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CU Medicine reveals dietary interventions with fermentable carbohydrates boosts metformin efficacy in type 2 diabetes prevention
Researchers from The Chinese University of Hong Kong (CUHK)’s Faculty of Medicine (CU Medicine) have revealed that a moderate intake of fermentable carbohydrates, also referred to as FODMAPs[1], significantly enhances the efficacy of metformin, a first-line drug that prevents individuals with prediabetes from developing type 2 diabetes. This drug-food combination lowered post-meal blood sugar levels and improved gut microbiota. These results underscore the importance of more personalised nutrition to complement drug interventions. The findings from this research, conducted in collaboration with CU Medicine’s School of Pharmacy and Monash University, Australia, have been published in the internationally renowned journal Nature Metabolism.
Insulin is needed to regulate blood sugar levels. Individuals with prediabetes have impaired insulin secretion and actions. In China, one in five individuals with prediabetes may progress to type 2 diabetes every year[2]. Metformin is considered the first-line drug for preventing diabetes although it may cause gastrointestinal (GI) side effects. In clinical trials, as many as 15% of individuals with prediabetes treated with metformin experience gastrointestinal symptoms, such as nausea, flatulence or diarrhoea[2]. These side effects may reduce adherence to metformin despite its proven effectiveness in preventing progression from prediabetes to diabetes, calling for strategies to ensure that people continue taking it.
In the current study led by CU Medicine’s researchers, 26 individuals with prediabetes, aged between 48 and 60 years, participated in a double-blind, randomised, two-period, cross-over controlled feeding trial. Participants were assigned to receive two 10-day dietary interventions including a moderate-FODMAP (12 grams per day) and a low-FODMAP (2 grams per day) diet containing the same calories in a random order. In each dietary phase, metformin was administered during the last five days. All participants received blinded continuous glucose monitoring (CGM) to capture differences in blood sugar profiles.
During the trial, participants had better health indices during the phase of moderate-FODMAP diet with metformin (M-M intervention) than during the phase of low-FODMAP diet with metformin (L-M intervention). These improvements were independent of changes in intake:
- Improved blood sugar control: The M-M intervention led to a 21% decrease in post-meal blood sugar levels compared to 12% after the L-M intervention, indicating that a high FODMAP diet enhanced the glucose-lowering effect of metformin.
- Enhanced insulin response: Glucagon-like peptide 1 (GLP-1) is a gut hormone that augments meal-related insulin secretion and increases satiety. Compared with the L-M intervention, the M-M intervention tripled the baseline level of GLP-1, and induced a 98% higher late-phase GLP-1 secretion, with a 80% higher late-phase insulin secretion post-meal. There were minimal hormonal changes with the L-M intervention.
- A healthier gut microbiota: The M-M intervention doubled the abundance of the short-chain fatty acid-producing bacterium Butyricimonas virosa compared to the L-M intervention which contributes to better blood sugar control and reduced systemic inflammation.
- A predictive biomarker for metformin intolerance: Metformin-intolerant participants had higher baseline levels of Dorea formicigenerans than metformin-tolerant participants, suggesting this microbiota could be a promising biomarker for identifying individuals susceptible to GI side effects of metformin, paving the way for personalised treatment.
Dr Natural Chu Hoi-sing, the first author of the study and a post-doctoral fellow from the Department of Medicine and Therapeutics at CU Medicine, said: ‘‘Our findings unravel the benefits of moderate, rather than low FODMAP intake, in altering gut microbiota, which will enhance the glucose-lowering effects of metformin as the first-line drug for preventing type 2 diabetes.’’
Dr Elaine Chow Yee-kwan, the corresponding author and Associate Professor (Clinical) in the Department of Medicine and Therapeutics at CU Medicine, remarked: “The efficacy of a local, moderate-FODMAP diet suggests a promising diet-metformin combination for clinicians. Soy milk, watermelon and mushrooms are potentially suitable food choices that are rich in FODMAPs. We will conduct further studies on combining drugs with nutritional interventions to benefit more individuals with prediabetes and diabetes.”
Professor Juliana Chan Chung-ngor from Department of Medicine and Therapeutics at CU Medicine and the Founding Director of the Hong Kong Institute of Diabetes and Obesity added: ‘‘One in 10 adults in Hong Kong suffers from type 2 diabetes and preventing its onset is a top priority. Introducing transformative models that integrate precision medicine with personalised diabetes care including dietary management is key to addressing this major global health issue.’’
[1] Fermentable oligosaccharides, disaccharides, monosaccharides and polyols
[2] China Diabetes Prevention Program (CDPP) trial
Featured are research team members including (from left) Professor Juliana Chan Chung-ngor, Research Professor of CU Medicine’s Department of Medicine and Therapeutics and the Founding Director of the Hong Kong Institute of Diabetes and Obesity; Dr Natural Chu Hoi-sing, the first author of the study and a post-doctoral fellow; and Dr Elaine Chow Yee-kwan, the corresponding author and Associate Professor from CU Medicine’s Department of Medicine and Therapeutics; as well as Professor Joan Zuo Zhong from CU Medicine’s School of Pharmacy.
A better gut microbiota and glucose-lowering effect of metformin are shown in patients with prediabetes during the phase of moderate-FODMAP diet with metformin (M-M intervention) than during the phase of low-FODMAP diet with metformin (L-M intervention), resulting in more effective type 2 diabetes prevention.
The research introduces a novel diet-drug combination for type 2 diabetes prevention. The moderate FODMAP diet adopted include a variety of food rich in FODMAPs such as (top left) mangetout, onion and a drizzle of honey; (bottom left) butternut pumpkin and black bean garlic sauce; (top right) savory cabbage and the white part of spring onion; and (bottom right) butternut pumpkin, red date, and chopped cauliflower.
