The ‘cobiotic’ NM504 - a proprietary combination of purified inulin, beta-glucan and blueberry pomace extract - was developed by MicroBiome Therapeutics (formerly NuMe Health), a biotech firm co-founded by Whole Foods Market chairman John Elstrott.

NM504 is also the subject of two placebo-controlled, double-blinded, proof-of-concept trials. The first is assessing its ability to alter the GI microbiome to enhance insulin sensitivity and fasting blood glucose levels in prediabetics, and the second is testing its utility as an adjunctive therapy to Metformin.

Physicians report diarrhea as a frequent cause of Metformin discontinuation or dosage limitation ​

In the case study, ‘JH’, a 30-year old man just diagnosed with type 2 diabetes, developed diarrhea during the first few days of Metformin treatment and only saw a small drop in fasting blood sugar (FBS) from 375mg/dl to 325 mg/dl.

On the 9th day of Metformin treatment he started taking NM504 in a smoothie twice a day [in addition to Metformin], and saw rapid improvements.

After two days, his FBS dropped to 175 mg/dl and after eight weeks, his blood sugar was 100 mg/dl and he had lost 5.5 kg. His bowel movements, which returned to normal once he started taking the smoothies, reverted to diarrhea when he went off them for two days, and then returned to normal once he started drinking them again, said the authors.

Dr Mark Heiman: 'NM504 virtually eliminated the diarrhea caused by Metformin in this patient with type 2 diabetes and was also associated with additional large decreases in his highly elevated blood glucose levels.'

“Metformin is a safe, effective and inexpensive generic medication favoring weight loss, recommended as initial treatment of type 2 diabetes by the American Diabetes Association. However, a 20% incidence of diarrhea limits its tolerability.​

“Physicians report diarrhea as a frequent cause of Metformin discontinuation or dosage limitation. The second-line therapies prescribed as a substitute for metformin are expensive and carry risks of potentially serious side effects.”​

NM504 virtually eliminated the diarrhea caused by Metformin in this patient ​

Co-author Mark Heiman, Ph.D., chief scientific officer of MicroBiome Therapeutics, added: “NM504 virtually eliminated the diarrhea caused by Metformin in this patient with type 2 diabetes and was also associated with additional large decreases in his highly elevated blood glucose levels.​

“Research shows that the human GI microbiome plays an important role in the regulation of metabolic processes, including changes associated with type 2 diabetes. ​

“Modern diets often lack essential ingredients that support a healthy microbiome, so we designed NM504 to replace key missing elements that impact the GI microbiome in ways known to be beneficial to metabolic and gastrointestinal health.”​

The microbiome in people with type 2 diabetes is different in significant ways from that of healthy individuals​

In a recent interview with FoodNavigator-USA, MicroBiome Therapeutics CEO Dr Steve Orndorff said rodent studies on NM504 showed it can beneficially alter the balance of gut microflora, increase insulin sensitivity, improve oral glucose tolerance test results, lower overnight fasting blood glucose levels and improve lipid profiles.

The human trials are designed to show whether it can also help humans maintain healthy blood sugar levels by beneficially altering the balance of gut microflora, increasing Bacteriodetes​ microbiota and decreasing Firmicutes​ microbiota, he said.

“Research ​[analysis of fecal microbiota] shows that the microbiome in people with type 2 diabetes is different in significant ways from that of healthy individuals​.”

The status of medical foods for diabetics​

If current trends continue, says the American Diabetes Association, one in three American adults will have diabetes by 2050

Current advice given to people with pre-diabetes - being told to exercise more and lose weight - is not working, said Orndorrf, who said that in addition to exploring its potential as an adjunct therapy to Metformin, he was is in talks with consumer healthcare and pharmaceutical firms about developing medical foods containing NM504.

But are medical foods for diabetics going to be permitted in future now that the FDA has spelled out in new revised draft guidance (click here​) that it does not think they should be?

In the Q&A section of the guidance - which is already causing shockwaves in the industry​ although it is not legally binding - the agency writes:

Q: Does FDA consider type 1 or type 2 DM (Diabetes Mellitus) to be conditions for which a medical food could be labeled and marketed?​

A: No. Diet therapy is the mainstay of diabetes management. A regular diet can be modified to meet the needs of an individual affected by either type of DM along with appropriate drug therapy if necessary. Under 21 CFR 101.9(j)(8)(ii), a medical food must be intended for a patient who has a limited or impaired capacity to ingest, digest, absorb, or metabolize ordinary foodstuffs or certain nutrients, or who has other special medically determined nutrient requirements, the dietary management of which cannot be achieved by the modification of the normal diet alone. ​

Therefore, FDA generally would not ​ consider a product labeled and marketed for DM to meet the regulatory criteria for a medical food.​

Orndorrf declined to comment on the above guidance, but a spokesperson said: “This is draft guidance and just out recently, so we also currently evaluating it, as well as our response.”​

The ticking time bomb of type 2 diabetes​

According to the American Diabetes Association, pre-diabetes (elevated fasting blood glucose levels), is estimated to affect 79m or one in three American adults, and if unchecked, can lead to type 2 diabetes.

If current trends continue, says the charity, one in three American adults will have diabetes by 2050.

Source​: Beneficial Microbes​​ DOI 10.3920/BM2012.0063

‘A novel cobiotic containing a prebiotic and an antioxidant augments the glucose control and gastrointestinal tolerability of metformin: a case report’​

Authors​: F Greenway, S Wang, M Heiman