Blood Sugar and Weight Surge in the First 90 Days of Antipsychotic Treatment, Study Finds

The earliest weeks of antipsychotic treatment may matter far more than clinicians have traditionally assumed. A new observational study led by researchers at University College London, published in The Lancet Psychiatry and funded by the National Institute for Health and Care Research, reports that the most dramatic metabolic changes in people starting antipsychotic medication occur within the first 90 days. During this window, the researchers found that average blood sugar, measured by HbA1c, rose approximately 14 times faster than it had before treatment began, while body weight increased roughly nine times faster. The findings suggest that the opening months of therapy represent a critical opportunity for monitoring, and potentially for intervening before early metabolic shifts harden into long-term disease.

Second-generation antipsychotics are cornerstone treatments for severe mental illness, including schizophrenia and bipolar disorder, conditions that together affect tens of millions of people worldwide. Schizophrenia affects an estimated 23 million people globally, while around 37 million live with bipolar disorder. These illnesses do not only reshape thoughts, feelings and daily functioning; they also shorten lives substantially, with patients typically dying 10 to 20 years earlier than the general population. That mortality gap is driven primarily by higher rates of cardiovascular and metabolic disease, and second-generation antipsychotics are known contributors to this burden, since many cause weight gain and elevate the risk of diabetes. Balancing the clear psychiatric benefits of these drugs against their metabolic costs is therefore one of the central challenges in modern mental health care.

To quantify exactly when and how quickly these metabolic changes emerge, the UCL-led team turned to a remarkably large and detailed data source: anonymous National Health Service general practitioner records from nearly 97,000 adults in England aged 18 to 59 who had severe mental illness and started taking an antipsychotic medicine between 2000 and 2023. The drugs examined were olanzapine, quetiapine, risperidone and aripiprazole, four of the most commonly prescribed second-generation antipsychotics. The researchers reviewed information recorded from two years before patients began treatment to two years afterwards, focusing on fluctuations in weight and blood test results across that extended timeline.

The analytical design allowed the team to compare each patient’s metabolic trajectory before and after antipsychotic initiation, isolating the effect of starting the medication from background trends. The result was unambiguous: the steepest changes in both HbA1c, a measure of average blood sugar over recent weeks, and body weight clustered in the first 90 days after the prescription was started. Before treatment, these measures changed slowly or not at all; after initiation, they accelerated dramatically. The abruptness of the transition underscores how quickly the body’s metabolic regulation can be perturbed by these medications, and how narrow the window of earliest change really is.

One of the study’s most consequential findings is that blood sugar and weight did not always move together. Some patients showed significant changes in one measure without comparable changes in the other, a dissociation with direct clinical implications. If clinicians rely on weight alone as a proxy for metabolic risk, they may miss patients whose blood sugar is climbing dangerously even while the scales appear reassuring. The researchers argue that both weight and blood sugar should be checked before treatment starts and again during the first few months afterwards, rather than relying on a single indicator or on monitoring schedules that only kick in months or years later.

Not all four drugs carried the same early risk. Among the medications 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 in this group. That magnitude of acceleration, compressed into a single quarter of a year, illustrates how sharply individual antipsychotics can differ in their metabolic profiles and why drug choice at the point of initiation may shape a patient’s long-term physical health trajectory.

The study also identified groups who appear especially vulnerable. People who already had prediabetes when they started treatment showed greater metabolic vulnerability: 19 percent of those with prediabetes at baseline developed type 2 diabetes within two years, compared with just 3 percent of those who began with normal blood sugar levels. Sex mattered as well. Among women, HbA1c rose around 24 times faster and weight around 12 times faster during the first 90 days than before treatment, whereas among men the corresponding increases were around 10 times faster for both measures. Women, in other words, were disproportionately affected compared with men, a pattern that could inform more tailored monitoring protocols.

First author Dr Juan Carlos Bazo-Alvarez, of UCL Epidemiology and Health, emphasised that the findings are not a argument against antipsychotic treatment. Antipsychotic medicines, he noted, are valuable treatments that help many people with serious mental illnesses. Rather, the study shows that the first 90 days after starting treatment are a key period when changes linked to diabetes and weight gain can begin. By checking blood sugar and weight early, he said, doctors may be able to spot problems sooner and offer support, advice, or treatment to help prevent more serious health issues later on. The results may also help clinicians pay particular attention to groups who may be more at risk, so that patients can receive the benefits of antipsychotic medicines while reducing their risk of developing conditions such as type 2 diabetes.

Like all observational research, the study has limitations that shape how its conclusions should be read. The researchers could only analyse information that had already been recorded in GP records, and the study could not account for all factors that might influence blood sugar and weight, such as diet, exercise or additional medications. Even so, the sheer scale of the dataset, spanning nearly two decades of English primary care records and close to a hundred thousand patients, gives the central finding considerable weight. The message for practice is straightforward: the earliest weeks and months of antipsychotic therapy are when metabolic risk first surfaces, and routine monitoring of both weight and blood sugar during that window could give clinicians the chance to act before reversible changes become chronic disease.

Subject of Research: Metabolic changes in blood sugar and weight following antipsychotic initiation in people with severe mental illness

Article Title: First 90 days after starting antipsychotics are critical for monitoring diabetes risk

Article References: First 90 days after starting antipsychotics are critical for monitoring diabetes risk. (n.d.). Original publication

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Keywords: antipsychotics, schizophrenia, bipolar disorder, diabetes risk, HbA1c, weight gain, metabolic health, The Lancet Psychiatry, UCL, prediabetes, mental illness, NHS records