Nutrient intake order on metabolic outcomes in type 2 diabetes: a systematic review and meta-analysis

Macronutrient sequence has been proposed as a practical strategy to improve postprandial glycemia in individuals with type 2 diabetes (T2D). However, current evidence remains inconclusive. This meta-analysis aims to provide an updated evaluation of the impact of a carbohydrate-last (CL) strategy, compared to carbohydrate-first or unordered (CF) intake, on metabolic parameters in adults with T2D.

A systematic search was conducted in PubMed, Embase, and Cochrane Central for randomized controlled trials (RCTs) evaluating nutrient intake order in T2D. Outcomes were analyzed using mean difference (MD) with 95% confidence intervals (CI) under a random-effects model. Heterogeneity was assessed using Cochrane's Q test and I² statistics. Analyses were conducted using R, version 4.4.2.

Seventeen studies involving 389 participants were included, with 114 (29%) in a parallel design and 192 (49%) in a crossover design receiving CL. In the pooled analysis, the CL group had significantly lower postprandial glucose at 60 min (MD: -42.73 mg/dL; 95% CI: -55.51, -29.96; p < 0.01) and 120 min (MD: -13.00 mg/dL; 95% CI: -21.07, -4.94; p < 0.01), higher postprandial glucagon-like peptide-1 (GLP-1) levels (MD: 8.21 pmol/L; 95% CI: 2.34, 14.09; p < 0.01), delayed gastric emptying half-time (MD: 28.14 min; 95% CI: 16.06, 40.23; p < 0.01), and reduced glycated hemoglobin (HbA1c) at follow-up (MD: -0.16%; 95% CI: -0.31, -0.01; p = 0.04).

Carbohydrate-last eating pattern has been shown to improve postprandial glycemia, enhance GLP-1 secretion, and delay gastric emptying, with a minimal effect on HbA1c in individuals with mild T2D. Further research is needed to confirm its applicability in advanced disease stages and to establish long-term metabolic benefits.