The impact of semaglutide on wound healing in diabetes related foot ulcer patients: A TriNetX database study

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Abstract

Introduction

Diabetes related foot ulcers (DFUs) are common complications of type 2 diabetes mellitus (T2DM), affecting 15–25% of individuals living with diabetes and significantly contributing to healthcare costs ($9–13 billion annually in the U.S.). Without effective management, these wounds often lead to severe outcomes like amputations. This study aims to examine the association of semaglutide on DFU management.

Methods

This retrospective cohort study utilized TriNetX US Research Network data to assess the impact of semaglutide, a GLP-1 receptor agonist, on DFU outcomes between 2013 and 2023. The study compared outcomes between semaglutide users with DFU (Cohort A, N = 6329) and non-users with DFU (Cohort B, N = 118,821) across 64 healthcare organizations. We matched participants by age, gender, race, and ethnicity; however, we excluded patients with certain co-morbidities. Statistical analysis, such as chi-square analysis and risk ratio, using TriNetX software evaluated different complication outcomes.

Results

Semaglutide users with DFU demonstrated lower relative risks for complications compared to non-users. Within 1 year, semaglutide users were associated with lower relative risks for wound healing complications (0.19% vs 0.38%), chronic non-healing wounds (0.75% vs 1.23%), chronic pain (4.44% vs 8.06%), wound care (2.42% vs 4.86%), wound dehiscence (0.26% vs 0.56%), and amputation (2.34% vs 5.21%) ( p < .05). Similar trends persisted over 5 years. While these findings highlight potential benefits of semaglutide with patients with DFU, causation cannot be inferred due to the study’s observational design.

Conclusion

Semaglutide use was associated with favorable outcomes in patients with diabetes-related foot ulcers, including reductions in wound-related complications. While these findings suggest potential benefits of semaglutide as an adjunct in DFU management, further research is needed to confirm these associations and to better understand the mechanisms involved.

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Most cited references 28

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Challenges in the Treatment of Chronic Wounds

Robert G. Frykberg, Jaminelli Banks (2015)

Significance: Chronic wounds include, but are not limited, to diabetic foot ulcers, venous leg ulcers, and pressure ulcers. They are a challenge to wound care professionals and consume a great deal of healthcare resources around the globe. This review discusses the pathophysiology of complex chronic wounds and the means and modalities currently available to achieve healing in such patients. Recent Advances: Although often difficult to treat, an understanding of the underlying pathophysiology and specific attention toward managing these perturbations can often lead to successful healing. Critical Issues: Overcoming the factors that contribute to delayed healing are key components of a comprehensive approach to wound care and present the primary challenges to the treatment of chronic wounds. When wounds fail to achieve sufficient healing after 4 weeks of standard care, reassessment of underlying pathology and consideration of the need for advanced therapeutic agents should be undertaken. However, selection of an appropriate therapy is often not evidence based. Future Directions: Basic tenets of care need to be routinely followed, and a systematic evaluation of patients and their wounds will also facilitate appropriate care. Underlying pathologies, which result in the failure of these wounds to heal, differ among various types of chronic wounds. A better understanding of the differences between various types of chronic wounds at the molecular and cellular levels should improve our treatment approaches, leading to better healing rates, and facilitate the development of new more effective therapies. More evidence for the efficacy of current and future advanced wound therapies is required for their appropriate use.

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Preventing foot ulcers in patients with diabetes.

Nalini Singh (2005)

Among persons diagnosed as having diabetes mellitus, the prevalence of foot ulcers is 4% to 10%, the annual population-based incidence is 1.0% to 4.1%, and the lifetime incidence may be as high as 25%. These ulcers frequently become infected, cause great morbidity, engender considerable financial costs, and are the usual first step to lower extremity amputation. To systematically review the evidence on the efficacy of methods advocated for preventing diabetic foot ulcers in the primary care setting. The EBSCO, MEDLINE, and the National Guideline Clearinghouse databases were searched for articles published between January 1980 and April 2004 using database-specific keywords. Bibliographies of retrieved articles were also searched, along with the Cochrane Library and relevant Web sites. We reviewed the retrieved literature for pertinent information, paying particular attention to prospective cohort studies and randomized clinical trials. Prevention of diabetic foot ulcers begins with screening for loss of protective sensation, which is best accomplished in the primary care setting with a brief history and the Semmes-Weinstein monofilament. Specialist clinics may quantify neuropathy with biothesiometry, measure plantar foot pressure, and assess lower extremity vascular status with Doppler ultrasound and ankle-brachial blood pressure indices. These measurements, in conjunction with other findings from the history and physical examination, enable clinicians to stratify patients based on risk and to determine the type of intervention. Educating patients about proper foot care and periodic foot examinations are effective interventions to prevent ulceration. Other possibly effective clinical interventions include optimizing glycemic control, smoking cessation, intensive podiatric care, debridement of calluses, and certain types of prophylactic foot surgery. The value of various types of prescription footwear for ulcer prevention is not clear. Substantial evidence supports screening all patients with diabetes to identify those at risk for foot ulceration. These patients might benefit from certain prophylactic interventions, including patient education, prescription footwear, intensive podiatric care, and evaluation for surgical interventions.

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Update on management of diabetic foot ulcers.

Estelle Everett, Nestoras Mathioudakis (2018)

Diabetic foot ulcers (DFUs) are a serious complication of diabetes that results in significant morbidity and mortality. Mortality rates associated with the development of a DFU are estimated to be 5% in the first 12 months, and 5-year morality rates have been estimated at 42%. The standard practices in DFU management include surgical debridement, dressings to facilitate a moist wound environment and exudate control, wound off-loading, vascular assessment, and infection and glycemic control. These practices are best coordinated by a multidisciplinary diabetic foot wound clinic. Even with this comprehensive approach, there is still room for improvement in DFU outcomes. Several adjuvant therapies have been studied to reduce DFU healing times and amputation rates. We reviewed the rationale and guidelines for current standard of care practices and reviewed the evidence for the efficacy of adjuvant agents. The adjuvant therapies reviewed include the following categories: nonsurgical debridement agents, dressings and topical agents, oxygen therapies, negative pressure wound therapy, acellular bioproducts, human growth factors, energy-based therapies, and systemic therapies. Many of these agents have been found to be beneficial in improving wound healing rates, although a large proportion of the data are small, randomized controlled trials with high risks of bias.

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Author and article information

Journal

Journal ID (nlm-ta): Diab Vasc Dis Res

Journal ID (iso-abbrev): Diab Vasc Dis Res

Journal ID (hwp): spdvr

Journal ID (publisher-id): DVR

Title: Diabetes & Vascular Disease Research

Publisher: SAGE Publications (Sage UK: London, England )

ISSN (Print): 1479-1641

ISSN (Electronic): 1752-8984

Publication date (Electronic): 13 March 2025

Publication date Collection: Mar-Apr 2025

Volume: 22

Issue: 2

Electronic Location Identifier: 14791641251322909

Affiliations

[1 ]John Sealy School of Medicine, Ringgold 74950, universityUniversity of Texas Medical Branch; , Galveston, TX, USA

[2 ]Tilman J. Fertitta College of Medicine, Ringgold 653473, universityUniversity of Houston School of Medicine; , Houston, TX, USA

[3 ]School of Podiatric Medicine, Ringgold 43981, universityBarry University; , Miami, FL, USA

[4 ]Department of Family Medicine, Ringgold 12338, universityUniversity of Texas Medical Branch; , Galveston, TX, USA

Author notes

[*]Wei-Chen Lee, Department of Family Medicine, University of Texas Medical Branch, 301 University Boulevard, Galveston, Texas 77555, USA. Email: weilee@ 123456utmb.edu

Author information

Joshua E Lewis https://orcid.org/0009-0001-4785-2011

Diana K Omenge https://orcid.org/0009-0000-8116-4290

Amani R Patterson https://orcid.org/0009-0006-3082-8986

Ogechukwu Anwaegbu https://orcid.org/0009-0008-8776-5941

Article

Publisher ID: 10.1177_14791641251322909

DOI: 10.1177/14791641251322909

PMC ID: 11907515

PubMed ID: 40080656

SO-VID: 2cbd739a-dfde-4216-bbbb-b6ace520feeb

License:

This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

History

Date received : 22 July 2024

Date revision received : 3 January 2025

Date accepted : 8 February 2025

Funding

Funded by: National Center for Advancing Translational Sciences, FundRef https://doi.org/10.13039/100006108;

Award ID: UL1 TR001439

Funded by: Department of Health and Human Services, Health Resources and Services Administration (HRSA);

Award ID: 1 D34HP49234‐01‐00

Custom metadata

typesetter ts10

cover-date March-April 2025

ScienceOpen disciplines: Endocrinology & Diabetes

Keywords: diabetes related foot ulcers,semaglutide,glp-1 receptor agonists,wound healing,diabetes complications

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ScienceOpen disciplines: Endocrinology & Diabetes

Keywords: diabetes related foot ulcers, semaglutide, glp-1 receptor agonists, wound healing, diabetes complications

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The impact of semaglutide on wound healing in diabetes related foot ulcer patients: A TriNetX database study

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Abstract

Introduction

Methods

Results

Conclusion

Related collections

Journal of the ASEAN Federation of Endocrine Societies

Most cited references 28

Challenges in the Treatment of Chronic Wounds

Preventing foot ulcers in patients with diabetes.

Update on management of diabetic foot ulcers.

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