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Comparison of metformin and N-acetyl cysteine, as an adjuvant to clomiphene citrate, in clomiphene-resistant women with polycystic ovary syndrome.
Nemati, M, Nemati, S, Taheri, AM, Heidari, B
Journal of gynecology obstetrics and human reproduction. 2017;(7):579-585
Abstract
OBJECTIVE To evaluate the effects of short- and long-term treatment with metformin and NAC, in an adjuvant to clomiphene citrate (CC), on the improvement of hormonal profile (SHBG, total testosterone, FBS, and fasting insulin) and fertility status in CC-resistant women with PCOS. MATERIALS AND METHODS One hundred and eight CC-resistant PCOS patients participated in the study and received either metformin (1500mg/day) or NAC (1800mg/day) with 100mg/day of CC for 8 and 12 weeks. Mean BMI, hirsutism score, LH/FSH ratio, endometrial thickness, mature follicle number, and serum concentrations of LH, FSH, E2, fasting insulin, total testosterone and FBS were evaluated before and after short- and long-term treatment. Furthermore, ovulation and pregnancy rates in the first and second cycles were also determined in treated patients. RESULTS There was no significant difference in all variables before and 8 weeks after treatment with metformin and NAC. The BMI- and insulin-lowering effects of metformin were significantly higher than NAC after long-term treatment. However, the reducing-effect of NAC on hirsutism score and FBS levels was significantly more than metformin after 12 weeks. Treatment with metformin and NAC significantly increased ovulation and pregnancy rates in CC-resistant PCOS patients. In the first and second cycles, ovulation and pregnancy rates in patients treated with NAC were slightly higher than those received metformin. CONCLUSIONS Compared with metformin, administration of NAC in an adjuvant to CC is recommended for improving of hormonal profile and treatment of anovulatory infertility in hyperinsulinemic patients especially women with PCOS who are CC-resistant.
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Presurgical trial of metformin in overweight and obese patients with newly diagnosed breast cancer.
Kalinsky, K, Crew, KD, Refice, S, Xiao, T, Wang, A, Feldman, SM, Taback, B, Ahmad, A, Cremers, S, Hibshoosh, H, et al
Cancer investigation. 2014;(4):150-7
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INTRODUCTION We conducted a presurgical trial to assess the tissue-related effects of metformin in overweight/obese breast cancer (BC) patients. METHODS Metformin 1,500 mg daily was administered to 35 nondiabetics with stage 0-III BC, body mass index (BMI) ≥ 25 kg/m(2). The primary endpoint was tumor proliferation change (i.e., ki-67). Tumor proliferation change was compared to untreated historical controls, matched by age, BMI, and stage. RESULTS There was no reduction in ln(ki-67) after metformin (p = .98) or compared to controls (p = .47). There was a significant reduction in BMI, cholesterol, and leptin. CONCLUSION Despite no proliferation changes, we observed reductions in other relevant biomarkers.
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Enhancing treatment of obesity by using a distracting mini-meal: a new approach to an old problem.
Picarelli, A, Di Tola, M, Tabacco, F, Marino, M, Borghini, R, D'Amico, T, Lubrano, C, Gargiulo, P
Hormones (Athens, Greece). 2013;(1):101-10
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OBJECTIVE The management of obesity, apart from exercise, mainly involves a calorie restriction regimen. A pharmaceutical treatment is often used to improve patient compliance and diet effectiveness, although several side-effects have previously been described. To improve patient compliance and diet effectiveness without incurring unpleasant side-effects, we evaluated whether a distracting mini-meal can physiologically decrease the absorption of fats and carbohydrates. DESIGN Two minutes before each of the three meals consumed daily, 32 obese patients were treated with a distracting mini-meal, 32 with metformin, and 32 with placebo. At baseline and after 1, 3, and 6 months of treatment, body weight, body mass index, waist circumference, fasting/post-prandial insulinaemia and glycaemia, homeostasis model assessment-index, triacylglycerols, and total cholesterol were evaluated. RESULTS All patients showed good compliance. With the exception of post-prandial glycaemia, a significant reduction in all parameters was documented in every group, albeit the greater variation was observed in patients treated with a distracting mini-meal or metformin. No one showed noteworthy side-effects. CONCLUSIONS Our study focuses on a distracting mini-meal that could become a useful tool in enhancing weight loss. The beneficial effect of a distracting meal on insulin resistance, glucose, and lipid metabolism suggest its possible use to prevent or mitigate obesity-related disorders.
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Independent and combined effects of exercise training and metformin on insulin sensitivity in individuals with prediabetes.
Malin, SK, Gerber, R, Chipkin, SR, Braun, B
Diabetes care. 2012;(1):131-6
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OBJECTIVE Physical activity or metformin enhances insulin sensitivity and opposes the progression from prediabetes to type 2 diabetes. The combination may be more effective because each treatment stimulates AMP-activated protein kinase activity in skeletal muscle. We evaluated the effects of exercise training plus metformin on insulin sensitivity in men and women with prediabetes, compared with each treatment alone. RESEARCH DESIGN AND METHODS For 12 weeks, men and women with prediabetes were assigned to the following groups: placebo (P), 2,000 mg/day metformin (M), exercise training with placebo (EP), or exercise training with metformin (EM) (n = 8 per group). Before and after the intervention, insulin sensitivity was measured by euglycemic hyperinsulinemic (80 mU/m(2)/min) clamp enriched with [6,6-(2)H]glucose. Changes due to intervention were compared across groups by repeated-measures ANOVA. RESULTS All three interventions increased insulin sensitivity (P < 0.05) relative to the control group. The mean rise was 25-30% higher after EP than after either EM or M, but this difference was not significant. CONCLUSIONS Insulin sensitivity was considerably higher after 12 weeks of exercise training and/or metformin in men and women with prediabetes. Subtle differences among condition means suggest that adding metformin blunted the full effect of exercise training.
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Metformin induces reductions in plasma cobalamin and haptocorrin bound cobalamin levels in elderly diabetic patients.
Leung, S, Mattman, A, Snyder, F, Kassam, R, Meneilly, G, Nexo, E
Clinical biochemistry. 2010;(9):759-60
Abstract
OBJECTIVE To study the effect of short term metformin therapy on plasma levels of cobalamin, cobalamin related metabolites and cobalamin binding proteins in elderly patients. DESIGN AND METHODS Twenty patients with type 2 diabetes were assigned to receive metformin or not for 3 months. Cobalamin and its metabolites were measured before and after metformin therapy. RESULTS As compared to baseline measures, there was a metformin therapy specific significant decrease in plasma levels of total cobalamin, total haptocorrin and haptocorrin bound cobalamin. CONCLUSIONS Plasma total cobalamin and haptocorrin bound cobalamin levels are reduced by short term metformin therapy in an elderly diabetic population. Larger scale, longer term studies are necessary to determine if there is an unequivocal decrease in functional measures of cobalamin status.
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The role of family history in clinical symptoms and therapeutic outcomes of women with polycystic ovary syndrome.
Hu, Z, Wang, Y, Qiao, J, Li, M, Chi, H, Chen, X
International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. 2010;(1):35-9
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OBJECTIVE To investigate the association between family history and clinical symptoms of polycystic ovary syndrome (PCOS) that were thought to be inherited, by treating women with PCOS with contraceptive pills and metformin, and assessing outcomes. METHODS Of 164 women with PCOS, 49 with menstrual abnormalities, hyperandrogenism, and abnormal glucose and/or insulin levels underwent a 3-month treatment with contraceptive pills and metformin. Family history was taken, and physical and ultrasound examinations were performed. Serum levels of glucose, insulin, lipoproteins, lipids, and reproductive hormones were measured before and after treatment. RESULTS The serum levels of low-density lipoprotein, total cholesterol, apolipoprotein B, and triglycerides were higher in the patients with a family history of the studied symptoms than in those with no such family history. After treatment, changes in testosterone and glucose levels, glucose area under curve, and homeostasis model assessment value differed in the 2 groups. CONCLUSION The patients with a family history of PCOS symptoms thought to be inherited were more sensitive to oral contraceptive and metformin treatment.
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Metformin maintains the weight loss and metabolic benefits following rimonabant treatment in obese women with polycystic ovary syndrome (PCOS).
Sathyapalan, T, Cho, LW, Kilpatrick, ES, Coady, AM, Atkin, SL
Clinical endocrinology. 2009;(1):124-8
Abstract
OBJECTIVE Rimonabant has been shown to reduce weight, free androgen index (FAI) and insulin resistance in obese patients with polycystic ovary syndrome (PCOS) compared to metformin. Studies have shown that significant weight regain occurs following the cessation of rimonabant therapy. This study was undertaken to determine if subsequent metformin treatment after rimonabant would maintain the improvement in weight, insulin resistance and hyperandrogenaemia in PCOS. DESIGN An extension study for 3 months with the addition of metformin to the randomised open labelled parallel study of metformin and rimonabant in 20 patients with PCOS with a body mass index >or= 30 kg/m(2). Patients who were on 3 months of rimonabant were changed over to metformin for 3 months, whereas those on 3 months of metformin were continued on metformin for another 3 months. MEASUREMENTS The primary end-point was a change in weight; secondary end-points were a change in FAI and insulin resistance. RESULTS The mean weight loss of 6.2 kg associated with 3 months of rimonabant treatment was maintained by 3 months of metformin treatment (mean change +0.2 kg, P = 0.96). Therefore, the percentage reduction in weight remained significantly higher in the rimonabant/metformin group compared to metformin only subjects at 6 months compared to baseline (-6.0 +/- 0.1%vs. -2.8 +/- 0.1%, P = 0.04). The percentage change in testosterone and FAI from baseline to 6 months was also greater in the rimonabant/metformin group. [Testosterone (-45.0 +/- 5.0%vs. -16 +/- 2.0%, P = 0.02); FAI (-53.0 +/- 5.0%vs. -17.0 +/- 12.2%, P = 0.02)]. HOMA-IR continued to fall significantly in the rimonabant/metformin group between 0, 3 and 6 months (4.4 +/- 0.5 vs. 3.4 +/- 0.4 vs. 2.7 +/- 0.3, respectively, P < 0.01) but not at all in the metformin only group (3.4 +/- 0.7 vs. 3.4 +/- 0.8 vs. 3.7 +/- 0.8, respectively, P = 0.80). Total cholesterol and LDL reduced significantly in both groups, but improvements in triglycerides and HDL were limited to the rimonabant/metformin group. CONCLUSIONS In these obese patients with PCOS, metformin maintained the weight loss and enhanced the metabolic and biochemical parameters achieved by treatment with rimonabant, compared to 6 months of metformin treatment alone.
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[Primary preventive effect of metformin upon atherosclerosis in patients with type 2 diabetes mellitus].
Zhang, XY, Du, JL, Jia, YJ, Bai, R, Yang, Y, Ba, Y, Xing, Q, Men, LL
Zhonghua yi xue za zhi. 2009;(30):2134-7
Abstract
OBJECTIVE To investigate the preventive action of metformin for atherosclerosis (AS) in patients with type 2 diabetes mellitus (T2DM). METHODS A total of 140 cases with T2DM were assigned to 2 groups taking metformin (n = 75) or not (n = 65). All cases received intensive control of blood glucose, blood pressure and blood lipids for 100 weeks. The data before and after intensive control were recorded and statistically analyzed. Common carotid intima-media thickness (CC-IMT) was the efficacy endpoint of AS. RESULTS Diastolic blood pressure (DBP), fasting blood glucose, post 2-hour blood glucose, glycated hemoglobin A1c, triglyceride (TG) and total cholesterol (TC) decreased in both groups after intensive metabolic control for 100 weeks (P < 0.05). Body mass index (BMI), HOMA insulin resistance index (HOMA-IR) and CC-IMT decreased in metformin group (P < 0.05) while high-density lipoprotein cholesterol (HDL-C) increased (P < 0.05). BMI (23.1 +/- 0.98) kg/m2, HOMA-IR (1.68 +/- 0.20) and CC-IMT (0.55 +/- 0.13) mm in metformin group were lower than those in non-metformin group [(24.1 +/- 0.05) kg/m2, 2.03 +/- 1.38, (0.70 +/- 0.15) mm)] at 100 week (P < 0.05). CC-IMT was positively correlated with BMI (r = 0.489, P < 0.05) , TC (r = 0.429, P < 0.05), low-density lipoprotein cholesterol (LDL-C) (r = 0.426, P < 0.05) and HOMA-IR (r = 0.428, P < 0.05). CONCLUSION Metformin attenuates CC-IMT of patients with T2DM and it has the primary preventive effect upon AS in patients with T2DM.
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Metformin, arterial function, intima-media thickness and nitroxidation in metabolic syndrome: the mefisto study.
Meaney, E, Vela, A, Samaniego, V, Meaney, A, Asbún, J, Zempoalteca, JC, Elisa, ZN, Emma, MN, Guzman, M, Hicks, J, et al
Clinical and experimental pharmacology & physiology. 2008;(8):895-903
Abstract
1. Metabolic syndrome (MS) is one of the greatest public health problems in Mexico, where more than 75% of adults in urban populations are overweight or obese. Metabolic syndrome has several comorbidities, which result in a high cardiometabolic risk. 2. Some of the vasopathogenic phenomena in MS are caused by nitroxidant stress, secondary to cardiometabolic dysfunction. 3. The action of metformin to diminish or control MS remains a matter of debate. 4. In the present study, 60 patients with at least three diagnostic criteria for MS were divided into two groups. Both groups received similar dietary counselling, but one group was given 850 mg metformin daily. 5. The variables assessed were body mass index, waist circumference, systolic and diastolic blood pressures (SBP and DBP, respectively), total cholesterol (TC), high- and low-density lipoprotein-cholesterol, triglycerides (TG), fasting glucose, nitroxidant metabolites (free carbonyls, malondialdehyde, dityrosines and advanced oxidative protein products (AOPP)), nitric oxide (NO), carotid vascular stiffness, carotid intima-media thickness (IMT) and C-reactive protein (CRP). 6. After 1 year follow up, both groups reported weight loss, as well as decreases in waist circumference, SBP and DBP. 7. Patients on metformin exhibited reductions in TC and IMT and there were marked changes in nitroxidation: levels of carbonyls, dityrosines and AOPP were reduced, whereas those of NO were increased, indicating better endothelial function. In addition, in patients given metformin, CRP levels decreased. 8. In conclusion, metformin has a considerable beneficial effect on nitroxidation, endothelial function and IMT in patients with MS.
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Metformin is effective in achieving biochemical response in patients with nonalcoholic fatty liver disease (NAFLD) not responding to lifestyle interventions.
Duseja, A, Das, A, Dhiman, RK, Chawla, YK, Thumburu, KT, Bhadada, S, Bhansali, A
Annals of hepatology. 2007;(4):222-6
Abstract
BACKGROUND Insulin resistance plays an important role in the pathogenesis of NAFLD. Pharmacological treatment of patients with NAFLD is still evolving. Insulin sensitizing drugs like metformin may be effective in these patients. Twenty five adult patients with NAFLD who did not achieve normalization of alanine transaminases (ALT) after 6 months of lifestyle interventions and UDCA were treated with metformin 500mg tid for 6 months. Insulin resistance was determined by HOMA- IR. Liver function tests were done monthly and patients were defined having no response, partial response or complete biochemical response depending on the change in ALT. Results were compared with 25 patients with NAFLD from the same cohort treated only with lifestyle interventions (disease controls). RESULTS Thirteen (52%) patients had class III (n = 5) or class IV (n = 8) disease amounting to histological NASH. Of these 13 patients none had severe inflammation and none had stage 4 fibrosis (cirrhosis). All 25 patients with NAFLD had insulin resistance in comparison to healthy controls. In comparison to disease controls (127.5 +/- 41.8 vs. 118 +/- 21.6 p = NS), all patients treated with metformin had partial biochemical response (mean ALT 122.2 +/- 26.8 vs 74.3 +/- 4.2 p < 0.01) and 14 (56%) of them achieved complete normalization of ALT. CONCLUSIONS Metformin is effective to achieve biochemical response in patients with NAFLD who do not respond to lifestyle interventions and UDCA.