insulin-glargine and Non-alcoholic-Fatty-Liver-Disease

The aim of this study was to investigate the efficacy of exenatide and insulin glargine in patients with newly diagnosed type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD).. We performed a 24-week randomized controlled multicentre clinical trial. Seventy-six patients were randomly assigned 1:1 to receive exenatide or insulin glargine treatment. The endpoints included changes in liver fat content (LFC), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) measured by magnetic resonance spectroscopy, blood glucose, liver enzymes, lipid profile, body weight, and Fibrosis-4 index (FIB-4).. LFC, VAT, SAT, and FIB-4 were significantly reduced after exenatide treatment (ΔLFC, -17.55 ± 12.93%; ΔVAT, -43.57 ± 68.20 cm. Both exenatide and insulin glargine reduced LFC in patients with drug-naive T2DM and NAFLD; however, exenatide showed greater reductions in body weight, visceral fat area, liver enzymes, FIB-4, postprandial plasma glucose, and LDL-C.

Topics: Biomarkers; Blood Glucose; Diabetes Mellitus, Type 2; Exenatide; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Prognosis

Type 2 diabetes mellitus is closely related to nonalcoholic fatty liver disease(NAFLD). More and more attention has been paid to the efficacy of liraglutide in the treatment of NAFLD, but the clinical evidence is still insufficient.. The purpose of this study was to use proton magnetic resonance spectroscopy (H-MRS) assessment of metformin alone poor blood glucose control of obese patients type 2 diabetes with NAFLD, added with insulin glargine, liraglutide or placebo effect in improving the fatty liver.. This is a 26-week, single-center, prospective, randomized placebo-controlled study. From September 2016 to July 2018, 128 patients with type 2 diabetes and NAFLD were enrolled in the China joint logistics team 900 hospital. The primary endpoints were the changes in intrahepatic content of lipid (IHCL), abdominal adiposity [subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT)], from baseline to week 26 (end of treatment) and the changes in liraglutide group or insulin glargine group versus change in placebo group. Secondary endpoints included the changes in liver function (AST and ALT), glycemia (HbA1c and FPG), body weight, and BMI.. A total of 96 patients with type 2 diabetes and NAFLD under inadequate glycemic control by metformin were randomized (1:1:1) to receive add-on insulin glargine, liraglutide, or placebo. After 26 weeks of treatment, compared to the placebo group, in the liraglutide and insulin glargine groups, IHCL significantly decreased from baseline to week 26 (liraglutide 26.4% ± 3.2% to 20.6% ± 3.9%, P < 0.05; insulin glargine 25.0% ± 4.3% to 22.6% ± 5.8%, P > 0.05). SAT and VAT decreased significantly in the liraglutide group and in the insulin glargine group (P < 0.05). ΔSAT and ΔVAT were greater with liraglutide than insulin glargine, they were significantly different between the two groups (ΔSAT, -36 vs. - 24.5, P < 0.05; and ΔVAT, -47 vs. - 16.6, P > 0.05). In the liraglutide group, AST, ALT, and HOMA-IR decreased significantly from baseline. There was no significant difference in glucose-lowering among the three groups. During the treatment, the safety of the three groups performed well.. Compared with placebo, treatment with liraglutide plus an adequate dose of metformin (2000 g/ day) for 26 weeks is more effective in reducing IHCL, SAT and VAT in patients with type 2 diabetes and NAFLD. And it has additional advantages in weight loss, waist circumference reduction and liver function improvement.

Topics: Adult; Blood Glucose; Body Weight; China; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Intra-Abdominal Fat; Liraglutide; Liver; Male; Metformin; Middle Aged; Non-alcoholic Fatty Liver Disease; Obesity; Prospective Studies; Subcutaneous Fat; Treatment Outcome; Weight Loss

To investigate the effect of antidiabetic agents on nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM), 75 patients with T2DM and NAFLD under inadequate glycemic control by metformin were randomized (1:1:1) to receive add-on liraglutide, sitagliptin, or insulin glargine in this 26-week trial. The primary endpoint was the change in intrahepatic lipid (IHL) from baseline to week 26 as quantified by magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF). Secondary endpoints included changes in abdominal adiposity (subcutaneous adipose tissue [SAT] and visceral adipose tissue [VAT]), glycated hemoglobin, and body weight from baseline to week 26. We analysed data from intent-to-treat population. MRI-PDFF, VAT, and weight decreased significantly with liraglutide (15.4% ± 5.6% to 12.5% ± 6.4%, P < 0.001; 171.4 ± 27.8 to 150.5 ± 30.8, P = 0.003; 86.6 ± 12.9 kg to 82.9 ± 11.1 kg, P = 0.005, respectively) and sitagliptin (15.5% ± 5.6% to 11.7% ± 5.0%, P = 0.001; 153.4 ± 31.5 to 139.8 ± 27.3, P = 0.027; 88.2 ± 13.6 kg to 86.5 ± 13.2 kg, P = 0.005, respectively). No significant change in MRI-PDFF, VAT, or body weight was observed with insulin glargine. SAT decreased significantly in the liraglutide group (239.9 ± 69.0 to 211.3 ± 76.1; P = 0.020) but not in the sitagliptin and insulin glargine groups. Changes from baseline in MRI-PDFF, VAT, and body weight were significantly greater with liraglutide than insulin glargine but did not differ significantly between liraglutide and sitagliptin. Conclusion: Combined with metformin, both liraglutide and sitagliptin, but not insulin glargine, reduced body weight, IHL, and VAT in addition to improving glycemic control in patients with T2DM and NAFLD.

Topics: Adult; Aged; Blood Glucose; Body Weight; Comorbidity; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Hypoglycemic Agents; Insulin Glargine; Linear Models; Lipid Metabolism; Liraglutide; Male; Metformin; Middle Aged; Multivariate Analysis; Non-alcoholic Fatty Liver Disease; Prognosis; Prospective Studies; Sitagliptin Phosphate; Treatment Outcome

Diabetes mellitus type 2 (DMT2) and non-alcoholic fatty liver disease (NAFLD) are both characterized by decreased circulating adiponectin. Recently, glucagon-like peptide-1 receptor agonists have been shown to induce adiponectin's expression. However, their interaction on clinical grounds needs to be further elucidated.. DMT2 patients with abnormal aminotransferases were screened for NAFLD and subjected to liver biopsy (group A, n=17). A subgroup of patients (n=110), after assessed for eligibility criteria, was blindly randomized to receive either 6-month exenatide supplementation on glargine insulin (group B) or intense, self-regulated, insulin therapy alone (group C).. Baseline patient characteristics: 49(38.6%) males, aged 63.1 ± 7.5 years-old, BMI 32.9 ± 4.9 kg/m(2), HbA1c 8.1 ± 1.2% (65 ± 14 mmol/mol), median ALT 23 U/L (range 5-126), AST 20 U/L (7-72). Group A had biopsy-proven NAFLD with a median Activity Score of 5 and fibrosis stage 3. Presence of NAFLD was accompanied by a significant decline in adiponectin (p<0.001), which was negatively correlated with the degree of ALT in all groups (Spearman's correlation, rs=-0.644, p<0.001). In the subgroup intervention trial, adiponectin was significantly raised in both groups B and C (t-Student for paired samples, p=0.001) by Δ=+24.2% (interquartile range 14.8-53.2%). This elevation was not associated with the type of intervention but with weight loss, glycemic control and reduction of C-reactive protein (one-way ANCOVA).. Supplementation of exenatide to glargine insulin compared to standard insulin was: (i) effective in inducing weight loss, (ii) non-inferior in lowering HbA1c and (iii) non-inferior in increasing circulating adiponectin. Higher adiponectin was associated with lower ALT, suggesting a hepato-protective role for this cytokine.

Topics: Adiponectin; Aged; Blood Glucose; C-Reactive Protein; Diabetes Mellitus, Type 2; Exenatide; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Peptides; Prospective Studies; Venoms

The purpose of this study was to evaluate the advantages of exenatide treatment on obesity and non-alcoholic fatty liver disease (NAFLD) with elevated liver enzymes in patients with type 2 diabetes (T2D).. A total of 60 newly diagnosed patients with obesity, NAFLD with elevated liver enzymes and T2D were included in the study. The patients were randomly divided into two groups. The exenatide treatment group (n = 30) were treated with exenatide and insulin glargine, and the intensive insulin therapy group (n = 30) were treated with insulin aspart and insulin glargine for 12 weeks. Selected clinical characteristics were determined, and ultrasonography was performed at both baseline and 12 weeks following treatment.. At baseline, the clinical characteristics were matched between the two groups. After 12 weeks, fasting blood glucose (FBG), postprandial blood glucose (PBG), glycosylated haemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG) and total bilirubin levels were significantly decreased in the two groups (p < 0.001). Body weight and waist circumference were significantly decreased in the exenatide group but increased in the intensive insulin group (p < 0.001). The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyl transpeptidase (γGGT) in the exenatide group were significantly lower than in the intensive insulin group (p < 0.001). The mean body weight change correlated with the levels of ALT, AST and γGGT change (ALT, r = 0.761; AST, r = 0.733; γGGT, r = 0.752; p < 0.001). Moreover, the reversal rate of fatty liver was significantly higher in the exenatide group (93.3%) than the intensive insulin group (66.7%) (p < 0.01).. Exenatide has a better hepatic-protective effect than intensive insulin therapy and perhaps represents a unique option for adjunctive therapy for patients with obesity, non-alcoholic fatty liver disease with elevated liver enzymes and T2D.

Topics: Adult; Biomarkers; Body Mass Index; Combined Modality Therapy; Diabetes Mellitus, Type 2; Diet, Diabetic; Drug Therapy, Combination; Exenatide; Exercise; Female; Glycated Hemoglobin; Hepatic Insufficiency; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Liver; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Obesity; Peptides; Ultrasonography; Venoms; Waist Circumference; Weight Loss

Topics: Body Weight; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin Glargine; Lipids; Liraglutide; Metformin; Non-alcoholic Fatty Liver Disease; Sitagliptin Phosphate

Topics: Body Weight; Diabetes Mellitus, Type 2; Humans; Insulin Glargine; Lipids; Liraglutide; Metformin; Non-alcoholic Fatty Liver Disease; Sitagliptin Phosphate

We sincerely thank Dr. Sikarin Upala for his interest in our article and for sharing his experience in the treatment of nonalcoholic fatty liver disease (NAFLD). NAFLD is prevalent in patients with type 2 diabetes mellitus (T2DM), yet only preliminary evidence are available on the effect of anti-diabetic agents to NAFLD in T2DM patients. According to clinical practice guidelines for NAFLD management

Topics: Body Weight; Diabetes Mellitus, Type 2; Humans; Insulin Glargine; Lipids; Liraglutide; Metformin; Non-alcoholic Fatty Liver Disease; Sitagliptin Phosphate

We read with interest a recent article written by Yan et al.

Topics: Body Weight; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin Glargine; Lipids; Liraglutide; Metformin; Non-alcoholic Fatty Liver Disease; Sitagliptin Phosphate

Topics: Body Weight; Diabetes Mellitus, Type 2; Humans; Incretins; Insulin Glargine; Lipids; Liraglutide; Metformin; Non-alcoholic Fatty Liver Disease; Sitagliptin Phosphate

To explore the beneficial effects of dapagliflozin and/or insulin glargine on the pancreatic beta cell mass and hepatic steatosis in db/db mice.. Six-week-old db/db mice were assigned to one of four groups: untreated (Placebo), treated with dapagliflozin (Dapa), treated with insulin glargine (Gla), or treated with dapagliflozin and insulin glargine (Dapa+Gla). After 8 weeks of treatment, we determined glucose tolerance, beta cell mass, hepatic lipid content and gene expression.. Glucose tolerance was significantly ameliorated in the three treated groups to the same degree compared with the Placebo group. Immunohistochemical analysis revealed that the pancreatic beta cell mass was significantly maintained in the Dapa and Dapa+Gla groups, but not in the Gla group, compared with the Placebo group (Placebo 2.25 ± 1.44 mg, Dapa 5.01 ± 1.63 mg, Gla 3.79 ± 0.96 mg, Dapa+Gla 5.19 ± 1.78 mg). However, the triglyceride content of the liver was markedly elevated in the Gla group compared with that in the other three groups (Placebo 24.1 ± 11.5 mg, Dapa 30.6 ± 12.9 mg, Gla 128 ± 49.7 mg, Dapa+Gla 54.4 ± 14.1 mg per gram liver). The expression levels of genes related to fatty acid synthesis and lipid storage were significantly upregulated in the Gla group.. Our results showed that beta cell mass was sustained and hepatic steatosis was prevented, after 8 weeks of treatment with either dapagliflozin or dapagliflozin plus insulin glargine, but not with insulin glargine alone, in db/db mice.

Topics: Animals; Benzhydryl Compounds; Fatty Acids; Gene Expression; Glucose Intolerance; Glucosides; Hypoglycemic Agents; Insulin Glargine; Insulin-Secreting Cells; Lipid Metabolism; Liver; Male; Mice; Non-alcoholic Fatty Liver Disease; Sodium-Glucose Transporter 2 Inhibitors; Triglycerides

Topics: Animals; Benzhydryl Compounds; Glucose; Glucosides; Insulin Glargine; Mice; Non-alcoholic Fatty Liver Disease; Sodium; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors