Metabolic effects of two years of exenatide treatment on diabetes, obesity, and hepatic biomarkers in patients with type 2 diabetes: An interim analysis of data from the open-label, uncontrolled extension of three double-blind, placebo-controlled trials

Buse, John B.; Klonoff, David C.; Nielsen, Loretta L.; Guan, Xiaodan; Bowlus, Christopher L.; Holcombe, John H.; Maggs, David; Wintle, Matthew

doi:10.1016/j.clinthera.2007.01.015

Cited by 250 publications

(184 citation statements)

References 45 publications

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“…Patients with normal baseline ALT had no significant ALT change. However, patients with elevated ALT at baseline had a slight but significant reduction of ALT from baseline and 39% achieved normal ALT by week 104 [64] . This beneficial effect may be explained by the concomitant weight loss and better glucose control with exenatide, two changes that could reduce NAFLD [61] .…”

Section: Hepatic Safetymentioning

confidence: 93%

Pharmacokinetics in Patients with Chronic Liver Disease and Hepatic Safety of Incretin-Based Therapies for the Management of Type 2 Diabetes Mellitus

Scheen

2014

Clin Pharmacokinet

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SUMMARYPatients with type 2 diabetes have an increased risk of chronic liver disease such as nonalcoholic fatty liver disease and steatohepatitis, and about one third of cirrhotic patients have diabetes. However, the use of several antidiabetic agents, such as metformin and sulphonylureas, may be a concern in case of hepatic impairment (HI). New glucose-lowering agents targeting the incretin system are increasingly used for the management of type 2 diabetes. Incretin-based therapies comprise oral inhibitors of dipeptidyl peptidase-4 (DPP-4) (gliptins) or injectable glucagon-like peptide-1 (GLP-1) receptor agonists. This narrative review summarizes the available data regarding the use of both incretin-based therapies in patients with HI. In contrast to old glucose-lowering agents, they were evaluated in specifically designed acute pharmacokinetic studies in patients with various degrees of HI and -Obese patients with type 2 diabetes often have non-alcoholic fatty liver disease or steatohepatitis and the use of incretin-based therapies appears mostly favourable in these patients regarding both efficacy and safety.-There is no reported clinical experience with the use of either DPP-4 inhibitors or GLP-1 receptor agonists in diabetic patients with moderate to severe hepatic impairment, so that caution is required in patients with advanced cirrhosis.

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Section: Hepatic Safetymentioning

confidence: 93%

Pharmacokinetics in Patients with Chronic Liver Disease and Hepatic Safety of Incretin-Based Therapies for the Management of Type 2 Diabetes Mellitus

Scheen

2014

Clin Pharmacokinet

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“…These parameters can provide highly valuable information in assessing not only the extent and severity of liver damage, but also the type of liver damage [58]. ALT and AST are the most commonly used indicators of liver (hepatocellular) damage [58][59][60]. BBR, PS, or BBRPS did not induce liver and other tissue damage as indicated by the insignificant effect of either treatment on the concentration of AST and ALT in the plasma.…”

Section: Discussionmentioning

confidence: 99%

Co-administration of berberine and plant stanols synergistically reduces plasma cholesterol in rats

Xiao-ming¹,

Chen

Zidichouski³

et al. 2008

Atherosclerosis

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The objective of the present study was to determine the beneficial effects and the safety of oral administration of the combination of berberine (BBR) and plant stanols (PS) on plasma lipid profiles in male Sprague-Dawley rats. Four groups of animals were fed a cornstarch-casein-sucrose-based high-cholesterol (2%, w:w) and high-fat (27.5%) diet. Three treatment groups were supplemented with either BBR (100 mg kg −1 body weight d −1 ), PS (1% in diet, w:w), or the combination of both (BBRPS). After 6 wk, animals were sacrificed and followed immediately with the collection of blood and organ samples. Lipid analysis revealed that PS lowered plasma total cholesterol (T-C) by 18% (p = 0.067) and non-HDL-cholesterol (non-HDL-C) by 29% (p = 0.013) as compared with the control, while BBR had no effect on both T-C and non-HDL-C. The combination treatment of BBRPS reduced plasma T-C by 41% (p = 0.0002) and non-HDL-C by 59% (p < 0.0001) compared to the control group. BBR reduced plasma TG levels by 31% at a marginal significance relative to the control (p = 0.054), whereas PS had no effect. BBRPS showed an additive effect of BBR and PS on plasma TAG. PS and BBRPS both decreased liver cholesterol (p = 0.0027 and 0.0002, respectively). BBR and PS, either alone or in combination, did not show any toxic effects as assessed by plasma concentration of hepatic biochemical parameters. These results demonstrate that BBR and PS, when combined, synergistically lower plasma cholesterol levels and significantly reduce liver cholesterol, without the observation of any toxic effects. Crown

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“…Exenatide significantly improved transaminases in three RCTs enrolling diabetic patients [107], and its effects on liver histology in NASH are being tested in clinicaltrials.gov NCT00529204 and NCT00650546. In the Liraglutide Effect and Action in Diabetes (LEAD)-2 RCT, 2 years of liraglutide significantly reduced liver enzymes, CT-assessed hepatic steatosis, body fat and blood pressure and improved glycaemic control in diabetic patients with NAFLD (ESM Table 5) [108].…”

Section: %) (G) Homa Index Change (%) (H) Fpg Change (%) (I) Serummentioning

confidence: 99%

Impact of current treatments on liver disease, glucose metabolism and cardiovascular risk in non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of randomised trials

et al. 2012

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Aims/hypothesis Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum ranging from simple steatosis to non-alcoholic steatohepatitis (NASH): NAFLD causes an increased risk of cardiovascular disease, diabetes and liverrelated complications (the latter confined to NASH). The effect of proposed treatments on liver disease, glucose metabolism and cardiovascular risk in NAFLD is unknown. We reviewed the evidence for the management of liver disease and cardiometabolic risk in NAFLD. Methods Publications through November 2011 were systematically reviewed by two authors. Outcomes evaluated though standard methods were: histological/radiological/biochemical features of NAFLD, variables of glucose metabolism and cardiovascular risk factors. Seventy-eight randomised trials were included (38 in NASH, 40 in NAFLD): 41% assessed post-treatment histology, 71% assessed glucose metabolism and 88% assessed cardiovascular risk factors. Lifestyle intervention, thiazolidinediones, metformin and antioxidants were most extensively evaluated. Results Lifestyle-induced weight loss was safe and improved cardio-metabolic risk profile; a weight loss ≥7% improved histological disease activity, but was achieved by <50%

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Metabolic effects of two years of exenatide treatment on diabetes, obesity, and hepatic biomarkers in patients with type 2 diabetes: An interim analysis of data from the open-label, uncontrolled extension of three double-blind, placebo-controlled trials

Cited by 250 publications

References 45 publications

Pharmacokinetics in Patients with Chronic Liver Disease and Hepatic Safety of Incretin-Based Therapies for the Management of Type 2 Diabetes Mellitus

Pharmacokinetics in Patients with Chronic Liver Disease and Hepatic Safety of Incretin-Based Therapies for the Management of Type 2 Diabetes Mellitus

Co-administration of berberine and plant stanols synergistically reduces plasma cholesterol in rats

Impact of current treatments on liver disease, glucose metabolism and cardiovascular risk in non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of randomised trials

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