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Cited by 181Diabetes Management and ResearchDiabetes Treatment and ManagementDiabetes and associated disorders

Effect of Metformin Added to Insulin on Glycemic Control Among Overweight/Obese Adolescents With Type 1 Diabetes: A Randomized Clinical Trial

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Libman, Ingrid M., Miller, Kellee M., DiMeglio, Linda A., Bethin, Kathleen E., Katz, Michelle L., Shah, Avni, Simmons, Jill H., Haller, Michael J. +7 more·2015·JAMA
DOI 10.1001/jama.2015.16174
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Abstract

IMPORTANCE: Previous studies assessing the effect of metformin on glycemic control in adolescents with type 1 diabetes have produced inconclusive results. OBJECTIVE: To assess the efficacy and safety of metformin as an adjunct to insulin in treating overweight adolescents with type 1 diabetes. DESIGN, SETTING, AND PARTICIPANTS: Multicenter (26 pediatric endocrinology clinics), double-blind, placebo-controlled randomized clinical trial involving 140 adolescents aged 12.1 to 19.6 years (mean [SD] 15.3 [1.7] years) with mean type 1 diabetes duration 7.0 (3.3) years, mean body mass index (BMI) 94th (4) percentile, mean total daily insulin 1.1 (0.2) U/kg, and mean HbA1c 8.8% (0.7%). INTERVENTIONS: Randomization to receive metformin (n = 71) (≤2000 mg/d) or placebo (n = 69). MAIN OUTCOMES AND MEASURES: Primary outcome was change in HbA1c from baseline to 26 weeks adjusted for baseline HbA1c. Secondary outcomes included change in blinded continuous glucose monitor indices, total daily insulin, BMI, waist circumference, body composition, blood pressure, and lipids. RESULTS: Between October 2013 and February 2014, 140 participants were enrolled. Baseline HbA1c was 8.8% in each group. At 13-week follow-up, reduction in HbA1c was greater with metformin (-0.2%) than placebo (0.1%; mean difference, -0.3% [95% CI, -0.6% to 0.0%]; P = .02). However, this differential effect was not sustained at 26-week follow up when mean change in HbA1c from baseline was 0.2% in each group (mean difference, 0% [95% CI, -0.3% to 0.3%]; P = .92). At 26-week follow-up, total daily insulin per kg of body weight was reduced by at least 25% from baseline among 23% (16) of participants in the metformin group vs 1% (1) of participants in the placebo group (mean difference, 21% [95% CI, 11% to 32%]; P = .003), and 24% (17) of participants in the metformin group and 7% (5) of participants in the placebo group had a reduction in BMI z score of 10% or greater from baseline to 26 weeks (mean difference, 17% [95% CI, 5% to 29%]; P = .01). Gastrointestinal adverse events were reported by more participants in the metformin group than in the placebo group (mean difference, 36% [95% CI, 19% to 51%]; P < .001). CONCLUSIONS AND RELEVANCE: Among overweight adolescents with type 1 diabetes, the addition of metformin to insulin did not improve glycemic control after 6 months. Of multiple secondary end points, findings favored metformin only for insulin dose and measures of adiposity; conversely, use of metformin resulted in an increased risk for gastrointestinal adverse events. These results do not support prescribing metformin to overweight adolescents with type 1 diabetes to improve glycemic control. TRIAL REGISTRATION: clinicaltrials.org Identifier: NCT01881828.

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  • Metformin is the most commonly prescribed drug for type 1 diabetes patients with insulin resistance.

    “Metformin, an insulin sensitiser, is the most commonly prescribed drug for people with type 1 diabetes who have insulin resistance”

    From Type 1 diabetes (2018) · cites this paper as [86]

    The Introduction (page not provided) describes metformin’s glucose-lowering mechanisms, and the Abstract describes a trial of metformin added to insulin in overweight adolescents with type 1 diabetes. But our copy says metformin is commonly used for type 2 diabetes; it does not establish that metformin is the most commonly prescribed drug for people with type 1 diabetes and insulin resistance. (LLM, conf=0.82)

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  • Metformin has not been shown effective in people younger than 18 years who are overweight or obese and have type 1 diabetes.

    “it has not been shown to be effective in people younger than 18 years who are overweight or obese and have type 1 diabetes.86”

    From Type 1 diabetes (2018) · cites this paper as [86]

    The Abstract reports that adding metformin to insulin did not improve glycemic control after six months in overweight adolescents with type 1 diabetes. But the unqualified claim that it has not been shown effective overlooks favorable results for insulin dose and measures of adiposity. The trial also included participants up to age 19.6, rather than exclusively people younger than 18. (LLM, conf=0.88)

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Authors
Libman, I. M., Miller, K. M., DiMeglio, L. A., Bethin, K. E., Katz, M. L., Shah, A., Simmons, J. H., Haller, M. J., Raman, S., Tamborlane, W. V., Coffey, J. K., Saenz, A. M., Beck, R. W., Nadeau, K. J., & for the T1D Exchange Clinic Network Metformin RCT Study Group
Affiliations
  • Children's Hospital of Pittsburgh (US)
  • Jaeb Center for Health Research (US)
  • Indiana University School of Medicine (US)
  • University at Buffalo, State University of New York (US)
  • Joslin Diabetes Center (US)
  • Stanford Medicine (US)
  • Vanderbilt University (US)
  • University of Florida (US)
  • Children's Mercy Hospital (US)
  • Yale University (US)
  • University of Iowa (US)
  • University of Colorado Anschutz (US)
Corresponding author
Miller, Kellee M.
ORCID
Venue
JAMA
Publisher
American Medical Association (AMA)
Published
2015-12-01
Volume
314
Issue
21
Pages
2241
ISSN
  • 0002-9955 (ISSN-L)
  • 0098-7484
DOI
10.1001/jama.2015.16174
OpenAlex
W2188909866
Cited by
181
References
21
Citations by year
2026: 10 · 2025: 13 · 2024: 11 · 2023: 8 · 2022: 14 · 2021: 17 · 2020: 17 · 2019: 21 · 2018: 26 · 2017: 31 · 2016: 12 · 2015: 1
FWCI
20.28
Type
journal article
Language
en
Open access
Locations
  • JAMA (publishedVersion)
  • PubMed (publishedVersion)
  • IUScholarWorks (Indiana University) (submittedVersion)
Funders
National Institute of Diabetes and Digestive and Kidney Diseases (K12DK094721)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
Keywords
metformin, type 1 diabetes, adolescents, obesity, overweight, glycemic control, HbA1c, insulin dose reduction, continuous glucose monitoring, body composition, lipid profile, blood pressure, drug safety, placebo effect, weight gain, glycemic variability
MeSH terms
Adolescent, Blood Glucose, Body Weight, Child, Diabetes Mellitus, Type 1, Double-Blind Method, Drug Therapy, Combination, Female, Gastrointestinal Diseases, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Insulin, Male, Metformin, Obesity, Body Mass Index, Treatment Outcome, Young Adult

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