Review

Statins may increase diabetes, but benefit still outweighs risk

Byron J. Hoogwerf, MD, FACP, FACE
Cleveland Clinic Journal of Medicine January 2023, 90 (1) 53-62; DOI: https://doi.org/10.3949/ccjm.90a.22069

Article Figures & Data

Figures

  • Figure 1
    Figure 1

    Risk of new-onset diabetes according to statin use, prediabetes, and elevated triglyceride (TG) level in the Treating to New Targets trial and the Stroke Prevention by Aggressive Reduction in Cholesterol Levels trial. For triglycerides, 1.7 mmol/L = 150 mg/dL.

    Reprinted from Am J Cardiol, Vol 118(9), Kohli P, Knowles JW, Sarraju A, Waters DD, Reaven G. Metabolic markers to predict incident diabetes mellitus in statin-treated patients (from the Treating to New Targets and the Stroke Prevention by Aggressive Reduction in Cholesterol Levels Trials), pages 1275–1281; 2016, with permission from Elsevier.

  • Figure 2
    Figure 2

    Risk of new-onset diabetes by statin use, prediabetes, and body mass index (BMI) in the Treating to New Targets trial and the Stroke Prevention by Aggressive Reduction in Cholesterol Levels trial.

    Reprinted from Am J Cardiol, Vol 118(9), Kohli P, Knowles JW, Sarraju A, Waters DD, Reaven G. Metabolic markers to predict incident diabetes mellitus in statin-treated patients (from the Treating to New Targets and the Stroke Prevention by Aggressive Reduction in Cholesterol Levels Trials), pages 1275–1281; 2016, with permission from Elsevier.

  • Figure 3
    Figure 3

    Risk of new-onset diabetes by statin use, prediabetes, and body mass index in the Treating to New Targets and the Stroke Prevention by Aggressive Reduction in Cholesterol Levels trials (Atorva = atorvastatin; CI = confidence interval; HR = hazard ratio).

    Reprinted from Am J Cardiol, Vol 118(9), Kohli P, Knowles JW, Sarraju A, Waters DD, Reaven G. Metabolic markers to predict incident diabetes mellitus in statin-treated patients (from the Treating to New Targets and the Stroke Prevention by Aggressive Reduction in Cholesterol Levels Trials), pages 1275–1281; 2016, with permission from Elsevier.

Tables

  • TABLE 1

    Statins and diabetes: Results of 13 trials

    Trial and statinRisk of diabetes with statin use
    Trial of atorvastatin
     ASCOT-LLA (Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm)Higher
    Trials of simvastatin
     HPS (Heart Protection Study)Higher
     4S (Scandinavian Simvastatin Survival Study)Higher
    Trials of rosuvastatin
     JUPITER (Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin)Higher
     CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure)Higher
     GISSI HF (Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico–Heart Failure)Higher
    Trials of pravastatin
     WOSCOPS (West of Scotland Coronary Prevention StudyLower
     LIPID (Long-Term Intervention with Pravastatin in Ischaemic Disease)Lower
     MEGA (Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese)Higher
     ALLHAT-LLT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial)Higher
     GISSI PREVENZIONE (Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico–Prevenzione)Lower
     PROSPER (Prospective Study of Pravastatin in the Elderly at Risk)Higher
    Trial of lovastatin
     AFCAPS/TexCAPS (Air Force/Texas Coronary Atherosclerosis Prevention Study)Lower

    • Based on information from reference 5.

  • TABLE 2

    Categories of statin therapy

    High intensity (lowers LDL-C at least 50%)
    Atorvastatin 40–80 mg
    Rosuvastatin 20–40 mg
    Moderate intensity (lowers LDL-C 30%–49%)
    Atorvastatin 10–20 a mg
    Fluvastatin 40 mg twice a day
    Fluvastatin XL 80 mg a
    Pitavastatin 1–4 mg a
    Pravastatin 40–80 mg
    Rosuvastatin 5a–10 mg
    Simvastatin 20–40 mg
    Low intensity (lowers LDL-C less than 30%)
    Fluvastatin 20–40 mg a
    Lovastatin 20 mg
    Pravastatin 10–20 mg
    Simvastatin 10 mg a

    • ↵a Not evaluated in randomized controlled trials at dosage shown.

    • LDL-C = low-density lipoprotein cholesterol

    • Based on information in reference 9.

  • TABLE 3

    Starting statin therapy: Things to consider and discuss

    For all patients when considering statin therapy:
    Screen to determine baseline glycemic status
    Consider nonstatin therapies to lower cholesterol (resins, ezetimibe, bempedoic acid)
    Consider variables associated with an increased risk of diabetes, including potentially adverse antihypertensive drugs (thiazides and beta-blockers) and potentially beneficial antihypertensive drugs (angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers)
    When starting statin therapy in patients without diabetes, discuss:
    The possibility of developing diabetes mellitus
    Types and doses of statins
    Benefits of statins in reducing the risk of cardiovascular disease generally far outweigh risks on the development of new-onset diabetes
    For patients with diabetes mellitus, discuss:
    The possible adverse effects of statins on glycemic control, which are small
    The benefits of statins in reducing the risk of atherosclerotic cardiovascular disease, which significantly outweigh a small increase in hemoglobin A1c
    Adverse glycemic effects of statins can be mitigated by glucose-lowering therapies, especially those with favorable cardiovascular profiles

    • Based on recommendations from references 9, 40, and 41.

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