2. Article
Culver AL, Ockene IS, Balasubramanian R, et al.
Statin Use and Risk of Diabetes Mellitus in
Postmenopausal Women in the Women's
Health Initiative.
Arch Intern Med. 2012;172(2):144-52.
3. Background
Statins are used by a large proportion
of our population
The most recent and reliable data (gleaned from the 2003-
2004 NHANES) estimates that 24 million Americans
are on statins. That number has almost certainly risen
since then.
4. Background
With such a large number of people taking these
medications, even minor adverse effects become a
significant problem.
Recent studies reveal a correlation between statin use
and an increased risk of developing diabetes.
Note that there is still no causal evidence
linking statins to the development of diabetes.
5. Background
JUPITER Trial | RCT | 2008
Newly diagnosed diabetes was 3.0% in the rosuvastatin arm
(compared to 2.4% in the placebo arm)
Preiss D, et. al. | Meta-analysis | 2011
Dose-related increase in the incidence of diabetes with statin use
Sattar N, et. al. | Meta-analysis | 2010
9% relative risk increase in incidence diabetes for subjects receiving a
statin medication
6. Motivation
Meta-analyses are weakened by heterogeneity and
small study populations
Single-drug studies may not be applicable to the
entire class of medications
7. Objective
To evaluate the overall effect of statin medication use on
incident DM risk in a large dataset (in this case the
Women’s Health Initiative (WHI) data).
8. Design
Restrospective cohort using the Women’s Health Initiative
(WHI) dataset
The Women’s Health Initiative (WHI) was a large 15-year long
clinical and observational study.
There were three clinical trial groups (CT)…
1) Hormone Therapy Trial (HT) (27,347)
2) Dietary Modification Trial (DM) (48,835)
3) Calcium/Vitamin D Supplementation Trial (CaD) (36,282)
…and an additional (4) observational study group (OS)
10. SubjectsInclusion & Exclusion
Inclusion
Post menopausal women aged 50-79
Exclusion
Self-reported DM at baseline
Use of cerivastatin (removed from market)
11. Measurements
Statin use
“Inventoried” all current medications at baseline and year 3.
New-onset diabetes
Identified by questionnaire at each visit and defined as a
self-report of a new physician diagnosis of diabetes
13. Demographics
Large amount of
heterogeniety
Several character-
istics put the statin
group at increased
risk of developing
diabetes
Worse diet
Less exercise
Family hx
14. Outcomes
Statin use at base-
line was associated
with a statistically
significant increase
in incident DM
…even after multi-
variate adjustment
…and regardless of
duration or specific
statin usage.
15. Outcomes
The increased risk is
found throughout all
subgroups tested,
including:
Age
Race/ethnicity
BMI
This holds true even
after multivariate
adjustment†
†Exceptfor African Americans,
thought this maybe due to a lack
of power for this subgroup.
16. Outcomes
After multivariate adjustment, statin use was still associated with statis-
tically significant increase in incident DM regardless of the time period it
was used (baseline, 3 year follow-up, or both).
17. Outcomes
A subset of women with and without a history of CVD were analyzed to
address the effect of confounding variables and selection bias. There was
still a statistically significant increase in incidence DM in the women on
statin therapy, regardless of their CVD history (HR 1.46; 95% CI 1.29-1.65).
18. Outcomes
A propensity score adjusted model added to the
multivariate analysis continue to showed an increased risk
of incident DM (HR 1.40; 95% CI 1.31-1.51)
A unadjusted sensitivity analysis used fasting glucose in
approximately 3700 women (instead of self-reported new
physician diagnosed DM) did not show the increased risk
(HR 1.06; 95% CI 0.61-1.86)
19. Conclusions
There is clearly a relationship between statin use and the
development of diabetes.
A causal link has yet to be established.
Statins have proven cardiovascular benefits through
randomized, controlled trials.
Patients with a legitimate indication for statin therapy
should continue to take those medications.
