The first 90 days after starting antipsychotic treatment are crucial for changes in blood sugar and weight, finds a new study led by UCL researchers.
Second-generation antipsychotics are important treatments for severe mental illness, including schizophrenia and bipolar disorder. However, they can increase the risk of diabetes and weight gain.
New research, published in The Lancet Psychiatry and funded by the National Institute for Health and Care Research (NIHR), analysed anonymous NHS GP health records from nearly 97,000 adults in England (aged 18-59) who had severe mental illness and started taking an antipsychotic medicine (Olanzapine, Quetiapine, Risperidone or Aripiprazole) between 2000 and 2023.
Experts reviewed information recorded from both two years before patients started antipsychotic treatment to two years after - focusing on factors such as fluctuations in weight and blood test results.
They found that the most significant metabolic changes happened during the first 90 days after treatment started.
During this time, HbA1c (a measure of average blood sugar) rose around 14 times faster and weight around nine times faster, than before antipsychotic treatment began.
However, changes in blood sugar and weight did not always occur together, suggesting that monitoring weight alone may miss important metabolic changes.
First author, Dr Juan Carlos Bazo-Alvarez (UCL Epidemiology and Health) said: "Antipsychotic medicines are valuable treatments that help many people with serious mental illnesses.
"However, our study shows that the first 90 days after starting treatment are a key period when changes linked to diabetes and weight gain can begin.
"With this information in mind, healthcare professionals should check both weight and blood sugar before treatment starts and again during the first few months afterwards."
Schizophrenia affects around 23 million people worldwide, while around 37 million live with bipolar disorder.
Not only do these conditions have a major impact on a person's thoughts, feelings and daily life, but they can also substantially reduce life expectancy compared to the general population, with patients typically dying around 10-20 years earlier than average.
This is primarily driven by greater incidence of cardiovascular and metabolic disease.
Second-generation antipsychotics are known to contribute to this metabolic burden – as many cause weight gain and increase the risk of diabetes.
Of the four drugs reviewed, patients who took Olanzapine showed the largest early increases in both outcomes. During the first 90 days, HbA1c rose around 50 times faster and weight around 10 times faster than before treatment began.
Additionally, prediabetes also showed greater metabolic vulnerability.
As 19% of people with prediabetes at the start of treatment developed type 2 diabetes within two years, compared with 3% starting with normal blood sugar levels.
Women were also disproportionately affected compared to men. Among women, HbA1c rose around 24 times faster and weight around 12 times faster during the first 90 days than before treatment began. Whereas among men, the corresponding increases were around 10 times faster for HbA1c and 10 times faster for weight.
Dr Bazo-Alvarez said: "By checking blood sugar and weight early, doctors may be able to spot problems sooner and offer support, advice, or treatment to help prevent more serious health issues later on. Our findings may also help clinicians to pay particular attention to certain groups who may be more at risk.
"This could mean that patients are able to receive the benefits of antipsychotic medicines while reducing their risk of developing conditions such as type 2 diabetes."
The study was funded by the National Institute for Health and Care Research (NIHR), with additional funding and support from UK Research and Innovation (UKRI), The NIHR Biomedical Research Centre: UCLH and NIHR North Thames Applied Research Collaboration.
Study limitations
The researchers could only analyse information that had already been recorded in GP records, and the study could not look at all factors that might affect blood sugar and weight, such as diet, exercise or additional medications.
