Peripheral nerve complications from medications utilised for weight loss: a systematic review

A systematic review of 19 studies identified 31 individual cases and a 103-person cohort of new-onset or worsening peripheral nerve problems in people taking weight-loss medications, mainly semaglutide or tirzepatide. The most common presentations were fibular neuropathy, lumbosacral radiculoplexus neuropathy, and distal symmetric polyneuropathy.

Systematic review. Population: Patients with new-onset or worsening peripheral nerve complications associated with medications used for weight loss. Sample size: 31 cases plus one cohort of 103 individuals, from 19 studies. Interventions: weight-loss medications, mainly semaglutide or tirzepatide.

The systematic review identified 19 studies with 31 individual cases and one cohort of 103 individuals. Median weight loss was 20.4 kg (IQR 15.2), corresponding to 21.8% (IQR 16.4) of starting body weight, with a median rate of 3.7 kg/month (IQR 1.7) and symptom onset at 150 days (IQR 135). Semaglutide or tirzepatide were implicated in 83% of cases, and 67% of affected individuals had pre-diabetes/diabetes. Neurological presentations included fibular neuropathy (n=10), lumbosacral radiculoplexus neuropathy (n=9), and distal symmetric polyneuropathy (n=7). Electrodiagnostic and imaging data supported the diagnoses.

This paper is relevant to tirzepatide researchers because tirzepatide was among the agents implicated in the reported peripheral nerve cases, and the review quantifies the weight-loss context (median ~20 kg, ~3.7 kg/month) in which symptoms appeared. It does not establish that tirzepatide causes neuropathy, nor does it provide an incidence rate or a safe weight-loss threshold.

Key findings

• 19 studies comprising 31 cases and one cohort (103 individuals) were identified; all but one were published from 2024.
• Median weight loss before symptom onset was 20.4 kg (IQR 15.2), or 21.8% (IQR 16.4) of starting body weight.
• Median rate of weight loss was 3.7 kg/month (IQR 1.7), and symptom onset occurred at a median of 150 days (IQR 135).
• Semaglutide or tirzepatide were implicated in 83% of cases, and 67% had pre-diabetes/diabetes.
• Reported presentations included fibular neuropathy (n=10), lumbosacral radiculoplexus neuropathy (n=9), and distal symmetric polyneuropathy (n=7).

Limitations

• The authors state that prospective studies are needed to determine incidence and confirm safe rates of weight loss and glycemic correction.
• Case reports and small case series cannot establish causation or incidence.
• There was no control group or standardized neurological work-up across studies.
• Publication or reporting bias is likely, given that nearly all identified reports were published from 2024.

The record

• Journal: Journal of neurology 273(8): 503
• Published: 2026-08-03
• PMID: 42547656 — DOI: 10.1007/s00415-026-14048-w
• MeSH terms: Humans, Peripheral Nervous System Diseases, Obesity, Weight Loss, Anti-Obesity Agents, Semaglutide
• Funding: The University of Queensland
• Author countries: Australia

Peptide profiles: Tirzepatide.

All indexed evidence: Tirzepatide trials & papers.

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