Effects of sucralose on insulin and glucagon-like peptide-1 secretion in healthy subjects: a randomized, double-blind, placebo-controlled trial

Abstract

Objectives: Emerging evidence shows that non-nutritive sweeteners might induce glucose intolerance. This study aims to determine the effects of chronic exposure to sucralose on glycemic response, insulin secretion and sensitivity, and glucagon-like peptide-1 (GLP-1) release in healthy subjects.

Methods: Healthy volunteers who did not use non-nutritive sweeteners and were normoglycemia after oral glucose tolerance test (OGTT) were recruited. Subjects underwent a 75-g OGTT on two separate occasions, preceded by blindly consuming pills containing either 200 mg sucralose or placebo for 4 wk in a randomized crossover trial. Plasma glucose, insulin, and active GLP-1 levels were obtained after ingesting 75-g glucose. On the following day, intravenous glucose tolerance test (IVGTT) was performed to evaluate the acute insulin response (AIR).

Results: Fifteen participants (11 females, age 31.9 ± 10 y, body mass index 23.1 ± 3 kg/m²) participated in the study. AIR was lower after exposure to sucralose than placebo (58.9 ± 48.61 versus 69.94 ± 73.81 µU/mL, P < 0.001). Whole-body insulin sensitivity (estimated using the Matsuda index) was lower in sucralose than placebo (4.69 ± 1.67 versus 5.31 ± 2.56, P < 0.005). AUC of active GLP-1 was significantly higher in the sucralose than placebo (23.16 ± 18.86 versus 18.5 ± 22.22 pmol/L ⋅ 120 min, P < 0.001).

Conclusions: The continuous exposure to sucralose reduced AIR, decreased insulin sensitivity, and enhanced GLP-1 release in healthy subjects. However, the clinical significance of these results needs to be investigated in longer follow-up studies.

Keywords: Artificial sweeteners; Diabetes mellitus; Glucagon-like peptide 1; Insulin secretion; Insulin sensitivity; Non-nutritive sweeteners; Sucralose.