Effect of glucagon-like peptide-1 receptor agonists on glycemic control, and weight reduction in adults: A multivariate meta-analysis

Aims To explore the effect of glucagon-like peptide-1 receptor agonist (GLP-1 RAs) on glycemic control and weight reduction in adults. Methods Databases were searched from August 2021 to March 2022. Data were analyzed using mean difference (MD) values with 95% confidence intervals (CIs). Both random-and fixed-effect models were employed. Heterogeneity was explored using pre-specified subgroup analyses and meta-regression. Structural equation modeling fitting was used for the multivariate meta-analysis. Results A total of 31 double-blind randomized controlled trials with 22,948 participants were included in the meta-analysis. The MD and 95% CI of the pooled GLP1-RA-induced change in the glycated hemoglobin level was -0.78% (-0.97%, -0.60%) in the random-effects model and -0.45% (-0.47%, -0.44%) in the fixed-effect model, with a high heterogeneity (I2 = 97%). The pooled body weight reduction was -4.05 kg (-5.02 kg, -3.09 kg) in the random-effects model and -2.04 kg (-2.16 kg, -1.92 kg) in the fixed-effect model (I2 = 98%). The standardized pooled correlation coefficient between HbA1c levels and body weight was -0.42. A negative correlation between glycemic control and weight reduction was obtained. Conclusion Long-acting GLP-1 RAs significantly reduced the glycated hemoglobin level and body weight in adults.


Rationale
3 Describe the rationale for the review in the context of existing knowledge.

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Objectives 4 Provide an explicit statement of the objective(s) or question(s) the review addresses. 5-6

METHODS
Eligibility criteria 5 Specify the inclusion and exclusion criteria for the review and how studies were grouped for the syntheses. 7-9 Information sources 6 Specify all databases, registers, websites, organisations, reference lists and other sources searched or consulted to identify studies. Specify the date when each source was last searched or consulted.

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Search strategy 7 Present the full search strategies for all databases, registers and websites, including any filters and limits used. 7-9, reported Selection process 8 Specify the methods used to decide whether a study met the inclusion criteria of the review, including how many reviewers screened each record and each report retrieved, whether they worked independently, and if applicable, details of automation tools used in the process.

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Data collection process 9 Specify the methods used to collect data from reports, including how many reviewers collected data from each report, whether they worked independently, any processes for obtaining or confirming data from study investigators, and if applicable, details of automation tools used in the process.

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Data items 10a List and define all outcomes for which data were sought. Specify whether all results that were compatible with each outcome domain in each study were sought (e.g. for all measures, time points, analyses), and if not, the methods used to decide which results to collect.

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10b List and define all other variables for which data were sought (e.g. participant and intervention characteristics, funding sources). Describe any assumptions made about any missing or unclear information.

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Study risk of bias assessment 11 Specify the methods used to assess risk of bias in the included studies, including details of the tool(s) used, how many reviewers assessed each study and whether they worked independently, and if applicable, details of automation tools used in the process. 13b Describe any methods required to prepare the data for presentation or synthesis, such as handling of missing summary statistics, or data conversions.

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13c Describe any methods used to tabulate or visually display results of individual studies and syntheses. 8-9 13d Describe any methods used to synthesize results and provide a rationale for the choice(s). If meta-analysis was performed, describe the model(s), method(s) to identify the presence and extent of statistical heterogeneity, and software package(s) used.

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13e Describe any methods used to explore possible causes of heterogeneity among study results (e.g. subgroup analysis, meta-regression).

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13f Describe any sensitivity analyses conducted to assess robustness of the synthesized results. 8-9 Reporting bias assessment 14 Describe any methods used to assess risk of bias due to missing results in a synthesis (arising from reporting biases). 11 Certainty assessment 15 Describe any methods used to assess certainty (or confidence) in the body of evidence for an outcome. 11 16b Cite studies that might appear to meet the inclusion criteria, but which were excluded, and explain why they were excluded.

Study
10, Figure   1 Study characteristics 17 Cite each included study and present its characteristics. 10, Table   S