Evidence map›Paper›PMID 33596993›Full record

ArticleTrials2021

Efficacy of metformin and fermentable fiber combination therapy in adolescents with severe obesity and insulin resistance: study protocol for a double-blind randomized controlled trial.

Edward C Deehan, Eloisa Colin-Ramirez, Lucila Triador, Karen L Madsen, Carla M Prado, Catherine J Field, Geoff D C Ball, Qiming Tan, Camila Orsso, Irina Dinu and 9 more

Registry-linked trialOpen access · goldFull text readClinical Trial Protocol
PubMed Full text at PMC Publisher
In one paragraph

Article in Trials, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT04578652. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
0.6field-weighted citation impact, top 35% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04578652 phase3recruiting

Fiber Supplementation and Metformin Combination Therapy in Adolescents With Severe Obesity and Insulin Resistance: Interactions With the Gut Microbiome.

Ran2021Enrolled90Registered outcomes12Posted comparisons0ConditionsInsulin Resistance, Obesity, ChildhoodArmsMetformin 850 mg oral tablet bid, Supplemental fiber mixture (35 g total) composed of 6g of Oligofructose + 12g of resistant maltodextrin + 12g of acacia gum + 5g of PGX.
Open the trial in the graph
3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 1 synthesis or guideline pooled it, 6 citations in OpenAlex.

  1. Pooled it
  2. The Need forCJC open · 2023
    Article
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors at 5 institutions in 4 countries.

Edward C Deehan *Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, T6G 2E1, AB, Canada.
Eloisa Colin-Ramirez *Department of Pediatrics, University of Alberta, Edmonton, T6G 2E1, AB, Canada.
Lucila TriadorDepartment of Pediatrics, University of Alberta, Edmonton, T6G 2E1, AB, Canada.
Karen L MadsenDepartment of Medicine, University of Alberta, Edmonton, T6G 2C2, AB, Canada.
Carla M PradoDepartment of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, T6G 2E1, AB, Canada.
Catherine J FieldDepartment of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, T6G 2E1, AB, Canada.
Geoff D C BallDepartment of Pediatrics, University of Alberta, Edmonton, T6G 2E1, AB, Canada.
Qiming TanDepartment of Pediatrics, University of Alberta, Edmonton, T6G 2E1, AB, Canada.
Camila OrssoDepartment of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, T6G 2E1, AB, Canada.
Irina DinuSchool of Public Health, University of Alberta, Edmonton, T6G 1C9, AB, Canada.
Mohammadreza PaksereshtDepartment of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, T6G 2E1, AB, Canada.
Daniela RubinCalifornia State University Fullerton, Fullerton, USA.
Arya M SharmaDepartment of Medicine, University of Alberta, Edmonton, T6G 2C2, AB, Canada.
Hein TunUniversity of Hong Kong School of Public Health, Hong Kong, China.
Jens WalterDNational University of Ireland University College Cork, University College Cork, Cork, Ireland.
Christopher B NewgardDuke University Medical Center, Duke University Hospital, Durham, NC, USA.
Michael FreemarkDuke University Medical Center, Duke University Hospital, Durham, NC, USA.
Eytan WineDepartment of Pediatrics and Physiology, University of Alberta, Edmonton, T6G 1C9, BA, Canada.
Andrea M HaqqDepartment of Pediatrics, University of Alberta, Edmonton, T6G 2E1, AB, Canada. haqq@ualberta.ca.
University of Alberta · CADuke University Hospital · USCalifornia State University, Fullerton · USNational University of Ireland · IEUniversity of Hong Kong · HK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAccumulating evidence suggests that the metabolic effects of metformin and fermentable fibers are mediated, in part, through diverging or overlapping effects on the composition and metabolic functions of the gut microbiome. Pre-clinical animal models have established that the addition of fiber to metformin monotherapy improves glucose tolerance. However, possible synergistic effects of combination therapy (metformin plus fiber) have not been investigated in humans. Moreover, the underlying mechanisms of synergy have yet to be elucidated. The aim of this study is to compare in adolescents with obesity the metabolic effects of metformin and fermentable fibers in combination with those of metformin or fiber alone. We will also determine if therapeutic responses correlate with compositional and functional features of the gut microbiome.

methodsThis is a parallel three-armed, double-blinded, randomized controlled trial. Adolescents (aged 12-18 years) with obesity, insulin resistance (IR), and a family history of type 2 diabetes mellitus (T2DM) will receive either metformin (850 mg p.o. twice/day), fermentable fibers (35 g/day), or a combination of metformin plus fiber for 12 months. Participants will be seen at baseline, 3, 6, and 12 months, with a phone follow-up at 1 and 9 months. Primary and secondary outcomes will be assessed at baseline, 6, and 12 months. The primary outcome is change in IR estimated by homeostatic model assessment of IR; key secondary outcomes include changes in the Matsuda index, oral disposition index, body mass index z-score, and fat mass to fat-free mass ratio. To gain mechanistic insight, endpoints that reflect host-microbiota interactions will also be assessed: obesity-related immune, metabolic, and satiety markers; humoral metabolites; and fecal microbiota composition, short-chain fatty acids, and bile acids. DISCUSSION: This study will compare the potential metabolic benefits of fiber with those of metformin in adolescents with obesity, determine if metformin and fiber act synergistically to improve IR, and elucidate whether the metabolic benefits of metformin and fiber associate with changes in fecal microbiota composition and the output of health-related metabolites. This study will provide insight into the potential role of the gut microbiome as a target for enhancing the therapeutic efficacy of emerging treatments for T2DM prevention.

trial registrationClinicalTrials.gov NCT04578652 . Registered on 8 October 2020.

Indexed as

Diabetes Mellitus, Type 2Insulin ResistanceMetforminObesity, MorbidAdolescentDouble-Blind MethodHumansHypoglycemic AgentsRandomized Controlled Trials as TopicHypoglycemic AgentsMetforminAdolescentsDiabetesDietary fiberGut microbiomeInsulin resistanceMetforminObesity

Identifiers

PMID33596993
PMCPMC7890810
OpenAlexW3130485722

What Socratic holds

Textfull text, public
LicenceCC BY
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.