Effects of Behavioral Weight Loss and Metformin on Insulin-like Growth Factors in Cancer Survivors: A Randomized Trial.

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Higher levels of insulin-like growth factor-1 (IGF-1) are associated with increased risk of cancers and higher mortality. Therapies that reduce IGF-1 have considerable appeal as means to prevent recurrence.Randomized, 3-parallel-arm controlled clinical trial.Cancer survivors with overweight or obesity were randomized to 1) self-directed weight loss (comparison), 2) coach-directed weight loss, or 3) metformin treatment. Main outcomes were changes in IGF-1 and IGF-1:IGFBP3 molar ratio at six months. The trial duration was 12 months.Of the 121 randomized participants, 79% were women, 46% were African Americans, and the mean age was 60 years. At baseline, the average BMI was 35 kg/m 2; mean IGF-1 was 72.9 (SD, 21.7) ng/ml; and mean IGF1:IGFBP3 molar ratio was 0.17 (SD, 0.05). At 6 months, weight changes were -1.0% (p=0.07), -4.2% (p<0.0001), and -2.8% (p<0.0001) in self-directed, coach-directed, and metformin groups, respectively. Compared to the self-directed group, participants in metformin had significant decreases on IGF-1 (mean difference in change: -5.50 ng/ml, p=0.02) and IGF1:IGFBP3 molar ratio (mean difference in change: -0.0119, p=0.011) at 3 months. The significant decrease of IGF-1 remained in participants with obesity at 6 months (mean difference in change: -7.2 ng/ml; 95% CI: -13.3 to -1.1), but not in participants with overweight (p-for interaction=0.045). There were no significant differences in changes between the coach-directed and self-directed groups. There were no differences in outcomes at 12 months.In cancer survivors with obesity, metformin may have a short-term effect on IGF-1 reduction that wanes over time.


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Authors: Hsin-Chieh Yeh, Nisa M Maruthur, Nae-Yuh Wang, Gerald J Jerome, Arlene T Dalcin, Eva Tseng, Karen White, Edgar R Miller, Stephen P Juraschek, Noel T Mueller, Jeanne Charleston, Nowella Durkin, Ahmed Hassoon, Dina Lansey, Norma Kanarak, Michael A Carducci, Lawrence J Appel

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