chiglitazar and Insulin-Resistance

To evaluate glycemic variations, changes in insulin resistance and oxidative stress after chiglitazar or sitagliptin treatment in untreated patients with type 2 diabetes mellitus (T2DM).. Based on the study inclusion and exclusion criteria, 81 patients with T2DM were randomly divided to receive chiglitazar or sitagliptin treatment for 24 weeks. Continuous glucose monitoring (CGM) systems were conducted for 72 h in eligible patients. We analyzed the following glycemic variation parameters derived from the CGM data and measured the serum levels of hemoglobin A1c (HbA1c), fasting blood glucose (FBG), 2-h postprandial blood glucose (2-h PBG), fasting insulin (Fins) and inflammatory-related indicators at baseline and the end of the study.. After treatment for 24 weeks, our data showed a similar reduction in HbA1c between chiglitazar and sitagliptin. The 24-h mean blood glucose (MBG), standard deviation (SD) and mean amplitude of glycemic excursion (MAGE) were significantly decreased, and the time in range (TIR) was increased after chiglitazar and sitagliptin therapy. Chiglitazar administration led to significant improvement in insulin resistance/insulin secretion (HOMA-IR, HOMA-IS), interleukin-6 (IL-6), prostaglandin F2α (PGF-2α), 17-hydroxyprogesterone (17-OHP) and adiponectin (ADP) score values compared with sitagliptin administration.. Chiglitazar therapy effectively reduced glucose variation and showed a larger improvement in insulin resistance and inflammatory parameters than sitagliptin.

Topics: Biomarkers; Blood Glucose; Blood Glucose Self-Monitoring; Carbazoles; Diabetes Mellitus, Type 2; Glucose; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Resistance; Propionates; Sitagliptin Phosphate

We evaluated the efficacy and significant changes in the levels of retinol-binding protein 4 (RBP-4) and insulin resistance in patients with type 2 diabetes mellitus (T2DM) treated with chiglitazar versus sitagliptin.. Eighty-one T2DM patients with haemoglobin A1c (HbA1c) level of 7.5%-10.0% were selected. Based on the study criteria, patients were randomly assigned to receive chiglitazar (32 mg), chiglitazar (48 mg), or sitagliptin (100 mg) orally for 24 weeks. Sociodemographic and anthropometric characteristics, lipid profiles, glucose profiles, and serum RBP-4 levels were determined at baseline and at the end of the therapy.. After treatment for 24 weeks, significant changes in fasting blood glucose (FBG), fasting insulin (Fins), 2 h-blood glucose (2h-BG), the score values of insulin resistance/insulin secretion/β cell function (HOMA-IR, HOMA-IS, and HOMA-β), triglyceride (TG), free fatty acid (FFA), high-density lipoprotein cholesterol (HDL-C), and RBP-4 levels were detected in patients with chiglitazar administration and sitagliptin administration. Changes in RBP-4 levels were positively correlated with changes in HOMA-IR and 2 h-BG in linear regression.. Chiglitazar showed a greater improvement in parameters of diabetes than sitagliptin, and changes in serum RBP-4 levels were associated with changes in insulin-sensitizing parameters.. ClinicalTrials.gov, CT.gov identifier: NCT02173457.

Topics: Blood Glucose; Carbazoles; Diabetes Mellitus, Type 2; Humans; Insulin; Insulin Resistance; Propionates; Sitagliptin Phosphate

1. The aim of this study was to investigate the capacity of chiglitazar to improve insulin resistance and dyslipidemia in monosodium L-glutamate (MSG) obese rats and to determine whether its lipid-lowering effect is mediated through its activation of PPARalpha. 2. Chiglitazar is a PPARalpha/gamma dual agonist. 3. The compound improved impaired insulin and glucose tolerance; decreased plasma insulin level and increased the insulin sensitivity index and decreased HOMA index. Euglycemic hyperinsulinemic clamp studies showed chiglitazar increased the glucose infusion rate in MSG obese rats. 4. Chiglitazar inhibited alanine gluconeogenesis, lowered the hepatic glycogen level in MSG obese rats. Like rosiglitazone, chiglitazar promoted the differentiation of adipocytes and decreased the maximal diameter of adipocytes. In addition, chiglitazar decreased the fibrosis and lipid accumulation in the islets and increased the size of islets. 5. Chiglitazar reduced plasma triglyceride, total cholesterol (TCHO), nonesterified fatty acids (NEFA) and low density lipoprotein-cholesterol levels; lowered hepatic triglyceride and TCHO contents; decreased muscular NEFA level. Unlike rosiglitazone, chiglitazar showed significant increase of mRNA expression of PPARalpha, CPT1, BIFEZ, ACO and CYP4A10 in the liver of MSG obese rats. 6. These data suggest that PPARalpha/gamma coagonist, such as chiglitazar, affect lipid homeostasis with different mechanisms from rosiglitazone, chiglitazar may have better effects on lipid homeostasis in diabetic patients than selective PPARgamma agonists.

Topics: Adipose Tissue; Animals; Blood Glucose; Carbazoles; Disease Models, Animal; Dyslipidemias; Gene Expression; Gluconeogenesis; Hypoglycemic Agents; Insulin Resistance; Lipids; Liver; Liver Glycogen; Muscles; Obesity; Pancreas; Pioglitazone; PPAR alpha; PPAR gamma; Propionates; Pyrimidines; Rats; Rats, Wistar; Rosiglitazone; Sodium Glutamate; Thiazolidinediones