Cited by 204Diabetes Treatment and ManagementLiver Disease Diagnosis and TreatmentDiabetes, Cardiovascular Risks, and Lipoproteins

Effect of canagliflozin treatment on hepatic triglyceride content and glucose metabolism in patients with type 2 diabetes

Cusi, Kenneth, Bril, Fernando, Barb, Diana, Polidori, David, Sha, Sue, Ghosh, Atalanta, Farrell, Kristin, Sunny, Nishanth E. +5 more·2019·Diabetes, Obesity and Metabolism

Abstract

Aim: To evaluate the impact of the sodium glucose co‐transporter 2 inhibitor canagliflozin on intrahepatic triglyceride (IHTG) accumulation and its relationship to changes in body weight and glucose metabolism. Materials and methods: In this double‐blind, parallel‐group, placebo‐controlled, 24‐week trial subjects with inadequately controlled type 2 diabetes mellitus (T2DM; HbA1c = 7.7% ± 0.7%) from two centres were randomly assigned (1:1) to canagliflozin 300 mg or placebo. We measured IHTG by proton‐magnetic resonance spectroscopy (primary outcome), hepatic/muscle/adipose tissue insulin sensitivity during a 2‐step euglycaemic insulin clamp, and beta‐cell function during a mixed meal tolerance test. Analyses were per protocol. Results: Between 8 September 2014‐13 June 2016, 56 patients were enrolled. Canagliflozin reduced HbA1c (placebo‐subtracted change: −0.71% [−1.08; −0.33]) and body weight (−3.4% [−5.4; −1.4]; both P ≤ 0.001). A numerically larger absolute decrease in IHTG occurred with canagliflozin (−4.6% [−6.4; −2.7]) versus placebo (−2.4% [−4.2; −0.6]; P = 0.09). In patients with non‐alcoholic fatty liver disease (n = 37), the decrease in IHTG was −6.9% (−9.5; −4.2) versus −3.8% (−6.3; −1.3; P = 0.05), and strongly correlated with the magnitude of weight loss (r = 0.69, P < 0.001). Body weight loss ≥5% with a ≥30% relative reduction in IHTG occurred more often with canagliflozin (38% vs. 7%, P = 0.009). Hepatic insulin sensitivity improved with canagliflozin ( P < 0.01), but not muscle or adipose tissue insulin sensitivity. Beta‐cell glucose sensitivity, insulin clearance, and disposition index improved more with canagliflozin ( P < 0.05). Conclusions: Canagliflozin improves hepatic insulin sensitivity and insulin secretion and clearance in patients with T2DM. IHTG decreases in proportion to the magnitude of body weight loss, which tended to be greater and occur more often with canagliflozin.

Integrity signals

Registry

Crossref · 10.1111/dom.13584

Cites

41 of 41 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The moderate weight loss effects of SGLT2I are explained at least in major parts by drug-elicited increase in glucosuria with consecutive calory loss of about 200 kcal per day.

    “which is explainedat least in major parts -by the drug-elicited increase in glucosuria with a consecutive calory loss of about 200 kcal per day [149].”

Cites

Flagged first, then by citations

1 of the 42 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Authors
Cusi, K., Bril, F., Barb, D., Polidori, D., Sha, S., Ghosh, A., Farrell, K., Sunny, N. E., Kalavalapalli, S., Pettus, J., Ciaraldi, T. P., Mudaliar, S., & Henry, R. R.
Affiliations
  • University of Florida Health (US)
  • Janssen Research &amp; Development LLC San Diego California
  • Janssen Research & Development (United States) (US)
  • University of California San Diego (US)
Corresponding author
Cusi, Kenneth
Venue
Diabetes, Obesity and Metabolism
Publisher
Wiley
Published
2018-12-18
Volume
21
Issue
4
Pages
812-821
ISSN
  • 1462-8902 (ISSN-L)
  • 1463-1326
OpenAlex
W2901946789
Cited by
204
References
42
Citations by year
2026: 18 · 2025: 28 · 2024: 27 · 2023: 26 · 2022: 33 · 2021: 33 · 2020: 29 · 2019: 9 · 2015: 1
FWCI
14.13
Type
journal article
Language
en
Open access
closed
Locations
  • Diabetes Obesity and Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Funders
Janssen Research & Development, LLC
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords
canagliflozin, SGLT2 inhibitors, type 2 diabetes, hepatic steatosis, non-alcoholic fatty liver disease, hepatic insulin sensitivity, beta-cell function, glucose metabolism, weight loss, HbA1c, insulin clearance, disposition index, 1H NMR
MeSH terms
Canagliflozin, Sodium-Glucose Transporter 2 Inhibitors, Insulin Secretion, Aged, Diabetes Mellitus, Type 2, Double-Blind Method, Female, Glycated Hemoglobin, Humans, Insulin Resistance, Liver, Male, Middle Aged, Triglycerides, Glucose Clamp Technique, Weight Loss, Treatment Outcome, Insulin-Secreting Cells, Proton Magnetic Resonance Spectroscopy

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review