Trial of an Intervention to Improve Metformin Persistence and Adherence

Phase 4

Completed

• Conditions: Tolerance; Metformin Adverse Reaction
• Interventions: Drug: Placebo oral capsule; Drug: Metformin Extended Release Oral Tablet

• Registration Number: NCT03467763
• Lead Sponsor: Weill Medical College of Cornell University

Brief 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.

Detailed 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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2018-02-09
• Study First Submitted: 2018-03-05
• Study First Submitted QC: 2018-03-09
• Study First Posted: 2018-03-16
• Primary Completion: 2020-02-01
• Study Completion: 2020-08-01
• Results First Submitted: 2020-09-29
• Status Verified: 2020-11
• Results First Submitted QC: 2020-11-10
• Last Update Submitted: 2020-11-10
• Results First Posted: 2020-12-07
• Last Update Posted: 2020-12-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 13

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)

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Exclusion Criteria

• Contraindication to metformin (i.e, advanced renal or liver disease, history of metformin attributed lactic acidosis, or advanced heart failure)
• Pregnant women

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo oral capsule	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.
Metformin Hydrochloride Extended Release	Metformin Extended Release Oral Tablet	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.

Primary Outcome Measures

Name	Time	Method
Treatment Satisfaction as Measured by the Treatment Satisfaction Questionnaire for Medication (TSQM II)	4-months	The primary outcome of this portion of the study will be the global satisfaction subscale of the Treatment Satisfaction Questionnaire for Medication (TSMQ II). The TSQM II is a 12-question survey with four satisfaction domains: effectiveness, side effects, convenience and global satisfaction. Each domain is described by a single numeric score. For each of these domains the lowest possible score (less satisfaction, ie a worse outcome) is 0, the highest (more satisfaction, ie a better outcome) is 100. We report this score global satisfaction domain (ie, subscale). (Note that the global satisfaction score is not a synthesis of the various subscales associated with each domain. It is a subscale in its own right comprised of distinct questions.)
Number of Subjects Able to Tolerate Higher Dose of Metformin,	6-months	For aim 2 of this study, the primary objective is to test the hypothesis \> 30% of the patients enrolled in this study are able to tolerate (continue taking) a higher-dose of metformin at 6 months than they were taking at baseline.

Secondary Outcome Measures

Name	Time	Method
Change in Score of Gastrointestinal Symptom Rating Scale (GSRS)	Reoccurring every 2-weeks for 4-months	For aim 1, the secondary objectives are to test the hypotheses that scores on a gastrointestinal symptom questionnaire are the same between between placebo and intervention periods; that adherence is the same between periods; and that the answer to the question 'Were you taking placebo or metformin for the past two weeks' is correct no more often than would be predicted by chance. Each question in the Gastrointestinal Symptom Rating Scale (GSRS) is scored on scale from 1 to 7 with 1 being no discomfort at all and 7 being very severe discomfort. The GSRS has separate questions to separately assess each of a range of potential GI symptoms (abdominal pain, reflux, diarrhoea, indigestion and constipation). Each symptom area can be described with the mean score of its contributing questions (so that the range in each symptom area is also 1 to 7, with lower numbers being better)

Trial Locations

Locations (1)

Weill Cornell Medical College; 🇺🇸 New York, New York, United States