Diabetes Risk Rises Fastest in First 90 Days of Antipsychotics

Blood Sugar Rises Rapidly During the First Three Months

Metabolic changes occur fastest during the initial 90 days after a patient begins taking an antipsychotic medication. An observational study published in The Lancet Psychiatry analyzed anonymous National Health Service (NHS) general practice records from 96,887 adults in England between 2000 and 2023. Researchers evaluated patients aged 18 to 59 with severe mental illnesses, including schizophrenia and bipolar disorder, who started treatment with olanzapine, quetiapine, risperidone, or aripiprazole.

The research team from University College London (UCL) examined health records from two years before medication start dates to two years after. During the first 90 days, glycated hemoglobin (HbA1c), a laboratory marker of average blood sugar, rose approximately 14 times faster than before treatment began. Weight also climbed roughly nine times faster during this same initial window.

Changes in blood sugar did not consistently match weight gain in individual patients. This divergence indicates that tracking body weight alone can miss early metabolic disruptions.

Olanzapine and Prediabetes Increased Metabolic Risk

Patients taking olanzapine experienced the steepest early changes among the four medications studied. During the first 90 days on olanzapine, HbA1c climbed roughly 50 times faster than baseline rates, and weight increased about 10 times faster. The other evaluated medications showed metabolic shifts, but olanzapine had the most pronounced early effect.

Existing metabolic vulnerability substantially altered two-year health outcomes. Among patients with prediabetes at the start of treatment, 19 percent developed type 2 diabetes within two years. By comparison, 3 percent of patients who began treatment with normal blood sugar levels developed type 2 diabetes over the same period.

Sex differences also influenced blood sugar trajectories across the cohort. Among women, HbA1c rose around 24 times faster and weight climbed around 12 times faster during the first 90 days compared with baseline. For men, HbA1c and weight each increased approximately 10 times faster than before treatment began.

The Practical Role of Early Metabolic Testing

Baseline and early follow-up testing give clinicians an objective window to detect glucose dysregulation before chronic complications emerge. Second-generation antipsychotics remain essential therapies for managing conditions that affect roughly 23 million people with schizophrenia and 37 million people with bipolar disorder globally. These conditions already correlate with a life expectancy reduction of 10 to 20 years, largely driven by cardiovascular and metabolic diseases.

Lead author Dr. Juan Carlos Bazo-Alvarez noted that testing blood sugar and weight before starting therapy and repeating those checks during the first few months allows clinicians to spot metabolic shifts early. This monitoring strategy helps clinicians provide preventive guidance or medical therapy without discontinuing psychiatric treatment.

Patients starting an antipsychotic can discuss scheduling a baseline HbA1c test and a 90-day follow-up panel with their healthcare provider. Regular glucose checks provide data that visual inspection of body weight cannot supply on its own.

Study Design and Observational Limitations

The findings rely on routinely collected primary care electronic health records, which carries methodological constraints. The researchers evaluated only the data previously entered into general practitioner records across the 23-year review window. Unrecorded blood tests or missing follow-up visits could affect the documented rate of change across the patient cohort.

The dataset also lacked information on several non-pharmacological factors that influence glucose regulation. Variables such as daily dietary intake, physical activity, and concurrent non-psychiatric medications were not recorded in the analyzed records.

Because this was an observational study rather than a randomized trial, the data demonstrate statistical associations between medication initiation and metabolic rates rather than isolated direct causation. Clinical teams must weigh these metabolic findings alongside each patient's psychiatric stabilization requirements.