Retagliptin as add-on therapy to metformin in Chinese patients with type 2 diabetes inadequately controlled with metformin: A multicentre, randomized, double-blind, placebo-controlled, phase 3 trial.

AIM: To evaluate the efficacy and safety of retagliptin in Chinese patients with type 2 diabetes (T2D) inadequately controlled with metformin. MATERIALS AND METHODS: This multicentre, phase 3 trial consisted of a 16-week, randomized, double-blind, placebo-controlled period, where patients with HbA1c levels between 7.5% and 11.0% were randomized to receive either once-daily (QD) retagliptin 100 mg (n = 87) or placebo (n = 87), both as an add-on to metformin. The primary endpoint was the change in HbA1c from baseline to week 16. RESULTS: At week 16, the least squares mean change in HbA1c from baseline, compared with placebo, was -0.82% (95% CI, -1.05% to -0.58%) for the retagliptin 100 mg QD group (P < .0001) per treatment policy estimand. Significantly higher proportions of patients in the retagliptin 100 mg QD group achieved HbA1c levels of less than 6.5% (11.5%) and less than 7.0% (26.4%) compared with those receiving placebo (0% and 4.6%; P = .0016 and P < .0001, respectively) at week 16. Retagliptin 100 mg QD also lowered fasting plasma glucose and 2-hour postprandial plasma glucose levels. The incidence of adverse events (AEs) during the treatment period was similar between the two groups. However, slightly higher proportions of increased lipase and increased amylase in the retagliptin 100 mg QD group were observed. No patients discontinued treatment permanently because of AEs, and no episodes of severe hypoglycaemia were reported. CONCLUSIONS: Retagliptin 100 mg QD as an add-on therapy to metformin offers a new therapeutic option for treating Chinese patients with T2D inadequately controlled by metformin alone, and is generally well tolerated.

GPSM1 impairs metabolic homeostasis by controlling a pro-inflammatory pathway in macrophages.

G-protein-signaling modulator 1 (GPSM1) exhibits strong genetic association with Type 2 diabetes (T2D) and Body Mass Index in population studies. However, how GPSM1 carries out such control and in which types of cells are poorly understood. Here, we demonstrate that myeloid GPSM1 promotes metabolic inflammation to accelerate T2D and obesity development. Mice with myeloid-specific GPSM1 ablation are protected against high fat diet-induced insulin resistance, glucose dysregulation, and liver steatosis via repression of adipose tissue pro-inflammatory states. Mechanistically, GPSM1 deficiency mainly promotes TNFAIP3 transcription via the Gαi3/cAMP/PKA/CREB axis, thus inhibiting TLR4-induced NF-κB signaling in macrophages. In addition, we identify a small-molecule compound, AN-465/42243987, which suppresses the pro-inflammatory phenotype by inhibiting GPSM1 function, which could make it a candidate for metabolic therapy. Furthermore, GPSM1 expression is upregulated in visceral fat of individuals with obesity and is correlated with clinical metabolic traits. Overall, our findings identify macrophage GPSM1 as a link between metabolic inflammation and systemic homeostasis.

Serum growth differentiation factor 11 is closely related to metabolic syndrome in a Chinese cohort.

AIMS/INTRODUCTION: Despite increasing interest in growth differentiation factor 11 (GDF11) based on its involvement in age-related disorders, clinical implications - especially for metabolic diseases - remain unclear. Therefore, we assessed the association between serum GDF11 levels and metabolic disturbance in the Chinese population. MATERIALS AND METHODS: A total of 381 individuals from the Shanghai Nicheng Cohort Study were included. In addition to anthropometry, laboratory and ultrasonography measurements, serum concentrations of GDF11 were measured by enzyme-linked immunosorbent assay. RESULTS: Circulating GDF11 concentrations were unchanged with age (r = -0.064, P = 0.210), but showed an inverse relationship to body mass index, waist circumference and fat-free mass index (all P < 0.05). Correlation analysis showed decreased GDF11 concentrations accompanied by elevated diastolic blood pressure, fasting and 2-h plasma glucose, triglycerides, and low-density lipoprotein cholesterol after adjusting for sex, age and body mass index, whereas variations in aspartate aminotransferase and free thyroxine were consistent with GDF11 (all P < 0.05). Furthermore, people, especially men, with abnormal glycometabolism, body mass index and/or fat accumulation in the liver had lower serum levels of GDF11 (P < 0.05); an increase in metabolic syndrome morbidity along with the circulatory decline of GDF11 was found when stratified by GDF11-level quartiles (P-trend <0.001). Logistic regression showed that serum GDF11 levels were independently correlated with the presence of metabolic syndrome (odds ratio 0.665, 95% confidence interval 0.510-0.867, P = 0.003). CONCLUSIONS: We confirmed GDF11 as an endocrine factor playing a significant role in multiple metabolic processes and an indicator of metabolic syndrome in the Chinese population, particularly in males.

Relationship between circulating miR-132 and non-alcoholic fatty liver disease in a Chinese population.

BACKGROUND: Non-invasive diagnostic markers are of great importance for early screening nonalcoholic fatty liver disease (NAFLD). MicroRNAs (miRNAs) play significant roles in many metabolic disease, including NAFLD. Therefore, this study focusd on a Chinese population to explore the possible correlation between circulating miR-132 and NAFLD. RESULTS: Serum miR-132 was positively associated with NAFLD in non-type 2 diabetes mellitus (T2DM) groups by logistic regression (OR = 3.082 [1.057, 8.988], P = 0.039) after adjusting age, sex, and body mass index (BMI). Additionally, in non-T2DM subgroup, after adjusting age, sex, bmi, serum miR-132 was significantly associated with ALT (ß ± SE = 0.005 ± 0.002, P = 0.018), TG (ß ± SE = 0.072 ± 0.029, P = 0.015), FPG (ß ± SE = 0.123 ± 0.058, P = 0.036), γ-GT (ß ± SE = 0.002 ± 0.001, P = 0.047), apoE (ß ± SE = 0.038 ± 0.002, P = 0.017) . CONCLUSIONS: Serum miR-132 was found to be associated with NAFLD risk in a Chinese cross-section study. This finding provides a prospective research direction for early screening and diagnosing NAFLD.