Trends in baseline HbA1c and body-mass index in randomised trials of people with type 1 diabetes from 1993 to 2025: an IMI2 SOPHIA systematic review and meta-analysis

Background

The prevalence of obesity has increased globally over the past few decades for the general population and people with type 2 diabetes. Existing research suggests that the body-mass index (BMI) of individuals living with type 1 diabetes has also increased substantially. This double burden of type 1 diabetes and obesity is concerning and may further increase the risk for microvascular and macrovascular complications associated with type 1 diabetes. We aimed to evaluate trends in BMI (as an indicator for adiposity/obesity) and haemoglobin A1c (HbA1c; as a measure of long-term glucose management) in people with type 1 diabetes, based on clinical trial data. 

Methods

In this systematic review and meta-analysis, PubMed, Web of Science, Scopus, Embase, Cochrane, and ClinicalTrials.gov were searched for clinical trials involving individuals with type 1 diabetes, covering all publications between January 1, 1993, and May 20, 2025. Randomised controlled trials (RCTs) were included when performed in adults, with baseline data on BMI and HbA1c, and featuring a sample size exceeding 100 participants. Studies were excluded if they applied overly narrow cut-off ranges (difference between upper and lower cut-off) for BMI (<5 kg/m ²) or HbA1c (<3%) or if they focused solely on individuals with either overweight or underweight. Spearman correlation and linear regression were applied to evaluate trends in baseline HbA1c and BMI, as the primary outcomes of interest the study. Subgroup analyses were performed for age, diabetes duration, sex and the type of intervention. The Cochrane Risk of Bias tool was used to assess study quality, with disagreements resolved through consultation. Funnel plots were used to evaluate publication bias. The robustness of the study results was checked by performing leave-one-out sensitivity analyses for BMI and HbA1c. Strength of the body of evidence was assessed using GRADE. This work was registered with PROSPERO, CRD42023449198.

Findings

12,346 unique studies were identified, of which 148 were RCTs with a combined population of 56,411 participants were included. Included studies represented research conducted in Europe (55 studies), North America (25 studies), Asia (13 studies) and Oceania (2 studies), in addition to 53 multicontinental studies. BMI increased from 25.0 (24.7–25.3) kg/m ²in the first decade studied (1993–2002) to 26.9 (26.4–27.3) kg/m ²in the last decade (2016–2025). Baseline HbA1c was 7.9% (7.6–8.2) for 1993–2002 and 7.9% (7.8–8.0) for 2016–2025. 

Interpretation

The increasing trend in BMI may indicate that weight gain is also occurring in people with type 1 diabetes. More research is needed on the BMI and HbA1c trends in people with type 1 diabetes, using real-world data on the individual level and investigating these trends in relation to the insulin dose. 

Funding

The Stratification of Obesity Phenotypes to Optimize Future Obesity Therapy (SOPHIA) project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No. 875534, supported by the European Union's Horizon 2020 research and innovation program and EFPIA, with additional support from T1D Exchange, Breakthrough T1D (former JDRF), and Obesity Action Coalition.