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Comparing the individual effects of metformin and rosiglitazone and their combination in obese women with polycystic ovary syndrome: a randomized controlled trial.
Li, Y, Tan, J, Wang, Q, Duan, C, Hu, Y, Huang, W
Fertility and sterility. 2020;(1):197-204
Abstract
OBJECTIVE To compare the effects of metformin, rosiglitazone, and their combination in obese polycystic ovary syndrome (PCOS) patients with insulin resistance. DESIGN Prospective randomized controlled trail. SETTING Tertiary teaching hospital. PATIENT(S): Obese Chinese women (body mass index [BMI] ≥25 kg/m2) with insulin resistance who fulfilled the Rotterdam criteria of PCOS. INTERVENTION(S): In group 1, 68 patients administered metformin (1,500 mg/day); in group 2, 67 patients administered rosiglitazone (4 mg/day); in group 3, 69 patients administered metformin (1,000 mg/day) and rosiglitazone (4 mg/day) for 6 months, all with the same diet and regular exercise lifestyle recommendation. MAIN OUTCOME MEASURE(S): Average menstrual interval, anthropometric measurements, androgen-related parameters, and metabolic features of insulin, carbohydrates, and lipids, with intention-to-treat analysis. RESULT(S): The baseline parameters showed no statistically significant differences. After the 6-month treatment, most participants showed an improved menstrual pattern. There were statistically significant decreases in acne scores, weight, BMI, waist circumference, waist-to-hip ratio, and serum testosterone. The metabolic indexes of insulin, carbohydrates, and lipids were improved obviously compared with the baseline in each group. Among the three groups, the patients administered 1,500 mg/day metformin experienced greater reductions in weight. However, the rosiglitazone users (alone or combined with metformin) showed a more notable decline in total cholesterol and triglyceride levels. CONCLUSION(S): Considering the benefits of metformin on weight loss, high-dose metformin (1,500 mg/day) along with lifestyle modification should be recommended for obese, insulin-resistant women with PCOS. Rosiglitazone alone or combined with low-dosage metformin plus lifestyle modification should be considered for the women with abnormal lipid profiles. CLINICAL TRIAL REGISTRATION NUMBER ChiCTR-TRC-13003642 (Chinese Clinical Trial Registry).
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Pharmacokinetics and Preliminary Pharmacodynamics of Single- and Multiple-dose Lyophilized Recombinant Glucagon-like Peptide-1 Receptor Agonist (rE-4) in Chinese Patients with Type 2 Diabetes Mellitus.
Wang, Y, Xu, B, Zhu, L, Lou, K, Chen, Y, Zhao, X, Wang, Q, Xu, L, Guo, X, Ji, L, et al
Clinical drug investigation. 2017;(12):1107-1115
Abstract
BACKGROUND AND OBJECTIVES Recombinant glucagon-like peptide-1 receptor agonist (rE-4) is a glucagon-like peptide-1 receptor agonist, which has the same amino acid sequence to exenatide, except for the C-terminal deamidated. This study assessed the pharmacokinetics and preliminary pharmacodynamics of rE-4, following single and multiple subcutaneous injections in Chinese patients with type 2 diabetes mellitus (T2DM). DESIGN AND METHODS In the randomized, open-label study, Chinese patients with T2DM (n = 36) were randomly assigned to three groups of rE-4 (n = 12), rE-4 with metformin (n = 12) and exenatide (n = 12, as the control group) for 12 weeks. rE-4 and exenatide were administered by subcutaneous injection in the abdomen, and metformin was given by oral administration. Patients received rE-4 or exenatide 5 μg twice a day for the first 4 weeks and adjusted the dose of rE-4 or exenatide to 10 μg twice a day at day 29 for the following 8 weeks, if their glycated albumin (GA) values were still greater than 17%. We evaluated pharmacokinetic parameters of rE-4 and exenatide, fasting plasma glucose (FPG), 2-h postprandial blood glucose (PG2 h), glycosylated hemoglobin (HbA1c) and body weight at designated time points. RESULTS Thirty-six patients were enrolled, and 29 subjects finished the study. rE-4 was absorbed quickly with a median peak-reaching time (t max) of 0.8-1.5 h and eliminated rapidly with a median terminal half-life (t 1/2z) of 1.6-1.9 h. The exposure of rE-4 increased in an approximately dose-proportional method without accumulation. rE-4 10 μg twice a day could reduce FPG (~2.29 mmol/L), PG2 h (~6.00 mmol/L), HbA1c (~1.19%) and body weight (~0.48 kg) from baseline to 12 weeks, with no statistical significance compared with exenatide (FPG: ~1.88 mmol/L; PG2 h: ~6.66 mmol/L; HbA1c: ~1.13%; body weight: ~0.47 kg) and rE-4 with metformin (FPG: ~2.33 mmol/L; PG2 h: ~6.51 mmol/L; HbA1c: ~0.84%; body weight: ~1.16 kg) (p > 0.05). CONCLUSIONS rE-4 twice a day has a pharmacokinetic profile similar to exenatide and rE-4 with metformin after single and multiple doses in Chinese patients with T2DM. Also, rE-4 could improve glycemic control effectively. CLINICALTRIALS. GOV IDENTIFIER NCT01342042.
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Roux-en-Y gastric bypass for diabetes (the Diabetes Surgery Study): 2-year outcomes of a 5-year, randomised, controlled trial.
Ikramuddin, S, Billington, CJ, Lee, WJ, Bantle, JP, Thomas, AJ, Connett, JE, Leslie, DB, Inabnet, WB, Jeffery, RW, Chong, K, et al
The lancet. Diabetes & endocrinology. 2015;(6):413-422
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Abstract
BACKGROUND Conventional treatments for patients with type 2 diabetes are often inadequate. We aimed to assess outcomes of diabetes control and treatment risks 2 years after adding Roux-en-Y gastric bypass to intensive lifestyle and medical management. METHODS We report 2-year outcomes of a 5-year randomised trial (the Diabetes Surgery Study) at four teaching hospitals (three in the USA and one in Taiwan). At baseline, eligible participants had to have HbA1c of at least 8·0% (64 mmol/mol), BMI between 30·0 and 39·9 kg/m(2), and type 2 diabetes for at least 6 months, and be aged 30-67 years. We randomly assigned participants to receive either intensive lifestyle and medical management alone (lifestyle and medical management), or lifestyle and medical management plus standard Roux-en-Y gastric bypass surgery (gastric bypass). Staff from the clinical centres had access to data from individual patients, but were masked to other patients' data and aggregated data until the 2-year follow-up. Drugs for hyperglycaemia, hypertension, and dyslipidaemia were prescribed by protocol. The primary endpoint was achievement of the composite treatment goal of HbA1c less than 7·0% (53 mmol/mol), LDL cholesterol less than 2·59 mmol/L, and systolic blood pressure less than 130 mm Hg at 12 months; here we report the composite outcome and other pre-planned secondary outcomes at 24 months. Analyses were done on an intention-to-treat basis, with multiple imputations for missing data. This study is registered with ClinicalTrials.gov, number NCT00641251, and is still ongoing. FINDINGS Between April 21, 2008, and Nov 21, 2011, we randomly assigned 120 eligible patients to either lifestyle and medical management alone (n=60) or with the addition of gastric bypass (n=60). One patient in the lifestyle and medical management group died (from pancreatic cancer), thus 119 were included in the primary analysis. Significantly more participants in the gastric bypass group achieved the composite triple endpoint at 24 months than in the lifestyle and medical management group (26 [43%] vs eight [14%]; odds ratio 5·1 [95% CI 2·0-12·6], p=0·0004), mainly through improved glycaemic control (HbA1c <7·0% [53 mmol/mol] in 45 [75%] vs 14 [24%]; treatment difference -1·9% (-2·5 to -1·4); p=0·0001). 46 clinically important adverse events occurred in the gastric bypass group and 25 in the lifestyle and medical management group (mainly infections in both groups [four in the lifestyle and medical management group, eight in the gastric bypass group]). With a negative binomial model adjusted for site, the event rate for the gastric bypass group was non-significantly higher than the lifestyle and medical management group by a factor of 1·67 (95% CI 0·98-2·87, p=0·06). Across both years of the study, the gastric bypass group had seven serious falls with five fractures, compared with three serious falls and one fracture in the lifestyle and medical management group. All fractures happened in women. Many more nutritional deficiencies occurred in the gastric bypass group (mainly deficiencies in iron, albumin, calcium, and vitamin D), despite protocol use of nutritional supplements. INTERPRETATION The addition of gastric bypass to lifestyle and medical management in patients with type 2 diabetes improved diabetes control, but adverse events and nutritional deficiencies were more frequent. Larger and longer studies are needed to investigate whether the benefits and risk of gastric bypass for type 2 diabetes can be balanced. FUNDING Covidien, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases Nutrition Obesity Research Centers, and the National Center for Advancing Translational Sciences.
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Chinese herbal medicine Tianqi reduces progression from impaired glucose tolerance to diabetes: a double-blind, randomized, placebo-controlled, multicenter trial.
Lian, F, Li, G, Chen, X, Wang, X, Piao, C, Wang, J, Hong, Y, Ba, Z, Wu, S, Zhou, X, et al
The Journal of clinical endocrinology and metabolism. 2014;(2):648-55
Abstract
CONTEXT Living in a prediabetes state significantly increases a patient's risk for both diabetes and cardiovascular disease. Tianqi capsule, containing 10 Chinese herbal medicines, is used in China for the treatment of type 2 diabetes mellitus (T2DM). OBJECTIVE The purpose of this study was to assess whether Tianqi prevented T2DM in subjects with impaired glucose tolerance (IGT) over the course of a 12-month treatment. METHODS Individuals with IGT were randomly allocated in a double-blind manner to receive Tianqi (n = 210) or a placebo (n = 210) for 12 months. Oral glucose tolerance tests were conducted every 3 months to assess the development of diabetes or restoration to normal glucose tolerance. All subjects received the same lifestyle education. The primary endpoint was the conversion of IGT to T2DM. Body weight and body mass index were observed. Adverse effects were monitored. RESULTS Of the 420 enrolled subjects with IGT, 389 completed the trial (198 in the Tianqi group and 191 in the placebo group). At the end of the 12-month trial, 36 subjects in the Tianqi group (18.18%) and 56 in the placebo group (29.32%) had developed diabetes (P = .01). There was a significant difference in the number of subjects who had normal glucose tolerance at the end of the study between the Tianqi and placebo groups (n = 125, 63.13%, and n = 89, 46.60%, respectively; P = .001). Cox's proportional hazards model analysis showed that Tianqi reduced the risk of diabetes by 32.1% compared with the placebo. No severe adverse events occurred in the trial. There were no statistical differences in body weight and body mass index changes between the Tianqi group and the placebo group during the 12-month trial. CONCLUSIONS Treatment with a Tianqi capsule for 12 months significantly decreased the incidence of T2DM in subjects with IGT, and this herbal drug was safe to use.