Glucose Homeostasis Study

Lack of effect of sucralose on glucose homeostasis in subjects with type 2 diabetes.

Grotz VL, Henry RR, McGill JB, et al. J Am Diet Assoc. 2003;103(12):1607-1612

Introduction

Patients with diabetes often use no calorie sweeteners to reduce their sugar intake. While clinical studies have demonstrated that sucralose does not affect blood glucose or insulin levels in normal nondiabetic animals and humans, studies in patients with diabetes are limited.

The purpose of this study is to evaluate the effects of high daily doses of sucralose in patients with type 2 diabetes over a period of 3 months.

Methodology

This double-blind, randomized, placebo-controlled, parallel-group, multicenter study enrolled patients based on the following criteria:

• Diagnosis of type 2 diabetes at least 1 year prior
• 31 to 70 years of age
• Management of diabetes with either insulin or an oral hypoglycemic agent, but not both
• Relatively stable diabetes with HbA1c of <10
• Familiarity with blood glucose monitoring and standard dietary guidelines for diabetes management
• General good health

The study was conducted in 3 phases:

• 6-week screening phase - patients were asked to follow a standard diet (approximately 14% protein, 30% to 36% fat, and 48% to 55% carbohydrate), and to monitor their blood glucose levels at least 3-times per day, two days per week, for the duration of the study. Two weeks after entering this phase, patients received placebo capsules for 4 weeks (patients were blinded to the nature of the capsules), and at the end of this period, baseline measurements were taken for:
• HbA1c
• Fasting plasma glucose (FPG)
• Fasting serum C-peptide
• Insulin/oral hypoglycemic agent dosage level



• 13-week test phase - patients were randomized to receive 2 capsules daily of either sucralose (667mg/day) or placebo, to be taken at breakfast and dinnertime for 13 weeks.
• HbA1c, FPG, and fasting serum C-peptide levels were assessed every 2 weeks
• Adverse events and changes in medications were recorded



• 4-week follow-up phase - while still blind to the treatment regimen, all patients were switched back to placebo. During this time:
• Blood glucose control was evaluated as in the test phase
• Adverse events and changes in medications were recorded
• Physical examinations and hematology, blood chemistry and urinalysis assessments were performed at the conclusion of follow-up

Results

Of the 136 patients enrolled in the test phase of the study, 67 received sucralose and 69 received placebo; 4 patients in each treatment group discontinued after randomization, none due to an adverse event. Baseline patient demographics were comparable between the two groups. Overall, patients were obese, and in each treatment group, approximately half took oral hypoglycemia agents. The remainder of patients took insulin.

No statistically significant differences were observed between treatment groups with regard to changes in HbA1c, FPG or fasting serum C-peptide levels.

• There were no statistically significant differences between groups in HbA1c at baseline, at any visit (P=0.23 to 0.93), or in the overall estimated change over time (ANOVA using repeated measures; P=0.57)
• FPG levels were comparable at baseline, at all individual test visits, and over the course of the study (P=0.89)
• Fasting serum C-peptide levels were comparable at baseline, at each test visit, and in the overall estimated change over time (P=0.29)

Safety

The safety of sucralose was comparable to placebo:

• There were no significant differences between groups in the type, number or severity of adverse events reported
• No patients withdrew due to an adverse event
• No adverse events were documented as a possible or definite result of sucralose
• No clinically meaningful difference between groups in changes in concomitant medications or any other safety measures were reported

Conclusion

• Despite consumption of significant doses approximately 3-times the maximum estimated daily intake of 2.4mg/kg/day, sucralose did not affect any measure of glucose control evaluated in this study, nor was a trend toward loss of blood glucose control observed
• These findings are consistent with the results of studies in nondiabetic animal and human subjects, suggesting that patients who are not obese, or whose diabetes is managed by diet alone, would respond similarly to sucralose consumption

The authors conclude that foods and beverages sweetened with sucralose may be beneficial for the dietary management of patients who have, or are at risk for, diabetes.