

4. Irie F, Fitzpatrick AL, Lopez OL, Kuller LH, Peila R, Newman AB, et al. Enhanced risk for Alzheimer disease in persons with type 2 diabetes and APOE epsilon4: the Cardiovascular Health Study Cognition Study. Arch Neurol. 2008 Jan;65(1):89-93.

5. Ott A, Stolk RP, van Harskamp F, Pols HA, Hofman A, Breteler MM. Diabetes mellitus and the risk of dementia: The Rotterdam Study. Neurology. 1999 Dec 10;53(9):1937-42.

6. Peila R, Rodriguez BL, Launer LJ. Type 2 diabetes, APOE gene, and the risk for dementia and related pathologies: The Honolulu-Asia Aging Study. Diabetes. 2002 Apr;51(4):1256-62.

Corresponding: Kevin Lu, luk@sccp.sc.edu

Methods

Controls

• 1:5 matching

• Age, gender, race and year of the initial

interview.

Exposure

• presence of at least one prescription of

anti-diabetics drugs

• Self/proxy-reported use or pharmacy

claims

Data analysis

• Descriptive statistics

– t tests for continuous variables and

– chi-square tests for categorical variables

• Association between drug use and

dementia

– conditional logistic regressions

– control for potential confounders

• Confounders include demographics,

socioeconomics, smoking status, BMI,

ADL difficulties, and comorbidities.

Characteristics Dementia Alzheimer's

Disease

OR 95% CI OR 95% CI

Anti-diabetic drugs

No Ref ─ Ref ─

Yes 0.96 (0.70-1.32) 0.93 (0.59-1.47)

Education

< high school Ref ─ Ref ─

High school/GED 0.85 (0.72-1.00) 0.85 (0.68-1.08)

>high school 0.84 (0.70-1.02) 0.78 (0.59-1.03)

Income

$10,000 or less Ref ─ Ref ─

$10,001-25,000 0.72 (0.62-0.85) 0.70 (0.55-0.88)

$25,001-50,000 0.65 (0.54-0.79) 0.73 (0.56-0.95)

$50,001 and more 0.76 (0.59-0.97) 0.88 (0.62-1.23)

Metropolitan Statistical Areas

No Ref ─ Ref ─

Yes 1.00 (0.88-1.15) 1.00 (0.82-1.22)

Census regions

Northeast Ref ─ Ref ─

Midwest 1.03 (0.86-1.24) 0.99 (0.77-1.28)

South 1.11 (0.94-1.31) 1.10 (0.87-1.39)

West 0.94 (0.78-1.14) 0.87 (0.66-1.14)

Prescription Coverage

No Ref ─ Ref ─

Yes 1.02 (0.89-1.16) 1.11 (0.92-1.33)

Smoking

Never Ref ─ Ref ─

Past 0.96 (0.85-1.09) 0.87 (0.73-1.04)

Current 1.10 (0.89-1.36) 0.93 (0.69-1.25)

Any ADL Difficulty

No Ref ─ Ref ─

Yes 1.55 (1.37-1.76) 1.43 (1.20-1.71)

BMI, kg/m2

<25.0 Ref ─ Ref ─

25.0-29.9 0.83 (0.73-0.94) 0.82 (0.69-0.98)

≥30.0 0.62 (0.52-0.73) 0.55 (0.43-0.70)

Diabetes

No Ref ─ Ref ─

Yes 1.05 (0.86-1.29) 0.89 (0.66-1.20)

Charlson Comorbidity Index 1.07 (1.03-1.10) 1.02 (0.97-1.07)

Characteristics Dementia Alzheimer's

Disease

OR 95% CI OR 95% CI

Insulins

No Ref ─ Ref ─

Yes 1.62 (1.22-2.16) 1.87 (1.26-2.78)

Metformin

No Ref ─ Ref ─

Yes 0.97 (0.75-1.26) 1.25 (0.87-1.81)

Sulfonylurea

No Ref ─ Ref ─

Yes 1.05 (0.81-1.36) 1.05 (0.73-1.52)

TZD

No Ref ─ Ref ─

Yes 1.32 (0.99-1.79) 1.04 (0.66-1.66)

DDP-4

No Ref ─ Ref ─

Yes 1.05 (0.60-1.84) 1.40 (0.69-2.83)

Combination

No Ref ─ Ref ─

Yes 0.89 (0.59-1.34) 1.06 (0.58-1.92)

The Association of Anti-Diabetic Drugs Use and Alzheimer's Disease and Related Dementia

Among the Medicare Beneficiaries