title: Addition of a Gastrointestinal Microbiome Modulator to Metformin Improves Metformin Tolerance and Fasting Glucose Levels.
abstract: BACKGROUND
  Adverse effects of metformin are primarily related to gastrointestinal (GI) intolerance that could limit titration to an efficacious dose or cause discontinuation of the medication. Because some metformin side effects may be attributable to shifts in the GI microbiome, we tested whether a GI microbiome modulator (GIMM) used in combination with metformin would ameliorate the GI symptoms.
  
  
  METHODS
  A 2-period crossover study design was used with 2 treatment sequences, either placebo in period 1 followed by GIMM in period 2 or vice versa. Study periods lasted for 2 weeks, with a 2-week washout period between. During the first week, type 2 diabetes patients (T2D) who experienced metformin GI intolerance took 500 mg metformin along with their assigned NM504 (GIMM) or placebo treatment with breakfast and with dinner. In the second week, the 10 subjects took 500 mg metformin (t.i.d.), with GIMM or placebo consumed with the first and third daily metformin doses. Subjects were permitted to discontinue metformin dosing if it became intolerable.
  
  
  RESULTS
  The combination of metformin and GIMM treatment produced a significantly better tolerance score to metformin than the placebo combination (6.78 ± 0.65 [mean ± SEM] versus 4.45 ± 0.69, P = .0006). Mean fasting glucose levels were significantly (P < .02) lower with the metformin-GIMM combination (121.3 ± 7.8 mg/dl) than with metformin-placebo (151.9 ± 7.8 mg/dl).
  
  
  CONCLUSIONS
  Combining a GI microbiome modulator with metformin might allow the greater use of metformin in T2D patients and improve treatment of the disease.
authors: Pennington Biomedical Research Center, Baton Rouge, LA, USA.
authors: Jeffrey H
authors: JH
authors: Burton
authors: Pennington Biomedical Research Center, Baton Rouge, LA, USA Louisiana State University Health Sciences Center, Baton Rouge, LA, USA.
authors: Matthew
authors: M
authors: Johnson
authors: Louisiana State University Health Sciences Center, Baton Rouge, LA, USA.
authors: Jolene
authors: J
authors: Johnson
authors: Pennington Biomedical Research Center, Baton Rouge, LA, USA.
authors: Daniel S
authors: DS
authors: Hsia
authors: Pennington Biomedical Research Center, Baton Rouge, LA, USA.
authors: Frank L
authors: FL
authors: Greenway
authors: MicroBiome Therapeutics, Broomfield, CO, USA mheiman@mbiome.com.
authors: Mark L
authors: ML
authors: Heiman
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis*; D015992:Body Mass Index; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D005215:Fasting; D005260:Female; D005526:Food, Formulated; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects; D007444:Inulin / Q000008:administration & dosage; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D010865:Pilot Projects; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry; D059808:Polyphenols / Q000008:administration & dosage; D016896:Treatment Outcome; D047071:beta-Glucans / Q000008:administration & dosage
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D010936:Plant Extracts; D059808:Polyphenols; D047071:beta-Glucans; D007444:Inulin; D008687:Metformin
keywords: GI adverse events; NM504; glucose; metformin; metformin intolerance; microbiome modulator