To compare the efficacy and safety of adding liraglutide, saxagliptin and vildagliptin to current therapy in Chinese type 2 diabetes subjects with poor glycemic control.A 24-week, randomized, open-label, parallel clinical trial was performed. A total 178 patients completed the trial who had been randomly assigned to add-on once daily liraglutide (1.2 mg/day injected subcutaneously), to saxagliptin (5 mg once daily) or to vildagliptin (50 mg twice daily). Glycosylated hemoglobin (HbA1c) values, fasting and postprandial blood glucose (FBG and P2BG), body weight, body mass index (BMI), episodes of hypoglycemia and adverse events were evaluated.Over the 24-week treatment period, greater lowering of mean of HbA1c was achieved with 1.2 mg liraglutide (-1.50%, 95% CI [-1.67, -1.34]) than with saxagliptin (-1.23%, 95% CI [-1.36, -1.11]) and vildagliptin (-1.25%, 95% CI [-1.37, -1.13]). There was no significant between-group difference of percentages of subjects who reached a target HbA1c<7.0%, but significantly more subjects with liraglutide achieved HbA1c≤6.5% compared with saxagliptin and vildagliptin. The mean reduction of FBG value from baseline was 2.23 mmol/L with liraglutide, much greater than 1.83 mmol/L with saxagliptin (p=0.013), but similar to 2.03 mmol/L with -vildaglitpin group. As to the P2BG value, greater reductions was found with liraglutide (-4.80 mmol/L) than -3.56 mmol/L with saxagliptin (p=0.000) and -3.57 mmol/L with vildagliptin (p=0.000). Moreover, greater mean reductions of body weight and BMI with liraglutide (-6.0 kg and -2.1 kg/m(2)) were achieved than with saxagliptin and vildagliptin (both p<0.001), whereas no significant difference was found between saxagliptin and vildagliptin group. The incidence of hypoglycemia was recorded low and similar in each treatment group. Nausea was more common with liraglutide (27%) than with saxagliptin (3.2%) and vildagliptin (5.2%), but no significant between-group difference was reported in other AEs.Adding liraglutide demonstrated superiority to saxagliptin and vildagliptin for reductions of HbA1c and weight loss in Chinese subjects with T2DM who had inadequate glycemic control with conventional oral hypoglycemic agents. These findings support the add-on of liraglutide could offer notable advantages over DPP-4 inhibitors in both efficacy and safety.

4-Methylcatechol (4-MC) is a potential neuroprotective drug because it stimulates the synthesis of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in neurons. The present study explored the effect of 4-MC on cell growth and testosterone synthesis in the TM3 Leydig cells of mice. 4-MC did not enhance expression of both BDNF and NGF in these cells. However, this compound significantly inhibited cell proliferation and increased the number of apoptotic cells in a dose-dependent manner. The expression profile of Bax/Bcl-2 gene was altered considerably, and mitochondrial activity was significantly decreased in cells. 4-Methylcatechol also inhibited testosterone synthesis in TM3 Leydig cells. The inhibitory roles of this compound in relation to growth and testosterone synthesis in TM3 Leydig cells maybe associated with increased Bax gene expression and decreased mitochondrial activity. As a result, caspase cascade is activated.