Metformin induces short-term IGF-I reduction among cancer survivors with obesity
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Metformin significantly reduces insulin-like growth factor I levels after 3 to 6 months among cancer survivors with obesity, but the effect wanes over time, according to data published in The Journal of Clinical Endocrinology & Metabolism.
In a randomized, three-parallel-arm controlled clinical trial, researchers also found that a remotely delivered behavioral weight-loss intervention and metformin treatment up to 2,000 mg per day both decreased body weight significantly, with 39%, and 30% of participants achieving at least 5% of weight loss at 6 months with the coach-directed weight-loss program and metformin treatment, respectively.
“Some previous short-term studies showed metformin treatment reduced IGF-I levels in patients with endometrial cancer, in women with polycystic ovary syndrome, and in healthy men,” Hsin-Chieh “Jessica” Yeh, PhD, associate professor of medicine, epidemiology and oncology at Johns Hopkins University, told Healio. “Our findings were consistent with those studies, and additionally suggested that the effect from metformin on IGF-I levels may diminish over time.”
For the SPIRIT trial, Yeh and colleagues analyzed data from 121 cancer survivors with overweight or obesity (BMI 25 kg/m²) recruited between August 2015 and December 2016 (79% women; 46% Black; mean age, 60 years; majority of participants with history of breast cancer). Participants were randomly assigned to self-directed weight loss (controls), coach-directed weight loss or metformin treatment of up to 2,000 mg daily with flexible dosing with meals for 12 months. Primary outcome was 6-month change in IGF-I level.
At baseline, the average BMI was 35 kg/m²; mean IGF-1 was 72.9 ng/mL; and mean IGF-I/IGF binding protein-3 molar ratio was 0.17. During the study, 11 participants in the metformin group discontinued the drug due to cancer recurrence or adverse effects.
At 6 months, weight changes were –1% (P = .07), –4.2% (P < .0001) and –2.8% (P < .0001) in self-directed, coach-directed and metformin groups, respectively.
Compared with the self-directed group, participants in the metformin group experienced significant decreases in IGF-I levels, with a mean difference in change of –5.5 ng/mL (P = .02) and mean difference in change for IGF-I/IGF binding protein-3 molar ratio of –0.0119 at 3 months (P = .011). The decrease of IGF-I persisted among participants with obesity at 6 months, with a mean difference in change of –7.2 ng/mL (95% CI, –13.3 to –1.1), but not among participants with overweight.
There were no significant differences in changes between the coach-directed and self-directed groups, and there were no differences in outcomes at 12 months.
“Most of our trial participants did not have diabetes,” Yeh told Healio. “With regular clinical monitoring, weight loss and metformin treatment can be safely implemented in cancer survivors with obesity but without diabetes.”
Yeh noted that the study did not find a significant effect from behavioral weight loss on IGF-I levels; however, she said the noninvasive, lifestyle modification approach is meaningful to improve cardiovascular risk factors and overall well-being.
“Many cancer survivors live a normal life; maintaining a healthy lifestyle and body weight should be encouraged,” Yeh said.
Yeh said additional studies of metformin and behavioral weight loss are warranted to understand their effects on other cancer-related biomarkers and potential clinical outcomes.
For more information:
Hsin-Chieh “Jessica” Yeh, PhD, can be reached at hyeh1@jhmi.edu.
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