Study Of Drinks With Artificial Sweeteners in People With Type 2 Diabetes (SODAS)

Effect of Artificially Sweetened Beverages on Diabetes Control in Adults With Type 2 Diabetes

Diet beverages sweetened with artificial sweeteners occupy a unique category in the food environment as they are a source of intensely sweet taste with no calories. Diet beverages are the single largest contributor to artificial sweetener intake in the U.S. diet, and people with diabetes are the highest consumers of diet beverages, tending to consume them as a replacement for dietary sources of sugar, especially in place of sugar-sweetened beverages. This behavior has been endorsed by dietetic and scientific organizations, and diet beverages are marketed as being synonymous with better health, suitable for weight loss, and thus advantageous for diabetes control. The underlying public health concern is that there are few data to support or refute the benefit or harm of habitual diet beverage consumption by people with diabetes; therefore randomized trials with relevant outcomes must be conducted because they would address many limitations of previous research and have major implications for dietary recommendations on diet beverage intake and primary and secondary prevention of chronic disease. To begin addressing this important scientific gap the investigators are testing the effect of diet beverage intake on diabetes control parameters in free-living adults with type 2 diabetes in a randomized, two arm parallel trial with a run-in period of 2-weeks and an active intervention period of 24-weeks. This study will recruit 200 patients with type 2 diabetes who are usual consumers of commercial diet beverages and randomize them to receive and consume either: 1) A commercial diet beverage of choice (3 servings or 24 oz. daily); or 2) Unflavored bottled water of choice (sparkling or plain) (3 servings or 24 oz. daily). The primary outcome will be a central measure of clinical diabetes control in glycated hemoglobin (HbA1c). The study will also measure the nature and magnitude of glycemic excursions via continuous glucose monitors, as well as clinical markers of cardiometabolic risk and kidney function. Lastly, investigators will measure plausible mechanisms whereby diet beverage intake may alter risk by assessing the effect of diet beverage intake on the functional composition of the gut microbiome via stool samples and comprehensive metabolomics, satiety hormones, as well as usual dietary intake, and upstream behavioral pathways which may inform dietary intake patterns.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Behavioral: Diet Beverage; Behavioral: Water

• Study Type: Interventional
• Enrollment (Actual): 181
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Irvine, California, United States, 92697
      • University of California, Irvine
  • Minnesota
    • Minneapolis, Minnesota, United States, 55454
      • University of Minnesota

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 31 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria: We will include men, women and non-binary participants with T2D, age 35 years and older, able to provide informed consent, otherwise healthy, who meet the following criteria:

• Physician diagnosed type 2 diabetes ≥ 6 months prior to screening
• HbA1c 6.5-8.5% at participant screening
• Current treatment with lifestyle changes or stable diabetes-related medication levels for the past 3 months
• Willingness to provide consent to contact treating physician and physician agreement to refrain from changing diabetes-related medications during the trial (change defined as > 2 fold change in dose of any 1 hyperglycemic agent or addition or subtraction of an agent)
• No physician-directed medication change for 3 months if prescribed medication for lipids or blood pressure
• Usual consumers of diet beverages (≥ 3 servings/ week (24 oz.) and the willingness to maintain fidelity of the intervention, and participate in all aspects of the intervention
• Not actively looking to make major lifestyle alterations during the study period with stable weight for 2 months (within 3%).

Exclusion Criteria:

• Type 1 diabetes or suspected type 1 diabetes (lean with polyuria, polydipsia, and weight loss with little response to metformin)
• "Secondary" diabetes due to specific causes (e.g. monogenic syndromes, pancreatic surgery, and pancreatitis)
• Diabetic Ketoacidosis hospitalization within last 6 months
• Severe/major hypoglycemia in the last 3 months-severe/major hypoglycemia is defined as a hypoglycemic event in which patient requires assistance of another person to manage the episode
• Glucocorticoid use (prednisone 2.5 mg/d or more or its equivalent)
• History of intolerance or allergy to diet beverages or AS or phenylketonuria
• Any condition that is known to affect the validity of the glycemic measures (Hba1c)
• Major cardiovascular disease event or surgery within past 6 months
• Gastrointestinal disease
• Renal or liver disease
• Current treatment for cancer
• Those with major surgery planned or history of bariatric surgery
• Antibiotic treatment (> 6 days) within past 6 months
• Currently pregnant (via self-report) or planning to become pregnant during study period; <1 year postpartum and breast feeding
• Current participation in another interventional clinical trial
• Previous randomization in this study,
• Heavy alcohol consumption (on average >2 drinks/day for women and >3 drinks/day for men)
• Habitual consumer of SSB ≥ 1 serving / day (8 oz.)
• Does not drink diet beverages
• BMI < 20.0 kg/m2

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Diet Beverage; Participants will receive and consume three daily servings (24 ounces) of a non-caloric commercial diet beverage of their choice sweetened with FDA approved artificial sweeteners.	Behavioral: Diet Beverage; Participants will receive and consume three daily servings (24 ounces) of a non-caloric commercial diet beverage of their choice sweetened with FDA approved artificial sweeteners.
Experimental: Water; Participants will receive and consume three daily servings (24 ounces) of plain bottled/canned water in place of their usual commercial diet beverage. The water will be unflavored, unsweetened, non-caloric, and may be plain or sparkling. Participants randomized to consume water will be instructed to avoid intake of diet beverages.	Behavioral: Water; Participants will receive and consume three daily servings (24 ounces) of plain bottled/canned water in place of their usual commercial diet beverage. The water will be unflavored, unsweetened, non-caloric, and may be plain or sparkling. Participants randomized to consume water will be instructed to avoid intake of diet beverages.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HbA1c	Glycated hemoglobin	Time 0 (directly after 2-week run-in), 12, 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time In Range	Time in range is collected by a masked Continuous Glucose Monitor (CGM), which measures individual glucose levels every 15 minutes for two weeks via a sensor placed on the participants upper arm (underside). Time in Range is defined as the % of time each day with a glucose measure between 70-180 mg/dl. The range of CGM data for inclusion in this study will be 5 to 14 days, consistent with manufacturer's recommendations.	All 14 day periods: Run-in (2-weeks, usual-baseline), weeks 11 and 12 (14 days), weeks 23 and 24 (14 days)
Glycemic Variability	Glycemic variability is collected by a masked Continuous Glucose Monitor (CGM), which measures individual glucose levels every 15 minutes for two weeks via a sensor placed on the participants upper arm (underside). Glycemic variability is defined as the Standard Deviation (SD) of the mean glucose during the wear period. The range of CGM data for inclusion in this study will be 5 to 14 days, consistent with manufacturer's recommendations.	All 14 day periods: Run-in (2-weeks, usual-baseline), weeks 11 and 12 (14 days), weeks 23 and 24 (14 days)
Mean Glucose (mg/dl)	A measure of the mean, 24 hour glucose concentration calculated across all recorded glucose readings during the wear period	All 14 day periods: Run-in (2-weeks, usual-baseline), weeks 11 and 12 (14 days), weeks 23 and 24 (14 days)
Fasting Glucose	Standard (mg/dl) measure taken fasting (morning) during baseline, 12 weeks, 24 weeks	Time 0 (directly after 2-week run-in), 12, 24 weeks
Fasting Insulin (Pmol/L)	Standard lab measurement for fasting insulin assessment	Time 0 (directly after 2-week run-in), week 12, week 24
Fructosamine	Fructosamine (umol/L) represents usual glycemia over the past 2-3 weeks, and is considered a valid marker of short term clinical glycemic patterns by the American Diabetes Association	Time 0 (directly after 2-week run-in),12, 24 weeks
Weight (kg)	Weight measured on standardized scale in gown	Time 0 (directly after 2-week run-in), 12, 24 weeks
Total Cholesterol (mg/dL)	Total cholesterol was measured as part of a lipid panel, a standard measurement for assessing clinical CVD risk	Time 0 (directly after 2-week run-in), 12, 24 weeks
Kidney Function	eGFR-Cystatin-C (estimated glomerular filtration rate) = mL/min/1.73 m^2	Time 0 (directly after 2-week run-in),12, 24 weeks
Systolic Blood Pressure	Systolic blood pressure (mmHg)	Time 0 (directly after 2-week run-in),12, 24 weeks
Diastolic Blood Pressure	Standard part of blood pressure measurement (mmHG)	Time 0 (directly after 2-week run-in), 12, 24 weeks
Apolipoprotein-AI	Apo-AI the major protein component of high density lipoprotein (HDL)	Time 0 (directly after 2-week run-in), 12, 24 weeks
Apolipoprotein B	ApoB levels indicate the atherogenic particle concentration independent of the particle cholesterol content	Time 0 (directly after 2-week run-in), 12, 24 weeks
Fibrinogen (mg/dL)	A protein involved in forming blood clots in the body	Time 0 (directly after 2-week run-in), 12, 24 weeks
C-reactive Protein	biomarker of inflammation	Time 0 (directly after 2-week run-in), 12, 24 weeks
Aspartate Aminotransferase (AST) (U/L)	AST (aspartate aminotransferase) is an enzyme that reflects liver function	Time 0 (directly after 2-week run-in), 12, 24 weeks
Aminotransferase (ALT) (U/L)	ALT (alanine transaminase) is an enzyme, a protein that reflects liver function	Time 0 (directly after 2-week run-in), 12, 24 weeks
Alkaline Phosphatase (ALKPhos ) (U/L)	ALP is an enzyme, a protein, that reflects liver function	Time 0 (directly after 2-week run-in), 12, 24 weeks
Thyroid Stimulating Hormone (TSH)	Hormone measured in the blood with energy balance related role	Time 0 (directly after 2-week run-in), 12, 24 weeks
Dietary Quality (Healthy Eating Index -HEI)	The Healthy Eating Index (HEI) is a measure of diet quality used to assess how well a set of foods aligns with key recommendations and dietary patterns published in the Dietary Guidelines for Americans (Dietary Guidelines). The overall HEI scores are made up of 13 components that reflect the different food groups and key recommendations in the Dietary Guidelines for Americans. The HEI is scored 0-100 (low to high), with higher scores representing greater reported intake of an overall dietary pattern aligning with USDA Dietary Guidelines. In the SODAS study, dietary intake was assessed by multiple unannounced 24-hour dietary recalls that occurred during the 2-week run-in period to assess usual habits (2 recalls over 2 weeks) and the active intervention (5 recalls over 24 weeks: 2 to 3 recalls during weeks 1-12 (period 1), and 2 to 3 recalls during weeks 13-24 (period 2). to measure any changes in diet quality. Scores during each period represent the average score of recalls.	Run-in period (2 weeks) - baseline, Week 1-12 (period 1), Week 13-24 (period 2).
The Diabetes Health Profile (DHP-18)	The Diabetes Health Profile (DHP-18) is used to assess health related quality of life in diabetes across three domains (psychological distress, barriers to activity and disinhibited eating). Each item is scored on a 4-point scale, and the subscale scores are then rescaled to a 0-100 range, with higher scores indicating poorer well-being.	Time 0 (directly after 2-week run-in), 12, 24 weeks
Food Craving Inventory (FCI)	The FCI is a valid and reliable self-report measure of specific food cravings. The inventory consists of 4 factors or subscales measuring cravings for high fats (8 items), carbohydrates/starches (8 items), sweets (8 items), and fast food fats (4 items), and a total score is calculated by summing the subscales. Participants rate each food on a 5-point Likert scale ranging from 0 (never) to 4 (always/almost every day). We calculated the total score by summing the individual item responses in each subscale. Higher scores indicate more frequent cravings of the 28 items.	Time 0 (directly after 2-week run-in), 12, 24 weeks
The Pittsburgh Sleep Quality Index (PSQI)	The Pittsburgh Sleep Quality Index (PSQI) is a self-report questionnaire that assesses sleep quality over a one-month time interval. Each component score of the PSQI ranges from 0 to 3, with 3 indicating the greatest dysfunction or disturbance. The seven component scores are then summed to obtain a global PSQI score, which ranges from 0 to 21. Higher scores indicate poorer sleep quality, with a score greater than 5 suggesting significant sleep difficulties	Time 0 (directly after 2-week run-in), 12, 24 weeks
Medication Effect Score (MES)	The medication effect score (MES) is a measure of overall diabetes regimen intensity, and is based on the dosages of medications used and their potencies. The MES is calculated for each diabetes medication in a regimen using the following equation: (actual drug dose/maximum drug dose) × drug-specific adjustment factor. The adjustment factor equates to the expected decrease in HbA1c achieved by the drug as monotherapy. The MES presumes a linear relationship between medication dosage and HbA1c, and the sum of MES values attributed to individual medications represents the maximum A1c reduction that may be expected by the regimen. It is a continuous variable with range 0 (no medications), and the maximum achievable MES is patient specific and dependent on the total number of and dose of medications reported.	Time 0 (directly after 2-week run-in), 6, 12, 18, 24 weeks
Therapeutic Intensity Score (TIS)	The therapeutic intensity score (TIS) is a summary measure that accounts for the number of medications and the relative doses a patient received to lower blood pressure. It is a continuous variable with range 0 (no medications), and the maximum achievable TIS is patient specific and dependent on the total number of antihypertensive medications reported.	Time 0 (directly after 2-week run-in), 6, 12, 18, 24 weeks

Collaborators and Investigators

• Sponsor: University of California, Irvine
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); University of Minnesota

Study record dates

Study Major Dates

• Study Start (Actual): June 6, 2019
• Primary Completion (Actual): March 21, 2024
• Study Completion (Actual): March 21, 2024

Study Registration Dates

• First Submitted: November 19, 2018
• First Submitted That Met QC Criteria: May 8, 2019
• First Posted (Actual): May 9, 2019

Study Record Updates

• Last Update Posted (Estimated): September 11, 2025
• Last Update Submitted That Met QC Criteria: September 9, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: gut microbiome; diet; continuous glucose monitor; metabolomics; diabetes control; Diet beverages; artificial sweeteners
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 2; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Inorganic Chemicals; Beverages; Anions; Ions; Electrolytes; Hydroxides; Alkalies; Oxides; Oxygen Compounds; Water; Artificially Sweetened Beverages
• Other Study ID Numbers: 20184756; 1R01DK117028-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: It is not yet known if there will be a plan to make IPD available.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No