NCT04089280: ProGasMet

Probiotics in Metformin Intolerant Patients With Type 2 Diabetes

Completed NA Last updated 6 May 2022

What this trial tests

NA trial testing Sanprobi Barrier-multispecies probiotic in Diabetes Mellitus, Type 2 in 37 participants. Completed in 31 December 2021.

Timeline

16 October 2018

Primary endpoint
31 December 2021

31 December 2021

Quick facts

Lead sponsor	Medical University of Silesia
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	quadruple
Primary purpose	treatment
Enrollment	37
Start date	16 October 2018
Primary completion	31 December 2021
Estimated completion	31 December 2021
Sites	1 location across Poland

Drugs / interventions tested

• Sanprobi Barrier-multispecies probiotic
• Placebo Comparator

Conditions studied

• Diabetes Mellitus, Type 2 — all drugs for Diabetes Mellitus, Type 2 →
• Metformin Adverse Reaction — all drugs for Metformin Adverse Reaction →

Sponsor

Medical University of Silesia

Who can join

Adults 18 to 75, any sex, with Diabetes Mellitus, Type 2 or Metformin Adverse Reaction. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Metformin, the first-line drug in the treatment of type 2 diabetes (T2DM), may cause dose dependent undesirable side-effects like diarrhea, abdominal pain, nausea or bloating which may affect up to 20 % of patients treated with this drug. The mechanism of the gastrointestinal intolerance in patients treated with metformin is poorly understood. The number of studies on this topic increases and data are mounting that metformin treatment is associated with changes in gut bacterial composition. Among other drugs, metformin also leads to enrichment of short chain fatty acids (SCFAs) producing microbiota which exert positive influence on the human metabolic state.

It has been shown that the therapeutic effect of metformin depends on the microbiota and metformin's main site of action in humans is the intestine. It is also known that patients with T2DM, in general, show evidence of gut dysbiosis followed by alterations of an intestinal barrier leading to an increase in intestinal permeability and elevated inflammatory state.

Therefore, it has been speculated that metformin's versatile effect mediated through the gut microbiota is responsible not only for its therapeutic effect but also for its undesirable digestive symptoms.

Probiotics, defined as "live microorganisms, that when administered in adequate amounts, confer a health benefit on the host", may have the potential to modulate the gut bacterial composition. This is why the investigators hypothesize that it may also reduce the intensity of adverse effects associated with metformin use.

The investigators have chosen Sanprobi Barrier multi-strain formula probiotic because it is identical, in relation to bacterial strains and number, to Ecologic® BARRIER which has been proven in in vitro studies to improve the function of epithelial barrier of the intestine. It was also shown that 12-week administration of strains included in Ecologic® BARRIER in obese postmenopausal women improved intestinal barrier permeability marker (lipopolysaccharide) and cardiometabolic risk factors (waist, fat mass, subcutaneous fat, uric acid, total cholesterol, triglycerides, low-density lipoprotein cholesterol, glucose, insulin, and homeostatic model assessment - insulin resistance (HOMA-IR).

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

1. Gut microbiota in the pathogenesis and therapeutic approaches of diabetes.
   Crudele L, Gadaleta RM, Cariello M, Moschetta A. · · 2023 · cited 147× · PMID 37804567 · DOI 10.1016/j.ebiom.2023.104821
2. The Relationship between the Gut Microbiome and Metformin as a Key for Treating Type 2 Diabetes Mellitus.
   Lee CB, Chae SU, Jo SJ, Jerng UM, et al · · 2021 · cited 102× · PMID 33808194 · DOI 10.3390/ijms22073566
3. Modulating the Microbiota as a Therapeutic Intervention for Type 2 Diabetes.
   Huda MN, Kim M, Bennett BJ. · · 2021 · cited 89× · PMID 33897618 · DOI 10.3389/fendo.2021.632335
4. The Promising Role of Microbiome Therapy on Biomarkers of Inflammation and Oxidative Stress in Type 2 Diabetes: A Systematic and Narrative Review.
   Paul P, Kaul R, Abdellatif B, Arabi M, et al · · 2022 · cited 13× · PMID 35711547 · DOI 10.3389/fnut.2022.906243