The Interaction Between Metformin and Microbiota - the MEMO Study.

• Conditions: Type 2 Diabetes Mellitus
• Interventions: Drug: Metformin

• Registration Number: NCT03718715
• Lead Sponsor: Umeå University

Brief Summary

Metformin has been used in Sweden since 1957, and it is recommended as first line therapy for type 2-diabetes (T2D) in national and international guidelines. However, adverse effects involving diarrhea, constipation, bloating, and abdominal pain are common which leads to discontinuation of medication or not being able to reach therapeutic doses. Here the investigators will perform a prospective study to investigate whether i) participants with T2D who experience adverse events following metformin treatment have an altered microbiota at baseline compared to participants without adverse events and ii) if the microbiota is altered in participants during onset of adverse events. The investigators hypothesis is that adverse effects associated with metformin are caused by an altered gut microbiota, either at base line or following metformin treatment. The study design is a nested case-cohort study. The investigators will recruit 600 patients and expect 200 individuals to have side effects and 400 without during a 24-month study period. Fecal samples will be collected at baseline, 2 months, and 4 months or when gastrointestinal symptoms occur. All fecal samples will be sequenced by 16s rRNA (ribosomal ribonucleic acid) sequencing to obtain a baseline microbiota profile; a subpopulation consisting of homogenous groups of participants will be in depth-analyzed using shotgun sequencing. If the hypothesis is confirmed this project may lead to bacterial therapies that will allow more patients tolerate metformin.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2018-05-04
• Study First Submitted QC: 2018-10-23
• Study First Posted: 2018-10-24
• Study Start: 2019-02-20
• Status Verified: 2020-11
• Last Update Submitted: 2020-11-03
• Last Update Posted: 2020-11-04
• Primary Completion: 2021-12
• Study Completion: 2022-03

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 600

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
prospective cohort	Metformin	All participants receive Metformin in accordance to the ordinary therapy practice. They will be part of one subject group/cohort. After onset of metformin treatment the subjects who develop gastrointestinal side effects will be compared with cases without gastrointestinal side effects.

Primary Outcome Measures

Name	Time	Method
change from baseline in the fecal microbiota composition by detecting bacteria families with help of relative abundance (%) and diversity metrics	4 months	Faeces samples will be collected at baseline, after 2 months and after 4 months of Metformin treatment and analysed using 16S rRNA sequencing, whole genome shotgun sequencing and metagenomic analyses

Secondary Outcome Measures

Name	Time	Method
rate of gastrointestinal side effects	4 months	Changes in the rate of side effects using questionnaire at baseline, after 2 and 4 months.The answer possibilities are: never, one or a few times, daily, multiple times a day.
time to first appearance of side effects which requires termination of the Metformin treatment	4 months	Analysing length of metformin treatment and relation to appearance of side effects
time to first appearance of side effects which requires dose changes in the Metformin treatment	4 months	Analysing changes in metformin treatment and relation to appearance of side effects
number of patients with gastrointestinal side effects	4 months	A questionnaire will be answered at baseline, after 2 and 4 months and refers to a period of 2 weeks before study visit. Six different side effects will be monitored: loss of appetite, nausea, vomiting, diarrhea, meteorism, stomach ache.
time to first appearance of gastrointestinal side effects	4 months	How many months till the onset of side effects during metformin treatment: depending on the time of assessment, 2 or 4 months
genetic correlation between Microbiota and gastrointestinal side effects	4 months	The microbiota genome and the relation to the appearance of gastrointestinal side effects will be analysed.
correlation between microbiota and beneficial glucose lowering response	4 months	Plasma glucose will be analysed at baseline, after 2 and 4 months of Metformin treatment and correlated to the changes in the composition of microbiota.

Trial Locations

Locations (1)

Region Västerbotten; 🇸🇪 Umeå, Sweden