Clinical trial · Observational
Pre-Diagnosis GLP-1 Receptor Agonist Use and Post-Cancer Mortality in Adults With Obesity and Type 2 Diabetes
Pre-Diagnosis GLP-1 Receptor Agonist Use and Post-Cancer Mortality in Adults With Obesity and Type 2 Diabetes: A Target Trial Emulation
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
This study will examine whether the type of diabetes treatment used before cancer diagnosis is associated with survival and serious complications after obesity-associated cancer in adults with obesity and type 2 diabetes. The study focuses on glucagon-like peptide-1 receptor agonists (GLP-1 RA) and compares them with other commonly used glucose-lowering therapies, including SGLT2 inhibitors, DPP-4 inhibitors, sulfonylureas, metformin, and usual care. Using de-identified electronic health record data from the TriNetX US Collaborative Network, the study will assess whether patients who used GLP-1 RA before cancer diagnosis have different risks of death, hospitalization, sepsis, and other major outcomes after cancer diagnosis. This is an observational study designed to evaluate associations in routine clinical care and not to prove a treatment effect.
Conditions
Conditions (3)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Diabetes Mellitus Type 2 | — | UNRESOLVED | — |
| Neoplasms | Neoplasm | ONTOLOGY_EXACT | 0.90 |
| Obesity & Overweight | — | UNRESOLVED | — |
Interventions
Interventions (0)
Data not yet available
Design
Arms and outcomes
Arms (2)
- label
- GLP-1 RA
- description
- Adults with obesity and type 2 diabetes who developed an obesity-associated cancer after initiating a GLP-1 receptor agonist before cancer diagnosis. This cohort served as the GLP-1 RA exposure cohort in the overall study population and represents the unique participants with pre-diagnosis GLP-1 receptor agonist use.
- label
- Usual Care Without GLP-1 RA
- description
- Adults with obesity and type 2 diabetes who developed an obesity-associated cancer and had no GLP-1 receptor agonist prescriptions before cancer diagnosis. This cohort served as the non-GLP-1 RA comparator cohort in the overall study population. Participants could receive routine clinical care, including other non-GLP-1 RA glucose-lowering medications. This cohort represents the unique participants without pre-diagnosis GLP-1 receptor agonist use.
Primary outcomes (5)
- measure
- All-cause Mortality (Comparison 1)
- timeFrame
- From obesity-associated cancer diagnosis through 36 months
- description
- All-cause mortality within 36 months after obesity-associated cancer diagnosis in the propensity score-matched cohort for Comparison 1, comparing adults with obesity and type 2 diabetes treated with GLP-1 receptor agonist without prior SGLT2 inhibitor use versus SGLT2 inhibitor-treated adults.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: * Adults aged 18 years or older * BMI ≥27 kg/m2, or diagnosis codes consistent with obesity * Type 2 diabetes mellitus * Initiation of a glucose-lowering medication before obesity-associated cancer diagnosis * Incident obesity-associated cancer diagnosed after medication initiation * No dispensing of the study drug class during the 6-month washout period before the first qualifying prescription Exclusion Criteria: * Type 1 diabetes mellitus, Other specified diabetes types that are not type 2 diabetes * Human immunodeficiency virus infection * End-stage renal disease * Prior bariatric surgery * Prior organ transplantation * Transplant-related complications * Any use of tirzepatide before cohort entry
References
Publications (38)
- BACKGROUNDKim C, Dinan MA, Robinson TJ, Ross JS, Jastreboff AM, Krumholz HM, Lu Y. Semaglutide and Tirzepatide Prescribing for Obesity in Patients With Preexisting Comorbid Cancers. JAMA Oncol. 2025 Nov 6;12(1):101-4. doi: 10.1001/jamaoncol.2025.4560. Online ahead of print. PMID 41196576
- BACKGROUNDTsujimoto T, Kajio H, Sugiyama T. Association between hyperinsulinemia and increased risk of cancer death in nonobese and obese people: A population-based observational study. Int J Cancer. 2017 Jul 1;141(1):102-111. doi: 10.1002/ijc.30729. Epub 2017 Apr 22. PMID 28390156
- BACKGROUNDZhang AMY, Wellberg EA, Kopp JL, Johnson JD. Hyperinsulinemia in Obesity, Inflammation, and Cancer. Diabetes Metab J. 2021 May;45(3):285-311. doi: 10.4093/dmj.2020.0250. Epub 2021 Mar 29. PMID 33775061
- BACKGROUNDPerkovic V, Tuttle KR, Rossing P, Mahaffey KW, Mann JFE, Bakris G, Baeres FMM, Idorn T, Bosch-Traberg H, Lausvig NL, Pratley R; FLOW Trial Committees and Investigators. Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes. N Engl J Med. 2024 Jul 11;391(2):109-121. doi: 10.1056/NEJMoa2403347. Epub 2024 May 24. PMID 38785209
- BACKGROUNDWong CK, McLean BA, Baggio LL, Koehler JA, Hammoud R, Rittig N, Yabut JM, Seeley RJ, Brown TJ, Drucker DJ. Central glucagon-like peptide 1 receptor activation inhibits Toll-like receptor agonist-induced inflammation. Cell Metab. 2024 Jan 2;36(1):130-143.e5. doi: 10.1016/j.cmet.2023.11.009. Epub 2023 Dec 18. PMID 38113888
- BACKGROUNDRohm TV, Meier DT, Olefsky JM, Donath MY. Inflammation in obesity, diabetes, and related disorders. Immunity. 2022 Jan 11;55(1):31-55. doi: 10.1016/j.immuni.2021.12.013. PMID 35021057
- BACKGROUNDWong CK, Drucker DJ. Antiinflammatory actions of glucagon-like peptide-1-based therapies beyond metabolic benefits. J Clin Invest. 2025 Nov 3;135(21):e194751. doi: 10.1172/JCI194751. eCollection 2025 Nov 3.