The use of statins in people at risk of developing diabetes mellitus: evidence and guidance for clinical practice.
Reducing low-density lipoprotein cholesterol (LDL-C) levels using statins is associated with significant reductions in cardiovascular (CV) events in a wide range of patient populations. Although statins are generally considered to be safe, recent studies suggest they are associated with an increased risk of developing Type 2 diabetes (T2D). This led the US Food and Drug Administration (FDA) to change their labelling requirements for statins to include a warning about the possibility of increased blood sugar and HbA1c levels and the European Medicines Agency (EMA) to issue guidance on a small increased risk of T2D with the statin class. This review examines the evidence leading to these claims and provides practical guidance for primary care physicians on the use of statins in people with or at risk of developing T2D. Overall, evidence suggests that the benefits of statins for the reduction of CV risk far outweigh the risk of developing T2D, especially in individuals with higher CV risk. To reduce the risk of developing T2D, physicians should assess all patients for T2D risk prior to starting statin therapy, educate patients about their risks, and encourage risk-reduction through lifestyle changes. Whether some statins are more diabetogenic than others requires further study. Statin-treated patients at high risk of developing T2D should regularly be monitored for changes in blood glucose or HbA1c levels, and the risk of conversion from pre-diabetes to T2D should be reduced by intensifying lifestyle changes. Should a patient develop T2D during statin treatment, physicians should continue with statin therapy and manage T2D in accordance with relevant national guidelines.
Institute of Cardiovascular & Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University Of Glasgow, 126 University Place, Glasgow G12 8TA, UK. Electronic address: naveed.sattar@glasgow.ac.uk.
Naveed A
NA
Sattar
Irving Institute for Clinical and Translational Research, PH 10-305, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA. Electronic address: hng1@columbia.edu.
Henry
H
Ginsberg
Cardiovascular Sciences Research Centre, St Georges University of London, Cranmer Terrace, London SW17 0RE, UK. Electronic address: kray@sgul.ac.uke.
Kausik
K
Ray
Dyslipidemia and Atherosclerosis Research Unit, INSERM UMR-S939, Pitie-Salpetriere University Hospital, 75651 Paris, France. Electronic address: john.chapman@upmc.fr.
M John
MJ
Chapman
Department of Internal Medicine and Allied Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy. Electronic address: marcelloarca@libero.it.
Marcello
M
Arca
Dept. of Internal Medicine and Medical Specialties, School of Medicine, University of Palermo, Italy. Electronic address: maurizio.averna@unipa.it.
Maurizio
M
Averna
University College London, Middlesex Hospital, London, UK. Electronic address: rmhajbe@ucl.ac.uk.
D John
DJ
Betteridge
Diabetes Centre, The Royal Oldham Hospital, Rochdale Road, Oldham, UK. Electronic address: deepak.bhatnagar@manchester.ac.uk.
Deepak
D
Bhatnagar
Lipid Clinic, Cardiology Department, Tzanio Hospital, Pireas, Greece. Electronic address: elenib1@otenet.gr.
Elena
E
Bilianou
Department of Medicine, University of Valencia, Spain. Electronic address: Rafael.Carmena@uv.es.
Rafael
R
Carmena
Center of Preventive Cardiology, IIIrd Dept. Int. Med. Charles University and University General Hospital, Prague, Czech Republic. Electronic address: richard.ceska@vfn.cz.
Richard
R
Ceška
Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy. Electronic address: alberto.corsini@unimi.it.
Alberto
A
Corsini
Department of Cardiology, West German Heart Centre, University of Essen, Germany. Electronic address: Raimund.Erbel@uk-essen.de.
Raimund
R
Erbel
The Lipid Clinic, Box 153, Addenbrooke's Hospital, Cambridge CB0 2QQ, UK. Electronic address: pdf21@cam.ac.uk.
Paul D
PD
Flynn
Unitat Hospitalització, Servei de Cardiologia, Hospital de la Santa Creu i Sant Pau, Spain. Electronic address: XGarcia-Moll@santpau.cat.
Xavier
X
Garcia-Moll
Katedra i Klinika Chorób Wewętrznych, Diabetologii i Nefrologii, Śląski Uniwersytet Medyczny, Katowice, Poland. Electronic address: jgumprecht@sum.edu.pl.
Janusz
J
Gumprecht
Department of Internal Medicine, Division of Endocrinology and Metabolism, Jichi Medical University, 3311-1, Yakushiji Shimotsuke-shi, Tochigi 329-0498, Japan. Electronic address: ishibash@jichi.ac.jp.
Shun
S
Ishibashi
St-Joseph University Faculty of Medicine, and Head, Endocrinology and Metabolism Division, Hotel-Dieu de France Hospital, Beirut, Lebanon. Electronic address: sjambart@dm.net.lb.
Selim
S
Jambart
Academic Medical Center/University of Amsterdam, Dept. of Vascular Medicine, F4-159.2, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Electronic address: j.j.kastelein@amc.uva.nl.
John J P
JJ
Kastelein
Department of Cardiology, Tallaght Hospital, Dublin, Ireland. Electronic address: vmaher@gmail.com.
Vincent
V
Maher
Arterial Investigation Unit, Medicine IV, Santa Marta's Hospital, CHLC, Lisboa, Portugal. Electronic address: pedro.silva@hsmarta.min-saude.pt.
Pedro Marques
PM
da Silva
Unitat de Recerca en Lipids i Arteriosclerosi, IISPV, CIBERDEM, Universitat Rovira i Virgili, Sant Llorenç, 21, 43201 Reus, Spain. Electronic address: luis.masana@urv.cat.
Luis
L
Masana
Division of Diabetology, Endocrinology and Metabolism, The Third Department of Internal Medicine, Tokyo Medical University, 6-7-1, Nisi-shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan. Electronic address: odawara@tokyo-med.ac.jp.
Masato
M
Odawara
University of Oslo and Oslo University Hospital, Ullevål Centre of Preventive Medicine, Medical Clinic, Oslo, Norway. Electronic address: t.r.pedersen@medisin.uio.no.
Terje R
TR
Pedersen
Department of Endocrinology, University of Florence Medical School, Italy. Electronic address: c.rotella@dfc.unifi.it.
Carlo Maria
CM
Rotella
Division of Endocrinology and Metabolism, American University of Beirut, Lebanon. Electronic address: isalti@aub.edu.lb.
Ibrahim
I
Salti
Teikyo University, Teikyo Academic Research Center, Japan. Electronic address: ttera@med.teikyo-u.ac.jp.
Tamio
T
Teramoto
Professor of Cardiology, Hacettepe University, Çankaya, Ankara, Turkey. Electronic address: lalet@hacettepe.edu.tr.
Lale
L
Tokgozoglu
University of Illinois College of Medicine, Peoria, IL, USA. Electronic address: peter.toth@cghmc.com.
Peter P
PP
Toth
Department of Endocrinology Diabetology Nutrition, APHP, CRNH-IdF, CINFO, Paris Nord University, Bondy, France. Electronic address: paul.valensi@jvr.aphp.fr.
Paul
P
Valensi
Service Endocrinologie, Diabétologie et Maladies Métaboliques, University Hospital Dijon, France. Electronic address: bruno.verges@chu-dijon.fr.
Bruno
B
Vergès
D000328:Adult; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000517:prevention & control; D008078:Cholesterol, LDL / Q000097:blood*; D015331:Cohort Studies; D015897:Comorbidity; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D004198:Disease Susceptibility; D005215:Fasting / Q000097:blood; D005544:Forecasting; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D015337:Multicenter Studies as Topic / Q000706:statistics & numerical data; D064887:Observational Studies as Topic; D017410:Practice Guidelines as Topic; D011236:Prediabetic State / Q000453:epidemiology*; D018570:Risk Assessment; D012307:Risk Factors
D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D006442:Glycated Hemoglobin; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors
CVD; Cardiovascular; Diabetes; Diabetogenicity; Statins; T2D