ArticleJNCI cancer spectrum2020
Randomized Phase II Trial of Exercise, Metformin, or Both on Metabolic Biomarkers in Colorectal and Breast Cancer Survivors.
Article in JNCI cancer spectrum, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The effect of metformin on esophageal cancer risk in patients with type 2 diabetes mellitus: a systematic review and meta‑analysis.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021 · on this mapPooled it
- Effects of exercise or metformin on myokine concentrations in patients with breast and colorectal cancer: A phase II multi-centre factorial randomized trial.Journal of cachexia, sarcopenia and muscle · 2024Trial
- Effect of Exercise or Metformin on Biomarkers of Inflammation in Breast and Colorectal Cancer: A Randomized Trial.Cancer prevention research (Philadelphia, Pa.) · 2020Trial
- Exercise therapy in cancer prevention and treatment.Nature reviews. Clinical oncology · 2026Review
- Metabolic adaptations of the tumor macroenvironment and their role in cancer progression and survivorship.Genes & development · 2026Review
- Rewiring cancer metabolism: oncogenic signaling pathways and targeted therapeutics.Science China. Life sciences · 2025Review
- Translating Metabolic Interventions into Breast Cancer Therapy: A Comprehensive Review.Life (Basel, Switzerland) · 2025Review
- Metformin for the treatment of breast cancer: a scoping review of randomized clinical trials.BMC cancer · 2025Article
- Metformin and Breast Cancer: Current Findings and Future Perspectives from Preclinical and Clinical Studies.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Effect of metformin as an adjuvant therapy to letrozole on estradiol and other biomarkers involved in the pathogenesis of breast cancer in overweight and obese postmenopausal women: a pilot study.European journal of clinical pharmacology · 2023Article
- The impact of obesity and adipokines on breast and gynecologic malignancies.Annals of the New York Academy of Sciences · 2022Review
- Ameliorative effect of metformin on methotrexate-induced genotoxicity: AnBiomedical reports · 2021Article
- Is Metformin a Possible Beneficial Treatment for Psoriasis? A Scoping Review.Journal of personalized medicine · 2021Article
- Improvement Effect of Metformin on Female and Male Reproduction in Endocrine Pathologies and Its Mechanisms.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Metformin and Exercise in Cancer: Better Together.JNCI cancer spectrum · 2020Article
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19 authors.
Funding
Abstract
backgroundObservational data support inverse relationships between exercise or metformin use and disease outcomes in colorectal and breast cancer survivors, although the mechanisms underlying these associations are not well understood.
methodsIn a phase II trial, stage I-III colorectal and breast cancer survivors who completed standard therapy were randomly assigned to structured exercise or metformin or both or neither for 12 weeks. The primary outcome was change in fasting insulin levels; secondary outcomes included changes in other blood-based energetic biomarkers and anthropometric measurements. Analyses used linear mixed models.
resultsIn total, 139 patients were randomly assigned; 91 (65%) completed follow-up assessments. Fasting insulin levels statistically significantly decreased in all three intervention arms (-2.47 μU/mL combination arm, -0.08 μU/mL exercise only, -1.16 μU/mL metformin only, + 2.79 μU/mL control arm). Compared with the control arm, all groups experienced statistically significant weight loss between baseline and 12 weeks (-1.8% combination arm, -0.22% exercise only, -1.0% metformin only, +1.55% control). The combination arm also experienced statistically significant improvements in the homeostatic model assessment for insulin resistance (-30.6% combination arm, +61.2% control) and leptin (-42.2% combination arm, -0.8% control), compared with the control arm. The interventions did not change insulin-like growth factor-1 or insulin-like growth factor binding protein-3 measurements as compared with the control arm. Tolerance to metformin limited compliance (approximately 50% of the participants took at least 75% of the planned dosages in both treatment arms).
conclusionsThe combination of exercise and metformin statistically significantly improved insulin and associated metabolic markers, as compared to the control arm, with potential greater effect than either exercise or metformin alone though power limited formal synergy testing. Larger efforts are warranted to determine if such a combined modality intervention can improve outcomes in colorectal and breast cancer survivors.
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