Exenatide decreases liver fat content and epicardial adipose tissue in patients with obesity and type 2 diabetes: a prospective randomized clinical trial using magnetic resonance imaging and spectroscopy

Dutour, Anne; Abdesselam, Inès; Ancel, Patricia; Kober, Frank; Mrad, G.; Darmon, Patrice; Ronsin, O.; Pradel, Vincent; Lesavre, Nathalie; Martin, Jean‐Charles; Jacquier, Alexis; Lefur, Yann; Bernard, Monique; Gaborit, Bénédicte

doi:10.1111/dom.12680

Cited by 190 publications

(165 citation statements)

References 51 publications

(64 reference statements)

Supporting

Mentioning

156

Contrasting

Unclassified

Order By: Relevance

“…In addition, GLP-1RAs activate several anti-inflammatory pathways, including reductions in oxidative stress via reactive oxygen species, nuclear factor-kB binding/activation, expression of inflammatory cytokines and C-reactive protein, and increases in adiponectin (37). Also, GLP-1RAs seem to have beneficial effects on NASH and NAFLD by reductions in body weight, de novo hepatic lipogenesis, oxidative stress, inflammatory cytokines, and endoplasmatic reticulum stress and improvements in hepatic insulin sensitivity, triglyceride handling, and neural regulation of hepatic metabolism (38,39). In the Liraglutide Efficacy and Action in Non-Alcoholic Steatohepatitis (LEAN) trial, liraglutide reduced liver enzymes and oxidative stress and improved liver histology in patients NAFLD and T2D (40 , in which drug B reduces the effect of drug A threefold (indicated by the red inhibition line) but has no effect on its own, and interference (bottom), in which drug B reduces the effect of drug A threefold (indicated by the red inhibition line), preventing it from exerting its full response, but drug B nonetheless has a beneficial effect on its own.…”

Section: Sglt2 Inhibition In Combination Therapymentioning

confidence: 99%

SGLT2 Inhibitors in Combination Therapy: From Mechanisms to Clinical Considerations in Type 2 Diabetes Management

et al. 2018

View full text Add to dashboard Cite

The progressive nature of type 2 diabetes (T2D) requires practitioners to periodically evaluate patients and intensify glucose-lowering treatment once glycemic targets are not attained. With guidelines moving away from a one-size-fits-all approach toward setting patient-centered goals and allowing flexibility in choosing a second-/third-line drug from the growing number of U.S. Food and Drug Administration-approved glucose-lowering agents, keen personalized management in T2D has become a challenge for health care providers in daily practice. Among the newer generation of glucose-lowering drug classes, sodium-glucose cotransporter 2 inhibitors (SGLT2is), which enhance urinary glucose excretion to lower hyperglycemia, have made an imposing entrance to the T2D treatment armamentarium. Given their unique insulin-independent mode of action and their favorable efficacy-to-adverse event profile and given their marked benefits on cardiovascular-renal outcome in moderate-to-high risk T2D patients, which led to updates of guidelines and product monographs, the role of this drug class in multidrug regimes is promising. However, despite many speculations based on pharmacokinetic and pharmacodynamic properties, physiological reasoning, and potential synergism, the effects of these agents in terms of glycemic and pleiotropic efficacy when combined with other glucose-lowering drug classes are largely understudied. In this perspective, we review the currently emerging evidence, discuss prevailing hypotheses, and elaborate on necessary future studies to clarify the potential risks and benefits of using an SGLT2i in dual combination with metformin and triple combination with a glucagon-like peptide 1 receptor agonist, dipeptidyl peptidase 4 inhibitor, or other glucose-lowering agent that is recommended by the American Diabetes Association and European Association for the Study of Diabetes (i.e., a sulfonylurea, thiazolidinedione, or insulin) to treat patients with T2D.

show abstract

Section: Sglt2 Inhibition In Combination Therapymentioning

confidence: 99%

SGLT2 Inhibitors in Combination Therapy: From Mechanisms to Clinical Considerations in Type 2 Diabetes Management

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Currently, the pharmacological therapy for NAFLD includes Vitamin E, angiotensin receptor blockers, thiazolidinedione 17 and glucagon-like peptide-1 analogues, which were recently reported to be effective for treatment of NAFLD. 6 Thiazolidinedione improves liver fat deposition, inflammation and fibrosis 4 in T2D patients with NAFLD. However, because of its potential adverse effects such as weight gain, body fat gain, edema and volume overload, 18 it is discouraged for patients with NAFLD, which often coexists with obesity.…”

Section: Discussionmentioning

confidence: 99%

Luseogliflozin improves liver fat deposition compared to metformin in type 2 diabetes patients with non‐alcoholic fatty liver disease: A prospective randomized controlled pilot study

Shibuya¹,

Fushimi²,

Kawai³

et al. 2017

Diabetes Obesity Metabolism

165

144

View full text Add to dashboard Cite

This study aimed to assess the effect of luseogliflozin on liver fat deposition and compare luseogliflozin to metformin in type 2 diabetes (T2D) patients with non-alcoholic fatty liver disease (NAFLD). Thirty-two T2D patients with NAFLD diagnosed by computed tomography or abdominal sonography were recruited. Participants were randomly assigned to receive either luseogliflozin (2.5 mg, newly administered) or metformin (1500 mg, newly or additionally administrated). Data on the liver-to-spleen attenuation ratio (L/S), visceral fat area, body mass index, glycated hemoglobin (HbA1c), alanine aminotransferase (ALT), fasting plasma glucose, C-peptide immunoreactivity (CPR), and CPR index were collected at baseline and after 6 months. The change in L/S was significantly greater in the luseogliflozin group than in the metformin group. Similarly, the changes in the visceral fat area, HbA1c, and body mass index were significantly greater in the luseogliflozin group than in the metformin group. The changes in ALT, fasting glucose, CPR, and CPR index were not significant in both groups. In conclusion, luseogliflozin significantly reduced liver fat deposition as compared to metformin, which may indicate clinical relevant benefits for NAFLD.

show abstract

“…Short-term (3 months) use of glucagon-like-receptor agonists (exenatide, liraglutide) decreased the volume of EAT in type 2 diabetic patients [91]. In a longer (26 weeks) randomized controlled trial, exenatide twice daily (versus standard antidiabetic treatment) proved to be effective in reducing both epicardial and liver fat content in obese patients with type 2 diabetes; the effects were mainly weight loss dependent [92]. In another study, sitagliptin, a dipeptidyl-peptidase-4 inhibitor, also decreased the volume of EAT in a 24-week long study with obese type 2 diabetic patients [93].…”

Section: Treatment Options For Modifying Epicardial Adipose Tissue Vomentioning

confidence: 99%

Clinical importance of epicardial adipose tissue

Nagy¹,

Jermendy²,

Merkely³

et al. 2017

aoms

102

View full text Add to dashboard Cite

Different visceral fat compartments have several systemic effects and may play a role in the development of both insulin resistance and cardiovascular diseases. In the last couple of years special attention has been paid to the epicardial adipose tissue (EAT), which can be quantified by non-invasive cardiac imaging techniques. The epicardial fat is a unique fat compartment between the myocardium and the visceral pericardium sharing a common embryologic origin with the visceral fat depot. Epicardial adipose tissue has several specific roles, and its local effects on cardiac function are incorporated in the complex pathomechanism of coronary artery disease. Importantly, EAT may produce several adipocytokines and chemokines that may influence – through paracrine and vasocrine effects – the development and progression of coronary atherosclerosis. Epicardial adipose tissue volume has a relatively strong genetic dependence, similarly to other visceral fat depots. In this article, the anatomical and physiological as well as pathophysiological characteristics of the epicardial fat compartment are reviewed.

show abstract

Exenatide decreases liver fat content and epicardial adipose tissue in patients with obesity and type 2 diabetes: a prospective randomized clinical trial using magnetic resonance imaging and spectroscopy

Abstract: Our data indicate that exenatide is an effective treatment to reduce liver fat content and epicardial fat in obese patients with type 2 diabetes, and these effects are mainly weight loss dependent.

Cited by 190 publications

References 51 publications

SGLT2 Inhibitors in Combination Therapy: From Mechanisms to Clinical Considerations in Type 2 Diabetes Management

SGLT2 Inhibitors in Combination Therapy: From Mechanisms to Clinical Considerations in Type 2 Diabetes Management

Luseogliflozin improves liver fat deposition compared to metformin in type 2 diabetes patients with non‐alcoholic fatty liver disease: A prospective randomized controlled pilot study

Clinical importance of epicardial adipose tissue

Contact Info

Product

Resources

About