Long-term cancer risk in users of GLP-1 agonists in Denmark: a nationwide emulated trialResearch in context
Summary: Background: The long-term cancer safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in real-world settings remains unclear, with limited long-term clinical and observational studies. We clarify the long-term cancer risk. Methods: This register-based nationwide emulated trial in...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-08-01
|
| Series: | The Lancet Regional Health. Europe |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666776225001383 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850220685631160320 |
|---|---|
| author | Mads Gamborg Mia Klinten Grand Kathrine Grell Susanne Rosthøj Ulrik Pedersen-Bjergaard Christian Torp-Pedersen Lina Steinrud Mørch |
| author_facet | Mads Gamborg Mia Klinten Grand Kathrine Grell Susanne Rosthøj Ulrik Pedersen-Bjergaard Christian Torp-Pedersen Lina Steinrud Mørch |
| author_sort | Mads Gamborg |
| collection | DOAJ |
| description | Summary: Background: The long-term cancer safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in real-world settings remains unclear, with limited long-term clinical and observational studies. We clarify the long-term cancer risk. Methods: This register-based nationwide emulated trial includes all Danes initiating treatment with GLP-1RA or dipeptidyl peptidase-4 inhibitors (DPP-4i) 2007–2019, propensity score matched 1:1 on baseline characteristics and followed 10 years. The primary outcome was risk differences for cancer, estimated for long-term sustained use of GLP-1RA vs DPP-4i using g-computation accounting for time-varying patient characteristics. Secondary outcomes included “death without prior cancer” and the composite outcome “death or cancer”. Analyses included sex stratified estimates and Cox hazard ratios (HR). Findings: After 195,702 person-years 4758 developed cancer. Among sustained users of GLP-1RA, 4·1 (95% CI 0·4–7·2) more patients developed cancer per 100, compared to 100 DPP-4i patients 10-years post-initiation (HR: 1·35 [95% CI 1·05–1·73] 6–10 years post-initiation). The excess cancer risk was 6·6 (95% CI 1·8–10·7) per 100 women and 2·2 (95% CI −2·2 to 6·2) per 100 men. Fewer patients “died without prior cancer” in users of GLP-1RA (per 100 users: −4·9 [95% CI −7·6 to −2·4]). There was no difference in risk of “death or cancer” per 100 users: −1·15 (95% CI −4·9 to 2·5). Interpretation: Long-term sustained users of GLP-1RA had a small increased risk of cancer; potentially explained by a survival benefit. Residual confounding by body mass index cannot be ruled out. Funding: The Scientific Committee of the Danish Cancer Society (R354-A20492-23-S3 to LSM). |
| format | Article |
| id | doaj-art-a7d612cf99cf42ce9f26533f49a6b50d |
| institution | OA Journals |
| issn | 2666-7762 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | The Lancet Regional Health. Europe |
| spelling | doaj-art-a7d612cf99cf42ce9f26533f49a6b50d2025-08-20T02:06:58ZengElsevierThe Lancet Regional Health. Europe2666-77622025-08-015510134610.1016/j.lanepe.2025.101346Long-term cancer risk in users of GLP-1 agonists in Denmark: a nationwide emulated trialResearch in contextMads Gamborg0Mia Klinten Grand1Kathrine Grell2Susanne Rosthøj3Ulrik Pedersen-Bjergaard4Christian Torp-Pedersen5Lina Steinrud Mørch6Cancer and Medicine, Danish Cancer Institute, Danish Cancer Society, Copenhagen, Denmark; Corresponding author. Cancer and Medicine, Danish Cancer Institute, Danish Cancer Society, Strandboulevarden 49, DK-2100, Copenhagen Ø, Denmark.Statistics and Data Analysis, Danish Cancer Institute, Danish Cancer Society, Copenhagen, DenmarkStatistics and Data Analysis, Danish Cancer Institute, Danish Cancer Society, Copenhagen, DenmarkStatistics and Data Analysis, Danish Cancer Institute, Danish Cancer Society, Copenhagen, DenmarkFaculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Endocrine Section, Department of Endocrinology and Nephrology, Nordsjaellands Hospital, Hilleroed, DenmarkDepartment of Public Health, Section of Biostatistics, University of Copenhagen, Copenhagen, Denmark; Department of Cardiology, Nordsjaellands Hospital, Hilleroed, DenmarkCancer and Medicine, Danish Cancer Institute, Danish Cancer Society, Copenhagen, Denmark; Corresponding author. Cancer and Medicine, Danish Cancer Institute, Danish Cancer Society, Strandboulevarden 49, DK-2100, Copenhagen Ø. Denmark.Summary: Background: The long-term cancer safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in real-world settings remains unclear, with limited long-term clinical and observational studies. We clarify the long-term cancer risk. Methods: This register-based nationwide emulated trial includes all Danes initiating treatment with GLP-1RA or dipeptidyl peptidase-4 inhibitors (DPP-4i) 2007–2019, propensity score matched 1:1 on baseline characteristics and followed 10 years. The primary outcome was risk differences for cancer, estimated for long-term sustained use of GLP-1RA vs DPP-4i using g-computation accounting for time-varying patient characteristics. Secondary outcomes included “death without prior cancer” and the composite outcome “death or cancer”. Analyses included sex stratified estimates and Cox hazard ratios (HR). Findings: After 195,702 person-years 4758 developed cancer. Among sustained users of GLP-1RA, 4·1 (95% CI 0·4–7·2) more patients developed cancer per 100, compared to 100 DPP-4i patients 10-years post-initiation (HR: 1·35 [95% CI 1·05–1·73] 6–10 years post-initiation). The excess cancer risk was 6·6 (95% CI 1·8–10·7) per 100 women and 2·2 (95% CI −2·2 to 6·2) per 100 men. Fewer patients “died without prior cancer” in users of GLP-1RA (per 100 users: −4·9 [95% CI −7·6 to −2·4]). There was no difference in risk of “death or cancer” per 100 users: −1·15 (95% CI −4·9 to 2·5). Interpretation: Long-term sustained users of GLP-1RA had a small increased risk of cancer; potentially explained by a survival benefit. Residual confounding by body mass index cannot be ruled out. Funding: The Scientific Committee of the Danish Cancer Society (R354-A20492-23-S3 to LSM).http://www.sciencedirect.com/science/article/pii/S2666776225001383Glucagon-like peptide-1 (GLP-1) receptor agonistsGLP-1RACancer riskLong-term sustained useDuration of use |
| spellingShingle | Mads Gamborg Mia Klinten Grand Kathrine Grell Susanne Rosthøj Ulrik Pedersen-Bjergaard Christian Torp-Pedersen Lina Steinrud Mørch Long-term cancer risk in users of GLP-1 agonists in Denmark: a nationwide emulated trialResearch in context The Lancet Regional Health. Europe Glucagon-like peptide-1 (GLP-1) receptor agonists GLP-1RA Cancer risk Long-term sustained use Duration of use |
| title | Long-term cancer risk in users of GLP-1 agonists in Denmark: a nationwide emulated trialResearch in context |
| title_full | Long-term cancer risk in users of GLP-1 agonists in Denmark: a nationwide emulated trialResearch in context |
| title_fullStr | Long-term cancer risk in users of GLP-1 agonists in Denmark: a nationwide emulated trialResearch in context |
| title_full_unstemmed | Long-term cancer risk in users of GLP-1 agonists in Denmark: a nationwide emulated trialResearch in context |
| title_short | Long-term cancer risk in users of GLP-1 agonists in Denmark: a nationwide emulated trialResearch in context |
| title_sort | long term cancer risk in users of glp 1 agonists in denmark a nationwide emulated trialresearch in context |
| topic | Glucagon-like peptide-1 (GLP-1) receptor agonists GLP-1RA Cancer risk Long-term sustained use Duration of use |
| url | http://www.sciencedirect.com/science/article/pii/S2666776225001383 |
| work_keys_str_mv | AT madsgamborg longtermcancerriskinusersofglp1agonistsindenmarkanationwideemulatedtrialresearchincontext AT miaklintengrand longtermcancerriskinusersofglp1agonistsindenmarkanationwideemulatedtrialresearchincontext AT kathrinegrell longtermcancerriskinusersofglp1agonistsindenmarkanationwideemulatedtrialresearchincontext AT susannerosthøj longtermcancerriskinusersofglp1agonistsindenmarkanationwideemulatedtrialresearchincontext AT ulrikpedersenbjergaard longtermcancerriskinusersofglp1agonistsindenmarkanationwideemulatedtrialresearchincontext AT christiantorppedersen longtermcancerriskinusersofglp1agonistsindenmarkanationwideemulatedtrialresearchincontext AT linasteinrudmørch longtermcancerriskinusersofglp1agonistsindenmarkanationwideemulatedtrialresearchincontext |