W Timothy Garvey1, Luc Van Gaal2, Lawrence A Leiter3, Ujjwala Vijapurkar4, James List5, Robert Cuddihy6, Jimmy Ren7, Michael J Davies8. 1. Department of Nutrition Sciences and the UAB Diabetes Research Center, University of Alabama at Birmingham and the Birmingham VA Medical Center, 1675 University Blvd., Birmingham, AL 35294-3360, USA. Electronic address: garveyt@uab.edu. 2. Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital, Wilrijkstraat 10, B-2650 Edegem, Antwerp, Belgium. Electronic address: Luc.VanGaal@uza.be. 3. Division of Endocrinology & Metabolism, Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, 61 Queen St. East #6121, Toronto, ON M5C 2T2, Canada. Electronic address: LeiterL@smh.ca. 4. Janssen Research & Development, LLC, 920 Route 202 South, Raritan, NJ 08869, USA. Electronic address: UVijapur@its.jnj.com. 5. Janssen Research & Development, LLC, 920 Route 202 South, Raritan, NJ 08869, USA. Electronic address: jlist1@ITS.JNJ.com. 6. Janssen Global Services, LLC, 920 Route 202 South, Raritan, NJ 08869, USA. Electronic address: rcuddihy@ITS.JNJ.com. 7. Janssen Scientific Affairs, LLC, 1125 Trenton-Harbourton Rd, Titusville, NJ 08560, USA. Electronic address: JRen1@its.jnj.com. 8. Janssen Scientific Affairs, LLC, 1125 Trenton-Harbourton Rd, Titusville, NJ 08560, USA. Electronic address: mdavies9@its.jnj.com.
Abstract
OBJECTIVE:Type 2 diabetes and obesity are pro-inflammatory states associated with increased risk of cardiovascular disease. Canagliflozin, an SGLT2 inhibitor, demonstrated superiority in lowering HbA1c versus glimepiride with less hypoglycemia and greater weight reduction via loss of fat mass in a 52-week trial of type 2 diabetes patients. This post hoc, exploratory analysis assessed the effects of canagliflozin versus glimepiride on select adipokines, inflammatory biomarkers, and chemokines. METHODS: Changes from baseline to Week 52 in serum leptin, adiponectin, IL-6, TNFα, CRP, PAI-1, VCAM-1, and MCP-1 were measured in a randomly selected subset of type 2 diabetes patients on metformin receiving canagliflozin 300 mg (n = 100) or glimepiride (n = 100) in the overall study. Correlations between change in biomarkers and change in select metabolic and anthropometric variables were assessed. RESULTS: At Week 52, canagliflozin decreased median serum leptin by 25% (95% CI: -34%, -15%) and increased median serum adiponectin by 17% (95% CI: 11%, 23%) compared with glimepiride. There was a 22% reduction in median serum IL-6 (95% CI: -34%, -10%) and a 7% increase in median serum TNFα (95% CI: 1%, 12%) with canagliflozin versus glimepiride. No between-group differences were observed with the other biomarkers. The decrease in serum leptin with canagliflozin was correlated with change in weight (r ≥ 0.3) only; the increase in adiponectin and decrease in IL-6 with canagliflozin occurred independently of changes in HbA1c, weight, or lipids. CONCLUSIONS: These results indicate that canagliflozin may improve adipose tissue function and induce changes in serum leptin, adiponectin, and IL-6 that favorably impact insulin sensitivity and cardiovascular disease risk.
RCT Entities:
OBJECTIVE: Type 2 diabetes and obesity are pro-inflammatory states associated with increased risk of cardiovascular disease. Canagliflozin, an SGLT2 inhibitor, demonstrated superiority in lowering HbA1c versus glimepiride with less hypoglycemia and greater weight reduction via loss of fat mass in a 52-week trial of type 2 diabetespatients. This post hoc, exploratory analysis assessed the effects of canagliflozin versus glimepiride on select adipokines, inflammatory biomarkers, and chemokines. METHODS: Changes from baseline to Week 52 in serum leptin, adiponectin, IL-6, TNFα, CRP, PAI-1, VCAM-1, and MCP-1 were measured in a randomly selected subset of type 2 diabetespatients on metformin receiving canagliflozin 300 mg (n = 100) or glimepiride (n = 100) in the overall study. Correlations between change in biomarkers and change in select metabolic and anthropometric variables were assessed. RESULTS: At Week 52, canagliflozin decreased median serum leptin by 25% (95% CI: -34%, -15%) and increased median serum adiponectin by 17% (95% CI: 11%, 23%) compared with glimepiride. There was a 22% reduction in median serum IL-6 (95% CI: -34%, -10%) and a 7% increase in median serum TNFα (95% CI: 1%, 12%) with canagliflozin versus glimepiride. No between-group differences were observed with the other biomarkers. The decrease in serum leptin with canagliflozin was correlated with change in weight (r ≥ 0.3) only; the increase in adiponectin and decrease in IL-6 with canagliflozin occurred independently of changes in HbA1c, weight, or lipids. CONCLUSIONS: These results indicate that canagliflozin may improve adipose tissue function and induce changes in serum leptin, adiponectin, and IL-6 that favorably impact insulin sensitivity and cardiovascular disease risk.
Authors: Dimitrios A Vrachatis; Konstantinos A Papathanasiou; Konstantinos E Iliodromitis; Sotiria G Giotaki; Charalampos Kossyvakis; Konstantinos Raisakis; Andreas Kaoukis; Vaia Lambadiari; Dimitrios Avramides; Bernhard Reimers; Giulio G Stefanini; Michael Cleman; Georgios Giannopoulos; Alexandra Lansky; Spyridon G Deftereos Journal: Drugs Date: 2021-07-23 Impact factor: 9.546
Authors: Michele Provenzano; Maria Chiara Pelle; Isabella Zaffina; Bruno Tassone; Roberta Pujia; Marco Ricchio; Raffaele Serra; Angela Sciacqua; Ashour Michael; Michele Andreucci; Franco Arturi Journal: Front Med (Lausanne) Date: 2021-06-04