GLP-1 Receptor Agonists Linked to Lower Mortality After Diabetic Foot Ulcers, Nationwide French Study Finds

Key Takeaways:

• Nearly one in seven people experienced death within one year of a first diabetic foot ulcer, highlighting the severity of risk following ulcer onset.
  
• Treatment with GLP-1 receptor agonists was independently associated with improved survival, including after major lower-limb amputation.
  
• Multidisciplinary care and early specialist involvement were associated with better outcomes, reinforcing the importance of structured follow-up.
  
  
  

Background and study aims

Diabetic foot ulcers remain one of the most serious complications of diabetes, often signalling advanced disease and a high burden of comorbidity. Despite advances in diabetes care, mortality following a first diabetic foot ulcer continues to be substantial.

This nationwide observational study set out to identify factors associated with one-year mortality after a first recorded diabetic foot ulcer using data from the French National Health Data System (SNDS). A secondary objective was to examine mortality within one year following major lower-limb amputation in the same population.

Study design and data sources

Researchers conducted a retrospective cohort analysis using the SNDS, a comprehensive national database that captures hospital admissions, outpatient care, prescribed medications, and long-term disease registrations across France.

Adults with a first incident diabetic foot ulcer recorded between January 2017 and December 2018 were included. Case identification combined hospital discharge diagnoses and community care records, allowing capture of people diagnosed both in hospital and in outpatient settings. All individuals were followed for 12 months after ulcer identification.

To examine associations with mortality, the researchers used Cox proportional hazards models. These models adjusted for a wide range of variables, including demographic characteristics, clinical comorbidities, diabetes treatments, major amputation, and access to specialist care.

Mortality and amputation outcomes

In total, 133,791 people with a first diabetic foot ulcer were identified. Within one year of diagnosis, 14.6% died, underlining the high short-term mortality associated with this complication. During the same period, 3.5% underwent a major lower-limb amputation.

Outcomes following amputation were particularly poor. Among those who had a major amputation, 28.8% died within one year, indicating a markedly elevated risk compared with people who did not undergo amputation.

Factors associated with increased mortality

Several factors were independently associated with a higher risk of death within one year of a first diabetic foot ulcer. These included male sex, increasing age, and ulcers identified during a hospital admission rather than in the community.

Clinical and treatment-related predictors of higher mortality included insulin use, major lower-limb amputation, and a range of comorbid conditions. Cardiovascular disease, cancer, dementia, end-stage kidney disease, and liver disease were all strongly associated with poorer survival.

Similar patterns were observed when analysing mortality after major amputation, suggesting that underlying health status and disease severity play a central role in outcomes across the care pathway.

Protective factors and the role of GLP-1 receptor agonists

Several factors were associated with a lower risk of death. Use of lipid-lowering therapy emerged as a protective factor, as did prior contact with specialist healthcare professionals. People who had consulted diabetologists, ophthalmologists, or podiatrists before ulcer onset experienced better survival, pointing to the benefits of ongoing, multidisciplinary diabetes care.

Notably, treatment with glucagon-like peptide-1 receptor agonists was independently associated with reduced mortality at one year. This association persisted both in the overall cohort and among people who underwent major lower-limb amputation, suggesting a consistent survival benefit linked to this class of medication.

Interpretation and implications for care

The findings confirm that one-year mortality after a diabetic foot ulcer remains unacceptably high and is closely linked to age, comorbidity burden, and disease severity. Importantly, the inclusion of community-identified ulcers highlights that people with diabetic foot disease are highly vulnerable even outside hospital settings.

The observed association between GLP-1 receptor agonist use and improved survival adds to growing evidence that these therapies may offer benefits beyond glycaemic control. Alongside pharmacological treatment, structured follow-up and early involvement of specialist services appear to play a critical role in improving outcomes.

Conclusions

This nationwide study shows that mortality following a first diabetic foot ulcer is substantial, particularly among people with advanced comorbidities and those requiring major amputation. Glucagon-like peptide-1 receptor agonists and coordinated, multidisciplinary care were associated with better survival and should be prioritised in high-risk populations.

Together, these findings underscore the urgent need to strengthen preventive strategies, optimise care pathways, and ensure timely access to specialist diabetes and foot care services for people living with diabetes who are at risk of ulceration.