[Skip to Navigation]
Views 19,186
Citations 0
Original Investigation
October 4, 2021

Association of Statin Therapy Initiation With Diabetes Progression: A Retrospective Matched-Cohort Study

Author Affiliations
  • 1Department of Medicine, VA North Texas Health Care System, Dallas
  • 2Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas
  • 3Department of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas
  • 4Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center, Dallas
  • 5Department of Pharmacy Practice, Texas Tech University Health Sciences Center, Dallas
JAMA Intern Med. Published online October 4, 2021. doi:10.1001/jamainternmed.2021.5714
Key Points

Question  What is the association of statin treatment initiation and diabetes progression in patients with diabetes?

Findings  This large retrospective cohort study included 83 022 propensity-scored matched pairs of statin users and nonusers and found that the diabetes-progression composite outcome was significantly higher among patients with diabetes who used statins than among patients with diabetes who did not use statins. The study examined 12 years of data on patients covered by the Veterans Affairs health system and new-user and active-comparator designs to assess associations between statin initiation and diabetes progression from 2003 to 2015.

Meaning  Statin use was associated with diabetes progression in patients with diabetes—statin users had a higher likelihood of insulin treatment initiation, developing significant hyperglycemia, experiencing acute glycemic complications, and being prescribed an increased number of glucose-lowering medication classes.

Abstract

Importance  Statin therapy has been associated with increased insulin resistance; however, its clinical implications for diabetes control among patients with diabetes is unknown.

Objective  To assess diabetes progression after initiation of statin use in patients with diabetes.

Design, Setting, and Participants  This was a retrospective matched-cohort study using new-user and active-comparator designs to assess associations between statin initiation and diabetes progression in a national cohort of patients covered by the US Department of Veterans Affairs from fiscal years 2003-2015. Patients included were 30 years or older; had been diagnosed with diabetes during the study period; and were regular users of the Veterans Affairs health system, with records of demographic information, clinical encounters, vital signs, laboratory data, and medication usage.

Interventions  Treatment initiation with statins (statin users) or with H2-blockers or proton pump inhibitors (active comparators).

Main Outcomes and Measures  Diabetes progression composite outcome comprised the following: new insulin initiation, increase in the number of glucose-lowering medication classes, incidence of 5 or more measurements of blood glucose of 200 mg/dL or greater, or a new diagnosis of ketoacidosis or uncontrolled diabetes.

Results  From the 705 774 eligible patients, we matched 83 022 pairs of statin users and active comparators; the matched cohort had a mean (SD) age of 60.1 (11.6) years; 78 712 (94.9%) were men; 1715 (2.1%) were American Indian/Pacific Islander/Alaska Native, 570 (0.8%) were Asian, 17 890 (21.5%) were Black, and 56 633 (68.2 %) were White individuals. Diabetes progression outcome occurred in 55.9% of statin users vs 48.0% of active comparators (odds ratio, 1.37; 95% CI, 1.35-1.40; P < .001). Each individual component of the composite outcome was significantly higher among statin users. Secondary analysis demonstrated a dose-response relationship with a higher intensity of low-density lipoprotein-cholesterol lowering associated with greater diabetes progression.

Conclusions and Relevance  This retrospective matched-cohort study found that statin use was associated with diabetes progression, including greater likelihood of insulin treatment initiation, significant hyperglycemia, acute glycemic complications, and an increased number of prescriptions for glucose-lowering medication classes. The risk-benefit ratio of statin use in patients with diabetes should take into consideration its metabolic affects.

Limit 200 characters
Limit 25 characters
Conflicts of Interest Disclosure

Identify all potential conflicts of interest that might be relevant to your comment.

Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.

Err on the side of full disclosure.

If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.

Not all submitted comments are published. Please see our commenting policy for details.

Limit 140 characters
Limit 3600 characters or approximately 600 words
    1 Comment for this article
    EXPAND ALL
    Looking at the Whole Picture
    Marc Rendell, M.D. | The Rose Salter Medical Research Foundation and the Association of Diabetes Investigators
    The use of statins has  been associated with decreased cardiovascular mortality. Studies of overall mortality have been somewhat less conclusive (1), but a retrospective cohort study in the Veterans Administration population also using propensity scoring showed a hazard ratio favoring statin use of 0.75 (95% CI, 0.74-0.76) for all-cause mortality, and 0.80 (95% CI, 0.78-0.81) for cardiovascular mortality (2). The study by Mansi et al (3) suggests that statin use was associated with worsening events associated with diabetes. Certainly diabetes is a strong driver of increased mortality. It would be interesting for the authors  to broaden their investigation to look at overall mortality in their population to assure that the findings are not simply related to their propensity scoring approach.

    1) Alla VM, Agrawal V, DeNazareth A, et al.A reappraisal of the risks and benefits of treating to target with cholesterol lowering drugs.Drugs. 2013 Jul;73(10):1025-54

    2) Orkaby AR, Driver JA, Ho Y, et al. Association of Statin Use With All-Cause and Cardiovascular Mortality in US Veterans 75 Years and Older. JAMA. 2020;324(1):68–78.

    3) Mansi IA, Chansard M, Lingvay I, Zhang S, Halm EA, Alvarez CA. Association of Statin Therapy Initiation With Diabetes Progression: A Retrospective Matched-Cohort Study. JAMA Intern Med. Published online October 04, 2021
    CONFLICT OF INTEREST: None Reported
    READ MORE
    ×