Metformin had "modest" beneficial effects on weight and insulin resistance among obese young children in a systematic review. "Given the results of our study, metformin may be considered as an add-on therapy in children and adolescents with obesity in whom lifestyle interventions were not sufficient, and who have additional risk factors such as prediabetes, and type-2 diabetes," Dr. Reem Masarwa of McGill University in Montreal told Reuters Health by email. "Within our study scope we were unable to fully examine the efficacy of different dosage regimes," she noted. "If the primary indication for metformin is diabetes, and the patients' glycemic measures are within the desired range, then the dose should not be changed." Further, she said, "Metformin should be avoided in patients with severe renal dysfunction and acute or chronic metabolic acidosis." As reported in Pediatrics, Dr. Masarwa and colleagues searched the literature through November 2019 and selected randomized controlled trials in which researchers compared the efficacy and safety of metformin with lifestyle interventions versus placebo and lifestyle interventions, in children and adolescents with obesity. Twenty-four RCTs with a total of 1,623 patients were included. Ages ranged from four to 19, and follow-up, from two months to two years. Metformin resulted in a modest decrease in BMI (mean values range: 22.70 to 1.30 vs. 21.12 to 1.90 for placebo), BMI z score (20.37 to 20.03 vs. 20.22 to 0.15), and homeostatic model assessment of insulin resistance (23.74 to 1.00 vs. 21.40 to 2.66). The drug also resulted in a higher frequency of gastrointestinal adverse effects (2% to 74% vs. 0% to 42%). However, 14 of the 24 studies were of low-to-moderate quality, and heterogeneity was substantial. Loss to follow-up ranged from 5% to 80% across studies in the metformin arm, and adherence rates for metformin ranged from 60% to 90%. Dr. Masarwa said, "As treatment options for obesity and its complications are more readily available in adults, newer treatment options and interventions should be explored in children and adolescents. There is a pressing need for randomized controlled trials and real-world studies to further assess the benefits of metformin therapy alone and in combination with other drug treatments and interventions for obesity." Dr. Rachana Shah, Medical Director of the Adolescent PCOS Center and the Healthy Weight Program at Children's Hospital of Philadelphia told Reuters Health by email, "While the study did show what they call 'modest' weight loss, the actual decrease in weight is an average of less than five pounds, which is unlikely to make an appreciable difference in the child's health or future risk of obesity-related complications." "The study also doesn't address whether the weight loss is sustained—-if any weight loss is regained upon stopping the medication, this would mean long-term daily medication for children, for many years," she said. "The study also confirms what I see in clinical practice—-there is a high rate of gastrointestinal side effects," she noted. "While these effects may be mild in most children, some are severe enough to cause significant impact on quality of life - i.e., daily nausea, pain, or diarrhea." "I do not use metformin as a 'weight loss' agent, because at best, the weight loss is minimal and may require continued medication usage, too," she said. "I would urge caution in presenting metformin as a weight-loss drug, and have patients meet with a pediatric obesity specialist to discuss treatment options." —Marilynn Larkin Source
