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

Abstract

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.

Fig 1. Flowchart of the trial selection process.

Fig 2. Contour-enhanced and filled funnel plots of glycated hemoglobin level and body weight.

(upper left) Contour-enhanced funnel plot of the pooled glycated hemoglobin level after treatment with a glucagon-like peptide-1 receptor agonist. (lower left) Filled funnel plot of the pooled glycated hemoglobin level after treatment with a glucagon-like peptide-1 receptor agonist. (upper right) Contour-enhanced funnel plot of the pooled body weight after treatment with a glucagon-like peptide-1 receptor agonist. (lower right) Filled funnel plot of the pooled body weight after treatment with a glucagon-like peptide-1 receptor agonist.

Fig 3. The pooled effect sizes and their confidence ellipse for changes in glycated hemoglobin level and body weight in patients treated with a glucagon-like peptide-1 receptor agonist and placebo, in participants not restricted and restricted to diabetes.

(left) The pooled effect sizes and their confidence ellipse of the changes in the glycated hemoglobin level and body weight, in a comparison of glucagon-like peptide-1 receptor agonists and placebo in all participants. (middle) The pooled effect sizes and their confidence ellipse for changes in the glycated hemoglobin level and body weight, in a comparison of glucagon-like peptide-1 receptor agonists and placebo in patients with diabetes. (right) The pooled effect sizes and their confidence ellipse for changes in the glycated hemoglobin level and body weight, in a comparison of glucagon-like peptide-1 receptor agonists and placebo in patients without diabetes. x-axis: Effects of glucagon-like peptide-1 receptor agonists on glycated hemoglobin level; y-axis: effects of glucagon-like peptide-1 receptor agonists on body weight changes; black dots: individual studies; ellipses with dashed lines: 95% confidence interval; red diamond: pooled effect and 95% confidence interval; smaller gray ellipse: 95% confidence interval; larger red ellipse: 95% prediction interval.