METHODS: Post hoc analysis of patient-level data (Asian n = 235; non-Asian n = 3351) from 16 trials.

METHODS: HFD-fed mice were administered MD (50 mg/kg, 100 mg/kg, and 150 mg/kg) or 2 mg/kg metformin (positive control) orally for 16 weeks. Normal diet and HFD-fed control groups received normal saline.

RESULTS: MD dose of 50 mg/kg was better than 100 mg/kg and 150 mg/kg in significantly reducing weight-gain, glucose intolerance, insulin resistance, lipid accumulation in liver and kidney, and improving the serum lipid profile. Lowered protein carbonyls and lipid hydroperoxides in urine and tissue homogenates and elevated reduced glutathione, ferric reducing antioxidant power (FRAP), and Trolox equivalent antioxidant capacity (TEAC) levels in tissue homogenates indicated amelioration of oxidative stress.

METHOD: Multiple methods were used to determine molecular cognizance of AA in T2DM rats, when treated with different dosage levels. Histopathological and histomorphometry analysis was conducted using masson trichrome and H&E stains. While, protein and mRNA expressions of TLR-4/Wnt and insulin signaling were assessed using automated Western blotting (jess), immunohistochemistry, and RT-PCR.

RESULTS: Histopathological findings revealed that AA had reversed back the T2DM-induced apoptosis and necrosis caused to rats pancreas. Molecular findings exhibited prominent effects of AA in downregulating the elevated level of TLR-4, MyD88, NF-κB, p-JNK, and Wnt/β-catenin by blocking TLR-4/MyD88 and canonical Wnt signaling in diabetic pancreas, while IRS-1, PI3K, and pAkt were all upregulated by altering the NF-κB and β-catenin crosstalk during T2DM.

METHODS: This was a multi-centre, open-label randomised crossover study. Twenty-four overweight/obese T1DM patients aged ⩾18 years old with HbA1c ⩾ 7.0% (53 mmol/mol) were recruited and randomised into two study arms. For first 6-week, one arm remained on standard of care (SOC), the other arm received metformin, adjunctive to SOC. After 2-week washout, patients crossed over and continued for another 6 weeks. Glycaemic variability, other glycaemic parameters and metabolic profile were monitored.

RESULTS: There were significant reduction in metformin group for GV: mean (0.18 ± 1.73 vs -0.95 ± 1.24, p = 0.014), %CV (-15.84 (18.92) vs -19.08 (24.53), p = 0.044), glycemic risk assessment of diabetes equation (-0.69 (3.83) vs -1.61 (3.61), p = 0.047), continuous overlapping net glycaemic action (0.25 ± 1.62 vs -0.85 ± 1.22, p = 0.013), J-index (-0.75 (21.91) vs -7.11 (13.86), p = 0.034), time in range (1.13 ± 14.12% vs 10.83 ± 15.47%, p = 0.032); changes of systolic blood pressure (2.78 ± 11.19 mmHg vs -4.30 ± 9.81 mmHg, p = 0.027) and total daily dose (TDD) insulin (0.0 (3.33) units vs -2.17 (11.45) units, p = 0.012). Hypoglycaemic episodes were not significant in between groups.

METHODS: A prospective 12-week study using linagliptin 5mg once daily in 50 subjects (28 prediabetes and 22 T2D) who were stratified into high versus low fasting GLP-1 groups. A 75-g oral glucose tolerance test (OGTT) was performed at week 0 and 12. Primary outcomes were changes in HbA1c, fasting and post-OGTT glucose after 12 weeks. Secondary outcomes included changes in insulin resistance and beta cell function indices.

RESULTS: There was a greater HbA1c reduction in subjects with high GLP-1 compared to low GLP-1 levels in both the prediabetes and T2D populations [least-squares mean (LS-mean) change of -0.33% vs. -0.11% and -1.48% vs. -0.90% respectively)]. Linagliptin significantly reduced glucose excursion by 18% in high GLP-1 compared with 8% in low GLP-1 prediabetes groups. The reduction in glucose excursion was greater in high GLP-1 compared to low GLP-1 T2D by 30% and 21% respectively. There were significant LS-mean between-group differences in fasting glucose (-0.95 mmol/L), 2-hour glucose post-OGTT (-2.4 mmol/L) in the high GLP-1 T2D group. Improvement in insulin resistance indices were seen in the high GLP-1 T2D group while high GLP-1 prediabetes group demonstrated improvement in beta cell function indices. No incidence of hypoglycemia was reported.