People with severe mental illness experienced more rapid increases in both weight and long-term blood sugar levels during the first three months after starting treatment with antipsychotic medication. This is shown by a study from Karolinska Institutet and University College London, published in The Lancet Psychiatry.
The researchers analysed electronic health records from nearly 97,000 people in England aged between 18 and 59 with severe mental illness. The aim was to investigate how weight and HbA1c, a blood test that reflects average blood sugar levels over time, changed before and after treatment with second-generation antipsychotic medication was initiated.
During the first 90 days after treatment began, HbA1c increased by an average of 0.12 mmol/mol per week and weight by 0.21 kilograms per week. Before treatment, the corresponding increases were 0.01 mmol/mol and 0.02 kilograms per week, respectively.
After the first three months, the rate of change slowed. From day 91 and up to two years, HbA1c again increased by 0.01 mmol/mol per week, while weight increased by 0.03 kilograms per week.
The study is based entirely on health record data and shows how the values changed around the start of treatment, rather than reporting results from a randomised treatment study. In addition, only around a quarter of the participants had at least one recorded HbA1c measurement and just over three-quarters had at least one weight measurement.
Early follow-up may be important
Photo: Rickard Kilström
“The results show that the greatest changes occur early after treatment is initiated. This suggests that both weight and HbA1c need to be monitored from the start of treatment and during the first three months, alongside what is clinically appropriate for each patient,” says Magnus Boman , professor at the Department of Medicine , Solna, Karolinska Institutet, and one of the authors of the study.
The changes differed between medications. The largest increases were seen with olanzapine treatment. Quetiapine, by contrast, was associated with weight gain but only a small change in HbA1c. The increases were generally greater among women.
People who already had prediabetes when treatment began also had a higher risk of developing type 2 diabetes. The estimated proportion who developed the disease within two years was 19 per cent in this group, compared with 3 per cent among people who had normal HbA1c levels at the outset.
Juan Carlos Bazo-Alvarez , researcher at University College London and first author of the study.
The research was funded by several parts of the National Institute for Health and Care Research (NIHR), UK Research and Innovation, and the University College London Hospitals NIHR Biomedical Research Centre.
Publication
“Change in HbA1c and weight after initiation of antipsychotic treatment in people with severe mental illness in England: an individual-level interrupted time-series analysis” , Juan Carlos Bazo-Alvarez, Philip W Stone, Christina Avgerinou, Matteo Quartagno, Magnus Boman, Prof Kelvin P Jordan, Claudia Cooper, Joseph F Hayes, Kate Walters, Irene Petersen. The Lancet Psychiatry, online 16 October 2026, doi: 10.1016/S2215-0366(26)00274-9.
