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Background: Obesity and its related complications are increasing health issues. Since generally only minor weight loss is obtained with lifestyle intervention, additional pharmacological therapies such as metformin are often used., Objective: We conducted a systematic review to provide an overview of the efficacy of ≥ 6 months of metformin treatment in children and adults with respect to weight, insulin resistance, and progression toward type 2 diabetes mellitus (T2DM)., Methods: In September 2018, we searched PubMed, Embase, and the Cochrane Library for studies published in English using the keywords metformin, obesity/overweight, and weight loss. Prospective studies reporting weight/body mass index (BMI) as a primary or secondary outcome in patients with overweight/obesity with ≥ 6 months' metformin treatment were included. Included subjects were children and adults with overweight/obesity who received ≥ 6 months of metformin and/or lifestyle intervention, and/or placebo and/or lifestyle intervention, and/or standard care. Studies were independently screened by two reviewers. Data were extracted by one and verified by the other reviewer, and both reviewers assessed the risk of bias using the Cochrane risk-of-bias tool., Results: Our review includes 15 pediatric and 14 adult studies. In children, after 6 months, more than half the studies reported a greater reduction in BMI with metformin versus controls. Only six studies had an intervention of > 6 months, and these studies found no further improvement in BMI in the metformin users, though their BMI was lower than that of controls. Three studies showed a significant improvement in insulin sensitivity in the metformin versus the control group. Adults using metformin experienced and maintained small decreases in weight irrespective of duration of intervention. In 11 of 14 studies, a greater reduction in weight/BMI was observed with metformin than with placebo. Progression toward T2DM was significantly reduced in adults using metformin, ranging from 7 to 31%. The safety and tolerability of metformin, withdrawal of participants, and comparison with other drugs were not taken into account., Conclusions: The effects of metformin on weight/BMI vary, with smaller reductions in children than in adults. This could be because of differences in adherence, daily dosage, and insulin status. Metformin significantly reduced the progression toward T2DM in adults. Therefore, metformin should be considered as a treatment for obesity and its related complications.

Background: As adolescents with obesity and insulin resistance may be refractory to lifestyle intervention therapy alone, additional off-label metformin therapy is often used. In this study, the long-term efficacy and safety of metformin versus placebo in adolescents with obesity and insulin resistance is studied., Methods: In a randomized placebo-controlled double-blinded trial, 62 adolescents with obesity aged 10-16 years old with insulin resistance received 2000 mg of metformin or placebo daily and physical training twice weekly over 18 months. Primary end points were change in body mass index (BMI) and insulin resistance measured by the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR). Secondary end points were safety and tolerability of metformin. Other end points were body fat percentage and HbA1c., Results: Forty-two participants completed the 18-month study (66% girls, median age 13 (12-15) years, BMI 30.0 (28.3 to 35.0) kg m(-2) and HOMA-IR 4.08 (2.40 to 5.88)). Median ΔBMI was +0.2 (-2.9 to 1.3) kg m(-2) (metformin) versus +1.2 (-0.3 to 2.4) kg m(-2) (placebo) (P=0.015). No significant difference was observed for HOMA-IR. No serious adverse events were reported. Median change in fat percentage was -3.1 (-4.8 to 0.3) versus -0.8 (-3.2 to 1.6)% (P=0.150), in fat mass -0.2 (-5.2 to 2.1) versus +2.0 (1.2-6.4) kg (P=0.007), in fat-free mass +2.0 (-0.1 to 4.0) versus +4.5 (1.3 to 11.6) kg (P=0.047) and in ΔHbA1c +1.0 (-1.0 to 2.3) versus +3.0 (0.0 to 5.0) mmol mol(-1) (P=0.020) (metformin versus placebo)., Conclusions: Long-term treatment with metformin in adolescents with obesity and insulin resistance results in stabilization of BMI and improved body composition compared with placebo. Therefore, metformin may be useful as an additional therapy in combination with lifestyle intervention in adolescents with obesity and insulin resistance.

Background: In view of the alarming incidence of obesity in children, insight into the epidemiology of the prediabetic state insulin resistance (IR) seems important. Therefore, the aim of this systematic review was to give an overview of all population-based studies reporting on the prevalence and incidence rates of IR in childhood., Methods: PubMed, Embase, and Cochrane library were searched in order to find all available population-based studies describing the epidemiology of IR in pediatric populations. Prevalence rates together with methods and cut-off values used to determine IR were extracted and summarized with weight and sex specific prevalence rates of IR if available., Results: Eighteen population-based studies were identified, describing prevalence rates varying between 3.1 and 44%, partly explained by different definitions for IR. Overweight and obese children had higher prevalence rates than normal weight children. In seven out of thirteen studies reporting sex specific results, girls seemed to be more affected than boys., Conclusion: Prevalence rates of IR reported in children vary widely which is partly due to the variety of definitions used. Overweight and obese children had higher prevalence and girls were more insulin resistant than boys. Consensus on the definition for IR in children is needed to allow for comparisons between different studies.