Short-Term Effect of Non-Nutritive Sweeteners (Sucralose and Saccharin) Consumption on Glycaemic Control and Gut Microbiota in Type 2 Diabetes Patients
| Registry | NCT07124585 |
|---|---|
| Status | Not yet recruiting |
| Phase | Not applicable |
| Study type | Interventional; randomized, crossover, masking: double, prevention |
| Enrollment | 33 (Estimated) |
| Sponsor | National University of Malaysia (Other); collaborators: Monash University Malaysia |
| Conditions | Type 2 Diabetes Mellitus (T2DM) |
| Interventions | Sucralose, Saccharin, Placebo (Calcium Carbonate) (Dietary supplement, other) |
| Dates | start 2026-01-30 (estimated), primary completion 2026-09-30 (estimated), completion 2027-07-31 (estimated), first posted 2025-08-15, last updated 2025-12-10 |
| Locations | 1 site in Malaysia |
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This clinical trial investigates the short-term effects of two commonly used non-nutritive sweeteners (NNS), saccharin and sucralose, on blood glucose regulation and the gut microbiota in adults with Type 2 Diabetes Mellitus (T2DM). While NNS are widely promoted as sugar substitutes to aid glycaemic control, emerging evidence suggests that even small doses may influence metabolic health, potentially through interactions with the gut microbial community.
The study is designed as a double-blind, randomized, placebo-controlled, crossover trial involving 33 adults with T2DM. Each participant will receive all three interventions, saccharin, sucralose, and a placebo (calcium carbonate) in random order. Each intervention will be administered once daily in capsule form for 7 consecutive days, with a 4-week washout period between phases to minimize carryover effects.
Throughout the trial, data will be collected on anthropometry, blood-based glycaemic biomarkers, dietary intake, physical activity, and stool samples. Gut microbiota composition will be assessed via 16S rRNA gene sequencing.
The primary aim is to generate evidence on whether short-term exposure to NNS can affect glycaemic outcomes and gut microbial profiles in individuals with T2DM. The findings are expected to support future dietary recommendations on NNS use and improve our understanding of diet-microbiota-host interactions, particularly within Asian populations.
Although these sweeteners are generally recognized as safe, emerging studies have raised concerns regarding their potential metabolic effects. In particular, findings on their influence on glycaemic control in humans remain inconsistent. One proposed mechanism underlying these effects involves modulation of the gut microbiota, which is increasingly recognised as a critical regulator of host metabolic homeostasis. However, current evidence in human studies is limited and inconclusive.
Individuals with T2DM commonly exhibit pre-existing gut dysbiosis, raising important questions about whether the use of NNS may further impair microbial composition or function. To date, no clinical trial has comprehensively examined the short-term effects of sucralose and saccharin on both glycaemic responses and the gut microbiota in specific T2DM population. Moreover, data from Asian populations whose dietary patterns, gut microbial composition, and metabolic phenotypes differ significantly from Western cohorts are scarce. Given the widespread consumption of NNS in daily diets, especially among individuals seeking glycaemic control, this represents a critical evidence gap with potential implications for dietary recommendations and metabolic health.
This study aims to address these gaps through a clinical trial in adults with T2DM. The crossover design enables within-subject comparisons, thereby reducing inter-individual variability and enhancing statistical power to detect subtle biological effects. Reference to previous studies has shown inconsistencies arising from factors such as inconsistent dosing, varying administration routes (e.g., sachet vs. capsule; pure compound vs. commercial product), differences in intervention duration, and a lack of control for confounding variables such as habitual diet, medication use, and physical activity. To address these issues, we have incorporated several methodological improvements. Our study will implement a body weight-based individual dosing protocol, oral administration in a standardised pure compound capsule form, and detailed characterisation of participants' dietary intake and lifestyle behaviours.
Additionally, for our study phenotype, we have strictly controlled for patients' diabetes progression, including diagnosis duration (1-5 years), treatment type (oral antidiabetic medication only, no insulin), age group (30-50 years), demographic (male only), ethnicity (single ethnic group), and BMI range (specified). Through these measures, our study aims to minimise variability, particularly in gut microbiota outcomes and generate more robust results.
| Arm | Type | Interventions | Description |
|---|---|---|---|
| Crossover Arm 1 (Sucralose) | Active comparator | Dietary Supplement: Sucralose | Each participant will receive all three interventions, sucralose, saccharin, and placebo in a randomized sequence over three separate phases. Each intervention phase lasts for seven consecutive days and is separated by a washout period of 4 weeks to minimize carryover effects. |
| Crossover Arm 2 (Saccharin) | Active comparator | Dietary Supplement: Saccharin | Each participant will receive all three interventions, sucralose, saccharin, and placebo in a randomized sequence over three separate phases. Each intervention phase lasts for seven consecutive days and is separated by a washout period of 4 weeks to minimize carryover effects. |
| Crossover Arm 3 (Placebo) | Placebo comparator | Other: Placebo (Calcium Carbonate) | Each participant will receive all three interventions, sucralose, saccharin, and placebo in a randomized sequence over three separate phases. Each intervention phase lasts for seven consecutive days and is separated by a washout period of 4 weeks to minimize carryover effects. |
Sex: Male, ages: 30 Years to 50 Years
Inclusion criteria This study aims to recruit a cohort of patients with early-phase diagnosed T2DM whose conditions are stable that can best represent the Malaysian DM phenotypes. 1. Male citizens of Malaysia. 2. Aged between 30 and 59 years. 3. BMI between 23-29.9 kg/m² (Overweight). 4. Diagnosed with diabetes for a duration between 1-10 years. 5. Currently on oral antidiabetic medications and not on insulin. 6. Initial HbA1c less than 10%. 7. Patients with other stable, non-severe chronic conditions (e.g., hypertension, dyslipidemia) may be included if they have been on a stable prescribed oral treatment for at least 6 months. 8. Patients who have undergone dietary counselling for diabetes and are willing to maintain their habitual diabetes-friendly diet and usual physical activity patterns throughout the study period. 9. Willing to refrain from alcohol throughout the study period. 10. Must be literate in English or Bahasa Malaysia. Exclusion criteria The exclusion criteria will primarily focus on lifestyle behaviours or dietary practices that deviate from typical Malaysian lifestyles and while also considering behaviours that could significantly alter the gut microbiota. 1. Current smoking, alcohol use, or drug abuse. 2. Experienced more than a 5% change in body weight within the past 3 months. 3. Acute illness or significant cardiovascular, psychological, neurological, renal, or endocrine diseases, apart from diabetes. 4. Intolerance or allergy to test products. 5. Special dietary practices (e.g., intermittent fasting, vegetarian, ketogenic diet) that deviate from typical Malaysian dietary patterns. 6. Treatment with glucocorticoids, antibiotics or other medications and food supplements (e.g. probiotics) that can significantly alter intestinal function and gut microbiome. 7. Involvement in clinical trials within the last 3 months.
| Facility | City | Country | Status |
|---|---|---|---|
| Klinik Kesihatan Setapak | Kuala Lumpur | Malaysia |