Trial of an Intervention to Improve Metformin Persistence and Adherence (TreatMet)

Weill Cornell Medicine (WCM)

Status and phase: Completed; Phase 4

Conditions: Tolerance; Metformin Adverse Reaction

Treatments: Drug: Metformin Extended Release Oral Tablet; Drug: Placebo oral capsule

Study type: Interventional

Funder types: Other; Other U.S. Federal agency

Identifiers

NCT03467763

1706018342

K08HS023898 (U.S. AHRQ Grant/Contract)

Details and patient eligibility

About

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.

Full description

Results have been presented in a single study arm as the order in which patients received drug or placebo was unique for each patient.

Enrollment: 13 patients

Sex: All

Ages: 18 to 100 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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13 participants in 2 patient groups, including a placebo group

Metformin Hydrochloride Extended Release

Active Comparator group

Description:

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.

Treatment:

Drug: Metformin Extended Release Oral Tablet

Placebo

Placebo Comparator group

Description:

Patients will be assigned to take their baseline medication regimen plus 2 weeks of 250 mg per day of placebo, followed by 500 mg placebo, 750 mg, and 1,000 mg placebo with each treatment period separated by a 2-week course of metformin XR in the same increments of dosage.

Treatment:

Drug: Placebo oral capsule