Metformin in Co-morbid Diabetes or Prediabetes and Serious Mental Illness
Condition: Diabetes Mellitus, Type 2; Schizophrenia
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Prediabetic State; Schizophrenia; Mental Disorders
Study type: Interventional
Phase: Phase 4

Summary: 
      Schizophrenia is associated with a lifespan shortened by 20 years, due to cardiovascular
      disease (CVD), with antipsychotic (AP) medications understood to contribute to this risk
      through associated metabolic side-effects. Metformin, a medication used to treat prediabetes,
      and diabetes in the general population, holds promise with regard to reduction of AP-related
      metabolic problems, but has not been directly tested in early episode patients beyond weight
      loss, nor specifically in patients with diabetes or prediabetes and psychosis. We propose to
      replicate findings that metformin can reduce weight gain, and dysglycemia uniquely focusing
      on an early episode population diagnosed with prediabetes or diabetes. To help determine
      long-term risk/benefit of adjunctive metformin, we propose to look at changes in abdominal
      and liver fat, two well-established risk factors for CVD. Given links between dysglycemia,
      obesity with hippocampal volume loss and cognitive dysfunction, we will explore if
      improvements in metabolic indices are associated in changes in cognition and brain structure.
    

Detailed description: 
      This is a 16 week, double-blind, randomized pilot study, which proposes to recruit 24
      patients with schizophrenia, or schizoaffective disorders (DSM 5), who are overweight or
      obese (BMI >25) and have prediabetes or type 2 diabetes. Randomization occurs on a 2:1 basis,
      with 16 patients randomised to metformin, and 8 to placebo. Metfomin/placebo is dispensed
      monthly. The baseline and /or screening visit includes a physical exam (including
      anthropometric measures), medical history, fasting blood work (glucose, insulin, HbA1c,
      lipids, electrolytes, thyroid, liver/kidney function), in addition to a urine drug screen.
      Women of child-bearing age are given a pregnancy test. Patients who meet inclusion criteria
      and consent to the study have an oral glucose tolerance test (OGTT), and a baseline abdominal
      and brain MRI (to respectively assess visceral adiposity, a key risk factor for CV disease,
      and hippocampal volumes). Anthropometric measures and pill counts are repeated bi-weekly. At
      week 8, fasting insulin/glucose, HbA1C, and liver function tests are measured. End of study
      measures (week 16), include the same panel of bloodwork conducted at baseline, as well as a
      repeat OGTT, and an abdominal and brain MRI. Rountine psychopathology scales, including BPRS,
      CGI, and CDS will be measured at baseline, and week 16. The Brief Assessment of Cognition in
      Schizophrenia (BACS) will also be completed at baseline, and study end.
    

Intervention name(s): Metformin; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Metformin will be dispensed on a biweekly basis, and pill counts conducted at each visit.; Placebo will be dispensed on a biweekly basis, and pill counts conducted at each visit.
Other intervention name(s): Sugar pill
Intervention MeSH terms: Metformin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary purpose: Treatment