Lobeglitazone: A Novel Thiazolidinedione for the Management of Type 2 Diabetes Mellitus.
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ABSTRACT:
SUBMITTER: Bae J
PROVIDER: S-EPMC8164939 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Despite the rapidly increasing prevalence of non-alcoholic fatty liver disease (NAFLD) in type 2 diabetes (T2D), few treatment modalities are currently available. We investigated the hepatic effects of the novel thiazolidinedione (TZDs), lobeglitazone (Duvie) in T2D patients with NAFLD. We recruited drug-naïve or metformin-treated T2D patients with NAFLD to conduct a multicenter, prospective, open-label, exploratory clinical trial. Transient liver elastography (Fibroscan®; Echosens, Paris, France) with controlled attenuation parameter (CAP) was used to non-invasively quantify hepatic fat contents. Fifty patients with CAP values above 250 dB/m were treated once daily with 0.5 mg lobeglitazone for 24 weeks. The primary endpoint was a decline in CAP values, and secondary endpoints included changes in components of glycemic, lipid, and liver profiles. Lobeglitazone-treated patients showed significantly decreased CAP values (313.4 dB/m at baseline vs. 297.8 dB/m at 24 weeks; P = 0.016), regardless of glycemic control. Lobeglitazone improved HbA(1C) values (7.41% [57.5 mM] vs. 6.56% [48.2 mM]; P < 0.001), as well as the lipid and liver profiles of the treated patients. Moreover, multivariable linear regression analysis showed that hepatic fat reduction by lobeglitazone was independently associated with baseline values of CAP, liver stiffness, and liver enzymes, and metformin use. Lobeglitazone treatment reduced intrahepatic fat content, as assessed by transient liver elastography, and improved glycemic, liver, and lipid profiles in T2D patients with NAFLD. Further randomized controlled trials using liver histology as an end point are necessary to evaluate the efficacy of lobeglitazone for NAFLD treatment.
| S-EPMC5143300 | biostudies-literature
Project description:IntroductionThe aim of this analysis was to evaluate the efficacy of lobeglitazone on albuminuria at 24 weeks of follow-up in patients with type 2 diabetes mellitus (T2DM) compared with pioglitazone using data from a randomized, double-blinded phase III trial.MethodsIn the phase III trial, patients who were inadequately controlled with metformin received 0.5 mg of lobeglitazone or 15 mg of pioglitazone for 24 weeks. Post hoc, exploratory analysis was used to investigate mean changes from baseline in the urine albumin-creatinine ratio (UACR) between the lobeglitazone (N = 104) and pioglitazone (N = 101) treatment groups.ResultsAfter 24 weeks of treatment, UACR was slightly decreased in the lobeglitazone group (- 4.3 mg/g creatinine [Cr]) compared to baseline and slightly increased in the pioglitazone group (5.2 mg/g Cr), with no change in the estimated glomerular filtration rate in either group; this difference was not statistically significant (P = 0.476). The incidence of new-onset microalbuminuria (2.4%) and the progression of albuminuria by > 1 stage (2.9%) in the lobeglitazone group were lower than the respective values in the pioglitazone group (6.8 and 6.1%, respectively). Of the patients in the lobeglitazone group, 50% exhibited regression to normoalbuminuria, compared to 39.3% of the patients in the pioglitazone. In subjects in the lobeglitazone group with micro- and macroalbuminuria, UACR tended to be more decreased and HbA1c was more reduced compared to those with normoalbuminuria (P = 0.014).ConclusionLobeglitazone had a tendency to improve albuminuria in patients with T2DM and had comparable effects on albuminuria as pioglitazone which has demonstrated beneficial effects.Trial registrationClinicalTrials.gov identifier, NCT01106131.
| S-EPMC7843821 | biostudies-literature
Project description:GPR120, also called FFAR4, is preferentially expressed in the intestines, and can be stimulated by long-chain free fatty acids to increase the secretion of glucagon-like peptide-1 (GLP-1) from intestinal endocrine cells. It is known that GLP-1, as an incretin, can promote the insulin secretion from pancreatic cells in a glucose-dependent manner. Therefore, GPR120 is a potential drug target to treat type 2 diabetes. In this study, thiazolidinedione derivatives were found to be novel potent GPR120 agonists. Compound 5g, with excellent agonistic activity, selectivity, and metabolic stability, improved oral glucose tolerance in normal C57BL/6 mice in a dose-dependent manner. Moreover, compound 5g exhibited anti-diabetic activity by promoting insulin secretion in diet-induced obese mice. In summary, compound 5g might be a promising drug candidate for the treatment of type 2 diabetes.
| S-EPMC8981563 | biostudies-literature
Project description:BackgroundThiazolidinediones (TZDs) have been associated with various safety concerns including weight gain, bladder cancer, and congestive heart failure (CHF). This study evaluated the efficacy and safety of lobeglitazone, a novel TZD in patients with type 2 diabetes mellitus (T2DM) in real practice.MethodsIn this non-interventional, multi-center, retrospective, and observational study conducted at 15 tertiary or secondary referral hospitals in Korea, a total of 2,228 patients with T2DM who received lobeglitazone 0.5 mg for more than 1 year were enrolled.ResultsOverall adverse events (AEs) occurred in 381 patients (17.10%) including edema in 1.97% (n=44). Cerebrovascular and cardiovascular diseases were identified in 0.81% (n=18) and 0.81% (n=18), respectively. One case of CHF was reported as an AE. Edema occurred in 1.97% (n=44) of patients. Hypoglycemia occurred in 2.47% (n=55) of patients. Fracture occurred in 1.17% (n=26) of all patients. Lobeglitazone significantly decreased HbA1c level, resulting in a mean treatment difference of -1.05%± 1.35% (P<0.001), and decreased total cholesterol, triglyceride, and low-density lipoprotein cholesterol. However, it increased high-density lipoprotein cholesterol, regardless of statin administration. The patients who received lobeglitazone 0.5 mg showed an apparent reduction in glycosylated hemoglobin (HbA1c) from baseline during the first 6 months of treatment. The HbA1c levels remained stable between months 6 and 42.ConclusionLobeglitazone has long-term safety profile, good glycemic-lowering effect and long-term durability of glycemic control in real-world clinical settings.
| S-EPMC9723193 | biostudies-literature
Project description:No meta-analysis has analyzed the safety and efficacy of rivoglitazone in type-2 diabetes (T2DM). We undertook this meta-analysis to address this knowledge gap. Electronic databases were searched for RCTs involving T2DM patients receiving rivoglitazone in the intervention arm, and placebo/active comparator in the control arm. The primary outcome was to evaluate changes in HbA1c. Secondary outcomes were to evaluate alterations in glucose, lipids, and adverse events. From initially screened 24 articles, data from 3 RCTs (3591 patients) that fulfilled all criteria was analzsed. HbA1c was significantly lower with standard-dose (1 mg/d) [MD-0.86% (95%CI:-1.11--0.61); P < 0.01; I2 = 87%] and high-dose (1.5-2 mg/d) [MD-0.97%(95%CI:-1.03--0.90); P < 0.01; I2 = 19%] rivoglitazone compared to placebo. When compared to pioglitazone (30-45 mg/d), HbA1c lowering was comparable with standard-dose [MD 0.05%(95%CI:-0.01 - 0.11); P = 0.08; I2 = 11%], but superior with high-dose [MD -0.11%(95%CI:-0.18- -0.04); P < 0.01; I2 = 0%] rivoglitazone. Triglycerides were significantly lower with standard-dose [MD-17.95 mg/dl (95%CI:-34.23--1.66); P = 0.03; I2 = 0%] and high-dose [MD-40.41 mg/dl (95%CI:-72.90- -7.93);P = 0.01;I2 = 71%] rivoglitazone compared to placebo. Adiponectin significantly improved with standard-dose [MD 7.94 ng/ml (95%CI: 5.48-10.39); P < 0.01;I2 = 98%] and high-dose [MD 13.82 ng/ml (95%CI: 8.16-19.48); P < 0.01; I2 = 100%] rivoglitazone compared to placebo. hsCRP was significantly lower with standard-dose [MD -1.00 mg/L (95% CI: -1.20 - -0.80); P < 0.01; I2 = 6%] and high-dose [MD -1.50 mg/L (95%CI:-1.59- -1.40); P < 0.01; I2 = 0%] rivoglitazone compared to placebo. Treatment-emergent adverse events with standard-dose [Risk ratio (RR) 1.16 (95%CI: 0.84 -1.60); P = 0.38; I2 = 0%] and high-dose [RR1.34 (95%CI: 0.99-1.83); P = 0.06; I2 = 0%] rivoglitazone was comparable to placebo. Severe adverse events with standard-dose [RR1.88 (95%CI: 0.69-5.12);P = 0.22;I2 = 0%] and high-dose [RR 1.27 (95% CI: 0.45 - 3.59); P = 0.68; I2 = 0%] rivoglitazone was comparable to placebo. This meta-analysis highlights the good glycaemic efficacy and safety of both standard and high-dose rivoglitazone, and appears to be better than lobeglitazone in T2DM.
| S-EPMC10586552 | biostudies-literature
Project description:Type 2 Diabetes Mellitus (T2DM) is a chronic disease which corresponds to 90% of the worldwide cases of diabetes, mainly due to epigenetic factors such as unhealthy lifestyles. First line therapeutic approaches are based on lifestyle changes, most of the time complemented with medication mostly associated with several side effects and high costs. As a result, the scientific community is constantly working for the discovery and development of natural therapeutic strategies that provide lower financial impact and minimize side effects. This review focus on these nature-based therapeutic strategies for prevention and control of T2DM, with a special emphasis on natural compounds that present pharmacological activity as dipeptidyl peptidase-4 (DPP4), alpha-amylase, alpha-glucosidase, lipase, and protein tyrosine phosphatase 1B (PTP1B) inhibitors.
| S-EPMC7143818 | biostudies-literature
Project description:Background: The purpose of this article is to clarify and define medical qigong and to identify an appropriate study design and methodology for a large-scale study looking at the effects of qigong in patients with type 2 diabetes mellitus (T2DM), specifically subject enrollment criteria, selection of the control group and study duration. Methods: A comprehensive literature review of English databases was used to locate articles from 1980-May 2017 involving qigong and T2DM. Control groups, subject criteria and the results of major diabetic markers were reviewed and compared within each study. Definitions of qigong and its differentiation from physical exercise were also considered. Results: After a thorough review, it was found that qigong shows positive effects on T2DM; however, there were inconsistencies in control groups, research subjects and diabetic markers analyzed. It was also discovered that there is a large variation in styles and definitions of qigong. Conclusions: Qigong exercise has shown promising results in clinical experience and in randomized, controlled pilot studies for affecting aspects of T2DM including blood glucose, triglycerides, total cholesterol, weight, BMI and insulin resistance. Due to the inconsistencies in study design and methods and the lack of large-scale studies, further well-designed randomized control trials (RCT) are needed to evaluate the 'vital energy' or qi aspect of internal medical qigong in people who have been diagnosed with T2DM.
| S-EPMC5622394 | biostudies-literature
Project description:BackgroundType 2 diabetes mellitus (T2DM) and dementia cause heavy health burden in mainland China, where few studies have investigated the association between glucose-lowering agents and dementia risk. We aimed to assess the association between use of thiazolidinediones (TZDs) and dementia incidence in a mainland Chinese population with T2DM.MethodsA retrospective cohort of T2DM patients who were new users of TZDs or alpha glucosidase inhibitors (AGIs) was assembled using the Yinzhou Regional Health Care Database. A Cox model with inverse probability of treatment weighting (IPTW) for controlling potential founding was applied to estimate the hazard ratio (HR) of the association between use of TZDs and dementia risk.ResultsA total of 49 823 new users of AGIs and 12 752 new users of TZDs were included in the final cohort. In the primary analysis, the incidence of dementia was 195.7 and 78.2 per 100 000 person-years in users of AGIs and TZDs respectively. TZD use was associated with a reduced risk of incident dementia after adjusting for potential confounding using IPTW, with a HR of 0.51 (95% CI, 0.38-0.67). The results in various subgroup analyses and sensitivity analyses were consistent with the findings of the primary analysis.ConclusionsUse of TZDs is associated with a decreased risk of dementia incidence in a mainland Chinese population with T2DM.
| S-EPMC9934955 | biostudies-literature
Project description:Peroxisome proliferator-activated receptor γ (PPARγ) has received significant attention as a key regulator of glucose and lipid homeostasis. In this study, we synthesized and tested a library of novel 5-benzylidene-thiazolidin-2,4-dione (BTZD) derivatives bearing a substituent on nitrogen of TZD nucleus (compounds 1a-1k, 2i-10i, 3a, 6a, and 8a-10a). Three compounds (1a, 1i, and 3a) exhibited selectivity towards PPARγ and were found to be weak to moderate partial agonists. Surface Plasmon Resonance (SPR) results demonstrated binding affinity of 1a, 1i and 3a towards PPARγ. Furthermore, docking experiments revealed that BTZDs interact with PPARγ through a distinct binding mode, forming primarily hydrophobic contacts with the ligand-binding pocket (LBD) without direct H-bonding interactions to key residues in H12 that are characteristic of full agonists. In addition, 1a, 1i and 3a significantly improved hyperglycemia and hyperlipidaemia in streptozotocin-nicotinamide (STZ-NA)-induced diabetic rats at a dose of 36 mg/kg/day administered orally for 15 days. Histopathological investigations revealed that microscopic architecture of pancreatic and hepatic cells improved in BTZDs-treated diabetic rats. These findings suggested that 1a, 1i and 3a are very promising pharmacological agents by selectively targeting PPARγ for further development in the clinical treatment of type 2 diabetes mellitus.
| S-EPMC5663708 | biostudies-literature
Project description:Diabetes Mellitus Type 1 miRnome
| PRJEB51173 | ENA