Unconventional Applications of Semaglutide and Tirzepatide: From Oncology to Human Reproduction

A broad review of semaglutide and tirzepatide found that, beyond diabetes and obesity, these incretin-based drugs show promising but mostly early-stage signals in cancer, psychiatry and addiction, osteoarthritis, aesthetics, and reproduction. The supportive evidence is still largely preclinical or observational for most of these uses, with randomized controlled trials limited; effects appear to work through immune, metabolic, and neurochemical reprogramming rather than direct cytotoxicity.

Narrative review — Comprehensive review of preclinical and clinical evidence. Interventions: Semaglutide; Tirzepatide.

Both agents showed antitumor activity through immune and metabolic reprogramming, with signals in pancreatic, thyroid, breast, and colorectal cancers. In psychiatry, evidence suggested reductions in alcohol use disorder, substance use, and binge-eating behaviors, attributed to modulation of dopamine and GABAergic pathways. Orthopedic evidence indicated clinically meaningful improvements in knee osteoarthritis pain and function, with mixed bone-health signals. In reproductive medicine, metabolic improvements translated to benefits in polycystic ovary syndrome and male fertility, though periconception safety concerns remained. Across all domains, evidence came mostly from preclinical models, observational cohorts, and pharmacoepidemiologic studies, with randomized controlled trials limited.

This review consolidates emerging unconventional applications of semaglutide and tirzepatide across oncology, psychiatry, orthopedics, aesthetics, and reproduction, giving researchers a map of the evidence landscape beyond metabolic effects. It does not establish efficacy for any of these uses, and no dosing, safety, or patient-selection conclusions can be drawn from it.

Key findings

Both agents showed antitumor activity primarily through immune and metabolic reprogramming rather than direct cytotoxicity, with signals in pancreatic, thyroid, breast, and colorectal cancers.
Psychiatric evidence linked modulation of mesolimbic dopamine reward pathways and GABAergic neurotransmission to reductions in alcohol use disorder, substance use, and binge-eating behaviors.
Orthopedic applications reported clinically meaningful improvements in knee osteoarthritis pain and function, while bone health signals remained mixed.
In reproductive medicine, metabolic improvements translated to benefits in polycystic ovary syndrome and male fertility, with periconception safety concerns persisting.
Across five distinct therapeutic domains, evidence derived predominantly from preclinical models, observational cohorts, and pharmacoepidemiologic studies, with randomized controlled trials remaining limited.

Limitations

Most evidence derives from preclinical models, observational cohorts, and pharmacoepidemiologic studies rather than randomized controlled trials.
Observational and pharmacoepidemiologic data are susceptible to confounding.
Periconception safety concerns remain unresolved.
As a review, conclusions depend on the scope and quality of the underlying published evidence.

The record

Journal: Biomedicines 14(7): 1644
Published: 2026-07-21
PMID: 42512116 — DOI: 10.3390/biomedicines14071644
Author countries: Italy

Peptide profiles: Semaglutide.

All indexed evidence: Semaglutide trials & papers.