Efficacy and Safety of Lobeglitazone Monotherapy in Patients with Type 2 Diabetes Mellitus over 24-Weeks: A Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo Controlled Trial

Abstract

ObjectiveThe 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.Research Design and MethodsIn 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).ResultsAt 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.ConclusionsLobeglitazone 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.Trial RegistrationClinicaltrials.gov NCT01001611

Lobeglitazone, a Novel Thiazolidinedione, Improves Non-Alcoholic Fatty Liver Disease in Type 2 Diabetes: Its Efficacy and Predictive Factors Related to Responsiveness

“…Previous studies have shown that pioglitazone treatment increases body weight between 2.5 and 4.7 kg, depending on the study (23)(24)(25). In our study, lobeglitazone treatment showed a lower increase in the average body weight of 1.4 kg (from 76.5 ± 11.1 kg to 77.9 ± 11.8 kg [P = 0.001]), which is similar to the weight gain, ranging from 0.89 to 1.48 kg, that was observed in other clinical trials using 0.5 mg/day lobeglitazone (15)(16)(17).…”

“…Recently, a novel TZD called lobeglitazone was developed, and is currently being prescribed for T2D in Korea (14). The efficacy and safety of lobeglitazone in T2D has been well-investigated (15)(16)(17). To identify better treatment options for T2D patients with NAFLD, we investigated the effects of lobeglitazone on these patients by analyzing alterations in their CAP values using transient liver elastography, as well as in their glycemic, lipid, and liver profiles.…”

Lobeglitazone, a Novel Peroxisome Proliferator-Activated Receptor γ Agonist, Attenuates Renal Fibrosis Caused by Unilateral Ureteral Obstruction in Mice

“…Phase III clinical trial data show that lobeglitazone treatment resulted in an approximately 0.6% to 0.74% decrease in glycated hemoglobin compared with that of the placebo [1617]. It is administered as a once-daily dose and mainly excreted in feces, reducing concerns of bladder cancer unlike the classic TZD pioglitazone.…”

Nutrigenomic Functions of PPARs in Obesogenic Environments

“…It does not mean that these dual PPAR α and PPAR γ agonists have no side effects. For example, weight gain was still observed in lobeglitazone-treated diabetic subjects [50]. Collectively, existing evidence suggests that the usage of dual PPAR α and PPAR γ agonists was relatively well tolerated and acceptable considering the balance between efficacy and side effects.…”