Combining a gastrointestinal microbiome modulator with metformin may help alleviate intestinal adverse effects commonly related to type 2 diabetes, according to research in the Journal of Diabetes Science and Technology.

The double blind, randomized, crossover study suggests that a gastrointestinal microbiome modulator (GIMM), known to stimulate microbiota that generate short chain fatty acids instead of lactic acid, may help patients with type 2 diabetes better tolerate metformin when the two drugs are taken together. The most common adverse effects related to metformin are diarrhea, heartburn and nausea, followed by abdominal pain, bloating and retching, according to researchers.

“GI side effects prevent many patients from taking metformin and limit dosing in others, and a slow titration schedule is presently the only option to try to reduce metformin-related GI adverse effects,” Mark Heiman, PhD, vice president of research and chief scientific officer at MicroBiome Theraputics, told Endocrine Today. “These issues result in many patients having to turn to more costly anti-diabetic drugs with greater potential safety issues.”

Mark Heiman

Jeffrey Burton, PhD, of Pennington Biomedical Research Center in Baton Rouge, Louisiana, Heiman and colleagues from other institutions analyzed data from 10 patients (eight women) aged 29 to 71 years with type 2 diabetes who reported experiencing metformin adverse effects. Participants completed two treatment sequences between June 2013 and June 2014 — one with metformin/GIMM combination; one with metformin and a placebo — lasting 2 weeks each, with a 2-week break between the sequences. Participants were assigned 500 mg metformin along with their assigned GIMM or placebo at breakfast and dinner for the first week, followed by 500 mg metformin (three times a day) with GIMM or a placebo taken with the first and third metformin doses. Researchers used an adapted questionnaire about irritable bowel syndrome to evaluate GI symptoms and measured fasting blood glucose with a glucometer.

Researchers calculated a composite tolerability score using patient ratings of severity of four GI symptoms, which were then combined into a single score for each participant using a weighted sum.

Combining metformin and GIMM resulted in a better tolerance score than metformin combined with a placebo (6.78 vs. 4.45, P = .0006). In addition, mean fasting glucose levels were lower with the metformin/GIMM combination (121.3 mg/dL) than with the metformin/placebo combination (151.9 mg/dL, P < .02).

“Larger trials with a GIMM-metformin combination are needed to replicate and expand these findings,” Heiman said. “These trials might allow the greater use of metformin in type 2 diabetes patients and improve treatment of the disease.”

“The principal limitation for chronic metformin therapy in some patients is presentation of persistent adverse GI symptoms that may cause patients to discontinue metformin use,” the researchers wrote. “The data observed in this pilot clinical trial suggest that a modulator of the GI microbiome could both alleviate metformin-mediated GI symptoms and may improve glucose regulation.” – by Regina Schaffer