Trends in baseline HbA1c and body-mass index in randomised placebo-controlled trials of type 2 diabetes from 1987 to 2022: a systematic review and meta-analysis

Background: Curbing or reversing high glycated hemoglobin (HbA1c) and body mass index (BMI) are two essential parts in the clinical management of type 2 diabetes (T2D). We delineated the changing patterns of the baseline HbA1c and BMI in patients with T2D from placebo-controlled randomised trials to reflect the unmet clinical needs. Methods: PubMed, Medline, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched from inception to December 19, 2022. Placebo-controlled trials of T2D with reports of baseline HbA1c and BMI were included, of which summary data from published reports were extracted. Pooled effect sizes of baseline HbA1c and BMI of from studies published in the same year were computed in Random-effects model due to the high level of heterogeneity among studies. The main outcome was correlations between the pooled baseline HbA1c, the pooled baseline BMI, and study years. This study was registered in PROSPERO as CRD42022350482. Findings: We identified 6102 studies, of which 427 placebo-controlled trials with 261, 462 participants were finally included in the study. Baseline HbA1c level declined with time (Rs = −0.665, P ＜ 0.0001, I² = 99.4%). Baseline BMI increased over the past 35 years (R = 0.464, P = 0.0074, I² = 99.4%), rising by around 0.70 kg/m² per decade. Patients with BMI ≤25.0 kg/m² dropped substantially from the half in 1996 to none in 2022. Patients with BMI ranging from 25 kg/m² to 30 kg/m² stabilized at 30–40% since 2000. Interpretation: A substantial decline in baseline HbA1c levels and a constant increase in baseline BMI levels was found in placebo-controlled trials through the past 35 years, which indicated the improvement in glycemic control and the urgency for the management of obesity in T2D. Funding: National Natural Science Foundation of China (No. 81970698), Beijing Natural Science Foundation (No. 7202216) and National Natural Science Foundation of China (No. 81970708).