Lobeglitazone: A novel antidiabetic drug

This study analyzed the glucose-lowering effects of lobeglitazone, a novel antidiabetic drug.

Thiazolidinediones are a group of drugs used for improving insulin sensitivity and reducing the production of glucose in the liver in type 2 diabetes. These drugs initiate a response at the peroxisome proliferator-activated receptor (PPAR)-γ. PPAR- γ regulates fat storage and glucose metabolism. They are more durable than other drugs in controlling hyperglycemia (high levels of glucose in the blood), but do not increase the risk of hypoglycemia (dangerously low levels of glucose in the blood). However, they can contribute to weight gain, fluid retention, bone fractures, heart failure and increased risk of heart attack. Therefore, there is a need to develop more effective and safe antidiabetic drugs targeting PPAR- γ.

Lobeglitazone is a novel drug that targets PPAR- γ. Previous studies have shown this drug to be more potent than previous thiazolidinediones, and therefore it is expected to cause an effective response at lower doses. However, the safety and efficacy of lobeglitazone has not been established in a trial of type 2 diabetic patients. The aim of this study was to assess the glucose-lowering and lipid (fat)-modifying effects of lobeglitazone monotherapy (single therapy) compared to placebo.

173 patients were randomly assigned to either 0.5 mg of lobeglitazone (115 patients) or placebo (58 patients). The treatment period lasted 24 weeks, with 83.2% of the randomized patients completing the 24 weeks. The study’s main aim was to evaluate differences in HbA1c levels (a measurement of average blood glucose levels over the past 3 months).

Lobeglitazone significantly decreased HbA1c levels compared to placebo. HbA1c levels in the lobeglitazone group were 7.85% at the beginning of the study compared to 7.41% at the end of the study. HbA1c levels in the placebo group were 8.05% at the beginning of the study compared to 8.21% at the end of the study. The average difference between the two groups was therefore 0.6%. The goal of HbA1c levels of less than 7% was achieved significantly more in the lobeglitazone group (44%) than in the placebo group (12%).

Lobeglitazone significantly reduced fasting plasma glucose levels compared to placebo. Fasting plasma glucose levels were 150.91 mg/dL at the beginning of the study compared to 131.8 mg/dL at the end of the study for the lobeglitazone group. Fasting plasma glucose levels were 163.84 mg/dL at the beginning of the study compared to 164.47 at the end of the study mg/dL for the placebo group.

Lobeglitazone significantly improved levels of HDL (good) cholesterol compared to placebo. HDL cholesterol levels were 48.69 mg/dL at the beginning of the study compared to 52.99 mg/dL at the end of the study for the lobeglitazone group. HDL cholesterol levels were 46.33 mg/dL at the beginning of the study compared to 47.09 mg/dL at the end of the study for the placebo group. Lobeglitazone also significantly reduced the levels of triglycerides (the chemical form fat takes in the body) compared to placebo. Triglyceride levels were 137.51 mg/dL at the beginning of the study compared to 118.45 mg/dL at the end of the study for the lobeglitazone group. Triglyceride levels were 177.14 mg/dL at the beginning of the study compared to 193.28 mg/dL at the end of the study for the placebo group.

At 24 weeks, more weight gain was seen in the lobeglitazone group (0.89 kg) than the placebo group (-0.63 kg). 8.9% of patients taking lobeglitazone experienced an adverse event considered to be drug-related compared to 5.2% of the placebo group. Peripheral edema (swelling of tissues due to the accumulation of fluids) was considered to be a drug-related adverse event, and occured in 3.6% of the lobeglitazone patients compared to 0% of the placebo group. Blood pressure and pulse rate were not affected by treatment with lobeglitazone.

In conclusion, the authors stated that lobeglitazone 0.5 mg showed improvements in glucose and lipid (fat) endpoints with a favorable safety profile over 24 weeks, supporting a potential role in treatment of type 2 diabetes.