According to the Centers for Disease Control and Prevention (CDC), the prevalence of obesity among U.S. adults was 42.4% in 2017–2018 (1). The World Health Organization reports that >1 billion people worldwide have obesity. Complications associated with obesity include, but are not limited to, cardiovascular disease, diabetes, cancer, musculoskeletal disorders, and poorer outcomes from coronavirus disease 2019 (2).
Type 2 diabetes rates go hand in hand with rates of obesity. The CDC estimates that 130 million U.S. adults are living with diabetes or prediabetes (3). The International Diabetes Federation estimates that 537 million adults worldwide have diabetes, and this number is predicted to increase to 643 million by 2030 and 783 million by 2045 (4). For people with type 2 diabetes, the American Diabetes Association (ADA) supports, in addition to lifestyle change, the use of pharmacological agents that minimize weight gain or promote weight loss, such as glucagon-like peptide 1 (GLP-1) receptor agonists and sodium–glucose cotransporter 2 inhibitors (5).
It is understandable that people with diabetes and their health care professionals alike are interested in alternatives for the prevention and treatment of obesity and type 2 diabetes, as well as other disorders with a significant emphasis on gut health. The use of Akkermansia muciniphila, a bacterium touted to improve metabolic disorders has received growing attention. A. muciniphila is found in large amounts in the gut, especially in the colon, and decreasing levels have been associated with obesity, diabetes, and other metabolic disorders. In animal research, it was found to protect hosts from diet-induced obesity and decrease insulin resistance and intestinal and systemic inflammation (6,7).
Two products developed and manufactured by Pendulum contain A. muciniphila and are currently on the U.S. market. One is marketed for gut health, and the other is marketed for glucose control. The product for gut health contains A. muciniphila as the only beneficial microbe. The product for glucose control, sold under the trade name Pendulum Glucose Control, contains a proprietary, multistrain probiotic blend that contains A. muciniphila, Clostridium butyricum, Clostridium beijerinckii, Anaerobutyricum hallii, and Bifidobacterium infantis. Both products contain chicory inulin, oligofructose, and hypromellose (vegetarian capsule). The prebiotic inulin serves as an initial food source for the five probiotics in Pendulum’s glucose control product.
This review will concentrate on the formulation promoted for glucose control (8).
Indications
This is a medical probiotic (i.e., a medical food to be used under the supervision of a health care provider) that is marketed for the nutritional management of type 2 diabetes to help lower A1C, support gut health, lower glucose spikes, and enhance sugar metabolism. The product is taken as one capsule in the morning and one in the evening with food. It must be refrigerated and used within 6 months after its packaging is opened (8).
Mechanism of Action
Pendulum’s glucose control product restores the body’s ability to produce butyrate and restores the mucin lining of the gut. Butyrate binds to receptors in the gut mucosa and stimulates the release of GLP-1. It has been suggested that this increase may be responsible for restoration of satiety, reduced appetite, improved insulin secretion, reduced hepatic glucose output, and regulation of gastric emptying (6,8).
Potential Advantages
One small, short, multicenter, double-blind, randomized, placebo-controlled, proof-of-concept trial was conducted in people with type 2 diabetes. This 12-week, parallel study included 76 adults who were previously diagnosed with type 2 diabetes and being treated with metformin and/or a sulfonylurea. Participants were randomized to receive either placebo or one of two different active treatments twice daily with food. One treatment contained three strains and the other contained five strains of probiotics. There were no safety or tolerability differences across the three study arms. In the arm receiving the five-strain treatment, there was a statistically significant reduction in the primary outcome of total glucose area under the curve (AUC) of −36 mg/dL/180 minutes (P = 0.05) when compared with placebo. For a secondary outcome of A1C, there was a nonsignificant reduction in both treatment arms (−0.2% in the three-strain arm [P = 0.4684] and −0.6% in the five-strain arm [P = 0.054]). There was no reduction in fasting glucose concentrations; thus, the reduction in total glucose appeared to be driven by postprandial glucose reductions (7).
Potential Disadvantages
Although this proof-of-concept study of the proprietary probiotic blend showed some benefit in reduction of total glucose AUC that was likely driven by postprandial blood glucose reduction, it had a very short duration and a small sample size. There is insufficient evidence to show clear benefits of this product in people with type 2 diabetes in general. There are also no microvascular or microvascular outcome data available. There have been no other human trials with the five-strain blend. There is some very limited and inconsistent support in the literature for A. muciniphila alone and for probiotics in general in people with type 2 diabetes (7).
Cost
Pendulum’s glucose control product can be purchased on the company’s website for $215 for a 30-day supply. Alternatively, one can purchase a “membership” for $165 per month that includes a 30-day supply and optional nutrition coaching (8).
Commentary
There are minimal data to support this product to the greater population of people with diabetes. With that being said, in the small proof-of-concept study, the five-strain probiotic marketed for glucose control does not cause harm and may have a benefit in lowering postprandial blood glucose and A1C (7). Larger and longer trials are needed to determine whether these results can be replicated or improved upon, and if the use of this product could lead to any meaningful outcomes.
Given that there is significant evidence of cardiovascular, renal, and heart failure benefits with multiple available pharmacological treatments for diabetes, this probiotic blend product should not be used instead of validated therapies. If this medical probiotic product is recommended, it should be in addition to—not instead of—other proven therapies. This caution is especially important for people with cardiovascular disease, heart failure, or chronic kidney disease who are taking prescription agents with proven outcomes for these conditions, as described and recommended in ADA guidelines (5). Blood glucose should be monitored via fingerstick testing or continuous glucose monitoring if this probiotic blend product is added to a person’s treatment regimen, in the event that dose adjustments of baseline medications are required.
Bottom Line
This probiotic blend product marketed for glucose control is unlikely to be harmful and may be helpful in lowering postprandial blood glucose and A1C levels in people with type 2 diabetes. However, it is relatively expensive and is not covered by health insurance plans. People with type 2 diabetes should use evidence-based treatment options as a primary treatment when indicated. If the probiotic blend product is considered, it should be used as an add-on rather than as a primary treatment until more robust data are available.
