Evidence map›Statins × lipids›PMID 25262344›Full record

SynthesisLancet (London, England)2015

HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials.

Daniel I Swerdlow, David Preiss, Karoline B Kuchenbaecker, Michael V Holmes, Jorgen E L Engmann, Tina Shah, Reecha Sofat, Stefan Stender, Paul C D Johnson, Robert A Scott and 126 more

Registry-linked trialOpen access · hybridAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Lancet (London, England), 2015. The graph read 3 numbers from its abstract, feeding 1 cell of the map: it favours the comparator in 1. It reports registered trial NCT02437084. Cited by 345 papers, 12 of them syntheses that pooled it.

3numbers the graph read from it
1cell of the map it votes in
345citing papers in PubMed, 12 pooled it
46.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

Ratios

← favours the treatmentfavours the comparator →
1 · no effect
Lipidsfavours the comparator · against placebo · obesity, dyslipidemiafeeds one cell of the map
OR 1.121.06 to 1.18
In 129 170 individuals in randomised trials, statins lowered LDL cholesterol by 0.92 mmol/L (95% CI 0.18-1.67) at 1-year of follow-up, increased bodyweight by 0.24 kg (95% CI 0.10-0.38 in all trials; 0.33 kg, 95% CI 0.24-0.42 in placebo or standard care controlled trials and -0.15 kg, 95% CI -0.39 to 0.08 in intensive-dose vs moderate-dose trials) at a mean of 4.2 years (range 1.9-6.7) of follow-up, and increased the odds of new-onset type 2 diabetes (OR 1.12, 95% CI 1.06-1.18 in all trials; 1.11, 95% CI 1.03-1.20 in placebo or standard care controlled trials and 1.12, 95% CI 1.04-1.22 in intensive-dose vs moderate dose trials).
FeedsStatins×lipids

Differences

← favours the treatmentfavours the comparator →
-1.670.380 · no effect
Lipidsfavours the treatment · against placebo · obesity, dyslipidemiafeeds one cell of the map
lowered -0.92-1.67 to -0.18
In 129 170 individuals in randomised trials, statins lowered LDL cholesterol by 0.92 mmol/L (95% CI 0.18-1.67) at 1-year of follow-up, increased bodyweight by 0.24 kg (95% CI 0.10-0.38 in all trials; 0.33 kg, 95% CI 0.24-0.42 in placebo or standard care controlled trials and -0.15 kg, 95% CI -0.39 to 0.08 in intensive-dose vs moderate-dose trials) at a mean of 4.2 years (range 1.9-6.7) of follow-up, and increased the odds of new-onset type 2 diabetes (OR 1.12, 95% CI 1.06-1.18 in all trials; 1.11, 95% CI 1.03-1.20 in placebo or standard care controlled trials and 1.12, 95% CI 1.04-1.22 in intensive-dose vs moderate dose trials).
FeedsStatins×lipids
Lipidsfavours the comparator · against placebo · obesity, dyslipidemiafeeds one cell of the map
increase 0.240.10 to 0.38
In 129 170 individuals in randomised trials, statins lowered LDL cholesterol by 0.92 mmol/L (95% CI 0.18-1.67) at 1-year of follow-up, increased bodyweight by 0.24 kg (95% CI 0.10-0.38 in all trials; 0.33 kg, 95% CI 0.24-0.42 in placebo or standard care controlled trials and -0.15 kg, 95% CI -0.39 to 0.08 in intensive-dose vs moderate-dose trials) at a mean of 4.2 years (range 1.9-6.7) of follow-up, and increased the odds of new-onset type 2 diabetes (OR 1.12, 95% CI 1.06-1.18 in all trials; 1.11, 95% CI 1.03-1.20 in placebo or standard care controlled trials and 1.12, 95% CI 1.04-1.22 in intensive-dose vs moderate dose trials).
FeedsStatins×lipids

clause the extractor read what became the number

2 · Its place on the map

Where it lands on the map

Rows are treatments, columns are outcomes. The coloured squares are the cells this paper feeds, coloured by the vote it casts there. Click one to jump to what this paper adds to it.

supports the treatmentfavours the comparatorno clear differenceread, but no usable result
3 · What it changes

What it adds to each cell

For every cell the paper feeds: the belief in the claim with and without this paper, and this paper's estimate drawn against every other readable study in the cell. The ringed dot is this paper.

Statins×lipids

ContradictsOpen on the map →What to test next →

38 readable studies in this cell: 27 favour the treatment, 5 find no difference, 6 favour the comparator.

Belief with this paper
0.50contested · 21 families support, 7 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
NCT002899002,340 enrolled · 2006
Δ -13.2-16.8 to -9.60
Effect of evolocumab or ezetimibe added to moderate- or high-intensity…PMID 24825642 · 2,067 enrolled · 2013
reduced -66.0-73.0 to -58.0
NCT02546323543 enrolled · 2015
Δ -35.5-40.2 to -30.7
NCT01678820299 enrolled · 2012
Δ 0.50-4.80 to 5.80
NCT01218204287 enrolled · 2010
Δ 5.47-15.7 to 26.7
Lipid-Lowering Effect and Safety of Ezetimibe and Atorvastatin 5 mg in…PMID 40357888 · 252 enrolled · 2022
Δ -47.6
NCT0093525931 enrolled · 2009
Δ -51.7
Effect of Patient Financial Incentives on Statin Adherence and Lipid C…PMID 33034639 · 2020
reductions -33.6-38.8 to -28.4
Icosabutate, a Structurally Engineered Fatty Acid, Improves the Cardio…PMID 27160246 · 2016
Δ -7.40
Evidence for statin pleiotropy in humans: differential effects of stat…PMID 19075102 · 2009
RR 38.0
Efficacy and safety of fluvastatin in patients with non-insulin-depend…PMID 8198023 · 1994
decrease -24.3
Rosuvastatin in older patients with systolic heart failure.PMID 17984166 · 2007
Δ 45.0

This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.

4 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02437084 phase4completed

Relationship Between Insulin Resistance and Statin Induced Type 2 Diabetes, and Integrative Personal Omics Profiling

Ran2015Enrolled115Registered outcomes6Posted comparisons6ConditionsHyperlipidemia, Insulin Resistance, Type 2 DiabetesArmsAtorvastatin
PMID 22883507PMID 23219296PMID 18551118PMID 25754552PMID 27614854PMID 24326527PMID 25634843PMID 3056758PMID 24222016PMID 23706632PMID 22424236PMID 10491414other papers from this trial
Open the trial in the graph
5 · Its place in the literature

Who cites it

345 citing papers in PubMed, 12 syntheses or guidelines pooled it, 704 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Pooled it
  7. Pooled it
  8. Pooled it
  9. PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease.The Cochrane database of systematic reviews · 2020 · on this map
    Pooled it
  10. Pooled it
  11. Pooled it
  12. Statins for children with familial hypercholesterolemia.The Cochrane database of systematic reviews · 2019
    Pooled it
  13. Trial
  14. Trial
  15. Trial
  16. Trial
  17. Trial
  18. Trial
  19. Trial
  20. Statins Are Associated With Increased Insulin Resistance and Secretion.Arteriosclerosis, thrombosis, and vascular biology · 2021 · on this map
    Trial

285 more citing papers are in PubMed but not listed here.

6 · The record

Corrections and comments

7 · Who and what money

Authors and funding

136 authors at 20 institutions in 15 countries.

Daniel I SwerdlowUCL Institute of Cardiovascular Science and Farr Institute, University College London, London, UK. Electronic address: d.swerdlow@ucl.ac.uk.
David PreissBHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK. Electronic address: david.preiss@glasgow.ac.uk.
Karoline B KuchenbaeckerCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK; Department of Surgery, Division of Transplantation, and Clinical Epidemiology Unit, Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Michael V HolmesUCL Institute of Cardiovascular Science and Farr Institute, University College London, London, UK.
Jorgen E L EngmannUCL Institute of Cardiovascular Science and Farr Institute, University College London, London, UK.
Tina ShahUCL Institute of Cardiovascular Science and Farr Institute, University College London, London, UK.
Reecha SofatUCL Department of Medicine, University College London, London, UK.
Stefan StenderDepartment of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Paul C D JohnsonRobertson Centre for Biostatistics, University of Glasgow, Glasgow, UK.
Robert A ScottMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK.
Maarten LeusinkDivision of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, Netherlands.
Niek VerweijUniversity of Groningen, University Medical Centre Groningen, Department of Cardiology, Groningen, Netherlands.
Stephen J SharpMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK.
Yiran GuoCenter for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Claudia GiambartolomeiUCL Genetics Institute, University College London, London, UK.
Christina ChungUCL Research Department of Epidemiology and Public Health, University College London, London, UK.
Anne PeaseyUCL Research Department of Epidemiology and Public Health, University College London, London, UK.
Antoinette AmuzuLondon School of Hygiene & Tropical Medicine, London, UK.
KaWah LiCentre for Cardiovascular Genetics, University College London, London, UK.
Jutta PalmenCentre for Cardiovascular Genetics, University College London, London, UK.
Philip HowardCentre for Cardiovascular Genetics, University College London, London, UK.
Jackie A CooperCentre for Cardiovascular Genetics, University College London, London, UK.
Fotios DrenosCentre for Cardiovascular Genetics, University College London, London, UK.
Yun R LiCenter for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Gordon LoweInstitute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
John GallacherDepartment of Primary Care and Public Health, Cardiff University Medical School, Cardiff University, Cardiff, UK.
Marlene C W StewartCentre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.
Ioanna TzoulakiDepartment of Epidemiology and Biostatistics, Imperial College London, London, UK.
Sarah G BuxbaumJackson State University, Jackson, MS, USA.
Daphne L van der ANational Institute for Public Health and the Environment, Bilthoven, Netherlands.
Nita G ForouhiMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK.
N Charlotte Onland-MoretJulius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands.
Yvonne T van der SchouwJulius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands.
Renate B SchnabelUniversity Heart Center Hamburg, Department of General and Interventional Cardiology, Hamburg, Germany.
Jaroslav A HubacekCentre for Experimental Medicine, Institute of Clinical and Experimental Medicine, Prague, Czech Republic.
Ruzena KubinovaNational Institute of Public Health, Prague, Czech Republic.
Migle BacevicieneLithuanian University of Health Sciences, Kaunas, Lithuania.
Abdonas TamosiunasInstitute of Cardiology, Kaunas, Lithuania.
Andrzej PajakDepartment of Epidemiology and Population Studies, Institute of Public Health, Faculty of Health Sciences, Jagiellonian University Medical College, Krakow, Poland.
Roman Topor-MadryDepartment of Epidemiology and Population Studies, Institute of Public Health, Faculty of Health Sciences, Jagiellonian University Medical College, Krakow, Poland.
Urszula StepaniakDepartment of Epidemiology and Population Studies, Institute of Public Health, Faculty of Health Sciences, Jagiellonian University Medical College, Krakow, Poland.
Sofia MalyutinaInstitute of Internal and Preventive Medicine, Siberian Branch of Russian Academy of Medical Sciences, Novosibirsk, Russia.
Damiano BaldassarreDipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Milan, Italy; Centro Cardiologico Monzino IRCCS Milan, Milan, Italy.
Bengt SennbladAtherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden.
Elena TremoliDipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Milan, Italy; Centro Cardiologico Monzino IRCCS Milan, Milan, Italy.
Ulf de FaireDivision of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Fabrizio VegliaBiostatistics Unit, Milan, Italy.
Ian FordRobertson Centre for Biostatistics, University of Glasgow, Glasgow, UK.
J Wouter JukemaDepartment of Cardiology, Leiden University Medical Center, Leiden, Netherlands.
Rudi G J WestendorpDepartment of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, Netherlands.
Gert Jan de BorstDepartment of Vascular Surgery, University Medical Center Utrecht, Utrecht, Netherlands.
Pim A de JongDepartment of Radiology, University Medical Center Utrecht, Utrecht, Netherlands.
Ale AlgraJulius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands; Department of Neurology and Neurosurgery, University Medical Center Utrecht, Utrecht, Netherlands.
Wilko SpieringDepartment of Vascular Medicine, University Medical Center Utrecht, Utrecht, Netherlands.
Anke H Maitland-van der ZeeDivision of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, Netherlands.
Olaf H KlungelDivision of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, Netherlands.
Anthonius de BoerDivision of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, Netherlands.
Pieter A DoevendansDepartment of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, Netherlands.
Charles B EatonMemorial Hospital of Rhode Island, RI, USA.
Jennifer G RobinsonUniversity of Iowa, IA, USA.
David DugganTranslational Genomics Research Institute, Phoenix, AZ, USA.
DIAGRAM Consortium
MAGIC Consortium
InterAct Consortium
John KjekshusDepartment of Cardiology, Oslo University Hospital Rikshospitalet, University of Oslo, Oslo, Norway.
John R DownsDepartment of Medicine, University of Texas Health Science Centre, San Antonio, TX, USA; VERDICT, South Texas Veterans Health Care System, San Antonio, TX, USA.
Antonio M GottoWeill Cornell Medical College, New York, NY, USA.
Anthony C KeechNHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia.
Roberto MarchioliHematology and Oncology Therapeutic Delivery Unit, Quintiles, Milan, Italy.
Gianni TognoniDepartment of Clinical Pharmacology and Epidemiology, Consorzio Mario NegriSud, Santa Maria Imbaro, Chieti, Italy.
Peter S SeverInternational Centre for Circulatory Health, Imperial College London, London, UK.
Neil R PoulterInternational Centre for Circulatory Health, Imperial College London, London, UK.
David D WatersDepartment of Medicine, University of California, San Francisco, CA, USA.
Terje R PedersenCentre for Preventative Medicine, Oslo University Hospital Rikshospitalet, University of Oslo, Oslo, Norway.
Pierre AmarencoDenis Diderot University, Paris, France.
Haruo NakamuraMitsukoshi Health and Welfare Foundation, Tokyo, Japan.
John J V McMurrayBHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
James D LewseyInstitute of Health and Wellbeing, University of Glasgow, Glasgow, UK.
Daniel I ChasmanDivision of Preventive Medicine, Boston, MA, USA.
Paul M RidkerDivision of Preventive Medicine, Boston, MA, USA.
Aldo P MaggioniANMCO Research Center, Florence, Italy.
Luigi TavazziMaria Cecilia Hospital, GVM Care and Research, E.S. Health Science Foundation, Cotignola (RA), Italy.
Kausik K RayCardiac and Cell Sciences Research Institute, London, UK.
Sreenivasa Rao Kondapally SeshasaiCardiac and Cell Sciences Research Institute, London, UK.
JoAnn E MansonDivision of Preventive Medicine, Boston, MA, USA.
Jackie F PriceCentre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.
Peter H WhincupSt George's University of London, London, UK.
Richard W MorrisUCL Department of Primary Care and Population Health, University College London, London, UK.
Debbie A LawlorMRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK; School of Social and Community Medicine, University of Bristol, Bristol, UK.
George Davey SmithMRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK; School of Social and Community Medicine, University of Bristol, Bristol, UK.
Yoav Ben-ShlomoSchool of Social and Community Medicine, University of Bristol, Bristol, UK.
Pamela J SchreinerSchool of Public Health, Minneapolis, MN, USA.
Myriam FornageInstitute of Molecular Medicine and Human Genetics Center, University of Texas Health Science Center at Houston, Houston, TX, USA.
David S SiscovickCardiovascular Health Research Unit of the Department of Medicine, Department of Epidemiology, and Department of Health Services, University of Washington, Seattle, WA, USA.
Mary CushmanDepartments of Medicine and Pathology, University of Vermont, Colchester, VT, USA.
Meena KumariUCL Research Department of Epidemiology and Public Health, University College London, London, UK.
Nick J WarehamMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK.
W M Monique VerschurenNational Institute for Public Health and the Environment, Bilthoven, Netherlands.
Susan RedlineBrigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Sanjay R PatelDivision of Sleep Medicine, Boston, MA, USA.
John C WhittakerGlaxoSmithKline, Stevenage, UK.
Anders HamstenAtherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Joseph A DelaneyDepartment of Epidemiology, University of Washington, Seattle, WA, USA.
Caroline DaleDepartment of Non-Communicable Disease Epidemiology, London, UK.
Tom R GauntMRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Andrew WongMRCUnit for Lifelong Health and Ageing, Institute of Epidemiology and Health Care, University College London, London, UK.
Diana KuhMRCUnit for Lifelong Health and Ageing, Institute of Epidemiology and Health Care, University College London, London, UK.
Rebecca HardyMRCUnit for Lifelong Health and Ageing, Institute of Epidemiology and Health Care, University College London, London, UK.
Sekar KathiresanCardiology Division, Massachusetts General Hospital, Boston, MA, USA; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
Berta A CastilloCenter for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Pim van der HarstUniversity of Groningen, University Medical Centre Groningen, Department of Cardiology, Groningen, Netherlands.
Eric J BrunnerUCL Research Department of Epidemiology and Public Health, University College London, London, UK.
Anne Tybjaerg-HansenDepartment of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Michael G MarmotUCL Research Department of Epidemiology and Public Health, University College London, London, UK.
Ronald M KraussChildren's Hospital Oakland Research Institute, Oakland, CA USA.
Michael TsaiUniversity of Minnesota, Minneapolis, MN, USA.
Josef CoreshDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Ronald C HoogeveenBaylor College of Medicine, Department of Medicine, Division of Atherosclerosis and Vascular Medicine, Houston, TX, USA.
Bruce M PsatyCardiovascular Health Research Unit of the Department of Medicine, Department of Epidemiology, and Department of Health Services, University of Washington, Seattle, WA, USA.
Leslie A LangeDepartment of Genetics, University of North Carolina School of Medicine at Chapel Hill, Chapel Hill, NC, USA.
Hakon HakonarsonCenter for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Frank DudbridgeLondon School of Hygiene & Tropical Medicine, London, UK.
Steve E HumphriesCentre for Cardiovascular Genetics, University College London, London, UK.
Philippa J TalmudCentre for Cardiovascular Genetics, University College London, London, UK.
Mika KivimäkiUCL Research Department of Epidemiology and Public Health, University College London, London, UK.
Nicholas J TimpsonMRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK; School of Social and Community Medicine, University of Bristol, Bristol, UK.
Claudia LangenbergMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK.
Folkert W AsselbergsUCL Institute of Cardiovascular Science and Farr Institute, University College London, London, UK; Department of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, Netherlands; Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, Netherlands.
Mikhail VoevodaInstitute of Internal and Preventive Medicine, Siberian Branch of Russian Academy of Medical Sciences, Novosibirsk, Russia; Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Medical Sciences, Novosibirsk, Russia.
Martin BobakUCL Research Department of Epidemiology and Public Health, University College London, London, UK.
Hynek PikhartUCL Research Department of Epidemiology and Public Health, University College London, London, UK.
James G WilsonDepartment of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA.
Alex P ReinerDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Brendan J KeatingCenter for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Aroon D HingoraniUCL Institute of Cardiovascular Science and Farr Institute, University College London, London, UK.
Naveed SattarBHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
University College London · GBUniversity Medical Center Utrecht · NLUniversity of Glasgow · GBUniversity of Cambridge · GBChildren's Hospital of Philadelphia · USFarr Institute · GBUniversity of Bristol · GBUtrecht University · NLImperial College London · GBJagiellonian University · PLMRC Unit for Lifelong Health and Ageing · GBUniversity of Washington · USCopenhagen University Hospital · DKKarolinska Institutet · SELeiden University Medical Center · NLLondon School of Hygiene & Tropical Medicine · GBNational Institute for Public Health and the Environment · NLOslo University Hospital · NOResearch Institute of Therapy and Preventive Medicine · RUUniversity Medical Center Groningen · NL

Funding

SOCIAL AND OCCUPATIONAL INFLUENCES ON HEALTH AND ILLNESSR01HL036310 · UNIVERSITY OF LONDON · 1986 to 2005
$1.4M
Health disparities and aging in societies in transitionR01AG023522 · UNIVERSITY COLLEGE LONDON · 2004 to 2005
$903k
British Heart Foundation FS/07/011British Heart Foundation PG/07/133/24260British Heart Foundation PG/13/66/30442British Heart Foundation RG/07/008/23674British Heart Foundation RG 08/008British Heart Foundation RG/08/008/25291British Heart Foundation RG/08/013/25942British Heart Foundation RG/13/16/30528British Heart Foundation RG/13/2/30098Medical Research Council G0100222Medical Research Council G0500877Medical Research Council G0600705Medical Research Council G0601647Medical Research Council G0701830Medical Research Council G0802432Medical Research Council G0902037Medical Research Council G1000616Medical Research Council G19/35Medical Research Council G8802774Medical Research Council K013351Medical Research Council MC_U106179471Medical Research Council MC_UP_A100_1003Medical Research Council MC_UU_12013/1Medical Research Council MC_UU_12013/3Medical Research Council MC_UU_12013/5Medical Research Council MC_UU_12013/8Medical Research Council MC_UU_12015/1Medical Research Council MC_UU_12015/5Medical Research Council MC_UU_12019/1Medical Research Council MR/K006215/1Medical Research Council MR/K006584/1Medical Research Council MR/K013351/1NCI NIH HHS UM1 CA182913NHLBI NIH HHS HL036310NHLBI NIH HHS R01 HL036310NHLBI NIH HHS U19 HL065797NIA NIH HHS 1R01 AG23522-01NIA NIH HHS AG034454NIA NIH HHS R01 AG023522NIA NIH HHS R01 AG034454NIMHD NIH HHS P20 MD006899NIMHD NIH HHS P20MD006899Wellcome TrustWellcome Trust 064947/Z/01/ZWellcome Trust 081081/Z/06/ZWellcome Trust 81081/Z/06/Z
8 · The paper itself

Abstract

The marked sentences are the ones the graph read a number from.

backgroundStatins increase the risk of new-onset type 2 diabetes mellitus. We aimed to assess whether this increase in risk is a consequence of inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the intended drug target.

methodsWe used single nucleotide polymorphisms in the HMGCR gene, rs17238484 (for the main analysis) and rs12916 (for a subsidiary analysis) as proxies for HMGCR inhibition by statins. We examined associations of these variants with plasma lipid, glucose, and insulin concentrations; bodyweight; waist circumference; and prevalent and incident type 2 diabetes. Study-specific effect estimates per copy of each LDL-lowering allele were pooled by meta-analysis. These findings were compared with a meta-analysis of new-onset type 2 diabetes and bodyweight change data from randomised trials of statin drugs. The effects of statins in each randomised trial were assessed using meta-analysis.

findingsData were available for up to 223 463 individuals from 43 genetic studies. Each additional rs17238484-G allele was associated with a mean 0·06 mmol/L (95% CI 0·05-0·07) lower LDL cholesterol and higher body weight (0·30 kg, 0·18-0·43), waist circumference (0·32 cm, 0·16-0·47), plasma insulin concentration (1·62%, 0·53-2·72), and plasma glucose concentration (0·23%, 0·02-0·44). The rs12916 SNP had similar effects on LDL cholesterol, bodyweight, and waist circumference. The rs17238484-G allele seemed to be associated with higher risk of type 2 diabetes (odds ratio [OR] per allele 1·02, 95% CI 1·00-1·05); the rs12916-T allele association was consistent (1·06, 1·03-1·09). In 129 170 individuals in randomised trials, statins lowered LDL cholesterol by 0·92 mmol/L (95% CI 0·18-1·67) at 1-year of follow-up, increased bodyweight by 0·24 kg (95% CI 0·10-0·38 in all trials; 0·33 kg, 95% CI 0·24-0·42 in placebo or standard care controlled trials and -0·15 kg, 95% CI -0·39 to 0·08 in intensive-dose vs moderate-dose trials) at a mean of 4·2 years (range 1·9-6·7) of follow-up, and increased the odds of new-onset type 2 diabetes (OR 1·12, 95% CI 1·06-1·18 in all trials; 1·11, 95% CI 1·03-1·20 in placebo or standard care controlled trials and 1·12, 95% CI 1·04-1·22 in intensive-dose vs moderate dose trials).

interpretationThe increased risk of type 2 diabetes noted with statins is at least partially explained by HMGCR inhibition.

fundingThe funding sources are cited at the end of the paper.

Indexed as

AgedBody Mass IndexBody WeightCholesterol, HDLCholesterol, LDLDiabetes Mellitus, Type 2FemaleGenetic TestingHumansHydroxymethylglutaryl-CoA Reductase InhibitorsHydroxymethylglutaryl CoA ReductasesMaleMiddle AgedPolymorphism, Single NucleotideRandomized Controlled Trials as TopicRisk FactorsCholesterol, HDLCholesterol, LDLHMGCR protein, humanHydroxymethylglutaryl-CoA Reductase InhibitorsHydroxymethylglutaryl CoA Reductases

Identifiers

PMID25262344
PMCPMC4322187
OpenAlexW2097510503

What Socratic holds

Texttitle and abstract
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.