The effect of small doses of fructose and allulose on postprandial glucose metabolism in type 2 diabetes: A double-blind, randomized, controlled, acute feeding, equivalence trial

Diabetes Obes Metab. 2018 Oct;20(10):2361-2370. doi: 10.1111/dom.13374. Epub 2018 Jun 25.


Aim: To assess and compare the effect of small doses of fructose and allulose on postprandial blood glucose regulation in type 2 diabetes.

Methods: A double-blind, multiple-crossover, randomized, controlled, acute feeding, equivalence trial in 24 participants with type 2 diabetes was conducted. Each participant was randomly assigned six treatments separated by >1-week washouts. Treatments consisted of fructose or allulose at 0 g (control), 5 g or 10 g added to a 75-g glucose solution. A standard 75-g oral glucose tolerance test protocol was followed with blood samples at -30, 0, 30, 60, 90 and 120 minutes. The primary outcome measure was plasma glucose incremental area under the curve (iAUC).

Results: Allulose significantly reduced plasma glucose iAUC by 8% at 10 g compared with 0 g (717.4 ± 38.3 vs. 777.5 ± 39.9 mmol × min/L, P = 0.015) with a linear dose response gradient between the reduction in plasma glucose iAUC and dose (P = 0.016). Allulose also significantly reduced several related secondary and exploratory outcome measures at 5 g (plasma glucose absolute mean and total AUC) and 10 g (plasma glucose absolute mean, absolute and incremental maximum concentration [Cmax ], and total AUC) (P < .0125). There was no effect of fructose at any dose. Although allulose showed statistically significant reductions in plasma glucose iAUC compared with fructose at 5 g, 10 g and pooled doses, these reductions were within the pre-specified equivalence margins of ±20%.

Conclusion: Allulose, but not fructose, led to modest reductions in the postprandial blood glucose response to oral glucose in individuals with type 2 diabetes. There is a need for long-term randomized trials to confirm the sustainability of these improvements.

Keywords: clinical trial; dietary intervention; dose-response relationship; glucose; metabolism; randomized trial; type 2 diabetes.

Publication types

  • Equivalence Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Feeding Behavior / drug effects
  • Feeding Behavior / physiology
  • Female
  • Fructose / administration & dosage*
  • Fructose / adverse effects
  • Humans
  • Male
  • Middle Aged
  • Postprandial Period / drug effects


  • Blood Glucose
  • psicose
  • Fructose