Glycemic Effect Study

Mezitis NHE, Maggio CA, Koch P, et al. Diabetes Care. 1996;19(9):1004-1005.

This randomized, double-blind, placebo-controlled, crossover study was designed to assess the effect of a single oral high dose of sucralose on short-term glycemic control in patients with insulin-dependent diabetes mellitus (T1DM) or non-insulin-dependent diabetes mellitus (T2DM).

Introduction

Consumption of sucralose, a high-intensity sweetener that is synthesized from sucrose but appears to be metabolically inert, is expected to be high among patients with diabetes, who often use no-calorie sweeteners to reduce their sugar intake. Sucralose has not been shown to affect blood glucose or insulin levels in normal laboratory animals and human volunteers.

• The purpose of this study was to assess the effect of a single oral high dose of sucralose on short-term glycemic control in patients with insulin-dependent diabetes mellitus (T1DM) or non-insulin-dependent diabetes mellitus (T2DM).

Methodology

This randomized, double-blind, placebo-controlled, crossover study was divided into 3 phases:

• Screening phase — patient fasting blood glucose levels were evaluated at 3 clinic visits over a period of 2 to 6 weeks. Standard physical examinations, clinical chemistry, and blood and urine analyses were also performed

• Test phase — patients received 1,000 mg of sucralose or placebo 30 minutes after their usual dose of insulin or sulfonylurea, followed immediately by consumption of a standardized 360-kcal liquid breakfast. Tests were conducted approximately one week apart

  • In each test, blood samples for plasma glucose and serum C-peptide were collected for evaluation at 5 and 40 minutes before test substance administration and at 30, 60, 90, 120, 180, and 240 minutes after consumption of the breakfast. The primary end point was change in area under the curve for glucose, while change in area under the curve for C-peptide was the secondary end point. Area under the curve was estimated from the -5 minute before test substance administration data point and beyond

• Follow-up evaluation phase — took place approximately 1 week after the test phase for repeat physical examinations, including any intercurrent illnesses or adverse events that may have occurred following the final test visit

Subjects were asked to maintain generally consistent dietary habits throughout the study and to monitor and record preprandial capillary glucose levels 3x/day, 3 days/week during the screening and test phases.

Conclusions

• Established and adequately controlled diabetes (diagnosis at least 1 year prior; HbA1c to be 10% or less; repeat fasting capillary glucose <175mg/dL on 2 consecutive screening visits and on the first test visit)

• Age >18 and up to 65 years and age >40 and up to 65 years, for T1DM and T2DM patients, respectively

• C-peptide level <0.3 nmol/L and >0.6 nmol/L, 15 minutes following a 1-mg glucagon challenge, for T1DM and T2DM patients, respectively

Patient Participation

A total of 27 patients enrolled in the study and 26 patients completed all phases, including 13 patients with T1DM and 13 patients with T2DM.

Key findings

Sucralose did not significantly affect plasma glucose or C-peptide levels (P>0.05).

• In patients with T1DM:

  • Mean glucose area under the curve was 11.9 mmol/L (±3.3) for Placebo versus 10.3 mmol/L (±3.6) for sucralose

  • C-peptide area under the curve was 0.03 nmol/L (±0.03) for placebo and 0.15 nmol/L (±0.07) for sucralose

• In patients with T2DM:

  • Mean glucose area under the curve was 5.2 mmol/L (±1.9) for placebo versus 5.7 mmol/L (±1.7) for sucralose

  • Mean C-peptide area under the curve was 1.65 nmol/L (±0.15) for placebo and 1.86 nmol/L (±0.22) for sucralose

Three patients with T2DM experienced 1 episode of symptomatic hypoglycemia at 1.5 to 4 hours after the initiation of blood draws following sucralose administration during the first meal test. One of these episodes resulted in study withdrawal.

No meaningful changes in physical examination findings, clinical laboratory parameters, intercurrent illnesses or concomitant medications, including insulin or sulfonylurea, were observed in any patient during the study.

Inclusion criteria were:

• High doses of sucralose did not significantly affect glycemic control in patients with T1DM or T2DM

• The 3 episodes of symptomatic hypoglycemia reported in this study were not considered related to sucralose consumption:

  • Hypoglycemia is fairly common among patients with T1DM, especially in subjects such as these who were required by the study protocol to maintain relatively good glycemic control

  • The events occurred after nonusual morning fasting and concomitant blood draws, and symptoms subsided after the patients were allowed to eat

  • 2 of the 3 patients entered the test procedures with very low (2.5 and 1.8 mmol/L, respectively) FPG levels following their morning insulin administration, which likely increased the potential for symptomatic hypoglycemia as procedures progressed (a minimum baseline FPG level was not required for participation)

  • A similar number of patients experienced nonsymptomatic hypoglycemia during their placebo tests (3 with T1DM and 2 with T2DM), based on a plasma glucose level of <3.6 mmol/L. (Nonsymptomatic hypoglycemia was not recorded as an adverse event during the study)

The authors conclude that sucralose does not adversely affect short-term blood glucose control in patients with T1DM or T2DM.