Trial of an Intervention to Improve Metformin Persistence and Adherence
Condition: Metformin Adverse Reaction; Tolerance
Intervention: Metformin Extended Release Oral Tablet; Placebo oral capsule
Intervention description: Metformin hydrochloride extended release tablets in dosages of 250 mg, 500 mg, 750 mg, and 1,000 mg. Individual encapsulations of metformin will contain dosages of 250 mg or 500 mg.; Placebo capsule
Intervention MeSH terms: Metformin
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This study is an N-of-1 trial design that will recruit 20 previously metformin-intolerant patients for re-challenge with metformin in a double-blind scenario. Patients will be assigned to take their baseline medication regimen plus 2 weeks of 250 mg per day of metformin extended release, followed by 500 mg metformin XR, 750 mg, and 1,000 mg metformin XR with each treatment period separated by a 2-week course of placebo. Initial treatment, placebo or metformin XR, will be decided randomly.
Masking: Triple (Participant, Care Provider, Investigator)
Masking description: Patients, care providers, and investigators will be masked to the identity of the trial medication until the conclusion of the trial, and unblinding.
Enrollment: 13.0
Sex: All
Minimum age: 18 Years
Maximum age: 100 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      Metformin is a safe and effective first-line drug for type 2 diabetes that is also widely
      recommended for weight loss and diabetes prevention. But, metformin is associated with
      gastrointestinal and other side effects which prevent its use in 10-20% of patients and
      appear to limit the usable dose in others. This study is an N-of-1 trial design that will
      recruit 20 previously metformin-intolerant patients for re-challenge with metformin in a
      double-blind scenario. In this setting, 'intolerant' means either unable to take metformin at
      all, or unable to increase the dose past 1,000 mg despite the treating physician's
      recommendation to do so. Patients will be assigned to take their baseline medication regimen
      plus 2 weeks of 250 mg per day of metformin extended release, followed by 500 mg metformin
      XR, 750 mg, and 1,000 mg metformin XR with each treatment period separated by a 2-week course
      of placebo. Initial treatment, placebo or metformin XR, will be decided randomly. At the end
      of each two-week treatment period, participants will complete questionnaires assessing
      overall satisfaction with the medication, gastrointestinal symptoms, and adherence. Six
      months after the conclusion of the intervention, patients will be asked if they are
      continuing metformin at a higher dose than upon entry to the trial. This trial has two aims.
      First, to test the hypothesis that medication satisfaction will be the same during periods of
      placebo treatment and during periods of treatment with the active drug. The second aim is to
      test the hypothesis that > 30% of metformin-intolerant patients in an N of 1 crossover trial
      are able to tolerate higher-dose metformin at 6-months.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of diabetes, pre-diabetes, or obesity

          -  Previously attempted to take metformin for an above indication

          -  History of metformin intolerance (defined based on treating physician's assessment
             that a history of metformin intolerance (defined as the inability, due to side
             effects, to use metformin at the otherwise medically appropriate dose) exists,
             confirmed by the patient's recollection of the same history)

        Exclusion Criteria:

          -  Contraindication to metformin (i.e, advanced renal or liver disease, history of
             metformin attributed lactic acidosis, or advanced heart failure)

          -  Pregnant women