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Effect of canagliflozin treatment on hepatic triglyceride content and glucose metabolism in patients with type 2 diabetes
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.
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“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].”
From Obesity and MASLD: Is weight loss the (only) key to treat metabolic liver disease? (2024) · cites this paper as [149]
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Metadata
- 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 & Development LLC San Diego California
- Janssen Research & Development (United States) (US)
- University of California San Diego (US)
- Corresponding author
- Cusi, Kenneth
- ORCID
- 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
- 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 › Hepatology › 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
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