Impact of statin therapy on glycemic status in diabetes-naïve patients: a systematic review
DOI:
https://doi.org/10.18203/2320-6012.ijrms20260353Keywords:
Diabetes-naïve, Fasting plasma glucose, Glycemic status, HbA1c, New-onset diabetes mellitus, Systematic review, StatinsAbstract
While statins are widely prescribed for the primary prevention of cardiovascular disease, recent evidence suggests that they may influence glucose regulation and contribute to the development of new-onset diabetes mellitus (NODM) in individuals without pre-existing diabetes. This systematic review evaluates the impact of statin therapy on glycemic parameters in diabetes-naïve adults. Electronic databases were searched for studies assessing the effects of statins on fasting plasma glucose (FPG), HbA1c, insulin sensitivity and NODM, including randomized controlled trials, cohort studies and case–control studies. A qualitative synthesis was performed and results were summarized in tables. Fifteen studies involving more than 600,000 participants were included. Statin therapy was associated with increases in FPG ranging from 3 to 12 mg/dl and HbA1c from 0.1 to 0.4%. A higher risk of NODM was observed with high-dose and prolonged statin use. Findings regarding insulin sensitivity and β-cell function were variable and certain statins such as pitavastatin demonstrated a more favorable glycemic profile. Although a small deterioration in glycemic control was noted, the absolute risk of diabetes remained low. Overall, statin therapy in diabetes-naïve patients is associated with modest worsening of glycemic indices and a slight increase in NODM risk, particularly with high-intensity regimens or in individuals with baseline metabolic risk factors; however, the cardiovascular benefits of statins outweigh these potential glycemic effects, supporting their continued use with appropriate monitoring and individualized risk assessment.
Metrics
References
International Diabetes Federation. IDF Diabetes Atlas. 10th ed. Brussels: International Diabetes Federation. 2021.
American Diabetes Association. Classification and diagnosis of diabetes: Standards of Medical Care in Diabetes—2023. Diabetes Care. 2023;46(1):19–40.
Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, et al. 2018 AHA/ACC guideline on the management of blood cholesterol. Circulation. 2019;139(25):1082–143. DOI: https://doi.org/10.1161/CIR.0000000000000625
Cholesterol Treatment Trialists’ (CTT) Collaborators. Efficacy and safety of statin therapy in reducing cardiovascular risk. Lancet. 2010;376(9753):1670–81. DOI: https://doi.org/10.1016/S0140-6736(10)61350-5
Newman CB, Preiss D, Tobert JA, Jacobson TA, Page RL, Goldstein LB, et al. Statin safety and associated adverse events. Circulation. 2019;140(5):69–89.
Sattar N, Preiss D, Murray HM, Welsh P, Buckley BM, de Craen AJM, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomized statin trials. Lancet. 2010;375(9716):735–42. DOI: https://doi.org/10.1016/S0140-6736(09)61965-6
Preiss D, Seshasai SR, Welsh P, Murphy SA, Ho JE, Waters DD, et al. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy. JAMA. 2011;305(24):2556–64. DOI: https://doi.org/10.1001/jama.2011.860
Ridker PM, Danielson E, Fonseca FAH, Genest J, Gotto AM, Kastelein JJP, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359(21):2195–207. DOI: https://doi.org/10.1056/NEJMoa0807646
Koh KK, Quon MJ, Han SH, Chung WJ, Ahn JY, Kim JA. Atorvastatin causes insulin resistance and increases ambient glycemia in hypercholesterolemic patients. J Am Coll Cardiol. 2010;55(12):1209–16. DOI: https://doi.org/10.1016/j.jacc.2009.10.053
Cederberg H, Stancáková A, Yaluri N, Modi S, Kuusisto J, Laakso M. Increased risk of diabetes with statin treatment is associated with impaired insulin sensitivity and insulin secretion. Diabetologia. 2015;58(5):1109–17. DOI: https://doi.org/10.1007/s00125-015-3528-5
Mansi I, Frei CR, Pugh MJ, Makris U, Mortensen EM. Statins and new-onset diabetes mellitus. Am J Cardiol. 2015;115(3):390–6.
Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, et al. 2019 ESC/EAS guidelines for the management of dyslipidaemias. Eur Heart J. 2020;41(1):111–188. DOI: https://doi.org/10.1093/eurheartj/ehz455
Erqou S, Lee CC, Adler AI. Statins and glycaemic control in individuals with diabetes: a systematic review and meta-analysis. Diabetologia. 2014;57(12):2444–52.
Cui Y, Blumenthal RS, Flaws JA, Whiteman MK, Langenberg P, Bachorik PS. Non–high-density lipoprotein cholesterol level as a predictor of glycemic status in statin-treated patients. Am J Cardiol. 2014;113(7):1164–70.
Goldstein MR, Mascitelli L, Pezzetta F. Statins, diabetes and risk-benefit analysis. QJM. 2012;105(12):1141–9. DOI: https://doi.org/10.1093/qjmed/hcs204
Carter AA, Gomes T, Camacho X, Juurlink DN, Shah BR, Mamdani MM. Risk of incident diabetes among patients treated with statins: population based study. BMJ. 2013;346:2610. DOI: https://doi.org/10.1136/bmj.f2610
Zaharan NL, Williams D, Bennett K. Statins and risk of treated incident diabetes in a primary care population. Br J Clin Pharmacol. 2013;75(4):1118–24. DOI: https://doi.org/10.1111/j.1365-2125.2012.04403.x
Mansi I, Frei CR, Pugh MJ, Makris U, Mortensen EM. Statins and new-onset diabetes mellitus and diabetic complications in primary prevention. Am J Cardiol. 2015;115(3):390–6.
Sukhija R, Prayaga S, Marashdeh M, Bursac Z, Kakar P, Bansal D, et al. Effect of statins on fasting plasma glucose in diabetic and nondiabetic patients. J Investig Med. 2009;57(3):495–9. DOI: https://doi.org/10.2310/JIM.0b013e318197ec8b
Navarese EP, Buffon A, Andreotti F, Kozinski M, Welton N. Meta-analysis of impact of different types and doses of statins on new-onset diabetes mellitus. Am J Cardiol. 2013;111(8):1123–30. DOI: https://doi.org/10.1016/j.amjcard.2012.12.037
Erqou S, Lee CC, Adler AI. Statins and glycaemic control in individuals without diabetes: systematic review and meta-analysis. Diabetologia. 2014;57(12):2444–52. DOI: https://doi.org/10.1007/s00125-014-3374-x
Crandall JP, Mather K, Rajpathak SN, Goldberg RB, Watson KE, Ratner R, et al. Statin use and risk of developing diabetes: results from the Diabetes Prevention Program. BMJ Open Diabetes Res Care. 2017;5(1):438. DOI: https://doi.org/10.1136/bmjdrc-2017-000438
Freeman DJ, Norrie J, Sattar N, Neely RDG, Cobbe SM, Ford I, et al. Pravastatin and the development of diabetes mellitus: evidence from a randomized controlled trial. Circulation. 2001;103(3):357–62. DOI: https://doi.org/10.1161/01.CIR.103.3.357
Kearney PM, Blackwell L, Collins R, Keech A, Simes J, Peto R, et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of statin trials. Lancet. 2008;371(9607):117–25. DOI: https://doi.org/10.1016/S0140-6736(08)60104-X
Yada T, Nakagawa T, Uemura H, Yoshida S, Iwata H, Nakanishi M. Effects of pitavastatin on glucose metabolism in patients with dyslipidemia. J Atheroscler Thromb. 2016;23(8):941–50.
Dormuth CR, Filion KB, Paterson JM, James MT, Teare GF, Raymond CB, et al. Higher potency statins and the risk of new diabetes: multicentre observational study. BMJ. 2014;348:3244. DOI: https://doi.org/10.1136/bmj.g3244
Culver AL, Ockene IS, Balasubramanian R, Olendzki BC, Sepavich DM, Wactawski-Wende J, et al. Statin use and risk of diabetes mellitus in postmenopausal women. Arch Intern Med. 2012;172(2):144–52. DOI: https://doi.org/10.1001/archinternmed.2011.625
Djoussé L, Biggs ML, Mukamal KJ, Ix JH, Zieman SJ, Siscovick DS, et al. Statin use and risk of diabetes in the Cardiovascular Health Study. Diabetes Care. 2012;35(2):391–7. DOI: https://doi.org/10.2337/dc11-1690
Thakker D, Nair S, Pagada A, Jamdade V, Malik A. Statin use and the risk of developing diabetes: a network meta-analysis. Pharmacoepidemiol Drug Saf. 2016;25(10):1131–49. DOI: https://doi.org/10.1002/pds.4020
Betteridge DJ, Carmena R. The diabetogenic action of statins: mechanisms and clinical implications. Curr Opin Lipidol. 2016;27(6):597–604.
Downloads
Published
How to Cite
Issue
Section
