Statin use was associated with a statistically significant increased risk of developing diabetes in postmenopausal women according to a study using data from the Women's Health Initiative. The risk was found across all subgroups tested and persisted even after adjusting for potential confounding factors. However, the study did not prove causation and a subset analysis using fasting glucose did not replicate the increased risk finding. The authors conclude statins have cardiovascular benefits but more research is needed to establish if they causally increase diabetes risk.

1. Statins & Diabetes
by Theodore Graphos
February 2, 2012

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)

9. SubjectsSelection

10. SubjectsInclusion & 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

12. Results…

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.

20. Questions?