Interventions for Reversing Prediabetes: A Systematic Review and Meta-Analysis

Abstract

Introduction: Several interventions have been found to be effective for reversing prediabetes in adults. This systematic review and meta-analysis aims to compare the effectiveness of such interventions.

Methods: MEDLINE, Embase, and Cochrane Library databases were searched for articles published between January 1, 2000 and June 27, 2018. RCTs in adults with prediabetes, testing nonsurgical interventions lasting for ≥3 months, and reporting the number of participants achieving normal glucose levels at intervention end were eligible. The pooled risk difference and number needed to treat for achieving normoglycemia were estimated using a random-effects, arm-based network meta-analysis. The strength of the evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation. Data were obtained in 2018 and analyzed in 2019 and 2021.

Results: Of 54 studies included in the systematic review, 47 were meta-analyzed (n=26,460, mean age=53 years, 46% male, 31% White). Studies included 27 arms testing lifestyle modification interventions, 25 testing medications, 5 testing dietary supplements, and 10 testing Chinese medicine. There were 35 control/placebo arms. At a median follow-up of 1.6 years, more participants in the lifestyle modification groups achieved normoglycemia than those in the control (risk difference=0.18, number needed to treat=6). The strength of the evidence was strong for lifestyle modification. Over a median follow-up of 2.7 years, more participants receiving glucagon-like peptide-1 receptor agonists (risk difference=0.47, number needed to treat=2), α-glucosidase inhibitors (risk difference=0.29, number needed to treat=4), and insulin sensitizers (risk difference=0.23, number needed to treat=4) achieved normoglycemia than control. The strength of evidence was moderate for these medications.

Discussion: Although several pharmacological approaches can reverse prediabetes, lifestyle modification provides the strongest evidence of effectiveness and should remain the recommended approach to address this condition.

Conflict of interest statement

The authors have no conflicts of interest to declare during the course of this work. No financial disclosures were reported by the authors of this paper.

Copyright © 2021 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Figures

Appendix Figure 1.

PRISMA study selection flow chart.

Appendix Figure 2.

Risk of bias assessment results.

Appendix Figure 3.

Node-split showing risk difference obtained from direct treatment comparisons (i.e., in same study) and from indirect comparisons (i.e., obtained in this meta-analysis).

Figure 1.

Network structure showing an asymmetrical network. Notes: The size of the bubble represents the number of studies testing a treatment and the thickness of the connecting lines the number of arms testing that comparison. AGI, alpha-glucosidase inhibitors; DPP-4, dipeptidyl peptidase 4 inhibitors; GLP-1, glucagon-like peptide 1 receptor agonists; LSM, lifestyle modification; RAS, renin-angiotensin system.

Figure 2.

Forest plot showing pooled effects for each treatment against control/placebo. AGI, alpha-glucosidase inhibitors; DPP-4, dipeptidyl peptidase 4 inhibitors; GLP-1, glucagon-like peptide 1 receptor agonists; LSM, lifestyle modification; RAS, renin-angiotensin system; NNT, number needed to treat; RD, risk difference; RR, relative risk.