HbA1c and weight climb fastest in the first 90 days of an antipsychotic

Design

Individual-level interrupted time-series analysis, English primary care records

Population

96,849 adults aged 18 to 59 with severe mental illness starting an oral second-generation antipsychotic

Primary outcome

Rate of change in HbA1c and weight

Effect

First 90 days: HbA1c +0.12 mmol/mol per week (95% CI 0.09 to 0.15) vs +0.01 before

An English primary care records study followed 96,849 adults aged 18 to 59 with severe mental illness who started an oral second-generation antipsychotic, excluding those with diabetes. It modelled HbA1c and weight before starting, in the first 90 days, and from 91 days to two years.

In the first 90 days, HbA1c rose by 0.12 mmol/mol per week (95% CI 0.09 to 0.15), against 0.01 before treatment, and weight by 0.21 kg per week, against 0.02. After 90 days, HbA1c slowed back to its pre-treatment rate while weight kept rising slowly. Olanzapine showed the largest rises (HbA1c 0.18 mmol/mol and weight 0.28 kg per week). Quetiapine raised weight but barely moved HbA1c. Among people with prediabetes at baseline, an estimated 19% developed type 2 diabetes within two years, against 3% with normal HbA1c.

Weight and HbA1c did not move in step, so checking weight alone can miss glycaemic change. The authors support measuring both at baseline and at 12 weeks, then monitoring according to risk.

Only a quarter of the cohort had any HbA1c recorded, so measured patients may differ from the rest, but the timing signal is strong. Prediabetes at the start is the clearest flag for closer follow-up and early lifestyle or drug intervention.

• Measure HbA1c and weight before starting an antipsychotic and again at about 12 weeks.
• Flag prediabetes at baseline: about one in five developed diabetes within two years.
• With olanzapine, expect the steepest early rise in both HbA1c and weight.
• Do not use weight as a proxy for glucose; the two diverged, notably with quetiapine.
• After 12 weeks, set monitoring frequency by risk rather than a fixed annual check.

Why it matters

The metabolic damage is front-loaded, so a first check at one year is too late.

Don't overread it

HbA1c was recorded for only a quarter of the cohort; the timing pattern is robust but the exact rates may not be.

The statistics, in plain English

A rise of 0.12 mmol/mol per week adds up to roughly 1.5 mmol/mol over 12 weeks on average; small for most people but meaningful for someone already near the diabetes threshold. The 19% two-year diabetes incidence in prediabetes is an estimate from a smaller subgroup of 918 people.

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