The effects of weight loss and metformin on cognition among breast cancer survivors: Evidence from the Reach for Health study

Psychooncology. 2019 Aug;28(8):1640-1646. doi: 10.1002/pon.5129. Epub 2019 Jun 27.


Objective: Breast cancer survivors experience problems with cognition that interfere with daily life and can last for years. In the general population, obesity and diabetes are risk factors for cognitive decline, and weight loss can improve cognition; however, the impact of intentional weight loss on cancer survivors' cognition has not been tested. We investigated the impact of weight loss and metformin on changes in cognitive function in a sample of breast cancer survivors.

Methods: Overweight/obese postmenopausal breast cancer survivors (n = 333) were randomized to a weight loss intervention versus control and metformin versus placebo in a 2 × 2 factorial design. Outcomes were changes in five cognitive domains from baseline to 6 months measured by objective neurocognitive tests.

Results: There were no statistically significant intervention effects for the metformin or weight loss interventions in five neurocognitive domains. Baseline body mass index (BMI) was a significant effect modifier of the changes in verbal functioning for the weight loss (P = 0.009) and metformin interventions (P = 0.0125). These effect modifications were independent of percent weight loss achieved during the 6-month study period.

Conclusions: This randomized controlled trial of weight loss and metformin interventions that examined changes to cognition among breast cancer survivors suggests that these interventions may not improve cognitive functioning among breast cancer survivors in general. However, weight loss may improve verbal functioning among individuals with a higher BMI.

Keywords: cancer survivors; cognition; metformin; obesity; weight loss.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Breast Neoplasms* / complications
  • Cancer Survivors*
  • Cognitive Dysfunction / drug therapy
  • Cognitive Dysfunction / etiology
  • Cognitive Dysfunction / therapy*
  • Combined Modality Therapy
  • Female
  • Humans
  • Hypoglycemic Agents / pharmacology*
  • Metformin / pharmacology*
  • Middle Aged
  • Obesity / therapy
  • Outcome Assessment, Health Care
  • Overweight / drug therapy
  • Overweight / therapy*
  • Weight Loss*


  • Hypoglycemic Agents
  • Metformin