February 2012 FDA Drug Safety Warning About Lipitor Label Change Concerning New-Onset Diabetes Mellitus (DM) Has Gone Largely Unnoticed To Date
(Posted by Tom Lamb at DrugInjuryWatch.com)
Statins are a class of prescription drugs used together with diet and exercise to reduce blood levels of low-density lipoprotein (LDL) cholesterol (“bad cholesterol”). One of these medications is Lipitor (atorvastatin) from Pfizer.
From the February 28, 2012 "FDA Drug Safety Communication: Important safety label changes to cholesterol-lowering statin drug":
... High-dose [Lipitor (atorvastatin)] had also been associated with worsening glycemic control in the Pravastatin or Atorvastatin Evaluation and Infection Therapy – Thrombolysis In Myocardial Infarction 22 (PROVE-IT TIMI 22) substudy.
FDA also reviewed the published medical literature. A meta-analysis by Sattar et al., which included 13 statin trials with 91,140 participants, reported that statin therapy was associated with a 9% increased risk for incident diabetes (odds ratio [OR] 1.09; 95% confidence interval [CI] 1.02-1.17), with little heterogeneity (I2=11%) between trials. A meta-analysis by Rajpathak et al., which included 6 statin trials with 57,593 participants, also reported a small increase in diabetes risk (relative risk [RR] 1.13; 95% CI 1.03-1.23), with no evidence of heterogeneity across trials. A recent study by Culver et al., using data from the Women’s Health Initiative, reported that statin use conveys an increased risk of new-onset diabetes in postmenopausal women, and noted that the effect appears to be a medication class effect, unrelated to potency or to individual statin.
Based on clinical trial meta-analyses and epidemiological data from the published literature, information concerning an effect of statins on incident diabetes and increases in HbA1c and/or fasting plasma glucose was added to statin labels. [footnotes omitted]
Strictly Confidential, No Obligation.
Some of the medical journal articles reviewed by the FDA prior to issuing this Lipitor - diabetes warning include:
- High-dose atorvastatin associated with worse glycemic control: a PROVE-IT TIMI 22 substudy. Circulation. 2004;110(Suppl I):S834.
- Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet. 2010;375(9716):735-742.
- Statin therapy and risk of developing type 2 diabetes: a meta-analysis. Diabetes Care. 2009;32(10):1924-1929.
- Effect of statins on fasting plasma glucose in diabetic and nondiabetic patients. J Investig Med. 2009;57:495-499.
- Atorvastatin causes insulin resistance and increases ambient glycemia in hypercholesterolemic patients. J Am Coll Cardiol. 2010;55:1209-1216.
- Effects of maximal atorvastatin and rosuvastatin treatment on markers of glucose homeostasis and inflammation. Am J Cardiol. 2011;107:387-392.
- Do statins beneficially or adversely affect glucose homeostasis? Curr Vasc Pharmacol. 2010;8:612-631.
- Efficacy and safety of statin treatment for cardiovascular disease: a network meta-analysis of 170,255 patients from 76 randomized trials. QJM. 2011;104:109-124.
- Statin use and risk of diabetes mellitus in postmenopausal women in the Women's Health Initiative. Arch Intern Med. 2012;172(2):144-152.
From the Abstract for this last medical article listed above, which was published in the January 23, 2012 edition of Archives of Internal Medicine (now called JAMA Internal Medicine), we get these points about this still-emerging drug safety issue concerning diabetes and Lipitor, as well as other statin cholesterol drugs:
Background This study investigates whether the incidence of new-onset diabetes mellitus (DM) is associated with statin use among postmenopausal women participating in the Women's Health Initiative (WHI).
Methods The WHI recruited 161 808 postmenopausal women aged 50 to 79 years at 40 clinical centers across the United States from 1993 to 1998 with ongoing follow-up. The current analysis includes data through 2005....
Results ....Statin use at baseline was associated with an increased risk of DM (hazard ratio [HR], 1.71; 95% CI, 1.61-1.83). This association remained after adjusting for other potential confounders (multivariate-adjusted HR, 1.48; 95% CI, 1.38-1.59) and was observed for all types of statin medications....
Conclusions Statin medication use in postmenopausal women is associated with an increased risk for DM. This may be a medication class effect. Further study by statin type and dose may reveal varying risk levels for new-onset DM in this population.
And from the final paragraph of that January 2012 medical journal article: "However, the consequences of statin-induced DM have not been specifically defined and deserve more attention." [emphasis added]
We will continue to watch for medical and regulatory developments as regards new-onset diabetes mellitus (DM), or Type-2 diabetes, associated with Lipitor and other statins.