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Policaptil Gel Retard in adult subjects with the metabolic syndrome: Efficacy, safety, and tolerability compared to metformin.
Guarino, G, Della Corte, T, Strollo, F, Gentile, S, ,
Diabetes & metabolic syndrome. 2021;(3):901-907
Abstract
BACKGROUND Policaptil Gel Retard® (PGR), is a new macromolecule complex based on polysaccharides slowing the rate of carbohydrate and fat absorption. It proved to significantly reduce body weight, acanthosis nigricans expression, HbA1c levels, and glucose metabolism abnormalities in obese, hyper-insulinemic adolescents. No such data are available for adults. AIM: to compare the effects of PGR vs. metformin in adult subjects with the Metabolic Syndrome (MS) and T2DM on a Low Glycemic Index diet. SUBJECTS AND METHODS This spontaneous clinical, longitudinal, single-blind, randomized study based on a per-protocol analysis enrolled 100 outpatients with MS and T2DM consecutively referring to our clinic for three months, and randomly assigned to either the active treatment (Group A:, 6 tablets/day) or the comparator (Group B: Metformin tablets, 1500-2000 mg/day in two divided doses during the two main meals, to minimize side effects) to be taken 30 min before each main meal in equally divided doses. Serum lipid profile, anthropometry, HOMA-IR index, and tolerability parameters were evaluated before and after a 6-month follow-up period. RESULTS all parameters improved at a similar rate in both groups but for the lipid profile, which got even better in Group A. Group A also experienced less prominent gastrointestinal side effects than its counterpart. CONCLUSION For the first time, we showed the non-inferiority of PGR compared to metformin in obese adult subjects with the MS and T2DM as for glycemic control and a clear-cut superiority of PGR in terms of both serum lipid-lowering capacity and tolerability.
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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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A comparative study to illustrate the benefits of using ethinyl estradiol-cyproterone acetate over metformin in patients with polycystic ovarian syndrome.
Mhao, NS, Al-Hilli, AS, Hadi, NR, Jamil, DA, Al-Aubaidy, HA
Diabetes & metabolic syndrome. 2016;(1 Suppl 1):S95-8
Abstract
AIM: This study was done to illustrate the clinical and biochemical effects of ethinyl estradiol-cyproterone acetate (EE-AC) and metformin in this disease. METHODS This was a randomized control trial study, done on twenty-six female patients already diagnosed as cases of PCOS. Participants were divided into two study groups: group one (Group 1), received metformin of 500mg twice daily and the second group (Group 2), was given ethinyl estradiol-cyproterone acetate for 21 consecutive days followed by 7 days drug-free. The course of the treatment for both groups was continued for three consecutive months. RESULTS Group 1 showed a statistical significant increase in serum high density lipoprotein cholesterol (HDL-C) levels (P=0.006) and a decrease in the level of triglyceride (TG) (P=0.006). In addition, Group 1 had a significant reduction in the levels of very density lipoprotein cholesterol (VLDL-C) (P=0.006). Group 2 had a significant increase in serum TG levels (P=0.01), associated with a significant decrease in serum LDL-C (P=0.04). Serum testosterone was significantly reduced in group 1 (P=0.038). This was associated with an improvement in glucose tolerance test (GTT) and BMI in the same group (group 1). Group 2, had an improvement in the menstrual cycle control; hirsutism and acne. CONCLUSION This study showed that metformin treatment is beneficial in improving serum lipids; glucose homeostasis and BMI, however, the ethinyl estradiol-cyproterone acetate is superior in improving the clinical manifestation of patients with PCOS, including menstrual cycle regulation, hyperandrogenic state.
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[The influence of metformin and N-acetylcysteine on mammographic density in postmenopausal women].
Bershteĭn, LM, Vasil'ev, DA, Kovalenko, IG, Poroshina, TE, Kisel'nikov, KS, Boiarkina, MP, Zaĭtsev, AN
Voprosy onkologii. 2012;(1):45-9
Abstract
Mammographic breast density (MBD) value is currently one of the strong predictors for mammary carcinoma development. There are also other conditions predisposing to MBD increase with hormone-related markers different from those used in breast cancer, while pharmacological methods for MBD reduction are few and still considered experimental. In the current study 25 postmenopausal women received daily for a median 10.5 months 1-1.5 g of antidiabetic biguanide metformin (siofor) (n = 14) or 400-600 mg of antigenotoxic drug N-acetylcysteine (n = 11). In both groups MBD was measured before and after treatment. The effects of both drugs were quite similar. Metformin use lead to lower MBD in 4 of 14 (28.5%) women with mean MBD decrease of -1,24% (absolute dynamics) and -5.03% (relative value). In N-acetylcysteine group this effect was observed in 27.3% of cases, with -2.0% absolute dynamics and -6.1% relative dynamics. In metformin group the most evident absolute and relative dynamics was observed in patients with no signs of metabolic syndrome, -10.86% compared to -2.45%. In 7 women the metformin use also lead to decrease of dense and increase of non-dense areas on digital scans, leading to decrease in dense to non-dense area volume ratio. Therefore, the similar effects of metformin and N-acetylcysteine are probably explained mostly not by insulin resistance elimination by metformin, but by altered cell proliferation, apoptosis and DNA repair.
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Metformin versus lifestyle changes in treating women with polycystic ovary syndrome.
Curi, DD, Fonseca, AM, Marcondes, JA, Almeida, JA, Bagnoli, VR, Soares, JM, Baracat, EC
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2012;(3):182-5
Abstract
OBJECTIVE To compare the efficacy of metformin with that of lifestyle changes in patients with polycystic ovary syndrome (PCOS). DESIGN Prospective, randomized clinical trial of 40 women with PCOS to analyze the effects of metformin and lifestyle intervention treatments on menstrual pattern and hormone and metabolic profile. The duration of treatment was 6 months. Statistical analysis was done using Student's t-test. RESULTS Fifteen women in the metformin group and 12 in the lifestyle changes group completed the study. The menstrual pattern improved by ~67% in both groups. There was a significant decrease in waist circumference in the lifestyle changes group (101.8 ± 3.9 and 95.1 ± 3.6, at baseline and at 6 months of treatment, respectively; p < 0.001) and in body mass index (BMI) in both groups. The predictor of menstrual pattern improvement was BMI. CONCLUSIONS Both metformin and lifestyle changes may increase the number of menstrual cycles in PCOS. This effect was related to a decrease in BMI.
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Drospirenone/ethinyl estradiol versus rosiglitazone treatment in overweight adolescents with polycystic ovary syndrome: comparison of metabolic, hormonal, and cardiovascular risk factors.
Tfayli, H, Ulnach, JW, Lee, S, Sutton-Tyrrell, K, Arslanian, S
The Journal of clinical endocrinology and metabolism. 2011;(5):1311-9
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Abstract
CONTEXT Adolescents with polycystic ovary syndrome (PCOS) have insulin resistance and higher rates of the metabolic syndrome. OBJECTIVE Our objective was to compare the effects of 6 months treatment with drospirenone/ethinyl estradiol (EE) (3 mg/30 μg) vs. rosiglitazone (4 mg) daily on the hormonal and cardiometabolic profiles of overweight/obese adolescents with PCOS. DESIGN We conducted a randomized, double-blinded, parallel clinical trial in an academic hospital, with n = 46 patients. OUTCOME MEASURES The primary outcome measure was insulin sensitivity, hepatic with [6,6-(2)H(2)]glucose and peripheral with a 3-h hyperinsulinemic-euglycemic clamp. Other outcome measures included plasma androgen profile and response to ACTH stimulation, glucose and insulin response to oral glucose tolerance test, insulin secretion with a 2-h hyperglycemic clamp, fasting lipid profile, inflammatory markers, intima media thickness, aortic pulse wave velocity, body composition by dual-energy x-ray absorptiometry, and abdominal adiposity by computed tomography scan. RESULTS Drospirenone/EE resulted in greater reductions in androgenemia. Neither treatment led to change in weight or body mass index, but rosiglitazone led to a significant decrease in visceral adiposity. Compared with drospirenone/EE, treatment with rosiglitazone improved hepatic and peripheral insulin sensitivity and lowered fasting and stimulated insulin levels during the oral glucose tolerance test. Treatment with drospirenone/EE was associated with elevations in total cholesterol, high-sensitivity C-reactive protein and leptin concentrations, whereas treatment with rosiglitazone led to lower triglycerides and higher adiponectin concentrations. Neither treatment affected intima media thickness or pulse wave velocity. CONCLUSIONS In overweight/obese adolescents with PCOS, 6 months treatment with rosiglitazone was superior to drospirenone/EE in improving the cardiometabolic risk profile, and effective but inferior in attenuating hyperandrogenemia. Additional studies are needed to test insulin sensitizers in the treatment of the reproductive and cardiometabolic aspects of PCOS.
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Baseline characteristics of the Nateglinide and Valsartan Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial population: comparison with other diabetes prevention trials.
Krum, H, McMurray, JJ, Horton, E, Gerlock, T, Holzhauer, B, Zuurman, L, Haffner, SM, Bethel, MA, Holman, RR, Califf, RM
Cardiovascular therapeutics. 2010;(2):124-32
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The Nateglinide and Valsartan Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial is exploring two pharmacological strategies (nateglinide and valsartan, both alone and in combination) in the prevention of overt diabetes mellitus (DM) and the reduction of cardiovascular disease (CVD) in subjects at high risk for these events. In this analysis, we provide baseline characteristics of the randomized NAVIGATOR study population and contrast them with those from other trials of DM prevention. Key eligibility criteria include impaired glucose tolerance (IGT) and impaired fasting glucose (IFG), a history of CVD (in patients aged > or =50 years), and > or =1 cardiovascular risk factor (in patients aged > or =55 years). Baseline demographic characteristics, laboratory findings, cardiovascular risk factors, CVD history, and medication use are described and compared with other trials of DM prevention. The full analysis set of subjects (N = 9306) showed a clustering of risk factors consistent with the metabolic syndrome: high rates of hypertension (77.5%), dyslipidemia (44.7%), increased waist circumference (101.0 cm), and high body mass index (BMI) (47.5% with BMI > or =30 kg/m(2)). A minority of patients had a history of CVD (24.3%); of these, 11.7% had a history of myocardial infarction and most of the remainder had evidence of coronary artery disease. Subjects also had elevated blood pressure (BP) (predominantly systolic) (139.7/82.6 mm Hg), increased serum low-density lipoproteins cholesterol levels (3.27 mmol/L), and borderline elevation of triglyceride levels (1.97 mmol/L). Demographic data, BP, and lipid profiles in NAVIGATOR were similar to those of previous DM prevention trials, which were also based largely on meeting criteria for IGT. Medication use at baseline among NAVIGATOR subjects, which frequently included aspirin, beta-blockers, calcium channel blockers, diuretics, and lipid-lowering agents, reflects enhanced CVD risk. However, little prescribing of renin-angiotensin-aldosterone system blockers was observed, likely due to protocol exclusion criteria. In conclusion, the NAVIGATOR study comprises prediabetic subjects who typically have concurrent BP and metabolic disturbances and an enhanced risk of CVD, and are thus at higher risk for cardiovascular events than subjects in previous DM prevention trials.
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Moxonidine improves glycaemic control in mildly hypertensive, overweight patients: a comparison with metformin.
Chazova, I, Almazov, VA, Shlyakhto, E
Diabetes, obesity & metabolism. 2006;(4):456-65
Abstract
AIM: To compare the effects of moxonidine and metformin on glycaemic control in patients with impaired glucose tolerance and signs of the metabolic syndrome. METHODS A multicentre, prospective, randomized, open-label study design was adopted with blinded endpoint evaluation. Patients > or =40 years old, with impaired glucose tolerance (or diabetes mellitus treated with diet alone) and a body mass index (BMI) of at least 27 kg/m2 were treated twice daily with moxonidine 0.2 mg or metformin 500 mg for 16 weeks. Oral glucose tolerance test (OGTT) was performed at baseline and end-of-study; plasma insulin and plasma glucose levels were measured at 0, 60, 120 and 180 min after administration. RESULTS With regard to effects on insulin [mean area under the curve (AUC) for insulin], the primary efficacy endpoint of the study, both drugs did not show equivalence. On the contrary, in the per protocol (PP) population, moxonidine statistically significantly (p = 0.025) decreased the AUC for insulin from baseline in the PP population; for metformin, the treatment effect on insulin was a small, net increase resulting in a statistically significant between-group difference of 16.2% (95% CI = 0.1-35.0). The change in mean insulin AUC was most marked in the subgroup of patients with higher sympathetic activity (heart rate >80 bpm). Mean fasting plasma glucose (FPG) levels and HbA1c levels were largely unchanged by moxonidine treatment but significantly decreased by metformin treatment. The difference between the groups was 14.7% (p = 0.0523) in the intent-to-treat (ITT) sample. By study end, both treatments had significantly increased the Matsuda Insulin Sensitivity Index (ISI) from baseline to a comparable extent: moxonidine by reducing plasma insulin after a glucose challenge, metformin by reducing FPG. BMI fell significantly in both groups and blood pressure normalized; both drugs were well tolerated. CONCLUSIONS Moxonidine improved insulin sensitivity in response to glucose challenge in patients with evidence of metabolic syndrome. This improvement resulted from a reduction in plasma insulin levels and was most marked in patients with high sympathetic drive at baseline. By enhancing insulin sensitivity, moxonidine treatment may help prevent the development of diabetes and thereby ameliorate the risk for cardiovascular disease.
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Differential effect of glimepiride and rosiglitazone on metabolic control of type 2 diabetic patients treated with metformin: a randomized, double-blind, clinical trial.
Derosa, G, Gaddi, AV, Piccinni, MN, Salvadeo, S, Ciccarelli, L, Fogari, E, Ghelfi, M, Ferrari, I, Cicero, AF
Diabetes, obesity & metabolism. 2006;(2):197-205
Abstract
AIM: Accumulating evidence suggests that combination therapy using oral antidiabetic agents with different mechanisms of action may be highly effective in achieving and maintaining target blood glucose levels. The aim of our study is to evaluate the differential effect on glucose and lipid parameters of the association between glimepiride plus metformin and rosiglitazone plus metformin in patients affected by type 2 diabetes and metabolic syndrome. METHODS Patients were enroled, evaluated and followed at two Italian centres. We evaluated 99 type 2 diabetic patients with metabolic syndrome (48 males and 47 females; 23 males and 24 females, aged 52 +/- 5 with glimepiride; 25 males and 23 females, aged 54 +/- 4 with cglitazone). All were required to have been diagnosed as being diabetic for at least 6 months and did not have glycaemic control with diet and oral hypoglycaemic agents such as sulphonylureas or metformin, both to the maximum tolerated dose. All patients took a fixed dose of metformin, 1500 mg/day. We administered glimepiride (2 mg/day) or rosiglitazone (4 mg/day) in a randomized, controlled, double-blind clinical study. We evaluated body mass index (BMI), glycaemic control, lipid profile [total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol and triglycerides] and lipoprotein parameters [apolipoprotein A-I and apolipoprotein B (Apo B)] during 12 months of this treatment. RESULTS A total of 95 patients completed the study. Significant BMI decrease was observed at 12 months in glimepiride and rosiglitazone group (p < 0.05 and p < 0.01 respectively) as well as of glycated haemoglobin decrease (p < 0.05 and p < 0.01 respectively), mean fasting plasma glucose and postprandial plasma glucose levels (p < 0.05 and p < 0.01 respectively). A decrease in fasting plasma insulin and postprandial plasma insulin at 12 months (p < 0.05 and p < 0.01 respectively) compared with the baseline value in rosiglitazone group was observed. Furthermore, homeostasis model assessment index improvement was obtained only at 9 and 12 months (p < 0.05 and p < 0.01 respectively) compared with the baseline value in rosiglitazone group. Significant TC, LDL-C and Apo B improvement (p < 0.05 respectively) was present in glimepiride group after 12 months compared with the baseline values, and these variations were significant (p < 0.05) between groups. Of the 95 patients who completed the study, 8.5% of patients in glimepiride group and 12.5% of patients in rosiglitazone group had side-effects (p = not significant). Four patients had transient side-effects in glimepiride group and six patients in rosiglitazone group. Altogether, we did not have statistically significant changes in transaminases. CONCLUSIONS The rosiglitazone-metformin association significantly improve the long-term control of all insulin-resistance-related parameters in comparison with the glimepiride-metformin-treated group. On the other side, glimepiride treatment is associated to a slight improvement in cholesterolaemia, not observed in the rosiglitazone-treated patients.
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A randomized controlled trial of metformin versus vitamin E or prescriptive diet in nonalcoholic fatty liver disease.
Bugianesi, E, Gentilcore, E, Manini, R, Natale, S, Vanni, E, Villanova, N, David, E, Rizzetto, M, Marchesini, G
The American journal of gastroenterology. 2005;(5):1082-90
Abstract
OBJECTIVES Metformin proved useful in the treatment of nonalcoholic fatty liver disease (NAFLD), but its superiority over nutritional treatment and antioxidants has never been demonstrated. We aimed to compare the usefulness of metformin versus prescriptive diet or vitamin E. METHODS In an open label, randomized trial, nondiabetic NAFLD patients were given metformin (2 g/day; n = 55) for 12 months. The control cases were given either vitamin E (800 IU/day; n = 28) or were treated by a prescriptive, weight-reducing diet (n = 27). Outcome measures were liver enzymes, insulin resistance (homeostasis model assessment), parameters of the metabolic syndrome, and histology. RESULTS Aminotransferase levels improved in all groups, in association with weight loss. The effects in the metformin arm were larger (p < 0.0001), and alanine aminotransferase normalized in 56% of cases (odds ratio (OR) versus. controls, 3.11; 95% confidence interval (CI), 1.56-6.20; p= 0.0013). In multivariate analysis, metformin treatment was associated with higher rates of aminotransferase normalization, after correction for age, gender, basal aminotransferases, and change in body mass index (OR, 5.98; 95% CI, 2.05-17.45). Differences were maintained when the two control groups were separately analyzed. The distribution of positive criteria for the metabolic syndrome was reduced only in the metformin arm (p= 0.001, signed rank test). A control biopsy in 17 metformin-treated cases (14 nonresponders) showed a significant decrease in liver fat (p= 0.0004), necroinflammation, and fibrosis (p= 0.012 for both). No side effects were observed during metformin treatment. CONCLUSIONS Metformin treatment is better than a prescriptive diet or vitamin E in the therapy of NAFLD patients receiving nutritional counseling. Limited histological data support an association between improved aminotransferases and biopsy findings, which require confirmation in a double-blind trial with appropriate statistical power based on liver histology.