Jeffrey H Burton1, Matthew Johnson2, Jolene Johnson3, Daniel S Hsia1, Frank L Greenway1, Mark L Heiman4. 1. Pennington Biomedical Research Center, Baton Rouge, LA, USA. 2. Pennington Biomedical Research Center, Baton Rouge, LA, USA Louisiana State University Health Sciences Center, Baton Rouge, LA, USA. 3. Louisiana State University Health Sciences Center, Baton Rouge, LA, USA. 4. MicroBiome Therapeutics, Broomfield, CO, USA mheiman@mbiome.com.
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). CONCLUSION: Combining a GI microbiome modulator with metformin might allow the greater use of metformin in T2D patients and improve treatment of the disease.
RCT Entities:
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 diabetespatients (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). CONCLUSION: Combining a GI microbiome modulator with metformin might allow the greater use of metformin in T2D patients and improve treatment of the disease.
Authors: Jasmine F Plows; Florence Budin; Rebecka A M Andersson; Valerie J Mills; Katherine Mace; Sandra T Davidge; Mark H Vickers; Philip N Baker; Irma Silva-Zolezzi; Joanna L Stanley Journal: Nutrients Date: 2017-02-15 Impact factor: 5.717
Authors: Alexandra Zhernakova; Alexander Kurilshikov; Marc Jan Bonder; Ettje F Tigchelaar; Melanie Schirmer; Tommi Vatanen; Zlatan Mujagic; Arnau Vich Vila; Gwen Falony; Sara Vieira-Silva; Jun Wang; Floris Imhann; Eelke Brandsma; Soesma A Jankipersadsing; Marie Joossens; Maria Carmen Cenit; Patrick Deelen; Morris A Swertz; Rinse K Weersma; Edith J M Feskens; Mihai G Netea; Dirk Gevers; Daisy Jonkers; Lude Franke; Yurii S Aulchenko; Curtis Huttenhower; Jeroen Raes; Marten H Hofker; Ramnik J Xavier; Cisca Wijmenga; Jingyuan Fu Journal: Science Date: 2016-04-28 Impact factor: 47.728