Miriam E. Tucker
August 03, 2020
The findings were published online July 27 in BMJ Open Diabetes Research & Care by Fanny Perraudeau, PhD, and colleagues, all employees of Pendulum Therapeutics.
The product, classified as a medical food, is currently available for purchase on the company's website without a prescription.
It contains the oligosaccharide-consuming Akkermansia muciniphila and Bifidobacterium infantis, the butyrate producers Anaerobutyricum hallii, Clostridium beijerinckii, and Clostridium butyricum, along with the "prebiotic" dietary fiber inulin.
Participants in the active treatment arm had significantly reduced glucose levels after a 3-hour standard meal-tolerance test, by 36.1 mg/dL (P = .05), and average A1c reduction of 0.6 percentage points (P = .054) compared with those taking placebo.
There were no major safety or tolerability issues, only transient gastrointestinal symptoms (nausea, diarrhea) lasting 3-5 days. No changes were seen in body weight, insulin sensitivity, or fasting blood glucose.
Asked to comment on the findings, Nanette I. Steinle, MD, an endocrinologist with expertise in nutrition who was not involved in the research, told Medscape Medical News: "To me it looks like the research was designed well and they didn't overstate the results ... I would say for folks with mild to modest blood glucose elevations, it could be helpful to augment a healthy lifestyle."
However, the product is not cheap, so cost could be a limiting factor for some patients, said Steinle, who is associate professor of medicine at the University of Maryland School of Medicine, Baltimore, and chief of the endocrine section, Maryland VA Health Care System.
Product Could Augment Lifestyle Intervention in Early Type 2 Diabetes
Lead author Orville Kolterman, MD, chief medical officer at Pendulum, told Medscape Medical News that the formulation's specificity distinguishes it from most commercially available probiotics.
"The ones sold in stores are reconfigurations of food probiotics, which are primarily aerobic organisms, whereas the abnormalities in the microbiome associated with type 2 diabetes reside in anaerobic organisms, which are more difficult to manufacture," he explained.
The fiber component, inulin, is important as well, he said.
"This product may make the dietary management of type 2 diabetes more effective, in that you need both the fiber and the microbes to ferment the fiber and produce short-chain fatty acids that appear to be very important for many reasons."
The blood glucose-lowering effect is related in part to the three organisms' production of butyrate, which binds to epithelial cells in the gut to secrete glucagon-like peptide-1 (GLP-1), leading to inhibition of glucagon secretion among other actions.
And Akkermansia muciniphila protects the gut epithelium and has shown some evidence of improving insulin sensitivity and other beneficial metabolic effects in humans.
Kolterman, who was with Amylin Pharmaceuticals prior to moving to Pendulum, commented: "After doing this for 30 years or so, I've come to the strong appreciation that whenever you can do something to move back toward what Mother Nature set up, you're doing a good thing."
Clinically, Kolterman said, "I think perhaps the ideal place to try this would be shortly after diagnosis of type 2 diabetes, before patients go on to pharmacologic therapy."
However, for practical reasons the study was done in patients who were already taking metformin. "The results we have are that it's beneficial above and beyond metformin, since [these] patients weren't controlled with metformin."
He also noted that it might benefit patients who can't tolerate metformin or who have prediabetes; there's an ongoing investigator-initiated study of the latter.
Steinle, the endocrinologist with expertise in nutrition, also endorsed the possibility that the product may benefit people with prediabetes. "I would suspect this could be very helpful to augment attempts to prevent diabetes ... The group with prediabetes is huge."
However, she cautioned, "if the blood glucose is over 200 [mg/dL], I wouldn't think a probiotic would get them where they need to go."
Cost Could Be an Issue
Moreover, Steinle pointed out that cost might be a problem, given it is not covered by health insurance.
The product's website lists several options: a "no commitment" one-time 30-day supply for $198; a "3-month starter package" including two free A1c tests for $180/month; and a "membership" including free A1c tests every 90 days, free dietician consultations, and "additional exclusive membership benefits" for $165/month.
"There's a very large market out there of people who don't find traditional allopathic medicine to be where they want to go for their healthcare," Steinle observed.
"If they have reasonable means and want to try the 'natural' approach, they'll probably see results but they'll pay a lot for it," she said.
Overall, she pointed out that targeting the microbiome is a very active and potentially important field of medical research, and that it has received support from the US National Institutes of Health (NIH).
"I do think we'll see more of these types of products and use of the microbiome in various forms to treat a number of conditions."
"I think we're in the early stages of understanding how what grows in us, and on us, impacts our health and how we may be able to use these organisms to our benefit. I would expect we'll see more of these probiotics being marketed in various forms."
Kolterman is an employee of Pendulum. Steinle has reported receiving funding from the NIH, and she is conducting a study funded by Kowa through the VA.