russjcardiolРоссийский кардиологический журналRussian Journal of Cardiology1560-40712618-7620«SILICEA-POLIGRAF» LLC10.15829/1560-4071-2018-9-89-99russjcardiol-2962Research ArticleОБЗОРЫ ЛИТЕРАТУРЫREVIEWСахарный диабет, ассоциированный с терапией статинами: статус проблемы 2018 годStatins associated diabetes: state of the problem in 2018https://orcid.org/0000-0002-5873-1768КобалаваЖ. Д.KobalavaZh. D.

Кобалава Жанна Давидовна  — доктор медицинских наук, профессор, зав. кафедрой внутренних болезней с курсом кардиологии и функциональной диагностики медицинского института.

Москва

ResearcherID: S-3842-2016

Moscow

zkobalava@mail.ruhttps://orcid.org/0000-0003-4769-5834ЛазаревП. В.LazarevP. V.

Лазарев Павел Валерьевич — кандидат медицинских наук, ассистент кафедры внутренних болезней с курсом кардиологии и функциональной диагностики медицинского института.

Москва

ResearcherID: G-3242-2015

Moscow

spaceman665@gmail.comhttps://orcid.org/0000-0001-7652-3962ВиллевальдеС. В.VillevaldeS. V.

Виллевальде Светлана Вадимовна  — доктор медицинских наук, профессор, заведующая кафедрой кардиологии.

Санкт-Петербург

ResearcherID: R-8672-2016

Saint-Petersburg

villevaldes@mail.ruФГАОУ ВО Российский университет дружбы народовРоссияPeoples’ Friendship University of RussiaRussian FederationФГБУ НМИЦ им. В.А. Алмазова Минздрава РоссииРоссияAlmazov National Research Medical Center of the Ministry of HealthRussian Federation201823092018098999Copyright © Кобалава Ж.Д., Лазарев П.В., Виллевальде С.В., 20182018Кобалава Ж.Д., Лазарев П.В., Виллевальде С.В.Kobalava Z.D., Lazarev P.V., Villevalde S.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://russjcardiol.elpub.ru/jour/article/view/2962

Терапия статинами является незаменимым и высокоэффективным методом снижения сердечно-сосудистого риска при первичной и вторичной профилактике и хорошо переносится пациентами. Однако риск развития новых случаев сахарного диабета, ассоциированного с приемом статинов, остается предметом непрекращающейся дискуссии. В обзоре представлены актуальные данные о  распространенности этого нежелательного явления, соотношении “польза/риск”, возможных патогенетических механизмах и популяциях пациентов с наибольшим риском развития диабета на фоне терапии статинами. Проанализирована врачебная тактика при развитии диабета на фоне применения статинов. В статье приведены данные актуальных международных рекомендаций и согласительных документов, а также сравнение с новыми препаратами, используемыми в профилактике сердечно-сосудистых заболеваний.

Statin therapy is highly effective and obligatory method of cardiovascular risk reduction in primary and secondary prevention. It is well tolerated by patients. However the risk of new diabetes cases onset, associated with statins, remains discussed actively. The review is focused on recent data on the prevalence of this adverse event, risk/benefit ratio, possible mechanisms and patients populations with the highest risk of development of statin related diabetes. Practitioners tactics analyzed in diabetes development when taking statins. The article goes with recent international guidelines data, as the consensus letters; also, a comparison provided with novel medications used in cardiovascular prevention.

статинысахарный диабетсердечно-сосудистый рискstatinsdiabetescardiovascular riskReferencesЕжов М. В., Сергиенко И. В., Аронов Д. М. и др. Диагностика и коррекция нарушений липидного обмена с целью профилактики и лечения атеросклероза. Российские рекомендации. VI пересмотр. Атеросклероз и дислипидемии. 2017;3(38):5-22.Ezhov MV, Sergienko IV, Aronov DM, et al. Diagnosis and correction of impairments of lipid metabolism for prevention and treatment of atherosclerosis. Russian Guidelines. VI Revision. Atherosclerosis and dyslipidemias. 2017;3(38):5-22. (In Russ.)Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63(25 Pt B):2889-934. doi:10.1016/j.jacc.2013.11.002.Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63(25 Pt B):2889-934. doi:10.1016/j.jacc.2013.11.002.Catapano AL, Graham I, De Backer G, et al. 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias. Eur Heart J. 2016;37(39):2999-3058. doi:10.1093/eurheartj/ehw272.Catapano AL, Graham I, De Backer G, et al. 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias. Eur Heart J. 2016;37(39):2999-3058. doi:10.1093/eurheartj/ehw272.Baigent C, Blackwell L, Emberson J, et al. Cholesterol Treatment Trialists’ (CTT) Collaboration, Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376(9753):1670-81. doi:10.1016/S0140-6736(10)61350-5.Baigent C, Blackwell L, Emberson J, et al. Cholesterol Treatment Trialists’ (CTT) Collaboration, Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376(9753):1670-81. doi:10.1016/S0140-6736(10)61350-5.Mihaylova B, Emberson J, Blackwell L, et al. Cholesterol Treatment Trialists’ (CTT) Collaborators, The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet. 2012; 380(9841):581-90. doi:10.1016/S0140-6736(12)60367-5.Mihaylova B, Emberson J, Blackwell L, et al. Cholesterol Treatment Trialists’ (CTT) Collaborators, The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet. 2012; 380(9841):581-90. doi:10.1016/S0140-6736(12)60367-5.Taylor F, Huffman MD, Macedo AF, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2013;(1):CD004816. doi:10.1002/14651858.Taylor F, Huffman MD, Macedo AF, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2013;(1):CD004816. doi:10.1002/14651858.Maki KC, Ridker PM, Brown WV, et al. An assessment by the Statin Diabetes Safety Task Force: 2014 update. J Clin Lipidol. 2014;8(3 Suppl):S17-29. doi:10.1016/j.jacl.2014.02.012.Maki KC, Ridker PM, Brown WV, et al. An assessment by the Statin Diabetes Safety Task Force: 2014 update. J Clin Lipidol. 2014;8(3 Suppl):S17-29. doi:10.1016/j.jacl.2014.02.012.Mach F, Ray KK, Wiklund O, et al. Adverse effects of statin therapy: perception vs. the evidence — focus on glucose homeostasis, cognitive, renal and hepatic function, haemorrhagic stroke and cataract. Eur Heart J. 2018;39(27):2526-39. doi:10.1093/eurheartj/ehy182.Mach F, Ray KK, Wiklund O, et al. Adverse effects of statin therapy: perception vs. the evidence — focus on glucose homeostasis, cognitive, renal and hepatic function, haemorrhagic stroke and cataract. Eur Heart J. 2018;39(27):2526-39. doi:10.1093/eurheartj/ehy182.Кобалава Ж. Д., Виллевальде С. В. Терапия статинами и риск развития сахарного диабета. Эфективная фармакотерапия. 2015;11:3-11.Kobalava ZD, Villevalde SV. Statin therapy and the risk of diabetes mellitus. Effektivnaia farmakotherapia. 2015;11:3-11. (In Russ.)Freeman DJ, Norrie J, Sattar N, et al. Pravastatin and the development of diabetes mellitus: evidence for a protective treatment effect in the West of Scotland Coronary Prevention Study. Circulation. 2001;103:357-62.Freeman DJ, Norrie J, Sattar N, et al. Pravastatin and the development of diabetes mellitus: evidence for a protective treatment effect in the West of Scotland Coronary Prevention Study. Circulation. 2001;103:357-62.Ridker PM, Danielson E, Fonseca FA, 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: 10.1056/NEJMoa0807646.Ridker PM, Danielson E, Fonseca FA, 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: 10.1056/NEJMoa0807646.Ridker PM, Pradhan A, MacFadyen JG, et al. Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial. Lancet. 2012;380(9841):565-71. doi:10.1016/S0140-6736(12)61190-8.Ridker PM, Pradhan A, MacFadyen JG, et al. Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial. Lancet. 2012;380(9841):565-71. doi:10.1016/S0140-6736(12)61190-8.Sattar N, Preiss D, Murray HM, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet. 2010;375(9716):735-42. doi:10.1016/S0140-6736(09)61965-6.Sattar N, Preiss D, Murray HM, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet. 2010;375(9716):735-42. doi:10.1016/S0140-6736(09)61965-6.Preiss D, Seshasai SR, Welsh P, et al. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA. 2011;305(24):255664. doi:10.1001/jama.2011.860.Preiss D, Seshasai SR, Welsh P, et al. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA. 2011;305(24):255664. doi:10.1001/jama.2011.860.Food and Drug Administration. FDA drug safety communication: important safety label changes to cholesterol low-ering statin drugs. http://www.fda.gov/drugs/drugsafety/ucm293101.htm (28 Feb 2012).Food and Drug Administration. FDA drug safety communication: important safety label changes to cholesterol low-ering statin drugs. http://www.fda.gov/drugs/drugsafety/ucm293101.htm (28 Feb 2012).Wang S, Cai R, Yuan Y, et al. Association between reductions in low-density lipoprotein cholesterol with statin therapy and the risk of new-onset diabetes: a meta-analysis. Sci Rep 2017;7:39982. doi:10.1038/srep39982.Wang S, Cai R, Yuan Y, et al. Association between reductions in low-density lipoprotein cholesterol with statin therapy and the risk of new-onset diabetes: a meta-analysis. Sci Rep 2017;7:39982. doi:10.1038/srep39982.Thakker D, Nair S, Pagada A, et al. Statin use and the risk of developing diabetes: a network meta-analysis. Pharmacoepidemiol Drug Saf. 2016;25(10):1131-1149. doi:10.1002/pds.4020.Thakker D, Nair S, Pagada A, et al. Statin use and the risk of developing diabetes: a network meta-analysis. Pharmacoepidemiol Drug Saf. 2016;25(10):1131-1149. doi:10.1002/pds.4020.Macedo AF, Taylor FC, Casas JP, et al. Unintended effects of statins from observational studies in the general population: systematic review and metaanalysis. BMC Med. 2014;12:51. doi:10.1186/1741-7015-12-51.Macedo AF, Taylor FC, Casas JP, et al. Unintended effects of statins from observational studies in the general population: systematic review and metaanalysis. BMC Med. 2014;12:51. doi:10.1186/1741-7015-12-51.Casula M, Mozzanica F, Scotti L, et al. Statin use and risk of new-onset diabetes: A meta-analysis of observational studies. Nutr Metab Cardiovasc Dis. 2017;27(5):396-406. doi:10.1016/j.numecd.2017.03.001.Casula M, Mozzanica F, Scotti L, et al. Statin use and risk of new-onset diabetes: A meta-analysis of observational studies. Nutr Metab Cardiovasc Dis. 2017;27(5):396-406. doi:10.1016/j.numecd.2017.03.001.Dormuth CR, Filion KB, Paterson JM, et al. Canadian network for observational drug effect studies investigators. Higher potency statins and the risk of new diabetes: multicenter, observational study of administrative databases. BMJ. 2014;348:g3244. doi:10.1136/bmj.g3244.Dormuth CR, Filion KB, Paterson JM, et al. Canadian network for observational drug effect studies investigators. Higher potency statins and the risk of new diabetes: multicenter, observational study of administrative databases. BMJ. 2014;348:g3244. doi:10.1136/bmj.g3244.Cederberg H, Stančáková A, Yaluri N, et al. Increased risk of diabetes with statin treatment is associated with impaired insulin sensitivity and insulin secretion: a 6 year follow-up study of the METSIM cohort. Diabetologia. 2015;58(5):1109-17. doi:10.1007/s00125-015-3528-5.Cederberg H, Stančáková A, Yaluri N, et al. Increased risk of diabetes with statin treatment is associated with impaired insulin sensitivity and insulin secretion: a 6 year follow-up study of the METSIM cohort. Diabetologia. 2015;58(5):1109-17. doi:10.1007/s00125-015-3528-5.Yusuf S, Bosch J, Dagenais G, et al. Cholesterol Lowering in Intermediate-Risk Persons without Cardiovascular Disease. N Engl J Med. 2016;374(21):2021-31. doi:10.1056/NEJMoa1600176.Yusuf S, Bosch J, Dagenais G, et al. Cholesterol Lowering in Intermediate-Risk Persons without Cardiovascular Disease. N Engl J Med. 2016;374(21):2021-31. doi:10.1056/NEJMoa1600176.Collins R, Reith C, Emberson J, et al. Interpretation of the evidence for the efficacy and safety of statin therapy. Lancet. 2016;388(10059):2532-61. doi:10.1016/S01406736(16)31357-5.Collins R, Reith C, Emberson J, et al. Interpretation of the evidence for the efficacy and safety of statin therapy. Lancet. 2016;388(10059):2532-61. doi:10.1016/S01406736(16)31357-5.Mora S, Glynn RJ, Hsia J, et al. Statins for the primary prevention of cardiovascular events in women with elevated high-sensitivity C-reactive protein or dyslipidemia: results from the Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) and meta-analysis of women from primary prevention trials. Circulation. 2010;121(9):1069-77. doi:10.1161/CIRCULATIONAHA.109.906479.Mora S, Glynn RJ, Hsia J, et al. Statins for the primary prevention of cardiovascular events in women with elevated high-sensitivity C-reactive protein or dyslipidemia: results from the Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) and meta-analysis of women from primary prevention trials. Circulation. 2010;121(9):1069-77. doi:10.1161/CIRCULATIONAHA.109.906479.Kjekshus J, Apetrei E, Barrios V, et al. Rosuvastatin in older patients with systolic heart failure. N Engl J Med. 2007;357(22):2248-61.Kjekshus J, Apetrei E, Barrios V, et al. Rosuvastatin in older patients with systolic heart failure. N Engl J Med. 2007;357(22):2248-61.Tavazzi L, Maggioni AP, Marchioli R, et al. Effect of rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet. 2008;372(9645):1231-9. doi:10.1016/S0140-6736(08)61240-4.Tavazzi L, Maggioni AP, Marchioli R, et al. Effect of rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet. 2008;372(9645):1231-9. doi:10.1016/S0140-6736(08)61240-4.Waters DD, Ho JE, DeMicco DA, et al. Predictors of new-onset diabetes in patients treated with atorvastatin: results from 3 large randomized clinical trials. J Am Coll Cardiol. 2011;57(14):1535-45. doi:10.1016/j.jacc.2010.10.047.Waters DD, Ho JE, DeMicco DA, et al. Predictors of new-onset diabetes in patients treated with atorvastatin: results from 3 large randomized clinical trials. J Am Coll Cardiol. 2011;57(14):1535-45. doi:10.1016/j.jacc.2010.10.047.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. doi:10.1001/archinternmed.2011.625.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. doi:10.1001/archinternmed.2011.625.Kohli P, Waters DD, Nemr R, et al. Risk of new-onset diabetes and cardiovascular risk reduction from high-dose statin therapy in pre-diabetics and non-pre-diabetics: an analysis from TNT and IDEAL. J Am Coll Cardiol. 2015;65(4):402-4. doi:10.1016/j.jacc.2014.10.053.Kohli P, Waters DD, Nemr R, et al. Risk of new-onset diabetes and cardiovascular risk reduction from high-dose statin therapy in pre-diabetics and non-pre-diabetics: an analysis from TNT and IDEAL. J Am Coll Cardiol. 2015;65(4):402-4. doi:10.1016/j.jacc.2014.10.053.Chou R, Tracy Dana M, Blazina I, et al. Statins for prevention of cardiovascular disease in adults evidence report and systematic review for the US Preventive Services Task Force. JAMA 2016;316(19):2008-24. doi:10.1001/jama.2015.15629.Chou R, Tracy Dana M, Blazina I, et al. Statins for prevention of cardiovascular disease in adults evidence report and systematic review for the US Preventive Services Task Force. JAMA 2016;316(19):2008-24. doi:10.1001/jama.2015.15629.Crandall JP, Mather K, Rajpathak SN, et al. Statin use and risk of developing diabetes: results from the Diabetes Prevention Program. BMJ Open Diabetes Res Care. 2017;5(1):e000438. doi:10.1136/bmjdrc-2017-000438.Crandall JP, Mather K, Rajpathak SN, et al. Statin use and risk of developing diabetes: results from the Diabetes Prevention Program. BMJ Open Diabetes Res Care. 2017;5(1):e000438. doi:10.1136/bmjdrc-2017-000438.Naci H, Brugts J, Ades T. Comparative tolerability and harms of individual statins: a study-level network meta-analysis of 246 955 participants from 135 randomized, controlled trials. Circ Cardiovasc Qual Outcomes. 2013;6(4):390-9. doi:10.1161/CIRCOUTCOMES.111.000071.Naci H, Brugts J, Ades T. Comparative tolerability and harms of individual statins: a study-level network meta-analysis of 246 955 participants from 135 randomized, controlled trials. Circ Cardiovasc Qual Outcomes. 2013;6(4):390-9. doi:10.1161/CIRCOUTCOMES.111.000071.Mills EJ, Wu P, Chong G, et al. Efficacy and safety of statin treatment for cardiovascular disease: a network meta-analysis of 170,255 patients from 76 randomized trials. QJM. 2011;104(2):109-24. doi:10.1093/qjmed/hcq165.Mills EJ, Wu P, Chong G, et al. Efficacy and safety of statin treatment for cardiovascular disease: a network meta-analysis of 170,255 patients from 76 randomized trials. QJM. 2011;104(2):109-24. doi:10.1093/qjmed/hcq165.Navarese EP, Buffon A, Andreotti F, et al. 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:10.1016/j.amjcard.2012.12.037.Navarese EP, Buffon A, Andreotti F, et al. 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:10.1016/j.amjcard.2012.12.037.Shen L, Shah BR, Reyes EM, et al. Role of diuretics, β blockers, and statins in increasing the risk of diabetes in patients with impaired glucose tolerance: reanalysis of data from the NAVIGATOR study. BMJ. 2013;347:f6745. doi:10.1136/bmj.f6745.Shen L, Shah BR, Reyes EM, et al. Role of diuretics, β blockers, and statins in increasing the risk of diabetes in patients with impaired glucose tolerance: reanalysis of data from the NAVIGATOR study. BMJ. 2013;347:f6745. doi:10.1136/bmj.f6745.Jacobson TA, Ito MK, Maki KC, et al. National Lipid Association recommendations for patient-centered management of dyslipidemia: part 1 — executive summary. J Clin Lipidol. 2014;8(5):473-88. doi:10.1016/j.jacl.2014.07.007.Jacobson TA, Ito MK, Maki KC, et al. National Lipid Association recommendations for patient-centered management of dyslipidemia: part 1 — executive summary. J Clin Lipidol. 2014;8(5):473-88. doi:10.1016/j.jacl.2014.07.007.Colhoun HM, Betteridge DJ, Durrington PN, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet. 2004;364(9435):685-96.Colhoun HM, Betteridge DJ, Durrington PN, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet. 2004;364(9435):685-96.Collins R, Armitage J, Parish S, et al. MRC/BHF Heart Protection Study of cholesterollowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet. 2003;361(9374):2005-16.Collins R, Armitage J, Parish S, et al. MRC/BHF Heart Protection Study of cholesterollowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet. 2003;361(9374):2005-16.Simsek S, Schalkwijk CG, Wolffenbuttel BH. Effects of rosuvastatin and atorvastatin on glycaemic control in Type 2 diabetes — the CORALL study. Diabet Med. 2012;29(5):62831. doi:10.1111/j.1464-5491.2011.03553.x.Simsek S, Schalkwijk CG, Wolffenbuttel BH. Effects of rosuvastatin and atorvastatin on glycaemic control in Type 2 diabetes — the CORALL study. Diabet Med. 2012;29(5):62831. doi:10.1111/j.1464-5491.2011.03553.x.Zhou Y, Yuan Y, Cai RR, et al. Statin therapy on glycaemic control in type 2 diabetes: a meta-analysis. Expert Opin Pharmacother. 2013;14(12):1575-84. doi:10.1517/14656566.2013.810210.Zhou Y, Yuan Y, Cai RR, et al. Statin therapy on glycaemic control in type 2 diabetes: a meta-analysis. Expert Opin Pharmacother. 2013;14(12):1575-84. doi:10.1517/14656566.2013.810210.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. doi:10.1007/s00125-014-3374-x.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. doi:10.1007/s00125-014-3374-x.Cai R, Yuan Y, Sun J, et al. Statins worsen glycemic control of T2DM in target LDL-c level and LDL-c reduction dependent manners: a meta-analysis. Expert Opin Pharmacother. 2016;17(14):1839-49. doi:10.1080/14656566.2016.1220539.Cai R, Yuan Y, Sun J, et al. Statins worsen glycemic control of T2DM in target LDL-c level and LDL-c reduction dependent manners: a meta-analysis. Expert Opin Pharmacother. 2016;17(14):1839-49. doi:10.1080/14656566.2016.1220539.Swerdlow DI, Preiss D, Kuchenbaecker KB, et al. HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials. Lancet. 2015;385(9965):351-61. doi:10.1016/S0140-6736(14)61183-1.Swerdlow DI, Preiss D, Kuchenbaecker KB, et al. HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials. Lancet. 2015;385(9965):351-61. doi:10.1016/S0140-6736(14)61183-1.Hindy G, Rukh G, Almgren P, et al. Causal effect of decreased LDL cholesterol and increased blood pressure on higher incidence of type 2 diabetes by Mendelian randomization in the Malmo Diet and Cancer Study. Diabetologia. 2014;57(Suppl 1):S67. doi:10.1007/s00125-014-3355-0.Hindy G, Rukh G, Almgren P, et al. Causal effect of decreased LDL cholesterol and increased blood pressure on higher incidence of type 2 diabetes by Mendelian randomization in the Malmo Diet and Cancer Study. Diabetologia. 2014;57(Suppl 1):S67. doi:10.1007/s00125-014-3355-0.Besseling J, Kastelein JJ, Defesche JC, et al. Association between familial hypercholesterolemia and prevalence of type 2 diabetes mellitus. JAMA. 2015;313(10):1029-36. doi:10.1001/jama.2015.1206.Besseling J, Kastelein JJ, Defesche JC, et al. Association between familial hypercholesterolemia and prevalence of type 2 diabetes mellitus. JAMA. 2015;313(10):1029-36. doi:10.1001/jama.2015.1206.Lotta LA, Sharp SJ, Burgess S, et al. Association between low-density lipoprotein cholesterol-lowering genetic variants and risk of type 2 diabetes: a meta-analysis. JAMA. 2016;316(13):1383-91. doi:10.1001/jama.2016.14568.Lotta LA, Sharp SJ, Burgess S, et al. Association between low-density lipoprotein cholesterol-lowering genetic variants and risk of type 2 diabetes: a meta-analysis. JAMA. 2016;316(13):1383-91. doi:10.1001/jama.2016.14568.Filippatos TD, Panagiotopoulou T, Tzavella E, Elisaf MS. Hypolipidemic Drugs and Diabetes Mellitus-Mechanisms and Data From Genetic Trials. J Cardiovasc Pharmacol Ther. 2018;23(3):187-91. doi:10.1177/1074248418757011.Filippatos TD, Panagiotopoulou T, Tzavella E, Elisaf MS. Hypolipidemic Drugs and Diabetes Mellitus-Mechanisms and Data From Genetic Trials. J Cardiovasc Pharmacol Ther. 2018;23(3):187-91. doi:10.1177/1074248418757011.Labos C, Brophy JM, Smith GD, et al. Evaluation of the Pleiotropic Effects of Statins: A Reanalysis of the Randomized Trial Evidence Using Egger Regression-Brief Report. Arterioscler Thromb Vasc Biol. 2018;38(1):262-5. doi:10.1161/ATVBAHA.117.310052.Labos C, Brophy JM, Smith GD, et al. Evaluation of the Pleiotropic Effects of Statins: A Reanalysis of the Randomized Trial Evidence Using Egger Regression-Brief Report. Arterioscler Thromb Vasc Biol. 2018;38(1):262-5. doi:10.1161/ATVBAHA.117.310052.Xu H, Ryan KA, Jaworek TJ, et al. Familial hypercholesterolemia and type 2 diabetes in the Old Order Amish. Diabetes. 2017;66(7):2054-8. doi:10.2337/db17-0173.Xu H, Ryan KA, Jaworek TJ, et al. Familial hypercholesterolemia and type 2 diabetes in the Old Order Amish. Diabetes. 2017;66(7):2054-8. doi:10.2337/db17-0173.HPS3/TIMI55–REVEAL Collaborative Group, Bowman L, Hopewell JC, Chen F, et al. Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease. N Engl J Med. 2017;377(13):1217-27. doi:10.1056/NEJMoa1706444.HPS3/TIMI55–REVEAL Collaborative Group, Bowman L, Hopewell JC, Chen F, et al. Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease. N Engl J Med. 2017;377(13):1217-27. doi:10.1056/NEJMoa1706444.Baker WL, Talati R, White CM, Coleman CI. Differing effect of statins on insulin sensitivity in non-diabetics: a systematic review and meta-analysis. Diabetes Res Clin Pract. 2010;87(1):98-107. doi:10.1016/j.diabres.2009.10.008.Baker WL, Talati R, White CM, Coleman CI. Differing effect of statins on insulin sensitivity in non-diabetics: a systematic review and meta-analysis. Diabetes Res Clin Pract. 2010;87(1):98-107. doi:10.1016/j.diabres.2009.10.008.Anyanwagu U, Idris I, Donnelly R. Drug-Induced Diabetes Mellitus: Evidence for Statins and Other Drugs Affecting Glucose Metabolism. Clin Pharmacol Ther. 2016;99(4):390400. doi:10.1002/cpt.274.Anyanwagu U, Idris I, Donnelly R. Drug-Induced Diabetes Mellitus: Evidence for Statins and Other Drugs Affecting Glucose Metabolism. Clin Pharmacol Ther. 2016;99(4):390400. doi:10.1002/cpt.274.Henriksbo BD, Schertzer JD. Is immunity a mechanism contributing to statin-induced diabetes? Adipocyte. 2015;4(4):232-8. doi:10.1080/21623945.2015.1024394.Henriksbo BD, Schertzer JD. Is immunity a mechanism contributing to statin-induced diabetes? Adipocyte. 2015;4(4):232-8. doi:10.1080/21623945.2015.1024394.Wang HJ, Park JY, Kwon O, et al. Chronic HMGCR/HMG-CoA reductase inhibitor treatment contributes to dysglycemia by upregulating hepatic gluconeogenesis through autophagy induction. Autophagy. 2015;11(11):2089-101.Wang HJ, Park JY, Kwon O, et al. Chronic HMGCR/HMG-CoA reductase inhibitor treatment contributes to dysglycemia by upregulating hepatic gluconeogenesis through autophagy induction. Autophagy. 2015;11(11):2089-101.Fizelova M, Miilunpohja M, Kangas AJ, et al. Associations of multiple lipoprotein and apolipoprotein measures with worsening of glycemia and incident type 2 diabetes in 6607 non-diabetic Finnish men. Atherosclerosis. 2015;240(1):272-7. doi:10.1016/j.atherosclerosis.2015.03.034.Fizelova M, Miilunpohja M, Kangas AJ, et al. Associations of multiple lipoprotein and apolipoprotein measures with worsening of glycemia and incident type 2 diabetes in 6607 non-diabetic Finnish men. Atherosclerosis. 2015;240(1):272-7. doi:10.1016/j.atherosclerosis.2015.03.034.Nicholls SJ, Puri R, Anderson T, et al. Effect of evolocumab on progression of coronary disease in statin-treated patients: the GLAGOV randomized clinical trial. JAMA. 2016;316(22):2373-84. doi:10.1001/jama.2016.16951.Nicholls SJ, Puri R, Anderson T, et al. Effect of evolocumab on progression of coronary disease in statin-treated patients: the GLAGOV randomized clinical trial. JAMA. 2016;316(22):2373-84. doi:10.1001/jama.2016.16951.Ference BA, Robinson JG, Brook RD, et al. Variation in PCSK9 and hmgcr and risk of cardiovascular disease and diabetes. N Engl J Med. 2016;375(22):2144-53. doi:10.1056/NEJMoa1604304.Ference BA, Robinson JG, Brook RD, et al. Variation in PCSK9 and hmgcr and risk of cardiovascular disease and diabetes. N Engl J Med. 2016;375(22):2144-53. doi:10.1056/NEJMoa1604304.Schmidt AF, Swerdlow DI, Holmes MV, et al. PCSK9 genetic variants and risk of type 2 diabetes: a mendelian randomisation study. Lancet Diabetes Endocrinol. 2017;5(2):97105. doi:10.1016/S2213-8587(16)30396-5.Schmidt AF, Swerdlow DI, Holmes MV, et al. PCSK9 genetic variants and risk of type 2 diabetes: a mendelian randomisation study. Lancet Diabetes Endocrinol. 2017;5(2):97105. doi:10.1016/S2213-8587(16)30396-5.Sabatine MS, Leiter LA, Wiviott SD, et al. Cardiovascular safety and efficacy of the PCSK9 inhibitor evolocumab in patients with and without diabetes and the effect of evolocumab on glycaemia and risk of new-onset diabetes: a prespecified analysis of the FOURIER randomised controlled trial. Lancet Diabetes Endocrinol. 2017;5(12):941-50. doi:10.1016/ S2213-8587(17)30313-3.Sabatine MS, Leiter LA, Wiviott SD, et al. Cardiovascular safety and efficacy of the PCSK9 inhibitor evolocumab in patients with and without diabetes and the effect of evolocumab on glycaemia and risk of new-onset diabetes: a prespecified analysis of the FOURIER randomised controlled trial. Lancet Diabetes Endocrinol. 2017;5(12):941-50. doi:10.1016/ S2213-8587(17)30313-3.Leiter LA, Müller-Wieland D, Baccara-Dinet MT, et al. Efficacy and safety of alirocumab in people with prediabetes vs those with normoglycaemia at baseline: a pooled analysis of 10 phase III ODYSSEY clinical trials. Diabet Med. 2018;35(1):121-30. doi:10.1111/dme.13450.Leiter LA, Müller-Wieland D, Baccara-Dinet MT, et al. Efficacy and safety of alirocumab in people with prediabetes vs those with normoglycaemia at baseline: a pooled analysis of 10 phase III ODYSSEY clinical trials. Diabet Med. 2018;35(1):121-30. doi:10.1111/dme.13450.Karatasakis A, Danek BA, Karacsonyi J, et al. Effect of PCSK9 Inhibitors on Clinical Outcomes in Patients With Hypercholesterolemia: A Meta-Analysis of 35 Randomized Controlled Trials. J Am Heart Assoc. 2017;6(12). pii:e006910. doi:10.1161/JAHA.117.006910.Karatasakis A, Danek BA, Karacsonyi J, et al. Effect of PCSK9 Inhibitors on Clinical Outcomes in Patients With Hypercholesterolemia: A Meta-Analysis of 35 Randomized Controlled Trials. J Am Heart Assoc. 2017;6(12). pii:e006910. doi:10.1161/JAHA.117.006910.Cao YX, Liu HH, Dong QT, et al. Effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies on new-onset diabetes mellitus and glucose metabolism: A systematic review and meta-analysis. Diabetes Obes Metab. 2018;20(6):1391-8. doi:10.1111/dom.13235.Cao YX, Liu HH, Dong QT, et al. Effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies on new-onset diabetes mellitus and glucose metabolism: A systematic review and meta-analysis. Diabetes Obes Metab. 2018;20(6):1391-8. doi:10.1111/dom.13235.de Carvalho LSF, Campos AM, Sposito AC. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and incident type 2 diabetes mellitus: a systematic review and metaanalysis with over 96,000 patient-years. Diabetes Care. 2018;41(2):364-7. doi:10.2337/dc17-1464.de Carvalho LSF, Campos AM, Sposito AC. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and incident type 2 diabetes mellitus: a systematic review and metaanalysis with over 96,000 patient-years. Diabetes Care. 2018;41(2):364-7. doi:10.2337/dc17-1464.Lotta LA, Griffin SJ. PCSK9 inhibition and type 2 diabetes. Lancet Diabetes Endocrinol. 2017;5(12):926-7. doi:10.1016/S2213-8587(17)30321-2.Lotta LA, Griffin SJ. PCSK9 inhibition and type 2 diabetes. Lancet Diabetes Endocrinol. 2017;5(12):926-7. doi:10.1016/S2213-8587(17)30321-2.Tenenbaum A, Fisman EZ. Mirroring the CANTOS revolution: is anti-inflammatory therapy for diabetes just around the corner? Cardiovasc Diabetol. 2017;16(1):91. doi:10.1186/s12933-017-0573-z.Tenenbaum A, Fisman EZ. Mirroring the CANTOS revolution: is anti-inflammatory therapy for diabetes just around the corner? Cardiovasc Diabetol. 2017;16(1):91. doi:10.1186/s12933-017-0573-z.Everett BM, Donath MY, Pradhan AD, et al. Anti-Inflammatory Therapy With Canakinumab for the Prevention and Management of Diabetes. J Am Coll Cardiol. 2018;71(21):2392401. doi:10.1016/j.jacc.2018.03.002.Everett BM, Donath MY, Pradhan AD, et al. Anti-Inflammatory Therapy With Canakinumab for the Prevention and Management of Diabetes. J Am Coll Cardiol. 2018;71(21):2392401. doi:10.1016/j.jacc.2018.03.002.Verma S, Mathew V, Farkouh ME. Targeting Inflammation in the Prevention and Treatment of Type 2 Diabetes: Insights From CANTOS. J Am Coll Cardiol. 2018;71(21):2402-4. doi:10.1016/j.jacc.2018.03.480.Verma S, Mathew V, Farkouh ME. Targeting Inflammation in the Prevention and Treatment of Type 2 Diabetes: Insights From CANTOS. J Am Coll Cardiol. 2018;71(21):2402-4. doi:10.1016/j.jacc.2018.03.480.Chapman MJ, Orsoni A, Robillard P, et al. Effect of high-dose pitavastatin on glucose homeostasis in patients at elevated risk of new-onset diabetes: insights from the CAPITAIN and PREVAIL-US studies. Curr Med Res Opin. 2014;30(5):775-84. doi:10.1185/03007995.2013.874989.Chapman MJ, Orsoni A, Robillard P, et al. Effect of high-dose pitavastatin on glucose homeostasis in patients at elevated risk of new-onset diabetes: insights from the CAPITAIN and PREVAIL-US studies. Curr Med Res Opin. 2014;30(5):775-84. doi:10.1185/03007995.2013.874989.Mita T, Nakayama S, Abe H, et al. Comparison of effects of pitavastatin and atorvastatin on glucose metabolism in type 2 diabetic patients with hypercholesterolemia. J Diabetes Investig. 2013;4(3):297-303. doi:10.1111/jdi.12032.Mita T, Nakayama S, Abe H, et al. Comparison of effects of pitavastatin and atorvastatin on glucose metabolism in type 2 diabetic patients with hypercholesterolemia. J Diabetes Investig. 2013;4(3):297-303. doi:10.1111/jdi.12032.Huang CH, Huang YY, Hsu BR. Pitavastatin improves glycated hemoglobin in patients with poorly controlled type 2 diabetes. J Diabetes Investig. 2016;7(5):769-76. doi:10.1111/jdi.12483.Huang CH, Huang YY, Hsu BR. Pitavastatin improves glycated hemoglobin in patients with poorly controlled type 2 diabetes. J Diabetes Investig. 2016;7(5):769-76. doi:10.1111/jdi.12483.Vallejo-Vaz AJ, Seshasai SRK, Kurogi K, et al. Effect of pitavastatin on glucose, HbA1c and incident diabetes: a meta-analysis of randomized controlled clinical trials in individuals without diabetes. Atherosclerosis. 2015;241(2):409-18. doi:10.1016/j.atherosclerosis.2015.06.001.Vallejo-Vaz AJ, Seshasai SRK, Kurogi K, et al. Effect of pitavastatin on glucose, HbA1c and incident diabetes: a meta-analysis of randomized controlled clinical trials in individuals without diabetes. Atherosclerosis. 2015;241(2):409-18. doi:10.1016/j.atherosclerosis.2015.06.001.Park JB, Jung JH, Yoon YE, et al. Long-term Effects of high-doSe pitavaStatin on Diabetogenicity in comparison with atorvastatin in patients with Metabolic syndrome (LESS-DM): study protocol for a randomized controlled trial. Trials. 2017;18(1):501. doi:10.1186/s13063-017-2229-4.Park JB, Jung JH, Yoon YE, et al. Long-term Effects of high-doSe pitavaStatin on Diabetogenicity in comparison with atorvastatin in patients with Metabolic syndrome (LESS-DM): study protocol for a randomized controlled trial. Trials. 2017;18(1):501. doi:10.1186/s13063-017-2229-4.Cholesterol Treatment Trialists’ (CTT) Collaborators, Kearney PM, Blackwell L, Collins R, et al. Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet. 2008;371(9607):117-25. doi:10.1016/S0140-6736(08)60104-X.Cholesterol Treatment Trialists’ (CTT) Collaborators, Kearney PM, Blackwell L, Collins R, et al. Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet. 2008;371(9607):117-25. doi:10.1016/S0140-6736(08)60104-X.Rochlani Y, Kattoor AJ, Pothineni NV, et al. Balancing Primary Prevention and StatinInduced Diabetes Mellitus Prevention. Am J Cardiol. 2017;120(7):1122-8. doi:10.1016/j.amjcard.2017.06.054.Rochlani Y, Kattoor AJ, Pothineni NV, et al. Balancing Primary Prevention and StatinInduced Diabetes Mellitus Prevention. Am J Cardiol. 2017;120(7):1122-8. doi:10.1016/j.amjcard.2017.06.054.

The authors declare that there are no conflicts of interest present.