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Randomized Controlled Trial
. 2016 Aug 29;6(8):e228.
doi: 10.1038/nutd.2016.37.

Long-term treatment with metformin in obese, insulin-resistant adolescents: results of a randomized double-blinded placebo-controlled trial

M P van der Aa  1 , M A J Elst  1 , E M W van de Garde  2 , E G A H van Mil  3 , C A J Knibbe  2 , M M J van der Vorst  1
Affiliations
Randomized Controlled Trial

Long-term treatment with metformin in obese, insulin-resistant adolescents: results of a randomized double-blinded placebo-controlled trial

M P van der Aa et al. Nutr Diabetes. .

Abstract

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.

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Figures

Figure 1
Figure 1
Consort flow diagram.
Figure 2
Figure 2
Effect of metformin on primary end points BMI and HOMA-IR after 18 months. (a) Change in BMI and HOMA-IR between t=0 and 18 months; (b) median ΔBMI and ΔHOMA-IR over time; (c) median BMI and HOMA-IR over time.
Figure 3
Figure 3
Effect of metformin on HbA1c and body composition after 18 months. Boxplots represent the Δ values between t=0 and 18 months. Graphs represent median values.
See this image and copyright information in PMC

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