Evidence map›Paper›PMID 30354257›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2018

Mechanism of Increased LDL (Low-Density Lipoprotein) and Decreased Triglycerides With SGLT2 (Sodium-Glucose Cotransporter 2) Inhibition.

Debapriya Basu, Lesley-Ann Huggins, Diego Scerbo, Joseph Obunike, Adam E Mullick, Paul L Rothenberg, Nicholas A Di Prospero, Robert H Eckel, Ira J Goldberg

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed, 4 pooled it
8.2field-weighted citation impact, top 2% 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.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · 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.

3 · Its place in the literature

Who cites it

82 citing papers in PubMed, 4 syntheses or guidelines pooled it, 163 citations in OpenAlex.

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  20. Gliflozins in hypertension: basic mechanisms and clinical insights.American journal of physiology. Renal physiology · 2025
    Review

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

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

Debapriya BasuFrom the Division of Endocrinology, Diabetes and Metabolism, New York University School of Medicine (D.B., L.-A.H., D.S., J.O., I.J.G.).
Lesley-Ann HugginsFrom the Division of Endocrinology, Diabetes and Metabolism, New York University School of Medicine (D.B., L.-A.H., D.S., J.O., I.J.G.).
Diego ScerboFrom the Division of Endocrinology, Diabetes and Metabolism, New York University School of Medicine (D.B., L.-A.H., D.S., J.O., I.J.G.).
Joseph ObunikeFrom the Division of Endocrinology, Diabetes and Metabolism, New York University School of Medicine (D.B., L.-A.H., D.S., J.O., I.J.G.).
Adam E MullickCardiovascular Antisense Drug Discovery, Ionis Pharmaceuticals, Carlsbad, CA (A.E.M.).
Paul L RothenbergCardiovascular and Metabolism Clinical Development, Janssen Research & Development, LLC, Raritan, NJ (P.L.R., N.A.D.P.).
Nicholas A Di ProsperoCardiovascular and Metabolism Clinical Development, Janssen Research & Development, LLC, Raritan, NJ (P.L.R., N.A.D.P.).
Robert H EckelDivision of Endocrinology, University of Colorado, Anschutz Campus, Denver (R.H.E.).
Ira J GoldbergFrom the Division of Endocrinology, Diabetes and Metabolism, New York University School of Medicine (D.B., L.-A.H., D.S., J.O., I.J.G.).
New York University · USJanssen (United States) · USIonis Pharmaceuticals (United States) · US

Funding

PILOT STUDY--SUBSTRATE METABOLISM IN EXTREMELY LOW BIRTH WEIGHT INFANTSP30DK048520 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI Edward L Melanson · 1995 to 2026
$32.6M
Role of Serum Amyloid A in Diabetic Vascular DiseaseP01HL092969 · NHLBI · UNIVERSITY OF WASHINGTON · PI BORNFELDT, KARIN E. · 2008 to 2019
$23.5M
Pathways of Tissue Lipid UptakeR01HL045095 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ABUMRAD, NADA A., GOLDBERG, IRA J · 1991 to 2024
$6.9M
Diabetes-Mediated Effects on Myeloid Precursors and Vascular ComplicationsR01DK095684 · NIDDK · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI FISHER, EDWARD A, GOLDBERG, IRA J · 2012 to 2016
$2.7M
NHLBI NIH HHS P01 HL092969NHLBI NIH HHS R01 HL045095NIDDK NIH HHS R01 DK095684
6 · The paper itself

Abstract

Objective- SGLT2 (sodium-glucose cotransporter 2) inhibition in humans leads to increased levels of LDL (low-density lipoprotein) cholesterol and decreased levels of plasma triglyceride. Recent studies, however, have shown this therapy to lower cardiovascular mortality. In this study, we aimed to determine how SGLT2 inhibition alters circulating lipoproteins. Approach and Results- We used a mouse model expressing human CETP (cholesteryl ester transfer protein) and human ApoB100 (apolipoprotein B100) to determine how SGLT2 inhibition alters plasma lipoprotein metabolism. The mice were fed a high-fat diet and then were made partially insulin deficient using streptozotocin. SGLT2 was inhibited using a specific antisense oligonucleotide or canagliflozin, a clinically available oral SGLT2 inhibitor. Inhibition of SGLT2 increased circulating levels of LDL cholesterol and reduced plasma triglyceride levels. SGLT2 inhibition was associated with increased LpL (lipoprotein lipase) activity in the postheparin plasma, decreased postprandial lipemia, and faster clearance of radiolabeled VLDL (very-LDL) from circulation. Additionally, SGLT2 inhibition delayed turnover of labeled LDL from circulation. Conclusions- Our studies in diabetic CETP-ApoB100 transgenic mice recapitulate many of the changes in circulating lipids found with SGLT2 inhibition therapy in humans and suggest that the increased LDL cholesterol found with this therapy is because of reduced clearance of LDL from the circulation and greater lipolysis of triglyceride-rich lipoproteins. Most prominent effects of SGLT2 inhibition in the current mouse model were seen with antisense oligonucleotides-mediated knockdown of SGLT2.

Indexed as

Adipose TissueAngiopoietin-Like Protein 4AnimalsBlood GlucoseDiabetes Mellitus, ExperimentalDown-RegulationFatty Acids, NonesterifiedGene ExpressionLipoproteins, LDLMaleMice, Inbred C57BLMice, TransgenicMuscle, SkeletalMyocardiumRNA, MessengerSodium-Glucose Transporter 2 InhibitorsAngiopoietin-Like Protein 4ANGPTL4 protein, humanAngptl4 protein, mouseBlood GlucoseFatty Acids, NonesterifiedLipoproteins, LDLRNA, MessengerSodium-Glucose Transporter 2 InhibitorsTriglyceridescanagliflozindiabetes mellituslipoprotein lipaselipoproteinstriglycerides

Identifiers

PMID30354257
PMCPMC6207215
OpenAlexW2890539106

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.