lobeglitazone and dapagliflozin

Coadministration of lobeglitazone and dapagliflozin is expected to result in a blood glucose-lowering effect, followed by a gradual increase, in clinical usage; however, combining drugs could cause negative interactions. This study aimed to evaluate the effect of the coadministration of lobeglitazone and dapagliflozin on their individual pharmacokinetic properties at steady state in healthy male volunteers in the fasted state.. This study consisted of 2 parts, each of which was a randomized, open-labeled, multiple-dose, 2-way crossover study in 20 healthy male volunteers in each part. Blood samples were taken periodically over a 48-h period after dosing to derive total plasma lobeglitazone and dapagliflozin pharmacokinetic properties; safety profile was evaluated throughout the study.. When the pharmacokinetic properties of dapagliflozin were evaluated following its administration alone and in combination with lobeglitazone, point estimate and 90% CI of the geometric mean ratio of dapagliflozin AUC. Coadministration of lobeglitazone and dapagliflozin had no apparent clinically relevant effects on the pharmacokinetic properties of either drug. Based on these findings, it is anticipated that lobeglitazone and dapagliflozin can be coadministered without dose adjustment. ClinicalTrials.gov identifier: NCT03616392.

Topics: Adult; Benzhydryl Compounds; Cross-Over Studies; Drug Interactions; Fasting; Glucosides; Healthy Volunteers; Humans; Hypoglycemic Agents; Male; Pyrimidines; Therapeutic Equivalency; Thiazolidinediones; Young Adult

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

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