Effect of Metformin vs Placebo on weight and metabolic factors in NCIC CTG MA.32

Pamela J. Goodwin, Wendy R. Parulekar, Karen A. Gelmon, Lois E. Shepherd, Jennifer A. Ligibel, Dawn L. Hershman, Priya Rastogi, Ingrid A. Mayer, Timothy James Hobday, Julie Lemieux, Alastair M. Thompson, Kathleen I. Pritchard, Timothy J. Whelan, Som D. Mukherjee, Haji I. Chalchal, Conrad D. Oja, Katia S. Tonkin, Vanessa Bernstein, Bingshu E. Chen, Vuk Stambolic

Research output: Contribution to journalArticle

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Abstract

Background: Metformin may improve metabolic factors (insulin, glucose, leptin, highly sensitive C-reactive protein [hs-CRP]) associated with poor breast cancer outcomes. The NCIC Clinical Trials Group (NCIC CTG) MA.32 investigates effects of metformin vs placebo on invasive disease-free survival and other outcomes in early breast cancer. Maintaining blinding of investigators to outcomes, we conducted a planned, Data Safety Monitoring Committee-approved, analysis of the effect of metformin vs placebo on weight and metabolic factors at six months, including examination of interactions with baseline body mass index (BMI) and insulin, in the first 492 patients with paired blood samples. Methods: Eligible nondiabetic subjects with T1-3, N0-3, M0 breast cancer who had completed surgery and (neo)adjuvant chemotherapy (if given) provided fasting plasma samples at random assignment and at six months. Glucose was measured locally; blood was aliquoted, frozen, and stored at-80°C. Paired plasma aliquots were analyzed for insulin, hs-CRP, and leptin. Spearman correlation coefficients were calculated and comparisons analyzed using Wilcoxon signed rank test. All statistical tests were two-sided. Results: Mean age was 52.1 ± 9.5 years in the metformin group and 52.6 ± 9.8 years in the placebo group. Arms were balanced for estrogen/progesterone receptor, BMI, prior (neo)adjuvant chemotherapy, and stage. At six months, decreases in weight and blood variables were statistically significantly greater in the metformin arm (vs placebo) in univariate analyses: weight-3.0%, glucose-3.8%, insulin-11.1%, homeostasis model assessment-17.1%, leptin-20.2%, hs-CRP-6.7%; all P values were less than or equal to.03. There was no statistically significant interaction of change in these variables with baseline BMI or insulin. Conclusions: Metformin statistically significantly improved weight, insulin, glucose, leptin, and CRP at six months. Effects did not vary by baseline BMI or fasting insulin.

Original languageEnglish (US)
Article numberdjv006
JournalJournal of the National Cancer Institute
Volume107
Issue number3
DOIs
StatePublished - Mar 1 2015

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Metformin
Placebos
Clinical Trials
Insulin
Weights and Measures
Leptin
Body Mass Index
C-Reactive Protein
Glucose
Adjuvant Chemotherapy
Fasting
Clinical Trials Data Monitoring Committees
Breast Neoplasms
Progesterone Receptors
Nonparametric Statistics
Estrogen Receptors
Disease-Free Survival
Homeostasis
Research Personnel
Safety

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Goodwin, P. J., Parulekar, W. R., Gelmon, K. A., Shepherd, L. E., Ligibel, J. A., Hershman, D. L., ... Stambolic, V. (2015). Effect of Metformin vs Placebo on weight and metabolic factors in NCIC CTG MA.32. Journal of the National Cancer Institute, 107(3), [djv006]. https://doi.org/10.1093/jnci/djv006

Effect of Metformin vs Placebo on weight and metabolic factors in NCIC CTG MA.32. / Goodwin, Pamela J.; Parulekar, Wendy R.; Gelmon, Karen A.; Shepherd, Lois E.; Ligibel, Jennifer A.; Hershman, Dawn L.; Rastogi, Priya; Mayer, Ingrid A.; Hobday, Timothy James; Lemieux, Julie; Thompson, Alastair M.; Pritchard, Kathleen I.; Whelan, Timothy J.; Mukherjee, Som D.; Chalchal, Haji I.; Oja, Conrad D.; Tonkin, Katia S.; Bernstein, Vanessa; Chen, Bingshu E.; Stambolic, Vuk.

In: Journal of the National Cancer Institute, Vol. 107, No. 3, djv006, 01.03.2015.

Research output: Contribution to journalArticle

Goodwin, PJ, Parulekar, WR, Gelmon, KA, Shepherd, LE, Ligibel, JA, Hershman, DL, Rastogi, P, Mayer, IA, Hobday, TJ, Lemieux, J, Thompson, AM, Pritchard, KI, Whelan, TJ, Mukherjee, SD, Chalchal, HI, Oja, CD, Tonkin, KS, Bernstein, V, Chen, BE & Stambolic, V 2015, 'Effect of Metformin vs Placebo on weight and metabolic factors in NCIC CTG MA.32', Journal of the National Cancer Institute, vol. 107, no. 3, djv006. https://doi.org/10.1093/jnci/djv006
Goodwin PJ, Parulekar WR, Gelmon KA, Shepherd LE, Ligibel JA, Hershman DL et al. Effect of Metformin vs Placebo on weight and metabolic factors in NCIC CTG MA.32. Journal of the National Cancer Institute. 2015 Mar 1;107(3). djv006. https://doi.org/10.1093/jnci/djv006
Goodwin, Pamela J. ; Parulekar, Wendy R. ; Gelmon, Karen A. ; Shepherd, Lois E. ; Ligibel, Jennifer A. ; Hershman, Dawn L. ; Rastogi, Priya ; Mayer, Ingrid A. ; Hobday, Timothy James ; Lemieux, Julie ; Thompson, Alastair M. ; Pritchard, Kathleen I. ; Whelan, Timothy J. ; Mukherjee, Som D. ; Chalchal, Haji I. ; Oja, Conrad D. ; Tonkin, Katia S. ; Bernstein, Vanessa ; Chen, Bingshu E. ; Stambolic, Vuk. / Effect of Metformin vs Placebo on weight and metabolic factors in NCIC CTG MA.32. In: Journal of the National Cancer Institute. 2015 ; Vol. 107, No. 3.
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abstract = "Background: Metformin may improve metabolic factors (insulin, glucose, leptin, highly sensitive C-reactive protein [hs-CRP]) associated with poor breast cancer outcomes. The NCIC Clinical Trials Group (NCIC CTG) MA.32 investigates effects of metformin vs placebo on invasive disease-free survival and other outcomes in early breast cancer. Maintaining blinding of investigators to outcomes, we conducted a planned, Data Safety Monitoring Committee-approved, analysis of the effect of metformin vs placebo on weight and metabolic factors at six months, including examination of interactions with baseline body mass index (BMI) and insulin, in the first 492 patients with paired blood samples. Methods: Eligible nondiabetic subjects with T1-3, N0-3, M0 breast cancer who had completed surgery and (neo)adjuvant chemotherapy (if given) provided fasting plasma samples at random assignment and at six months. Glucose was measured locally; blood was aliquoted, frozen, and stored at-80°C. Paired plasma aliquots were analyzed for insulin, hs-CRP, and leptin. Spearman correlation coefficients were calculated and comparisons analyzed using Wilcoxon signed rank test. All statistical tests were two-sided. Results: Mean age was 52.1 ± 9.5 years in the metformin group and 52.6 ± 9.8 years in the placebo group. Arms were balanced for estrogen/progesterone receptor, BMI, prior (neo)adjuvant chemotherapy, and stage. At six months, decreases in weight and blood variables were statistically significantly greater in the metformin arm (vs placebo) in univariate analyses: weight-3.0{\%}, glucose-3.8{\%}, insulin-11.1{\%}, homeostasis model assessment-17.1{\%}, leptin-20.2{\%}, hs-CRP-6.7{\%}; all P values were less than or equal to.03. There was no statistically significant interaction of change in these variables with baseline BMI or insulin. Conclusions: Metformin statistically significantly improved weight, insulin, glucose, leptin, and CRP at six months. Effects did not vary by baseline BMI or fasting insulin.",
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T1 - Effect of Metformin vs Placebo on weight and metabolic factors in NCIC CTG MA.32

AU - Goodwin, Pamela J.

AU - Parulekar, Wendy R.

AU - Gelmon, Karen A.

AU - Shepherd, Lois E.

AU - Ligibel, Jennifer A.

AU - Hershman, Dawn L.

AU - Rastogi, Priya

AU - Mayer, Ingrid A.

AU - Hobday, Timothy James

AU - Lemieux, Julie

AU - Thompson, Alastair M.

AU - Pritchard, Kathleen I.

AU - Whelan, Timothy J.

AU - Mukherjee, Som D.

AU - Chalchal, Haji I.

AU - Oja, Conrad D.

AU - Tonkin, Katia S.

AU - Bernstein, Vanessa

AU - Chen, Bingshu E.

AU - Stambolic, Vuk

PY - 2015/3/1

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N2 - Background: Metformin may improve metabolic factors (insulin, glucose, leptin, highly sensitive C-reactive protein [hs-CRP]) associated with poor breast cancer outcomes. The NCIC Clinical Trials Group (NCIC CTG) MA.32 investigates effects of metformin vs placebo on invasive disease-free survival and other outcomes in early breast cancer. Maintaining blinding of investigators to outcomes, we conducted a planned, Data Safety Monitoring Committee-approved, analysis of the effect of metformin vs placebo on weight and metabolic factors at six months, including examination of interactions with baseline body mass index (BMI) and insulin, in the first 492 patients with paired blood samples. Methods: Eligible nondiabetic subjects with T1-3, N0-3, M0 breast cancer who had completed surgery and (neo)adjuvant chemotherapy (if given) provided fasting plasma samples at random assignment and at six months. Glucose was measured locally; blood was aliquoted, frozen, and stored at-80°C. Paired plasma aliquots were analyzed for insulin, hs-CRP, and leptin. Spearman correlation coefficients were calculated and comparisons analyzed using Wilcoxon signed rank test. All statistical tests were two-sided. Results: Mean age was 52.1 ± 9.5 years in the metformin group and 52.6 ± 9.8 years in the placebo group. Arms were balanced for estrogen/progesterone receptor, BMI, prior (neo)adjuvant chemotherapy, and stage. At six months, decreases in weight and blood variables were statistically significantly greater in the metformin arm (vs placebo) in univariate analyses: weight-3.0%, glucose-3.8%, insulin-11.1%, homeostasis model assessment-17.1%, leptin-20.2%, hs-CRP-6.7%; all P values were less than or equal to.03. There was no statistically significant interaction of change in these variables with baseline BMI or insulin. Conclusions: Metformin statistically significantly improved weight, insulin, glucose, leptin, and CRP at six months. Effects did not vary by baseline BMI or fasting insulin.

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