Cardiac Nerve Damage Is Rampant in Schizophrenia — Semaglutide Didn't Fix It in 30 Weeks | Research

The takeaway

84% of schizophrenia patients on antipsychotics had cardiac autonomic neuropathy (50% definite), correlating with BMI and clozapine use, but semaglutide did not improve CAN despite reducing BMI over 30 weeks.

84% have CAN
The vast majority of schizophrenia patients on antipsychotics have cardiac autonomic nerve damage, with half having definite neuropathy

What the researchers found

CAN prevalence: 84% (50% definite) in schizophrenia patients on antipsychotics. CAN correlated with BMI (p<0.05 from BMI 30+) and clozapine. Semaglutide reduced BMI but did not change CAN status over 30 weeks (p=0.516).

Why it matters

The 84% CAN prevalence reveals a hidden cardiovascular catastrophe in schizophrenia patients that may explain their excess cardiac mortality. Understanding it doesn't resolve quickly despite weight loss is clinically important.

How the study worked

Pre-specified analysis from a 30-week double-blind RCT (NCT05193578) with 154 schizophrenia patients (141 completers), assessing CAN prevalence, correlates, and semaglutide effects on CAN.

What this study cannot tell us

30 weeks may be too short for nerve regeneration. CAN measurement methods may lack sensitivity to early improvements. Cannot separate antipsychotic-induced from obesity-induced CAN.

How to read the evidence

Pre-specified analysis from a well-designed RCT. Definitive for the 30-week timeframe but longer follow-up needed.

When this study was published

Published in 2025.

The bigger picture

This reveals CAN as a major underrecognized cardiovascular risk in schizophrenia that isn't quickly reversible, potentially requiring prolonged intervention or specific neuroprotective treatments.

Questions still open

Would 1+ years of semaglutide eventually improve CAN?
Should schizophrenia patients be routinely screened for CAN?
Could direct neuroprotective agents combined with semaglutide address CAN?

Common questions

What is cardiac autonomic neuropathy?

CAN is damage to the nerves controlling heart rate and rhythm. It increases the risk of sudden cardiac death. This study found 84% of schizophrenia patients on antipsychotics have it — far higher than the general population.

Why didn't semaglutide fix the nerve damage?

Nerve regeneration takes much longer than 30 weeks. While semaglutide reduced weight and improved metabolic markers, the cardiac nerves likely need years of improved conditions to recover.

Read the original research

Cardiac autonomic neuropathy in patients with SGA-treated schizophrenia: a randomized controlled trial of 30 weeks' treatment with semaglutide.

Cardiovascular diabetology. Endocrinology reports, 12(1), 2

View on PubMed ↗Publisher’s paper ↗

Citation

Ganeshalingam, Ashok Ainkaran; Uhrenholt, Nicolai Gundtoft; Arnfred, Sidse; Gæde, Peter; Pedersen, Andreas Kristian; Bilenberg, Niels; Frystyk, Jan. (2026). Cardiac autonomic neuropathy in patients with SGA-treated schizophrenia: a randomized controlled trial of 30 weeks' treatment with semaglutide.. Cardiovascular diabetology. Endocrinology reports, 12(1), 2. https://doi.org/10.1186/s40842-025-00258-0