MATERIALS AND METHODS: This is a single-center, single-dose, open-label, randomized, 2-treatment, 2-sequence and 2- period crossover study with a washout period of 7 days. All 28 adult male subjects were required to fast for at least 10 hours prior to drug administration and they were given access to water ad libitum during this period. Thirty minutes prior to dosing, all subjects were served with a standardized high-fat and high-calorie breakfast with a total calorie of 1000 kcal which was in accordance to the EMA Guideline on the Investigation of Bioequivalence. Subsequently, subjects were administered either the test or reference preparation with 240mL of plain water in the first trial period. During the second trial period, they received the alternate preparation. Plasma levels of glibenclamide and metformin were analysed separately using two different high performance liquid chromatography methods.
RESULTS: The 90% confidence interval (CI) for the ratio of the AUC0-t, AUC0-∞, and Cmax of the test preparation over those of the reference preparation were 0.9693-1.0739, 0.9598- 1.0561 and 0.9220 - 1.0642 respectively. Throughout the study period, no serious drug reaction was observed. However, a total of 26 adverse events (AE)/side effects were reported, including 24 that were definitely related to the study drugs, namely giddiness (n=17), while diarrheoa (n=3), headache (n=2) and excessive hunger (n=2) were less commonly reported by the subjects.
CONCLUSION: It can be concluded that the test preparation is bioequivalent to the reference preparation.
METHOD: The NIH 3T3 and RAW 264.7 co-culture were induced with LPS and high glucose before it was treated with metformin in different concentration. After 24 hours of treatment, the media and the cells were collected for further examination. The collagen expression was measured using Sirius red dye in the media. The IL-6 and TGF β mRNA examination were done using real-time PCR.
RESULT: Our study showed that NIH 3T3 and RAW 264.7 coculture treated with metformin has higher collagen expression, but lower IL-6 mRNA expression compares to those on co-culture without treatment.
CONCLUSION: Metformin increases fibrosis markers in LPS and high glucose-induced NIH 3T3 and RAW 264.7 coculture despite its ability to improve IL-6 mRNA expression.
METHODS: A comprehensive systematic search was carried out in PubMed/MEDLINE, Web of Science, SCOPUS and Embase from inception until June 2019. Weighted mean difference (WMD) with the 95 % CI were applied for estimating the effects of metformin on serum IGF-1 levels.
RESULTS: 11 studies involving a total of 569 individuals reported changes in IGF-1 plasma concentrations as an outcome measure. Pooled results demonstrated an overall non-significant decline in IGF-1 following metformin intake (WMD: -8.292 ng/ml, 95 % CI: -20.248, 3.664, p = 0.174) with heterogeneity among (p = 0.000,I2 = 87.1 %). The subgroup analyses displayed that intervention duration <12 weeks on children (WMD:-55.402 ng/ml, 95 % CI: -79.845, -30.960, I2 = 0.0 %) significantly reduced IGF-1. Moreover, in age 18 < years older metformin intake (WMD: 15.125 ng/ml, 95 % CI: 5.522, 24.729, I2 = 92.5 %) significantly increased IGF-1 than 18 ≤ years older (WMD:-1.038 ng/ml, 95 % CI: -3.578,1.502,I2 = 78.0 %). Following dose-response evaluation, metformin intake reduced IGF-1 (coefficient for dose-response analysis= -13.14, P = 0.041 and coefficient for liner analysis= -0.066, P = 0.038) significantly based on treatment duration.
CONCLUSION: We found in children, intervention duration <12 weeks yielded significant reductions in IGF-1, whilst paradoxically, in participants >18 years old, metformin intake significantly increased IGF-1. We suggest that caution be taken when interpreting the findings of this review, particularly given the discordant supplementation practices between children and adults.
Subjects and methods: Sixty T2DM patients were recruited in a randomized, placebo-controlled, double-blinded, and multicenter trial. The patients, currently using Met, were randomly grouped into those treated with either GKB extract (120 mg/day) or placebo (starch, 120 mg/day) for 90 days. Blood glycated hemoglobin (HbA1c), fasting serum glucose, serum insulin, body mass index (BMI), waist circumference (WC), insulin resistance, and visceral adiposity index (VAI) were determined before (baseline) and after 90 days of GKB extract treatment.
Results: GKB extract significantly decreased blood HbA1c (7.7%±1.2% vs baseline 8.6%±1.6%, P<0.001), fasting serum glucose (154.7±36.1 mg/dL vs baseline 194.4±66.1 mg/dL, P<0.001) and insulin (13.4±7.8 μU/mL vs baseline 18.5±8.9 μU/mL, P=0.006) levels, BMI (31.6±5.1 kg/m2 vs baseline 34.0±6.0 kg/m2, P<0.001), waist WC (102.6±10.5 cm vs baseline 106.0±10.9 cm, P<0.001), and VAI (158.9±67.2 vs baseline 192.0±86.2, P=0.007). GKB extract did not negatively impact the liver, kidney, or hematopoietic functions.
Conclusion: GKB extract as an adjuvant was effective in improving Met treatment outcomes in T2DM patients. Thus, it is suggested that GKB extract is an effective dietary supplement for the control of DM in humans.
MATERIALS AND METHODS: In this up to 33-week, open-label, active-controlled, parallel-group trial, adults [glycated haemoglobin (HbA1c) 7%-10% (53-86 mmol/mol); body mass index ≥20 kg/m(2) ; intent to fast] were randomized (1:1) ≥10 weeks before Ramadan to either switch to once-daily liraglutide (final dose 1.8 mg) or continue pre-trial sulphonylurea at maximum tolerated dose, both with metformin.
PRIMARY ENDPOINT: change in fructosamine, a validated marker of short-term glycaemic control, during Ramadan.
RESULTS: Similar reductions in fructosamine levels were observed for both groups during Ramadan [liraglutide (-12.8 µmol/L); sulphonylurea (-16.4 µmol/L); estimated treatment difference (ETD) 3.51 µmol/L (95% CI: -5.26; 12.28); p = 0.43], despite lower fructosamine levels in the liraglutide group at start of Ramadan. Fewer documented symptomatic hypoglycaemic episodes were reported in liraglutide-treated (2%, three subjects) versus sulphonylurea-treated patients (11%, 18 subjects). No severe hypoglycaemic episodes were reported by either group. Body weight decreased more during Ramadan with liraglutide (ETD: -0.54 kg; 95% CI: -0.94;-0.14; p = 0.0091). The proportion of patients reporting adverse events was similar between groups. Liraglutide led to greater HbA1c reduction [ETD: -0.59% (-6.40 mmol/mol), 95% CI: -0.79; -0.38%; -8.63; -4.17 mmol/mol; p
METHOD: A 12-month single blinded multicenter randomized control trial was designed to investigate the measured variables [Glycated Hemoglobin (HbA1c), Renal function, Albumin Creatinine Ratio (ACR) etc.]. The trial was randomized into 2 experimental parallel arms (ascorbic acid vs acetylsalicylic acid) were blinded with study supplements in combination with metformin and findings were compared to control arm with metformin alone and blinded with placebo. Withdrawal criteria was defined to maintain the equity and balance in the participants in the whole trial.
FINDING: Patients with metformin and ascorbic acid (parallel arm I) was twice more likely to reduce HbA1c than metformin alone (control arm) in a year (OR 2.31 (95% CI 1.87-4.42) p metformin is more effective against reducing risks for diabetes related long-term complications (including ACR). TRIAL details Registration No: NTR-6100, Registry Name: Netherlands Trial Registry, URL: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=6100 , Date of Registration: 20th October, 2016, Date of first Enrollment: 1 November, 2015.