Trial reportArteriosclerosis, thrombosis, and vascular biology2021

Statins Are Associated With Increased Insulin Resistance and Secretion.

Fahim Abbasi, Cindy Lamendola, Chelsea S Harris, Vander Harris, Ming-Shian Tsai, Pragya Tripathi, Fakhar Abbas, Gerald M Reaven, Peter D Reaven, Michael P Snyder and 2 more

Open access · bronzeAbstract readClinical Trial
In one paragraph

Trial report in Arteriosclerosis, thrombosis, and vascular biology, 2021. The graph read 3 numbers from its abstract, feeding 2 cells of the map: it . Cited by 62 papers, 2 of them syntheses that pooled it.

3numbers the graph read from it
1cell of the map it votes in
62citing papers in PubMed, 2 pooled it
14.8field-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.

← favours the treatmentfavours the comparator →
0.050 · no effect
Glycemic controlfavours the comparator · head-to-head · dyslipidemia, t2dfeeds one cell of the map
median increase 0.05P=0.03
There were small increases in oral glucose tolerance test glucoseAUC (median increase, 0.05%; P=0.03) and fasting insulin (median increase, 7%; P=0.01).

Read, but not usablea number the graph found but could not read as for or against

Lipidscomparator not stated · dyslipidemia, t2dfeeds one cell of the map
median decrease -53.0P<0.001
Atorvastatin reduced LDL (low-density lipoprotein)-cholesterol (median decrease 53%, P<0.001) but did not change body weight.
Glycemic controldirection of benefit for this outcome is not defined · head-to-head · dyslipidemia, t2dfeeds one cell of the map
median increase 7.00P=0.01
There were small increases in oral glucose tolerance test glucoseAUC (median increase, 0.05%; P=0.03) and fasting insulin (median increase, 7%; P=0.01).

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.

Insulin×glycemic control

No readable resultOpen on the map →What to test next →

40 readable studies in this cell: 15 favour the treatment, 14 find no difference, 14 favour the comparator.

Belief with this paper
0.50contested · 9 families support, 6 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
This paper · 2021
median increase 0.05
NCT036893742,274 enrolled · 2018
Δ -0.29-0.38 to -0.20
NCT037306622,002 enrolled · 2018
Δ -0.99-1.13 to -0.86
NCT013360231,663 enrolled · 2011
Treatment contrast -0.64-0.75 to -0.53
NCT038829701,444 enrolled · 2019
Δ -0.86-1.00 to -0.72
NCT045379231,428 enrolled · 2020
Δ -1.10-1.24 to -0.97
NCT032680051,264 enrolled · 2017
Δ -0.04-0.11 to 0.03
NCT020581471,170 enrolled · 2014
Δ -0.78-0.90 to -0.67
NCT021289321,089 enrolled · 2014
Δ -0.81-0.96 to -0.67
NCT009606611,036 enrolled · 2009
Δ -0.04-0.18 to 0.11
NCT00856986987 enrolled · 2009
Δ -0.52-0.68 to -0.36
NCT01117350978 enrolled · 2010
Δ 2.54-3.88 to 8.93
NCT03214380933 enrolled · 2017
Δ 0.06-0.05 to 0.16

Statins×lipids

No readable resultOpen 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
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
NCT0093525931 enrolled · 2009
Δ -51.7
reductions -33.6-38.8 to -28.4

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

5 · Its place in the literature

Who cites it

62 citing papers in PubMed, 2 syntheses or guidelines pooled it, 92 citations in OpenAlex.

  1. Effect ofInternational journal of molecular sciences · 2024
    Pooled it
  2. Guideline
  3. Trial
  4. Trial
  5. Trial
  6. Trial
  7. Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. HMGCR and Rosuvastatin Regulates GLP-1 Secretion and Expression-A Translational Study.The Journal of clinical endocrinology and metabolism · 2026
    Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Review

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

6 · The record

Corrections and comments

7 · Who and what money

Authors and funding

12 authors at 4 institutions in 2 countries.

Fahim AbbasiDivision of Cardiovascular Medicine (F. Abbasi, C.L., C.S.H., V.H., P.T., F. Abbas, G.M.R., J.W.K.), Stanford University, CA.ORCID 0000-0002-3932-8375
Cindy LamendolaDivision of Cardiovascular Medicine (F. Abbasi, C.L., C.S.H., V.H., P.T., F. Abbas, G.M.R., J.W.K.), Stanford University, CA.
Chelsea S HarrisDivision of Cardiovascular Medicine (F. Abbasi, C.L., C.S.H., V.H., P.T., F. Abbas, G.M.R., J.W.K.), Stanford University, CA.
Vander HarrisDivision of Cardiovascular Medicine (F. Abbasi, C.L., C.S.H., V.H., P.T., F. Abbas, G.M.R., J.W.K.), Stanford University, CA.
Ming-Shian TsaiCardiovascular Institute (F. Abbasi, C.L., C.S.H., V.H., M.-S.T., P.T., F. Abbas, G.M.R., M.P.S., J.W.K.), Stanford University, CA.ORCID 0000-0003-2187-1350
Pragya TripathiDivision of Cardiovascular Medicine (F. Abbasi, C.L., C.S.H., V.H., P.T., F. Abbas, G.M.R., J.W.K.), Stanford University, CA.
Fakhar AbbasDivision of Cardiovascular Medicine (F. Abbasi, C.L., C.S.H., V.H., P.T., F. Abbas, G.M.R., J.W.K.), Stanford University, CA.
Gerald M ReavenDivision of Cardiovascular Medicine (F. Abbasi, C.L., C.S.H., V.H., P.T., F. Abbas, G.M.R., J.W.K.), Stanford University, CA.
Peter D ReavenUniversity of Arizona and Phoenix VA Health Care System (P.D.R.).
Michael P SnyderCardiovascular Institute (F. Abbasi, C.L., C.S.H., V.H., M.-S.T., P.T., F. Abbas, G.M.R., M.P.S., J.W.K.), Stanford University, CA.
Sun H KimDepartment of Medicine (F. Abbasi, C.L., C.S.H., V.H., F.A., G.M.R., S.H.K., J.W.K.), Stanford University, CA.ORCID 0000-0003-0895-7491
Joshua W KnowlesDivision of Cardiovascular Medicine (F. Abbasi, C.L., C.S.H., V.H., P.T., F. Abbas, G.M.R., J.W.K.), Stanford University, CA.ORCID 0000-0003-1922-7240
Cardiovascular Institute of the South · USABB (Switzerland) · CHPhoenix VA Health Care System · USStanford University · US

Funding

WU P&FP30DK020579 · NIDDK · WASHINGTON UNIVERSITY · 2022 to 2025
$5.6M
Stanford Islet Research CoreP30DK116074 · STANFORD UNIVERSITY · 2025 to 2025
$2.0M
NCATS NIH HHS UL1 TR003142NIDDK NIH HHS P30 DK020579NIDDK NIH HHS P30 DK116074NIDDK NIH HHS R01 DK106236NIDDK NIH HHS R01 DK116750NIDDK NIH HHS R01 DK120565
8 · The paper itself

Abstract

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

Objective: Statin treatment reduces the risk of atherosclerotic cardiovascular disease but is associated with a modest increased risk of type 2 diabetes, especially in those with insulin resistance or prediabetes. Our objective was to determine the physiological mechanism for the increased type 2 diabetes risk. Approach and Results: We conducted an open-label clinical trial of atorvastatin 40 mg daily in adults without known atherosclerotic cardiovascular disease or type 2 diabetes at baseline. The co-primary outcomes were changes at 10 weeks versus baseline in insulin resistance as assessed by steady-state plasma glucose during the insulin suppression test and insulin secretion as assessed by insulin secretion rate area under the curve (ISRAUC) during the graded-glucose infusion test. Secondary outcomes included glucose and insulin, both fasting and during oral glucose tolerance test. Of 75 participants who enrolled, 71 completed the study (median age 61 years, 37% women, 65% non-Hispanic White, median body mass index, 27.8 kg/m2). Atorvastatin reduced LDL (low-density lipoprotein)-cholesterol (median decrease 53%, P<0.001) but did not change body weight. Compared with baseline, atorvastatin increased insulin resistance (steady-state plasma glucose) by a median of 8% (P=0.01) and insulin secretion (ISRAUC) by a median of 9% (P<0.001). There were small increases in oral glucose tolerance test glucoseAUC (median increase, 0.05%; P=0.03) and fasting insulin (median increase, 7%; P=0.01). Conclusions: In individuals without type 2 diabetes, high-intensity atorvastatin for 10 weeks increases insulin resistance and insulin secretion. Over time, the risk of new-onset diabetes with statin use may increase in individuals who become more insulin resistant but are unable to maintain compensatory increases in insulin secretion.

Indexed as

Insulin ResistanceAdultAgedAtorvastatinBiomarkersBlood GlucoseDiabetes MellitusDyslipidemiasFemaleHumansHydroxymethylglutaryl-CoA Reductase InhibitorsInsulinLipidsMaleMiddle AgedProspective StudiesAtorvastatinBiomarkersBlood GlucoseHydroxymethylglutaryl-CoA Reductase InhibitorsInsulinLipidsatorvastatincardiovascular diseaseglucoseinsulin resistanceinsulin secretion

Identifiers

PMID34433298
PMCPMC8551023
OpenAlexW3194954047

What Socratic holds

Texttitle and abstract
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.