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

Autor: Kenneth Cusi, Sue Sha, Diana Barb, Nishanth E. Sunny, David Polidori, Jeremy Pettus, Robert R. Henry, Srilaxmi Kalavalapalli, Sunder Mudaliar, Fernando Bril, Theodore P. Ciaraldi, Kristin Farrell, Atalanta Ghosh
Rok vydání: 2019
Předmět:
Male
medicine.medical_specialty
Proton Magnetic Resonance Spectroscopy
Endocrinology
Diabetes and Metabolism
medicine.medical_treatment
030209 endocrinology & metabolism
Type 2 diabetes
030204 cardiovascular system & hematology
Carbohydrate metabolism
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Endocrinology
Insulin resistance
Double-Blind Method
Weight loss
Insulin-Secreting Cells
Internal medicine
Insulin Secretion
Weight Loss
Internal Medicine
medicine
Humans
Canagliflozin
Sodium-Glucose Transporter 2 Inhibitors
Triglycerides
Aged
Glycated Hemoglobin
Triglyceride
business.industry
Insulin
Fatty liver
Middle Aged
medicine.disease
Treatment Outcome
Diabetes Mellitus
Type 2
Liver
chemistry
Glucose Clamp Technique
Female
Insulin Resistance
medicine.symptom
business
medicine.drug
Zdroj: Diabetes, Obesity and Metabolism. 21:812-821
ISSN: 1463-1326
1462-8902
DOI: 10.1111/dom.13584
Popis: 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.
Databáze: OpenAIRE
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