Advancing pharmacotherapy for diabetic foot ulcers

ABSTRACT

Introduction: Standard treatment for diabetic foot ulcers (DFUs) includes off-loading, debridement, moisture balance, management of infection and peripheral arterial disease (PAD) as well as adequate glycemic control. The outcomes so far are unsatisfactory.

Areas covered: Herein, the authors provide an outline of newer pharmacological agents for the management of DFUs and give their expert perspectives on future treatment strategies.

Expert opinion: Evidence-based healthcare calls for high quality evidence from large RCTs before the implementation of new guidelines for the management of DFUs. Empagliflozin and liraglutide can be recommended for glucose control in patients with DFUs and PAD, while intensive lipid lowering therapy with evolocumab when primary cholesterol goals are not met could be offered to patients with DFUs. Further clinical studies are warranted to develop a structured algorithm for the treatment of DFUs that fail to heal after four weeks of current standard of care. Sucrose octasulfate dressings, becaplermin gel, and platelet-rich plasma (PRP) could also be considered as advanced treatment options for the management of hard to heal DFUs.

KEYWORDS:

• Diabetic foot ulcers
• wound healing
• topical treatment
• novel therapies
• glycemic control
• peripheral arterial disease
• diabetic foot infections

Article highlights

• Effective treatment of DFUs demands a multidisciplinary approach that involves current standard treatment strategies such as off-loading, wound debridement, moisture balance of the wound with wound dressings, management of ischemia and PAD and metabolic control.

• Empagliflozin and liraglutide are recommended as second line agents after metformin for glycemic control in patients with DFUs and PAD, while intensive lipid lowering therapy with evolocumab when primary cholesterol goals are not met should be offered to patients with DFUs.

• No official recommendations exist for the choice of advanced treatment modalities, but they should be considered if a 50% reduction in ulcer size is not achieved after 4 weeks of standard care.

• Sucrose octasulfate dressing efficacy has been demonstrated in a high quality RCT and can be considered for the management of neuro-ischemic DFUs without critical limb ischemia.

• Becaplermin gel is FDA approved for the management of diabetic wounds and can be considered for the treatment of non-infected DFUs.

This box summarizes key points contained in the article.

Declaration of interest

N Tentolouris has served on advisory boards for Merck Sharp and Dohme (MSD), AstraZeneca, Sanofi, Novo Nordisk, Elpen, Eli Lilly and Company, Boehringer Ingelheim, TrigoCare, Servier, and Novartis. He has also received research grants from Eli Lilly and Company, Novo Nordisk, Sanofi and Novartis and has participated on sponsored studies by Eli Lilly and Company, MSD, Novo Nordisk, Novartis, Karabinis Medical, Medical Pharmaquality, Pfizer, Janssen, Cilag, GlaxoSmithKline and Sanofi. N Papanas has served on advisory boards for TrigoCare International, Abbott, AstraZeneca, Elpen, MSD, Novartis, Novo Nordisk, Sanofi, and Takeda. He has also participated on sponsored studies by Eli Lilly, MSD, Novo Nordisk, Novartis, and Sanofi and has received speaker’s honoraria from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Elpen, Galenica, MSD, Mylan, Novartis, Novo Nordisk, Pfizer, Sanofi, Takeda and Vianex. Finally, he has attended conferences sponsored by TrigoCare International, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novartis, Novo Nordisk, Pfizer, and Sanofi. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was not funded.