Efficacy of a meal sequence in patients with type 2 diabetes: a systematic review and meta-analysis

INTRODUCTION: This systematic review investigated the efficacy of a meal sequence, the carbohydrate-later meal pattern (CL), on type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov until April 2020 to perform meta-analyses using random-effects models. Primary outcomes were hemoglobin A1c (HbA1c) and quality of life. Secondary outcomes were plasma concentrations of glucose, insulin and incretin 120 min after a meal, and any adverse outcomes. The revised Cochrane risk-of-bias tool and Grading of Recommendations, Assessment, Development, and Evaluation approach were used to assess the quality of individual studies and the body of evidence, respectively. The present study was registered in the UMIN Clinical Trials Registry. RESULTS: We included 230 participants in eight trials, including both trials that examined long-term changes (more than 2 months and less than 2 years) and short-term changes (in 2-hour postprandial values). CL resulted in a slight to no difference in HbA1c (mean difference (MD), -0.21% in the intervention group; 95% CI -0.44% to+0.03%), plasma glucose (MD,+4.94 mg/dL; 95% CI -8.34 mg/dL to +18.22 mg/dL), plasma insulin (MD, -3.63 μIU/mL; 95% CI -11.88 μIU/mL to +4.61 μIU/mL), plasma GLP-1 (MD, +0.43 pmol/L; 95% CI -0.69 pmol/L to +1.56 pmol/L), and plasma GIP (MD, -2.02 pmol/L; 95% CI -12.34 pmol/L to +8.31 pmol/L). All of these outcomes were of low-certainty evidence or very low-certainty evidence. None of the trials evaluated quality of life or adverse events. CONCLUSIONS: There was no evidence for the potential efficacy of recommending CL beyond standard dietary advice on T2DM. TRIAL REGISTRATION NUMBER: UMIN000039979.