The effects of once daily MXR on chronic glycaemia, BMI, lipid profiles, insulin resistance and islet function are comparable with that of thrice daily MIR in oriental population.

Aims Metformin treatment for type 2 diabetes mellitus (T2DM) can be limited by gastrointestinal (GI) adverse events (AEs), resulting in treatment discontinuation. We investigated whether once‐daily metformin extended release (XR) is superior in terms of GI tolerability, with non‐inferior efficacy, compared with thrice‐daily metformin immediate release (IR) in treatment‐naïve Chinese patients with T2DM. Materials and Methods This prospective, open‐label, randomized, multicentre, phase IV interventional study enrolled Chinese T2DM patients to receive either metformin XR or metformin IR with a 2‐week screening period, a 16‐week treatment period and a 2‐week follow‐up period without treatment. Co‐primary endpoints were a non‐inferiority assessment of metformin XR vs metformin IR in glycated haemoglobin (HbA1c) least squares mean (LSM) change from baseline to week 16 and the superiority of GI tolerability for metformin XR vs metformin IR. Results Overall, 532 patients were randomized to metformin IR (n = 267) or metformin XR (n = 265). The HbA1c LSM change was −1.61% and −1.58% in each group, respectively (LSM difference, 0.03; 95% confidence interval [CI], −0.10, 0.17). Incidences of drug‐related AEs were 26.5% (n = 66) in the metformin IR‐only group and 32.2% (n = 85) in the metformin XR‐only group, and GI AEs were 23.8% and 22.3% in each group, respectively (difference, −1.52; 95% CI, −8.60, 5.56). The treatment difference met the predefined non‐inferiority upper CI margin of 0.4% in HbA1c. Conclusions Metformin XR was non‐inferior to metformin IR for the LSM change in HbA1c from baseline to week 16 and not superior to metformin IR for overall GI AE incidence during treatment of Chinese T2DM patients.

BackgroundDiabetic nephropathy (DN) is a major microvascular complication in diabetes. An increasing body of evidence has shown that DN is related to chronic inflammation, kidney hypertrophy, and fibrosis. While thalidomide has been shown to have anti-inflammatory and antifibrotic effects, the effects of thalidomide on the pathogenesis of DN are unclear. This study was undertaken to explore whether thalidomide has renal-protective effects in diabetic rats.MethodsMale Sprague Dawley rats were injected intraperitoneally with 50 mg/kg streptozotocin to induce diabetes. Diabetic rats were treated with thalidomide (200 mg/kg/d) for 8 weeks, and then blood and urine were collected for measurement of renal function-related parameters. Histopathology, immunohistochemistry, enzyme-linked immunosorbent assay, and Western blot analyses were performed to assess renal proinflammatory cytokines, fibrotic protein, and related signaling pathways.ResultsDiabetic rats exhibited obvious renal structural and functional abnormalities, as well as renal inflammation and fibrosis. Compared with diabetic control rats, those treated with thalidomide showed significantly improved histological alterations and biomarkers of renal function, as well as reduced expression of renal inflammatory cytokines, including NF-κB and MCP-1. Furthermore, renal fibrotic proteins, such as TGF-β1, TβRII, TβRI, smad3, collagen IV, and fibronectin were also remarkably suppressed. Treatment with thalidomide markedly stimulated the phosphorylation of AMPKα.ConclusionIn this study, thalidomide suppressed the inflammatory and fibrotic processes in DN. These effects were partly mediated by the activation of AMPKα, and inhibition of the NF-κB/MCP-1 and TGF-β1/Smad signaling pathways. These results suggest that thalidomide may have therapeutic potential in diabetic renal injury through the anti-inflammatory pathway.

Background Anemia and electrolyte disturbances are adverse outcomes of chronic kidney disease (CKD). This study explored the association between metabolic parameters with anemia and electrolyte and mineral disorders among CKD patients in Taiwan. Methods This cross-sectional study with a total of 2176 CKD stages 3–5 patients were collected from the Department of Nephrology at Shuang Ho Hospital, Taipei Medical University through the “Chronic Kidney Disease Common Care Network” database from December 2008 to April 2019. A multivariable-adjusted logistic regression expressed as odd ratios (OR) was performed to assess the association of metabolic parameters with anemia and electrolyte and mineral disorders. Results Elevated diastolic blood pressure, fasting blood glucose, and glycated hemoglobin A1c (HbA1c) were associated with presence of anemia. Similarly, elevated fasting blood glucose and HbA1c were associated with hyponatremia (OR = 1.59 and 1.58, P for both < 0.01) and hypercalcemia (OR = 1.38 and 1.33, P for both < 0.05). There was no significant association in serum lipid levels with presence of anemia. However, total triglycerides, total cholesterol and low-density lipoprotein-cholesterol were only associated with presence of hypercalcemia (OR = 1.43, 1.95 and 3.08, respectively, P for all < 0.05). Conclusions Elevated diastolic blood pressure, fasting blood glucose, HbA1c and blood lipids are associated with anemia or electrolyte and mineral disorders in CKD patients.