GLP‐1 receptor agonists and serious adverse events: Evidence, uncertainty and clinical implications
- 1Centre for Pharmacoepidemiology Division of Clinical Epidemiology Department of Medicine, Solna Karolinska Institutet Stockholm Sweden
- 2Centre for Diabetes Academic Specialist Centre, Region Stockholm Stockholm Sweden
Abstract
Glucagon‐like peptide‐1 (GLP‐1) receptor agonists provide benefits in weight reduction, glycaemic control in Type 2 diabetes, and cardiovascular and renal outcomes. Their widespread use has given rise to concerns regarding rare but potentially serious adverse events. This narrative review appraises evidence regarding seven serious adverse events linked to GLP‐1 receptor agonists: thyroid cancer, non‐arteritic anterior ischaemic optic neuropathy (NAION), suicidal behaviours and self‐harm, diabetic retinopathy complications, acute pancreatitis, gallbladder and biliary disease and intestinal obstruction. Evidence from mechanistic studies, spontaneous reports, randomized trials and cohort studies is considered. Gallbladder and biliary disease has the most consistent evidence supporting a causal association. Worsening of diabetic retinopathy appears most consistent with early worsening after rapid glycaemic improvement in patients with pre‐existing retinopathy. For thyroid cancer, NAION, suicidal behaviour and self‐harm, acute pancreatitis and intestinal obstruction, evidence regarding causality remains uncertain. Rare events, incomplete ascertainment in trials and residual confounding in observational studies limit inference. Because these events are rare, even substantial relative risk increases generally correspond to small absolute risk increases in broad populations but may become relevant in patients with high baseline risk. Treatment decisions should consider the strength and uncertainty of safety evidence, individual baseline risk, expected benefits relative to available alternatives and patient preferences.
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BibTeX
@article{ueda2026glp1,
title = {{GLP‐1 receptor agonists and serious adverse events: Evidence, uncertainty and clinical implications}},
author = {Peter Ueda},
journal = {Journal of Internal Medicine},
year = {2026},
month = oct,
doi = {10.1111/joim.70170},
url = {https://doi.org/10.1111/joim.70170},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - GLP‐1 receptor agonists and serious adverse events: Evidence, uncertainty and clinical implications
AU - Peter Ueda
PY - 2026
DA - 2026/10/09
JO - Journal of Internal Medicine
DO - 10.1111/joim.70170
UR - https://doi.org/10.1111/joim.70170
AB - Glucagon‐like peptide‐1 (GLP‐1) receptor agonists provide benefits in weight reduction, glycaemic control in Type 2 diabetes, and cardiovascular and renal outcomes. Their widespread use has given rise to concerns regarding rare but potentially serious adverse events. This narrative review appraises evidence regarding seven serious adverse events linked to GLP‐1 receptor agonists: thyroid cancer, non‐arteritic anterior ischaemic optic neuropathy (NAION), suicidal behaviours and self‐harm, diabetic retinopathy complications, acute pancreatitis, gallbladder and biliary disease and intestinal obstruction. Evidence from mechanistic studies, spontaneous reports, randomized trials and cohort studies is considered. Gallbladder and biliary disease has the most consistent evidence supporting a causal association. Worsening of diabetic retinopathy appears most consistent with early worsening after rapid glycaemic improvement in patients with pre‐existing retinopathy. For thyroid cancer, NAION, suicidal behaviour and self‐harm, acute pancreatitis and intestinal obstruction, evidence regarding causality remains uncertain. Rare events, incomplete ascertainment in trials and residual confounding in observational studies limit inference. Because these events are rare, even substantial relative risk increases generally correspond to small absolute risk increases in broad populations but may become relevant in patients with high baseline risk. Treatment decisions should consider the strength and uncertainty of safety evidence, individual baseline risk, expected benefits relative to available alternatives and patient preferences.
SN - 0954-6820
SN - 1365-2796
ER -