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Randomized Controlled Trial
. 2021 Sep 27;106(10):e4179-e4191.
doi: 10.1210/clinem/dgab266.

Effects of Behavioral Weight Loss and Metformin on IGFs in Cancer Survivors: A Randomized Trial

Hsin-Chieh Yeh  1   2   3   4 , Nisa M Maruthur  1   2   3 , Nae-Yuh Wang  1   2   3   5 , Gerald J Jerome  1   6 , Arlene T Dalcin  1   3 , Eva Tseng  1   3 , Karen White  1 , Edgar R Miller  1   2   3 , Stephen P Juraschek  1   7 , Noel T Mueller  2   3 , Jeanne Charleston  2   3 , Nowella Durkin  1 , Ahmed Hassoon  2   4 , Dina G Lansey  4 , Norma F Kanarek  4   8 , Michael A Carducci  4 , Lawrence J Appel  1   2   3   9
Affiliations
Randomized Controlled Trial

Effects of Behavioral Weight Loss and Metformin on IGFs in Cancer Survivors: A Randomized Trial

Hsin-Chieh Yeh et al. J Clin Endocrinol Metab. .

Abstract

Context: 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.

Design: Randomized, 3-parallel-arm controlled clinical trial.

Interventions and outcomes: 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 6 months. The trial duration was 12 months.

Results: Of the 121 randomized participants, 79% were women, 46% were African Americans, and the mean age was 60 years. At baseline, the average body mass index was 35 kg/m2; 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 with 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.

Conclusions: In cancer survivors with obesity, metformin may have a short-term effect on IGF-1 reduction that wanes over time.

Keywords: IGF-1; IGFBP3; behavioral weight loss; insulin-like growth factors; metformin; weight.

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Figures

Figure 1.
Figure 1.
Study consort diagram.
Figure 2.
Figure 2.
(A) Percent weight change during study period. (B) Kernel estimates of percent weight change (%) at 6 months by study arm.
Figure 3.
Figure 3.
(A) Change in IGF-1 during study period. (B) Change in IGF1/IGFBP3 molar ratio during study period.
Figure 4.
Figure 4.
Change in IGF-1 at 6 months by subgroup.
See this image and copyright information in PMC

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