Human Trials, Real Results: GLP-1 Medications Lower Heart, Kidney Risks

This study provides strong, human-relevant evidence that GLP-1 drugs help protect the kidney and heart in people with type 2 diabetes, reinforcing the importance of clinical trials over animal studies for human health.

Article

Badve, SV, Bilal, A, Lee, MMY, Sattar, N, Gerstein, HC, Ruff, CT, McMurray, JJV, Rossing, P, Bakris, G, Mahaffey, KW, Mann, JFE, Colhoun, HM, Tuttle, KR, Pratley, RE & Perkovic, V, 2025. ‘Effects of GLP-1 receptor agonists on kidney and cardiovascular disease outcomes: a meta-analysis of randomised controlled trials.’ The Lancet Diabetes & Endocrinology, vol. 13, no. 1, pp. 15-28. https://doi.org/10.1016/S2213-8587(24)00271-7.

Authors

Sunil V Badve, Anika Bilal, Matthew M Y Lee, Naveed Sattar, Hertzel C Gerstein, Christian T Ruff, John J V McMurray, Peter Rossing, George Bakris, Kenneth W Mahaffey, Johannes F E Mann, Helen M Colhoun, Katherine R Tuttle, Richard E Pratley, Vlado Perkovic

Affiliations

• St George Hospital, Sydney, NSW, Australia
• Renal and Metabolic Division, The George Institute for Global Health, Sydney, NSW, Australia
• University of New South Wales, Sydney, NSW, Australia
• AdventHealth Translational Research Institute, Orlando, FL, US
• School of Cardiovascular and Metabolic Health, British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK
• Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada
• TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, US
• Steno Diabetes Center Copenhagen, Herlev, Denmark
• Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
• American Society of Hypertension Comprehensive Hypertension Center, University of Chicago Medicine and Biological Sciences, Chicago, IL, US
• Stanford Center for Clinical Research, Department of Medicine, Stanford School of Medicine, Palo Alto, CA, US
• KfH Kidney Center, Munich, Germany
• University Hospital, Friedrich-Alexander University, Erlangen, Germany
• Institute of Genetics and Molecular Medicine, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK
• University of Washington School of Medicine, Seattle, WA, US
• Providence Inland Northwest Health, Spokane, WA, US

Funders

None disclosed.

Aim

To assess the impact of GLP-1 receptor agonists on kidney and heart disease outcomes in people with type 2 diabetes.

Key Terms

• GLP-1 receptor agonists – Medications used to help regulate blood sugar, primarily for type 2 diabetes and obesity.
• Major adverse cardiovascular events (MACE) – Serious heart-related outcomes, such as heart attacks and strokes, used as a key measure in studies.
• Randomised controlled trials (RCTs) – High-quality studies that compare treatments to a placebo (inactive substance) or another intervention to evaluate effectiveness and safety in humans.
• Meta-analysis – A study that combines data from multiple clinical trials to provide stronger evidence on a treatment’s effectiveness.

Methods

• Comprehensive database search for RCTs with ≥ 500 participants with type 2 diabetes, comparing GLP-1 receptor agonists to placebo for ≥ 12 months, reporting kidney or heart-related outcomes.
• 5,140 records identified; 11 trials (85,373 participants) included in the meta-analysis.

Results

In people with type 2 diabetes, GLP-1 receptor agonists (compared to placebo) significantly reduced the risk of:

• Kidney problems by 18%.
• Kidney failure by 16%.
• Major heart events (MACE) by 13%.
• Death from any cause by 12%.

There was no increase in serious side effects like pancreatitis or severe low blood sugar. However, more people in the GLP-1 group stopped treatment due to side effects.

Conclusion

This meta-analysis provides strong evidence that GLP-1 receptor agonists protect the kidneys and heart.

Relevance

While the initial research into GLP-1 drugs involved animal studies, it’s misleading to conclude that these studies were directly responsible for their discovery. Animal models often fail to replicate the complexity of human diseases—especially chronic conditions that evolve over time. As a result, many promising findings from animal studies do not translate into effective treatments for humans.

Recognising these limitations has led to a shift toward non-animal research methods. While advanced technologies offer new ways to test drugs without animal models, meta-analyses of completed RCTs provide valuable, human-relevant data that is statistically powerful and cost-effective. The combination of new technologies and meta-analyses of clinical trials represent the future of research, offering more ethical and scientifically valid results.