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Metformin and GDF15: where are we now?

A recent publication in Cell Reports adds to the emerging consensus that metformin acts on the gut and kidneys to increase circulating levels of growth differentiation factor 15 (GDF15). However, the report also highlights circumstances in which the effects of metformin on body weight and energy balance seem to be independent of GDF15–GFRAL signalling.

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  1. Lachin, J. M. et al. Factors associated with diabetes onset during metformin versus placebo therapy in the Diabetes Prevention Program. Diabetes 56, 1153–1159 (2007).

    Article  CAS  Google Scholar 

  2. Gerstein, H. C. et al. Growth differentiation factor 15 as a novel biomarker for metformin. Diabetes Care 40, 280–283 (2016).

    Article  Google Scholar 

  3. Coll, A. P. et al. GDF15 mediates the effects of metformin on body weight and energy balance. Nature 578, 444–448 (2020).

    Article  CAS  Google Scholar 

  4. Day, E. A. et al. Metformin-induced increases in GDF15 are important for suppressing appetite and promoting weight loss. Nat. Metab. 1, 1202–1208 (2019).

    Article  CAS  Google Scholar 

  5. Klein, A. B. et al. The GDF15-GFRAL pathway is dispensable for the effects of metformin on energy balance. Cell Rep. 40, 111258 (2022).

    Article  CAS  Google Scholar 

  6. de Meijer, V. E., Le, H. D., Meisel, J. A. & Puder, M. Repetitive orogastric gavage affects the phenotype of diet-induced obese mice. Physiol. Behav. 100, 387–393 (2010).

    Article  Google Scholar 

  7. Carreras-Badosa, G. et al. A 24-month metformin treatment study of children with obesity: Changes in circulating GDF-15 and associations with changes in body weight and visceral fat. Pediatr. Obes. 17, e12845 (2022).

    Article  Google Scholar 

  8. Lu, J. F. et al. Camptothecin effectively treats obesity in mice through GDF15 induction. PLOS Biol. 20, e3001517 (2022).

    Article  CAS  Google Scholar 

  9. Zhang, S.-Y., Li, R. J. W., Danaei, Z., Lim, Y. & Lam, T. K. 154-OR: The site-specific role of GDF15 in metformin action. Diabetes 71, 154 (2022). -OR.

    Article  Google Scholar 

  10. Pénicaud, L., Hitier, Y., Ferré, P. & Girard, J. Hypoglycaemic effect of metformin in genetically obese (fa/fa) rats results from an increased utilization of blood glucose by intestine. Biochem. J. 262, 881–885 (1989).

    Article  Google Scholar 

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The authors gratefully acknowledge Professor Sir Stephen O’Rahilly (University of Cambridge) for helpful discussions in the preparation of this manuscript. A.P.C. acknowledges the support of the UK Medical Research Council (MRC) Metabolic Diseases Unit (MC_UU_00014/1).

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Correspondence to Anthony P. Coll.

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The authors declare no competing interests.

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Kincaid, J.W.R., Coll, A.P. Metformin and GDF15: where are we now?. Nat Rev Endocrinol 19, 6–7 (2023).

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