Effect of fructose on glycemic control in diabetes: a systematic review and meta-analysis of controlled feeding trials

Diabetes Care. 2012 Jul;35(7):1611-20. doi: 10.2337/dc12-0073.


Objective: The effect of fructose on cardiometabolic risk in humans is controversial. We conducted a systematic review and meta-analysis of controlled feeding trials to clarify the effect of fructose on glycemic control in individuals with diabetes.

Research design and methods: We searched MEDLINE, EMBASE, and the Cochrane Library (through 22 March 2012) for relevant trials lasting ≥7 days. Data were aggregated by the generic inverse variance method (random-effects models) and expressed as mean difference (MD) for fasting glucose and insulin and standardized MD (SMD) with 95% CI for glycated hemoglobin (HbA(1c)) and glycated albumin. Heterogeneity was assessed by the Cochran Q statistic and quantified by the I(2) statistic. Trial quality was assessed by the Heyland methodological quality score (MQS).

Results: Eighteen trials (n = 209) met the eligibility criteria. Isocaloric exchange of fructose for carbohydrate reduced glycated blood proteins (SMD -0.25 [95% CI -0.46 to -0.04]; P = 0.02) with significant intertrial heterogeneity (I(2) = 63%; P = 0.001). This reduction is equivalent to a ~0.53% reduction in HbA(1c). Fructose consumption did not significantly affect fasting glucose or insulin. A priori subgroup analyses showed no evidence of effect modification on any end point.

Conclusions: Isocaloric exchange of fructose for other carbohydrate improves long-term glycemic control, as assessed by glycated blood proteins, without affecting insulin in people with diabetes. Generalizability may be limited because most of the trials were <12 weeks and had relatively low MQS (<8). To confirm these findings, larger and longer fructose feeding trials assessing both possible glycemic benefit and adverse metabolic effects are required.

Trial registration: ClinicalTrials.gov NCT01363791.

Publication types

  • Clinical Trial
  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / blood*
  • Dietary Carbohydrates / pharmacology*
  • Fructose / therapeutic use*
  • Glycated Hemoglobin / drug effects*
  • Humans
  • Insulin / blood
  • Middle Aged


  • Blood Glucose
  • Dietary Carbohydrates
  • Glycated Hemoglobin A
  • Insulin
  • Fructose

Associated data

  • ClinicalTrials.gov/NCT01363791