Results
REGRESSION
After removing duplicate trials from the three systematic reviews, 382 RCTs with at least one placebo arm were eligible. Four trials had to be excluded because the full texts could not be retrieved and one trial had to be excluded because it lacked information on the placebo arm. Of the remaining 377 trials, 193 did not report on the outcome log(SD), 30 did not report on the sample size and 14 did not report on the mean HbAThe description of trial populations is given in Table Description of included trial arms, separated by placebo and verum armsBoxplots and observed values for the log(SD) of HbAThe results from the weighted meta-regression model for assessing the first prerequisite (treatment heterogeneity) are as follows. The key estimate for treatment that measures the difference in log(SD) values between verum and placebo arms is 0.037 (95% CI: 0.004, 0.069). That is, after using the full meta-regression model, we found a slightly larger log(SD) in the verum arms. Estimates for the log(mean) effect were 1.476 (95% CI: 1.128, 1.824), and 0.112 (95% CI: 0.089, 0.147) for the random effects variance.To put the size of this difference into perspective, we consider the median raw log(SD) across all placebo arms which is 0.10% (see Table The results from the extended weighted meta-regression models for assessing the second prerequisite are given in Fig. Scatterplots of the log(SD) values of HbAResults from assessing the second prerequisite, existence of clinical predictors for the log(SD) of HbAEach line reports on a separate meta-regression model for each individual predictor. The models are identical to the models for the first prerequisite, however, they were extended by an additional interaction term of the respective predictor with treatment. Given are the slopes of regression lines for the respective predictor in the placebo and the verum arms, as well as their difference, which actually measures the interaction between treatment and predictorDifferences in log(SD) values against placebo for all treatments (drug classes)Figure The analyses for the baseline-corrected log(SD) values as given in the ESM (ESM In view of the large and precisely estimated treatment heterogeneity effects of GLP-1 receptor agonists for both log(SD) outcomes, we repeated the investigation of predictors in the subgroup of trials that assessed GLP-1 receptor agonists. For both log(SD) outcomes there was a clear effect of baseline HbAScatterplot of the log(SD) of HbA