title: A prospective, randomized pilot study evaluating the effects of metformin and lifestyle intervention on patients with prostate cancer receiving androgen deprivation therapy.
abstract: Study Type - Therapy (RCT) Level of Evidence 1b What's known on the subject? and What does the study add? Men with prostate cancer have higher rates of non-cancer mortality and CV morbidity and some of that excess risk has been attributed to the treatment they receive. ADT is an established treatment option for men with locally-advanced and metastatic prostate cancer and, although it has been shown to confer a disease-free survival advantage, it has also been associated with an increased incidence of CV disease and the metabolic syndrome (characterized by a cluster of CV risk factors, including insulin resistance). The benefits of the insulin sensitizer metformin and lifestyle intervention for reducing the incidence of metabolic syndrome have been shown in patients with impaired glucose tolerance. At the time of writing, the present study is the first to use metformin and lifestyle intervention in men with prostate cancer with the aim of reducing the risk of developing ADT-related CV morbidity and the metabolic syndrome. The study shows that lifestyle changes and metformin may indeed reduce the complications of androgen suppression in these men. Although further investigations are needed to establish which of the two interventions may be most beneficial, the favourable effects of a combination of these interventions on patients' quality of life and the potential for improved overall survival are of clinical significance.
  
  
  OBJECTIVE
  To investigate the effects of metformin and lifestyle changes on the development of androgen deprivation therapy (ADT)-related metabolic syndrome.
  
  
  METHODS
  Men with prostate cancer due to receive ADT were recruited and randomized. Controls received ADT alone. Men in the intervention arm received ADT with 6 months of metformin, a low glycaemic index diet and an exercise programme. All patients were investigated pretreatment and at 6 months for the metabolic syndrome, as well as for related biochemical and physical parameters.
  
  
  RESULTS
  In total, 40 men were recruited and randomized (20 to each arm). After 6 months, significant improvements in abdominal girth (P= 0.05), weight (P < 0.001), body mass index (P < 0.001) and systolic blood pressure (P= 0.01) were seen in the intervention arm compared to controls. Biochemical markers of insulin resistance did not differ significantly.
  
  
  CONCLUSIONS
  The present study shows the potential benefits of metformin and lifestyle changes in ADT-treated men. Further studies will aim to determine which intervention is most important, and may show that overall survival can be improved.
authors.affiliation: Department of Diabetes and Endocrinology, The Royal Surrey County Hospital NHS Foundation Trust, Guildford, UK.
authors.forename: Jenny P
authors.initials: JP
authors.lastname: Nobes
authors.forename: Stephen E M
authors.initials: SE
authors.lastname: Langley
authors.forename: Tanya
authors.initials: T
authors.lastname: Klopper
authors.forename: David
authors.initials: D
authors.lastname: Russell-Jones
authors.forename: Robert W
authors.initials: RW
authors.lastname: Laing
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D001521:Behavior Therapy / Q000379:methods*; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007333:Insulin Resistance; D008019:Life Style; D008297:Male; D024821:Metabolic Syndrome / Q000139:chemically induced / Q000401:mortality / Q000517:prevention & control*; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000150:complications / Q000378:metabolism / Q000628:therapy*; D015996:Survival Rate / Q000639:trends; D016896:Treatment Outcome; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D000726:Androgen Antagonists; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D008687:Metformin