Peripheral nerve complications of weight loss associated with novel antihyperglycemic agents: a cohort study

Area of Science:

• Neurology
• Endocrinology
• Pharmacology

Background:

• Weight loss, often a goal for patients, can paradoxically cause or worsen peripheral nerve disorders like neuropathy and nerve entrapments.
• Newer antihyperglycemic medications, including glucagon-like peptide-1 receptor (GLP1R) agonists and sodium-glucose co-transporter 2 (SGLT2) inhibitors, are associated with significant weight loss alongside glucose control.

Purpose of the Study:

• To investigate the potential link between the use of novel antihyperglycemic agents (GLP1R agonists, SGLT2 inhibitors) and the development of peripheral nerve disorders.
• To describe cases of neuropathy temporally associated with weight loss induced by these medications.

Main Methods:

• A retrospective cohort review of adult patients evaluated for peripheral nerve dysfunction between 2020 and 2024.
• Inclusion criteria required clinical and/or electrodiagnostic confirmation of a peripheral nerve disorder within 12 months of initiating GLP1R agonists, SGLT2 inhibitors, or dipeptidyl peptidase-4 inhibitors.

Main Results:

• Five cases were identified, all demonstrating a temporal association between peripheral nerve disorders (femoral, fibular, median, ulnar neuropathies, and entrapments) and weight loss.
• The identified cases involved the use of GLP1R agonists or SGLT2 inhibitors.

Conclusions:

• Peripheral neuropathies and nerve entrapments may occur after rapid weight loss or glycemic normalization achieved with GLP1R agonists or SGLT2 inhibitors.
• The exact mechanism is unknown but likely not a direct drug effect; caution is advised.
• Further research is needed to establish safe targets for HbA1c and weight loss during treatment with these agents.