lobeglitazone and Diabetes-Mellitus--Type-2

Lobeglitazone (LGZ), a newly researched thiazolidinedione (TZD) thought to have lesser side effects compared with pioglitazone (PGZ), has been recently approved for the treatment of type 2 diabetes (T2D) in India. We aim to conduct an updated systematic review of LGZ to critically appraise its efficacy and safety in the context of PGZ.. A systematic literature search was carried out in the electronic database of PubMed until Jan 15, 2023, using specific keywords and MeSH terms. All studies which evaluated LGZ in people with T2D were retrieved and data were synthesized with regard to its efficacy and safety. A comparative critical appraisal was additionally made in the context of PGZ in T2D.. Four randomized controlled, one prospective observational, and two real-world studies have evaluated the safety and efficacy of LGZ against placebo or active comparators either as monotherapy or in combination therapy. HbA1c reduction with LGZ 0.5 mg was superior to the placebo but similar to PGZ 15 mg and sitagliptin (SITA) 100 mg. Weight gain with LGZ was significantly higher compared to placebo and SITA but similar to PGZ. Edema was more frequently observed with LGZ compared to placebo, PGZ, and SITA.. No substantial evidence is yet available that suggests LGZ could be a better alternative to PGZ both in the context of glycemic or extra-glycemic effects. At least in the short-term, adverse events of LGZ are indifferent from PGZ. More data is additionally needed to claim any advantage of LGZ over PGZ.

Topics: Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Observational Studies as Topic; Pioglitazone; Sitagliptin Phosphate; Thiazolidinediones

Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and β-cell dysfunction. Among available oral antidiabetic agents, only the thiazolidinediones (TZDs) primarily target insulin resistance. TZDs improve insulin sensitivity by activating peroxisome proliferator-activated receptor γ. Rosiglitazone and pioglitazone have been used widely for T2DM treatment due to their potent glycemic efficacy and low risk of hypoglycemia. However, their use has decreased because of side effects and safety issues, such as cardiovascular concerns and bladder cancer. Lobeglitazone (Chong Kun Dang Pharmaceutical Corporation), a novel TZD, was developed to meet the demands for an effective and safe TZD. Lobeglitazone shows similar glycemic efficacy to pioglitazone, with a lower effective dose, and favorable safety results. It also showed pleiotropic effects in preclinical and clinical studies. In this article, we summarize the pharmacologic, pharmacokinetic, and clinical characteristics of lobeglitazone.

Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Pyrimidines; Thiazolidinediones

To compare the efficacy and safety of adding low-dose lobeglitazone (0.25 mg/day) or standard-dose lobeglitazone (0.5 mg/day) to patients with type 2 diabetes mellitus (T2DM) with inadequate glucose control on metformin and dipeptidyl peptidase (DPP4) inhibitor therapy.. In this phase 4, multicentre, double-blind, randomized controlled, non-inferiority trial, patients with T2DM insufficiently controlled by metformin and DPP4 inhibitor combination therapy were randomized to receive either low-dose or standard-dose lobeglitazone. The primary endpoint was non-inferiority of low-dose lobeglitazone in terms of glycaemic control, expressed as the difference in mean glycated haemoglobin levels at week 24 relative to baseline values and compared with standard-dose lobeglitazone, using 0.5% non-inferiority margin.. At week 24, the mean glycated haemoglobin levels were 6.87 ± 0.54% and 6.68 ± 0.46% in low-dose and standard-dose lobeglitazone groups, respectively (p = .031). The between-group difference was 0.18% (95% confidence interval 0.017-0.345), showing non-inferiority of the low-dose lobeglitazone. Mean body weight changes were significantly greater in the standard-dose group (1.36 ± 2.23 kg) than in the low-dose group (0.50 ± 1.85 kg) at week 24. The changes in HOMA-IR, lipid profile and liver enzyme levels showed no significant difference between the groups. Overall treatment-emergent adverse events (including weight gain, oedema and hypoglycaemia) occurred more frequently in the standard-dose group.. Adding low-dose lobeglitazone to metformin and DPP4 inhibitor combination resulted in a non-inferior glucose-lowering outcome and fewer adverse events compared with standard-dose lobeglitazone. Therefore, low-dose lobeglitazone might be one option for individualized strategy in patients with T2DM.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; Double-Blind Method; Drug Therapy, Combination; Glucose; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Metformin; Protease Inhibitors; Pyrimidines; Thiazolidinediones; Treatment Outcome

We aimed to evaluate the efficacy and safety profile of lobeglitazone compared with sitagliptin as an add-on to metformin in patients with type 2 diabetes as well as other components of metabolic syndrome. Patients inadequately controlled by metformin were randomly assigned to lobeglitazone (0.5 mg, n = 121) or sitagliptin (100 mg, n = 126) for 24 weeks. The mean changes in HbA1c of the lobeglitazone and sitagliptin groups were -0.79% and -0.86%, respectively; the between-group difference was 0.08% (95% confidence interval, -0.14% to 0.30%), showing non-inferiority. The proportion of patients having two or more factors of other metabolic syndrome components decreased to a greater extent in the lobeglitazone group than in the sitagliptin group (-11.9% vs. -4.8%; P < .0174). Favourable changes in the lipid metabolism were also observed with lobeglitazone, which had a similar safety profile to sitagliptin. Lobeglitazone was comparable with sitagliptin as an add-on to metformin in terms of efficacy and safety.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Metabolic Syndrome; Metformin; Pyrimidines; Sitagliptin Phosphate; Thiazolidinediones; Treatment Outcome

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.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Elasticity Imaging Techniques; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Linear Models; Lipids; Liver; Male; Metformin; Middle Aged; Non-alcoholic Fatty Liver Disease; Prospective Studies; Pyrimidines; Thiazolidinediones; Treatment Outcome

We aimed to compare the efficacy and safety of lobeglitazone and pioglitazone as add-ons to metformin in patients with type 2 diabetes. Patients who were inadequately controlled by metformin were randomized and treated once daily with either lobeglitazone (0.5 mg, n = 128) or pioglitazone (15 mg, n = 125) for 24 weeks, with a 28-week extension trial of lobeglitazone treatment in patients who consented. The primary endpoint was the change in glycated haemoglobin (HbA1c) concentration from baseline to week 24. At week 24, the mean change from baseline in HbA1c was -0.74% for the lobeglitazone group and -0.74% for the pioglitazone group, with a mean difference of 0.01% [95% confidence interval (CI) of difference, -0.16 to 0.18]. The effects of lobeglitazone on lipid variables and the adverse events associated with lobeglitazone were similar to those observed with pioglitazone. Lobeglitazone was not inferior to pioglitazone as an add-on to metformin in terms of their efficacy and safety.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Resistance; Lipids; Male; Metformin; Middle Aged; Pioglitazone; Pyrimidines; Thiazolidinediones

We aimed to assess the safety and efficacy of lobeglitazone in patients with type 2 diabetes over 52 weeks through 28-week extension study. Clinical benefits in terms of glycemic and lipid control were maintained for 52 weeks. Lobeglitazone showed a favorable balance of efficacy and safety during the extension study.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Lipids; Male; Middle Aged; Pyrimidines; Thiazolidinediones

The aim of this study was to assess the glucose-lowering and lipid-modifying effects, and safety profile of lobeglitazone, a novel peroxisome proliferator-activated receptor- γ agonist, compared to placebo as a monotherapy in patients with type 2 diabetes.. In this 24-week, multicenter, randomized, double-blind, parallel-group, placebo controlled study, 173 patients were randomly assigned (a 2∶1 ratio) to lobeglitazone 0.5 mg (n=115) or matching placebo (n=58) orally once daily. The primary endpoint was the change in glycated hemoglobin (HbA1c) from baseline to the end of treatment. The secondary endpoints included various glycemic parameters, lipid parameters and safety profile (ClinicalTrials.gov number NCT01001611).. At 24 weeks, a significant reduction in HbA1c was observed with lobeglitazone versus placebo (-0.44% vs 0.16%, mean difference -0.6%, p<0.0001). The goal of HbA1c <7% was achieved significantly more in the lobeglitazone group compared to the placebo group (44% vs 12%, p<0.0001). Markers of insulin resistance were also improved in the lobeglitazone group. In addition, lobeglitazone treatment significantly improved triglycerides, high density lipoprotein cholesterol, small dense low density lipoprotein cholesterol, free fatty acid, and apolipoprotein-B/CIII compared to placebo (p<0.01, respectively). More weight gain was observed in the lobeglitazone group than the placebo group (0.89 kg vs - 0.63 kg, mean difference 1.52 kg, p<0.0001). The safety profile was comparable between the two groups and lobeglitazone was well tolerated.. Lobeglitazone 0.5 mg showed a favorable balance in the efficacy and safety profile. The results support a potential role of lobeglitazone in treating type 2 diabetes.. Clinicaltrials.gov NCT01001611.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Lipids; Male; Middle Aged; Pyrimidines; Thiazolidinediones; Time Factors; Treatment Outcome

Ischemic stroke patients with diabetes are at high risk for recurrent stroke and cardiovascular complications. Pioglitazone, a type of thiazolidinedione, has been shown to reduce cardiovascular complications in patients with ischemic stroke and type 2 diabetes (T2D) or insulin resistance. Lobeglitazone is a novel thiazolidinedione agent that improves insulin resistance and has similar glycemic efficacy to pioglitazone. Using population-based health claims data, we evaluated whether lobeglitazone has secondary cardiovascular preventive effects in patients with ischemic stroke and T2D.. This study has a nested case-control design. From nationwide health claims data in Korea, we identified patients with T2D admitted for acute ischemic stroke in 2014-2018. Cases were defined who suffered the primary outcome (a composite of recurrent stroke, myocardial infarction, and all-cause death) before December 2020. Three controls were selected by incidence density sampling for each case from those who were at risk at the time of their case occurrence with exact matching on sex, age, the presence of comorbidities, and medications. As a safety outcome, we also evaluated the risk of heart failure (HF) according to the use of lobeglitazone.. From the cohort of 70,897 T2D patients with acute ischemic stroke, 20,869 cases and 62,607 controls were selected. In the multivariable conditional logistic regression, treatment with lobeglitazone (adjusted OR 0.74; 95% CI 0.61-0.90; p = 0.002) and pioglitazone (adjusted OR 0.71; 95% CI 0.64-0.78; p < 0.001) were significantly associated with a lower risk for the primary outcome. In a safety outcome analysis for HF, treatment with lobeglitazone did not increase the risk of HF (adjusted OR 0.90; 95% CI 0.66-1.22; p = 0.492).. In T2D patients with ischemic stroke, lobeglitazone reduced the risk of cardiovascular complications similar to that of pioglitazone without an increased risk of HF. There is a need for further studies on the cardioprotective role of lobeglitazone, a novel thiazolidinedione.

Topics: Case-Control Studies; Diabetes Mellitus, Type 2; Heart Failure; Humans; Hypoglycemic Agents; Insulin Resistance; Ischemic Stroke; Logistic Models; Pioglitazone; Secondary Prevention; Stroke; Thiazolidinediones

Thiazolidinedione, an insulin sensitizer, has beneficial effects on glucose metabolism; however, there are concerns regarding weight gain and heart failure. Sodium-glucose co-transporter 2 (SGLT2) inhibitors can reduce body weight, increase diuresis, and play a protective role in heart failure. We examined the complementary effects of dapagliflozin, an SGLT2 inhibitor, and lobeglitazone, a thiazolidinedione, in high-fat diet (HFD)-induced obese mice. We treated HFD-induced obese mice with vehicle, dapagliflozin, lobeglitazone, and their combination for 12 weeks. Oral glucose tolerance and insulin tolerance tests were performed after 12-week treatment, and body composition was measured by dual-energy X-ray absorptiometry before and after treatment. We analyzed oxygen consumption rate (OCR) using 3T3-L1 cells after treatment of β-hydroxybutyrate and/or lobeglitazone. Treatment with a combination of dapagliflozin and lobeglitazone resulted in a significant decrease in postprandial hyperglycemia compared with dapagliflozin monotherapy, but not compared with lobeglitazone monotherapy. The addition of dapagliflozin to lobeglitazone treatment did not attenuate weight gain compared with lobeglitazone monotherapy in this study. However, this combination prevented the increase of organ weight of liver and heart, and OCR in 3T3-L1 cells was increased after treatment with a combination of β-hydroxybutyrate and lobeglitazone compared to lobeglitazone monotherapy. We confirmed the beneficial effect of lobeglitazone on glucose metabolism; however, we did not find any beneficial effect of dapagliflozin on body weight in HFD-induced obese mice. However, the protective effects of dapagliflozin and lobeglitazone combined therapy on the liver, heart, energy consumption, and β-cell senescence are worth investigating in clinical trials.

Topics: 3-Hydroxybutyric Acid; Animals; Benzhydryl Compounds; Blood Glucose; Diabetes Mellitus, Type 2; Diet, High-Fat; Disease Models, Animal; Heart Failure; Hypoglycemic Agents; Insulin; Mice; Mice, Obese; Obesity; Sodium-Glucose Transporter 2 Inhibitors; Thiazolidinediones; Weight Gain

Compare the efficacy and safety of sitagliptin, dapagliflozin, and lobeglitazone in patients with uncontrolled type 2 diabetes, despite metformin and sulfonylurea therapy.. The study randomized patients into three groups, receiving sitagliptin 100 mg, dapagliflozin 10 mg, or lobeglitazone 0.5 mg daily (n = 26 each) and monitored changes in biochemical parameters and body composition for 24 months. The primary efficacy endpoint was changes in HbA1c at 24 months.. The mean change in HbA1c in the sitagliptin, dapagliflozin, and lobeglitazone groups was -0.81 ± 0.21%, -1.05 ± 0.70%, and -1.08 ± 0.98%, after 24 months. Dapagliflozin treatment significantly lowered systolic blood pressure by 5.5 mmHg and alanine aminotransferase levels. Dapagliflozin and lobeglitazone treatment significantly reduced proteinuria and insulin resistance. Dapagliflozin decreased whole body fat percentage by 1.2%, whereas sitagliptin and lobeglitazone increased it by 1.1% and 1.8%, respectively. Whole body muscle percentage increased in the dapagliflozin group and decreased in the lobeglitazone group. The safety profiles of the three treatments were comparable.. All three drugs displayed good glucose-lowering efficacy and comparable safety profiles. However, dapagliflozin therapy produced favorable changes in body composition. Dapagliflozin may be a suitable adjunct therapy for patients with type 2 diabetes seeking to improve their body composition.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Metformin; Sitagliptin Phosphate; Sulfonylurea Compounds; Treatment Outcome

Transforming growth factor beta 1 (TGF-β1) is an important cytokine released after ocular surface injury to promote wound healing. However, its persistence at the injury site triggers a fibrotic response that leads to corneal scarring and opacity. Thiazolidinediones (TZDs) are synthetic peroxisome proliferator-activated receptor gamma (PPAR-γ) ligands used to regulate glucose and lipid metabolism in the management of type 2 diabetes. Studies have also showed TZDs have antifibrotic effect. In this study, we investigated the antifibrotic effect of the TZD lobeglitazone on TGF-β1-induced fibrosis in corneal fibroblasts.. Human primary corneal fibroblasts were cultivated and treated with TGF-β1 (5 ng/mL) to induce fibrosis, with or without pre-treatments with different concentrations of lobeglitazone. Myofibroblast differentiation and extracellular matrix (ECM) protein expression was evaluated by western blotting, immunofluorescence, real-time PCR, and collagen gel contraction assay. The effect of lobeglitazone on TGF-β1-induced reactive oxygen species (ROS) generation was evaluated by DCFDA-cellular ROS detection assay kit. Signaling proteins were evaluated by western blotting to determine the mechanism underlying the antifibrotic effect.. Our results showed lobeglitazone attenuated TGF-β1-induced ECM synthesis and myofibroblast differentiation of corneal fibroblasts. This antifibrotic effect appeared to be independent of PPAR signaling and rather due to the inhibition of the TGF-β1-induced Smad signaling. Lobeglitazone also blocked TGF-β1-induced ROS generation and nicotinamide adenine dinucleotide phosphate oxidase (Nox) 4 transcription.. These findings indicate that lobeglitazone may be a promising therapeutic agent for corneal scarring. KEY MESSAGES.

Topics: Cells, Cultured; Diabetes Mellitus, Type 2; Fibroblasts; Fibrosis; Humans; Pyrimidines; Signal Transduction; Smad Proteins; Thiazolidinediones; Transforming Growth Factor beta1

Thiazolidinediones (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.. In 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.. Overall 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.. Lobeglitazone has long-term safety profile, good glycemic-lowering effect and long-term durability of glycemic control in real-world clinical settings.

Topics: Cholesterol, LDL; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Republic of Korea; Retrospective Studies; Thiazolidinediones

This study aimed to evaluate the efficacy and tolerability of dapagliflozin as an add-on or a switch therapy to lobeglitazone plus metformin (MFM) in Korean patients with inadequately controlled type 2 diabetes mellitus (T2DM) in real-world clinical practice.. The study included 109 patients who started dapagliflozin as add-on or switch therapy to lobeglitazone plus MFM. The primary outcome was a change in glycated hemoglobin (HbA1c) level from baseline after 12 months of treatment. Secondary outcomes included changes in fasting plasma glucose (FPG), lipid profiles, body weight, visceral fat area (VFA), and blood pressure after 12 months of treatment.. Dapagliflozin, as an add-on or a switch therapy to lobeglitazone plus MFM, can be a suitable alternative for Korean patients with inadequately controlled T2DM. The combination therapy resulted in significant reductions in HbA1c levels, body weight, and blood pressure.

Topics: Benzhydryl Compounds; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Glucosides; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Metformin; Pyrimidines; Republic of Korea; Thiazolidinediones; Treatment Outcome

To compare the efficacy and safety of an initial triple therapy using metformin, a dipeptidyl peptidase-4 (DPP4) inhibitor, and thiazolidinedione with a stepwise approach using sulfonylurea and metformin in new-onset, drug-naïve patients with type 2 diabetes.. Among drug-naïve patients with 9.0%-12.0% glycated hemoglobin (HbA1c) but no hyperglycemic symptoms, 100 subjects who started triple medications (metformin 1000 mg/day, sitagliptin 100 mg/day, and lobeglitazone 0.5 mg/day) were selected as an initial triple therapy group. Age and body mass index-matched subjects (n=100) who started glimepiride (≥2 mg/day with uptitration) and metformin (≥1000 mg/day with uptitration) were selected as a conventional therapy group. We investigated changes in HbA1c level, dynamic indexes for insulin sensitivity and β-cell function, and hypoglycemia.. After 12 months of treatment, HbA1c levels decreased significantly in both groups: from 10.7%±1.0% to 6.7%±1.3% in the triple group, and from 10.5%±1.0% to 7.3%±1.2% in the conventional therapy group. At 12 months, achievement of the HbA1c target (<7.0%) was higher in the triple group than in the conventional group (70% vs 52%, p<0.01). Dynamic indexes related to β-cell function and insulin sensitivity improved, and albuminuria reduced significantly only in the triple group. Hypoglycemia was more common in the conventional group.. Initial triple combination therapy with the DPP4 inhibitor, metformin, and thiazolidinedione showed a higher achievement of the target HbA1c goal with a lower risk of hypoglycemia, better restoration of β-cell function, and multiple metabolic benefits, implying durable glycemic control. This strategy may be useful for patients presenting with type 2 diabetes and high HbA1c levels.

Topics: Biomarkers; Blood Glucose; Case-Control Studies; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin Resistance; Male; Metformin; Middle Aged; Prognosis; Pyrimidines; Republic of Korea; Sitagliptin Phosphate; Thiazolidinediones

Topics: Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Male; Middle Aged; Pyrimidines; Retrospective Studies; Thiazolidinediones; Treatment Outcome