Short-Term Effects of Sucralose and Saccharin on Blood Sugar and Gut Microbiota in Type 2 Diabetes

NCT07124585 | Not Yet Recruiting

• 1 other identifier: FRGS/1/2024/SKK06/UKM/03/4
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Type 2 Diabetes Mellitus (T2DM)

Keywords

Non-nutritive sweetener; artificial sweetener; gut microbiota; saccharin; sucralose; type 2 diabetes

Outcome Measures

Primary Outcomes (1)

• Glycaemic control

  The primary outcome of this study is to assess the change in glycaemic control, measured by insulin sensitivity using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), which will be calculated from fasting glucose and insulin levels following NNS consumption

  6 months

Secondary Outcomes (1)

• Gut microbiota composition and diversity

  6 months

Study Arms (3)

Crossover Arm 1 (Sucralose)

ACTIVE COMPARATOR

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.

Dietary Supplement: Sucralose

Crossover Arm 2 (Saccharin)

ACTIVE COMPARATOR

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.

Dietary Supplement: Saccharin

Crossover Arm 3 (Placebo)

PLACEBO COMPARATOR

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.

Other: Placebo (Calcium Carbonate)

Interventions

Sucralose DIETARY_SUPPLEMENT

Participants will consume one capsule containing sucralose 5mg/kg body weight, with the dosage individualized according to body weight. The capsule will be taken once daily in the morning, after breakfast, with plain water. This intervention will last for seven consecutive days.

Crossover Arm 1 (Sucralose)

Saccharin DIETARY_SUPPLEMENT

Participants will consume one capsule containing saccharin 2mg/kg body weight, with the dosage individualized according to body weight. The capsule will be taken once daily in the morning, after breakfast, with plain water. This intervention will last for seven consecutive days.

Crossover Arm 2 (Saccharin)

Placebo (Calcium Carbonate) OTHER

Participants will consume one capsule per day, containing a fixed dose of 500 mg. The capsule will be taken once daily in the morning, after breakfast, with plain water. This intervention will last for seven consecutive days.

Crossover Arm 3 (Placebo)

Eligibility Criteria

• Age: 30 Years - 50 Years
• Gender Eligibility Details: Male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male citizens of Malaysia.
• Aged between 30 and 59 years.
• BMI between 23-29.9 kg/m² (Overweight).
• Diagnosed with diabetes for a duration between 1-10 years.
• Currently on oral antidiabetic medications and not on insulin.
• Initial HbA1c less than 10%.
• 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.
• 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.
• Willing to refrain from alcohol throughout the study period.
• Must be literate in English or Bahasa Malaysia.

You may not qualify if:

• Current smoking, alcohol use, or drug abuse.
• Experienced more than a 5% change in body weight within the past 3 months.
• Acute illness or significant cardiovascular, psychological, neurological, renal, or endocrine diseases, apart from diabetes.
• Intolerance or allergy to test products.
• Special dietary practices (e.g., intermittent fasting, vegetarian, ketogenic diet) that deviate from typical Malaysian dietary patterns.
• Treatment with glucocorticoids, antibiotics or other medications and food supplements (e.g. probiotics) that can significantly alter intestinal function and gut microbiome.
• Involvement in clinical trials within the last 3 months.

Sponsors & Collaborators

• National University of Malaysia: lead
• Monash University Malaysia: collaborator

Study Sites (1)

Klinik Kesihatan Setapak

Kuala Lumpur, 53300, Malaysia

Location

Related Publications (11)

• Suez J, Korem T, Zeevi D, Zilberman-Schapira G, Thaiss CA, Maza O, Israeli D, Zmora N, Gilad S, Weinberger A, Kuperman Y, Harmelin A, Kolodkin-Gal I, Shapiro H, Halpern Z, Segal E, Elinav E. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature. 2014 Oct 9;514(7521):181-6. doi: 10.1038/nature13793. Epub 2014 Sep 17.

  PMID: 25231862 RESULT

• Serrano J, Smith KR, Crouch AL, Sharma V, Yi F, Vargova V, LaMoia TE, Dupont LM, Serna V, Tang F, Gomes-Dias L, Blakeslee JJ, Hatzakis E, Peterson SN, Anderson M, Pratley RE, Kyriazis GA. High-dose saccharin supplementation does not induce gut microbiota changes or glucose intolerance in healthy humans and mice. Microbiome. 2021 Jan 12;9(1):11. doi: 10.1186/s40168-020-00976-w.

  PMID: 33431052 RESULT

• Suez J, Cohen Y, Valdes-Mas R, Mor U, Dori-Bachash M, Federici S, Zmora N, Leshem A, Heinemann M, Linevsky R, Zur M, Ben-Zeev Brik R, Bukimer A, Eliyahu-Miller S, Metz A, Fischbein R, Sharov O, Malitsky S, Itkin M, Stettner N, Harmelin A, Shapiro H, Stein-Thoeringer CK, Segal E, Elinav E. Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance. Cell. 2022 Sep 1;185(18):3307-3328.e19. doi: 10.1016/j.cell.2022.07.016. Epub 2022 Aug 19.

  PMID: 35987213 RESULT

• Ahmad SY, Friel J, Mackay D. The Effects of Non-Nutritive Artificial Sweeteners, Aspartame and Sucralose, on the Gut Microbiome in Healthy Adults: Secondary Outcomes of a Randomized Double-Blinded Crossover Clinical Trial. Nutrients. 2020 Nov 6;12(11):3408. doi: 10.3390/nu12113408.

  PMID: 33171964 RESULT

• Wu J, Wang K, Wang X, Pang Y, Jiang C. The role of the gut microbiome and its metabolites in metabolic diseases. Protein Cell. 2021 May;12(5):360-373. doi: 10.1007/s13238-020-00814-7. Epub 2020 Dec 21.

  PMID: 33346905 RESULT

• Brown RJ, de Banate MA, Rother KI. Artificial sweeteners: a systematic review of metabolic effects in youth. Int J Pediatr Obes. 2010 Aug;5(4):305-12. doi: 10.3109/17477160903497027.

  PMID: 20078374 RESULT

• Mendez-Garcia LA, Bueno-Hernandez N, Cid-Soto MA, De Leon KL, Mendoza-Martinez VM, Espinosa-Flores AJ, Carrero-Aguirre M, Esquivel-Velazquez M, Leon-Hernandez M, Viurcos-Sanabria R, Ruiz-Barranco A, Cota-Arce JM, Alvarez-Lee A, De Leon-Nava MA, Melendez G, Escobedo G. Ten-Week Sucralose Consumption Induces Gut Dysbiosis and Altered Glucose and Insulin Levels in Healthy Young Adults. Microorganisms. 2022 Feb 14;10(2):434. doi: 10.3390/microorganisms10020434.

  PMID: 35208888 RESULT

• Thomson P, Santibanez R, Aguirre C, Galgani JE, Garrido D. Short-term impact of sucralose consumption on the metabolic response and gut microbiome of healthy adults. Br J Nutr. 2019 Oct 28;122(8):856-862. doi: 10.1017/S0007114519001570. Epub 2019 Sep 13.

  PMID: 31258108 RESULT

• Zhou Z, Sun B, Yu D, Zhu C. Gut Microbiota: An Important Player in Type 2 Diabetes Mellitus. Front Cell Infect Microbiol. 2022 Feb 15;12:834485. doi: 10.3389/fcimb.2022.834485. eCollection 2022.

  PMID: 35242721 RESULT

• Toews I, Lohner S, Kullenberg de Gaudry D, Sommer H, Meerpohl JJ. Association between intake of non-sugar sweeteners and health outcomes: systematic review and meta-analyses of randomised and non-randomised controlled trials and observational studies. BMJ. 2019 Jan 2;364:k4718. doi: 10.1136/bmj.k4718.

  PMID: 30602577 RESULT

• Tan HS, Gilcharan Singh HK, Mariappan V, Jamil NA, Mustapa SN, Misra S. Short-Term Effects of Nonnutritive Sweetener (Sucralose and Saccharin) Consumption on Glycemic Control and Gut Microbiota in Patients With Type 2 Diabetes: Protocol for a Double-Blind, Randomized, Placebo-Controlled, Crossover Trial. JMIR Res Protoc. 2025 Dec 10;14:e82695. doi: 10.2196/82695.

  PMID: 41370820 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

trichlorosucrose; Saccharin; Calcium Carbonate

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Benzothiazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Calcium Compounds; Inorganic Chemicals; Carbonates; Carbonic Acid; Carbon Compounds, Inorganic; Minerals

Central Study Contacts

Harvinder Kaur, Phd

CONTACT

603 8921 5555; harvinder_kaur@ukm.edu.my

Huey Shin Tan

CONTACT

p153672@siswa.ukm.edu.my

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Lecturer

Study Record Dates

• First Submitted: August 8, 2025
• First Posted: August 15, 2025
• Study Start: January 30, 2026
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): July 31, 2027
• Last Updated: December 10, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: De-identified individual participant data (IPD), study protocol, SAP, ICF, and analytic code will be available beginning 6 months after publication of the primary results and will remain available for 5 years thereafter. Extensions may be considered upon request. Data will not be available before publication.
• Access Criteria: Access to de-identified IPD and supporting documents will be granted to qualified researchers affiliated with academic institutions or non-profit organizations for scientific purposes only. Requests must include a methodologically sound proposal and be reviewed by the principal investigator and the study's ethics committee. Approved data will be shared through secure institutional data-sharing platforms or encrypted transfer, under a data use agreement that ensures participant confidentiality and responsible data handling.

Locations

MY (1)