Incretin-Based Therapies and Cancer: What’s New?
Abstract
1. Introduction
2. DPP-4 Inhibitors and Cancer
Type of Cancer | Study | Method | Design | No. of Participants/ Samples | Result |
---|---|---|---|---|---|
Animal studies | |||||
Liver | Sohji et al. [26] | In vitro | HCC cell lines, xenograft tumors injected in mice models | 41 | No antitumor effect in the in vitro models (p < 0.05) |
Lung | Zuo et al. [24] | In vitro | Tissue sampling of LC cells injected mice, fed with DPP-IV | 20 | Enhancement of immunotherapy effect by inhibition of tumor-associated macrophage activity (p < 0.05) |
Human Studies | |||||
Pancreas | Shah et al. [23] Elashoff et al. Wang et al. [21] | Real world Real world Real world | Patients with PC and T2D Database analysis of AE Database analysis of AE | 5.359 1863 5095 | No significant effect on overall survival (HR 17 (95% CI: 0.93–1.24, p = 0.68) Higher risk of PC (p < 0.8) No significant effect on cancer risk (OR 0.94 (95% CI 0.86–14, p < 0.23)) |
Colorectal | Saito et al. [22] | Real world | Patients with CRC and T2D | 260 | Lower disease-free survival (HR 1.98 (95% CI 15–3.71, p = 0.35)) |
Liver | Wang et al. [21] | Real world | Database analysis of AE | 344.550 | Higher risk of liver cancer (OR 1.14 (95% CI 12–1.26, p = 0.2)) |
Kidney | Wang et al. [21] Kamada et al. [25] | Real world In vitro | Database analysis of adverse events PDTS of patients with RCC and T2D | 344.550 769 | Higher risk of kidney cancer (OR 1.13 (95% CI 14–1.23, p < 0.01)) Enhancement of tumor-suppressive TKI efficacy (p < 0.05) |
Lung | Wang et al. [21] | Real world | Database analysis of AE | 344.550 | Reduced risk of LC (OR 0.91 (95% CI 0.86–0.97, p < 0.01)) |
Breast | Wang et al. [21] Shah et al. [23] | Real world Real world | Database analysis of AE Patients with BC and T2D | 344.550 1685 | Reduced risk of BC (OR 0.90 (95% CI 0.85–0.94, p < 0.01)) No significant effect on overall survival (HR 17 (95% CI: 0.93–1.25, p = 0.33) |
Prostate | Wang et al. [21] Shah et al. [23] | Real world Real world | Database analysis of AE Patients with PRC and T2D | 344.550 15.330 | Reduced risk of PRC (OR 0.87 (95% CI 0.82–0.91, p < 0.01)) Improves overall survival (HR 0.77 (95% CI: 0.64–0.93), p = 0.5) |
Bladder | Wang et al. [21] | Real world | Database analysis of AE | 344.550 | Higher risk of bladder cancer (OR 1.18 (95% CI 19–1.29, p < 0.01)) |
3. GLP-1 Receptor Agonists and Cancer
Type of Cancer | Study | Method | Design | No. of Participants | Result |
---|---|---|---|---|---|
Animal studies | |||||
Thyroid | Madsen et al. [48] | In vitro | Tissue sampling of GLP1RAinjected mice | 10 | Increased incidence of C cell hyperplasia and calcitonin levels in GLP1R wild type mice (p < 0.01) |
Human studies | |||||
Thyroid | Sun et al. [35] Wang et al. [37] Silverii et al. [50] | RCT RCT RCT | Database genetic analysis Database analysis of AE Database analysis | 65.328 64.230 46.228 | No increased risk of thyroid cancer (OR 0.83 (95% CI 0.63–1.10, p = 0.187)) Increased risk of thyroid cancer (aOR 1.65, p < 0.05) Increased overall risk of thyroid cancer (OR 1.52 (95% CI 11–2.29, p = 0.4)) |
Pancreas | Sun et al. [35] Dankner et al. [45] | RCT Real world | RCTs Prospective study | 65.328 33.370 | No increased risk of PC (OR 0.78 (95% CI 0.61–1, p = 0.19)) No increased risk of PC (HR 0.50 (95% CI, 0.15–1.71, p > 0.05)) |
Colorectal | Sun et al. [35] Wang et al. [37] | RCT RCT | Database genetic analysis Database analysis of AE | 65.328 64.230 | Increased risk of CRC (OR 1.12 (95% CI 17–1.18, p < 0.01)) Reduced risk of CRC (0.85, p < 0.3) |
Breast | Sun et al. [35] Wang et al. [21] | RCT RCT | Database genetic analysis Database analysis of AE | 65.328 14.752 | Reduced risk of BC (OR 0.92 (95% CI 0.88–0.96, p < 0.01)) No increased risk of BC (OR 0.99 (95% CI 0.91–17, p = 0.75)) |
Lung | Sun et al. [35] Wang et al. [37] | RCT RCT | Database genetic analysis Database analysis of AE | 65.328 64.230 | No increased risk of LC (OR 11 (95% CI 0.93–1.10, p = 0.76)) Reduced risk of LC (aOR 0.81, p = 0.5) |
Liver | Wang et al. [43] | Real world | Database analysis | 22.575 | Reduced risk of liver cancer (HR 0.63 (95% CI 0.26–1.50, p < 0.05)) |
Prostate | Sun et al. [35] Wang et al. [37] | RCT RCT | Database genetic analysis Database analysis of AE | 65.328 64.230 | Increased risk of PRC (OR 19 (95% CI 15–1.14, p < 0.01)) Reduced risk of PRC (aOR 0.72, p = 0.8) |
4. Dual GIP and GLP-1 Receptor Agonists and Cancer
5. Discussion
Balancing Risks and Benefits
6. Clinical Implications
7. New Agents Under Development
7.1. Emerging Therapies and Their Safety Profiles
Type of Cancer | Study | Method | Design | No. of Participants | Result |
---|---|---|---|---|---|
Animal studies | |||||
Colorectal | Prabakaran et al. [74] | In vitro | PCR analysis of GIP-R in mice CRC cell lines | / | Increased expression of GIP-R in colorectal cancer and dose-dependent CRC cell proliferation (p < 0.01) |
Thyroid | Waser et al. [70] | In vitro | PCR analysis of GLP-1R and GIP-R expression in MTC cells | / | Increased expression of GIP-R in MTC in rodents |
Human studies | |||||
Thyroid | Regazzo et al. [71] Popovic et al. [17] | In vitro RCTs | PCR analysis of GIP-R in tumor specimensDatabase analysis of AE | 49 978 | GIP-R expression in 80% of patients with MTC (p < 0.05) No increased risk of thyroid cancer (RR 0.35 (95% CI 0.13–0.95, p = 0.61)) |
Colorectal | Prabakaran et al. [74] | In vitro | PCR analysis of GIP-R in human CRC cell lines | / | Increased expression of GIP-R and dose-dependent CRC cell proliferation (p < 0.01) |
Breast | Samuel et al. [75] | In vitro | PCR analysis of GIP-R expression in cancer lines | 8.401 | Aberrations in GIP signaling associated with increased risk of BC |
7.2. Anticancer Potential of Novel Agents
8. Ongoing Challenges and Regulatory Oversight
9. Considerations for Clinical Practice
10. Future Directions
11. Conclusions
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
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Medenica, S.; Bogdanovic, J.; Vekic, J.; Vojinovic, T.; Babic, I.; Bogdanović, L.; Maggio, V.; Tanani, M.E.; Rizzo, M. Incretin-Based Therapies and Cancer: What’s New? Medicina 2025, 61, 678. https://doi.org/10.3390/medicina61040678
Medenica S, Bogdanovic J, Vekic J, Vojinovic T, Babic I, Bogdanović L, Maggio V, Tanani ME, Rizzo M. Incretin-Based Therapies and Cancer: What’s New? Medicina. 2025; 61(4):678. https://doi.org/10.3390/medicina61040678
Chicago/Turabian StyleMedenica, Sanja, Jelena Bogdanovic, Jelena Vekic, Tanja Vojinovic, Ivana Babic, Ljiljana Bogdanović, Viviana Maggio, Mohamed El Tanani, and Manfredi Rizzo. 2025. "Incretin-Based Therapies and Cancer: What’s New?" Medicina 61, no. 4: 678. https://doi.org/10.3390/medicina61040678
APA StyleMedenica, S., Bogdanovic, J., Vekic, J., Vojinovic, T., Babic, I., Bogdanović, L., Maggio, V., Tanani, M. E., & Rizzo, M. (2025). Incretin-Based Therapies and Cancer: What’s New? Medicina, 61(4), 678. https://doi.org/10.3390/medicina61040678