Efficacy and safety of metformin for treatment of overweight and obesity in adolescents: an updated systematic review and meta-analysis.

OBJECTIVE: To assess the efficacy and safety of using metformin in overweight and obese adolescents without related morbidity. METHODS: We conducted a systematic review and meta-analysis of randomized clinical trials published until June 2011, comparing metformin to placebo or other interventions. Our primary variables were baseline BMI changes and development of adverse effects. RESULTS: Nine studies (498 participants, mean age 14.2 years; mean BMI 36.4 kg/m² met the inclusion criteria. In all but one study, metformin was combined with lifestyle modification and was compared to placebo combined with changes in lifestyle. Analysis showed that metformin reduced mean BMI by 1.42 kg/m² (95% CI -2.18, 0.66), fasting insulin by 9.9 µU/ml (95% CI -13.8, -6.06) and the HOMA index by -1.78 (95% CI -3.32, -0.23). No changes in any other parameter were observed. No statistical differences were found in the rate of adverse events (33% metformin, 32% placebo).The withdrawal rates due to side effects in the metformin and placebo groups were 2.7% and 2.5%, respectively. CONCLUSIONS: The available evidence indicates that, in the short term, administration of metformin in addition to lifestyle modification is relatively effective for reducing BMI and hyperinsulinemia among obese adolescents without related morbidity, and displays an acceptable safety pattern. Nevertheless, its long-term impact is unknown.

Outcomes of new quality standards of follitropin alfa on ovarian stimulation: meta-analysis of previous studies.

BACKGROUND: Human follicle-stimulating hormone (hFSH; follitropin alfa) can be employed therapeutically to induce ovarian follicular development in assisted reproduction treatments. Current recombinant hFSH (r-hFSH) preparations available for clinical use are labeled either in terms of the bioactivity expressed in international units (IU) or in mass (microg). Several clinical trials have tried to assess the clinical implications of the physicochemical improvements in the dosing of follitropin alfa filled by mass (FbM). The aim of this study was to perform a meta-analysis of previous studies in order to assess the efficacy and safety of ovarian stimulation using follitropin alfa FbM compared with follitropin alfa filled by international units (FbIU). METHODS: A literature search was carried out in scientific databases to find published articles and abstracts comparing both hormone preparations. A fixed effects model meta-analysis was performed. The variables studied include the average dose (IU), days of treatment, estradiol peak, follicles >14 mm, number of extracted oocytes, number of embryos obtained, number of cases of ovarian hyperstimulation syndrome (OHSS), and clinical pregnancies. RESULTS: A total of six studies met the stated criteria and were included in the meta-analysis. In these studies, the average r-hFSH dose per patient was 230.29 IU less with administration of follitropin alfa FbM compared with FbIU, and the number of days of treatment was reduced by 0.48. In addition, a significantly greater number of oocytes (0.84) were extracted, more embryos (0.88) were obtained, and a higher peak level of estradiol (613.08 pmol/L) was achieved in the patients undergoing ovarian stimulation with follitropin alfa FbM. However, no statistically significant differences were observed in the number of follicles >14 mm, clinical pregnancies, or OHSS cases. CONCLUSION: Follitropin alfa FbM, a technologically modified formulation of r-hFSH, is as safe as follitropin alfa FbIU but requires a smaller dose over a shorter period to produce more oocytes and final embryos.