Cardiovascular Outcomes and Efficacy of the PCSK9 Inhibitor Evolocumab in Individuals With Type 1 Diabetes: Insights From the FOURIER Trial
Open accessAbstract
OBJECTIVE: To evaluate the clinical efficacy of intensive LDL cholesterol (LDL-C) lowering in type 1 diabetes mellitus (T1DM). RESEARCH DESIGN AND METHODS: Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) randomized participants with atherosclerotic cardiovascular disease (ASCVD) on statins to evolocumab or placebo (median follow-up 2.2 years). The primary end point (PEP) was cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. RESULTS: Of 27,564 participants, 10,834 (39.3%) had type 2 diabetes mellitus (T2DM), and 197 (0.7%) had T1DM. In the placebo arm, there was a stepwise increase in the 2.5-year PEP Kaplan-Meier rate from 11.0% to 15.2% to 20.4% in participants with no diabetes, T2DM, and T1DM, respectively (P < 0.0001). Hazard ratios for PEP with evolocumab were 0.87 (95% CI 0.79-0.96), 0.84 (0.75-0.93), and 0.66 (0.32-1.38) in the no diabetes, T2DM, and T1DM groups, and absolute risk reduction was 1.3%, 2.5%, and 7.3%, respectively. CONCLUSIONS: Intensive LDL-C lowering may provide substantial clinical benefit in individuals with T1DM and ASCVD. Additional randomized controlled cardiovascular outcomes trials are needed in this population.
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In FOURIER, the relative reduction in the risk of the primary major adverse cardiovascular event outcome with active compared with placebo evolocumab was similar across different types or statuses of diabetes.
“The relative reduction in the risk of the primary major adverse cardiovascular event outcome with active compared with placebo evolocumab was similar across different types or statuses of diabetes (type 1 diabetes HR 0.66, 95% CI 0.32–1.38; type 2 diabetes HR 0.84, 95% CI 0.75–0.93; no diabetes HR 0.87, 95% CI 0.79–0.96).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [114]
The Results (page unavailable) report exactly the three cited hazard ratios and confidence intervals for the primary outcome. However, they describe the relative risk reduction as numerically greater in type 1 diabetes (34% versus 16% and 13%), rather than similar across groups. The Conclusions note that the small type 1 diabetes group limited power to detect differences between groups. (LLM, conf=0.84)
Experimental — accuracy not yet measuredRecent data from the PCSK9 inhibitor trial FOURIER suggest that LDL cholesterol-lowering benefit has important cardiovascular risk reduction benefits in people with type 1 diabetes and established CVD.
“Recent data from the PCSK9 inhibitor trial FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk) suggest that LDL cholesterol–lowering benefit has important cardiovascular risk reduction benefits in people with type 1 diabetes and established CVD, as discussed in secondary prevention (people with ascvd), below (114).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [114]
The absolute risk reduction of major cardiovascular events with evolocumab in individuals with type 1 diabetes was at least as large, if not larger, than that seen for type 2 diabetes or no diabetes.
“These observations suggest that the absolute risk reduction of major cardiovascular events with evolocumab in individuals with type 1 diabetes was at least as large, if not larger, than that seen for type 2 diabetes or no diabetes.”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [114]
Of the 27,564 participants in FOURIER, 197 (0.7%) had type 1 diabetes and 10,834 (39.3%) had type 2 diabetes.
“Of the 27,564 participants in FOURIER, 197 (0.7%) had type 1 diabetes and 10,834 (39.3%) had type 2 diabetes.”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [114]
In FOURIER, participants with type 1 diabetes randomly assigned to placebo had a higher rate of major cardiovascular events (Kaplan-Meier event rate 20.4%) than those with type 2 diabetes (15.2%) and those without diabetes (11.0%).
“Participants with type 1 diabetes randomly assigned to placebo had a higher rate of major cardiovascular events (Kaplan-Meier event rate 20.4%) than those with type 2 diabetes (15.2%) and those without diabetes (11.0%).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [114]
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- Authors
- Kang, Y. M., Giugliano, R. P., Ran, X., Deedwania, P., De Ferrari, G. M., George, J. T., Gouni-Berthold, I., Paiva da Silva Lima, G., Handelsman, Y., Lewis, B. S., Ohman, E. M., Wang, H., López, J. A. G., Monsalvo, M. L., Sabatine, M. S., & Leiter, L. A.
- Affiliations
- Brigham and Women's Hospital (US)
- University of California, San Francisco (US)
- Division of Cardiology, Cardiovascular and Thoracic Department, University of Turin, Città della Salute e della Scienza Hospital 4 , Turin, Italy
- Amgen (United States) (US)
- Center for Endocrinology, Diabetes and Preventive Medicine, Faculty of Medicine, University Hospital Cologne, University of Cologne 6 , Cologne, Germany
- Global Development, Amgen, Inc. 5 , Thousand Oaks, CA
- Instituto de Diagnóstico e Investigaciones Metabólicas (AR)
- Technion – Israel Institute of Technology (IL)
- St. Michael's Hospital (CA)
- ORCID
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2025-06-22
- Volume
- 48
- Issue
- 9
- Pages
- 1512-1516
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- PMC
- PMC12368373
- OpenAlex
- W4411523842
- Cited by
- 9
- References
- 21
- Citations by year
- 2026: 6 · 2025: 3
- FWCI
- 8.47
- Type
- journal article
- Language
- en
- Open access
- green
- pmc.ncbi.nlm.nih.gov
- Locations
- Diabetes Care (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion)
- Funders
- Division of Diabetes, Endocrinology, and Metabolic Diseases (5T32DK007529)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- evolocumab, PCSK9 inhibitors, type 1 diabetes, type 2 diabetes, LDL cholesterol lowering, atherosclerotic cardiovascular disease, cardiovascular outcomes, FOURIER trial, statin therapy
- MeSH terms
- Proprotein Convertase 9, PCSK9 Inhibitors, Adult, Antibodies, Monoclonal, Anticholesteremic Agents, Cardiovascular Diseases, Diabetes Mellitus, Type 1, Female, Humans, Cholesterol, LDL, Male, Middle Aged, Antibodies, Monoclonal, Humanized
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