Short-Term Effect of Non-Nutritive Sweeteners (Sucralose and Saccharin) Consumption on Glycaemic Control and Gut Microbiota in Type 2 Diabetes Patients: Study Protocol for a Double-Blind, Randomised, Placebo-Controlled, Crossover Trial (Preprint)

BACKGROUND Non-nutritive sweeteners (NNS) are widely used as sugar substitutes to help individuals with diabetes manage glycaemic control. However, emerging evidence suggests that even low doses of NNS, such as saccharin and sucralose, may adversely affect metabolic health by impairing glycaemic regulation. These effects appear to be mediated, in part, by changes in the gut microbiome. In Malaysia, where gut microbiome research is still limited, particularly among individuals with Type 2 Diabetes Mellitus (T2DM) further investigation is needed to inform guidelines for NNS use. OBJECTIVE This is a double-blind, randomised, placebo-controlled, crossover trial designed to evaluate the short-term effects of saccharin and sucralose on glycaemic control and the gut microbiota. METHODS A total of 33 adults with T2DM will consume sucralose (5 mg/kg body weight), saccharin (2 mg/kg body weight), or a placebo (calcium carbonate) in capsule form daily for seven days in each intervention arm with a month wash-out period. Data collection will include anthropometric measurements, biochemical assessment for glycaemic control, dietary food records, physical activity levels, and stool samples for 16S rRNA gene sequencing to assess gut microbiota composition. RESULTS - CONCLUSIONS This trial will contribute novel insights into the effects of short-term NNS consumption on glycaemic control and gut microbiota composition in individuals with T2DM. This finding may support evidence-based recommendations for NNS use in diabetes management and enhance understanding of microbiome-diet interactions in an ethnically diverse Asian population. CLINICALTRIAL This trial is registered at ClinicalTrials.gov (NCT07124585).