Importance: Metformin hydrochloride use is increasing in children and adolescents. Previous meta-analyses have identified a large variability in the effects of metformin use on body mass index changes but have not considered height changes as a confounder, to our knowledge.
Objective: To conduct a systematic review and meta-analysis of the effects of metformin use on height in children and adolescents.
Data sources: Computerized databases, including MEDLINE and EMBASE, were searched up to September 9, 2014, for terms related to metformin and childhood or adolescence.
Study selection: Randomized clinical trials examining the effects of metformin use on height of participants younger than 19 years were considered eligible. Trials with cointerventions other than lifestyle changes were excluded.
Data extraction and synthesis: Height, weight, body mass index, age, sex, metformin dosage, and study duration were independently extracted by 2 reviewers. The weighted mean differences for changes in height, weight, and body mass index were compared between the metformin and control groups using random-effects models.
Main outcome and measure: Height changes.
Results: Ten studies were included, with a total of 562 participants, 330 (58.7%) of whom were female. The mean age within the studies ranged from 7.9 to 16.1 years, with a high variability in most studies. The duration of metformin interventions lasted from 3 to 48 months. Overall, height changes were not significantly different between the metformin and control groups. However, stratified analyses according to the cumulative metformin dose (in milligrams per day times the number of days of treatment) showed a greater increase in height with metformin use in the 5 studies providing the largest cumulative metformin doses (weighted mean difference, 1.0; 95% CI, 0.0 to 2.0 cm) but not in the 5 studies providing the lowest doses (weighted mean difference, -0.1; 95% CI, -0.7 to 1.0 cm) compared with the control group.
Conclusions and relevance: Preliminary evidence suggests a dose-response relationship between metformin use and increases in height in children and adolescents compared with a control group. While an approximate 1-cm increase in height may appear small, it is likely underestimated given that many studies were of short duration and included older adolescents, potentially after epiphyseal growth plate closure.