Table 1.

Therapeutic strategies for diabetic foot ulcer (DFU) management.

Therapy for	Method	Advantage	Disadvantage	Reference
Neuropathic Ulcer	Anticonvulsants: Gabapentin, Pregabalin	Neuropathic pain reduction.	Dyspnea, drowsiness, fatigue. The effect occurs after the second week.	[51,52]
	Antidepressants: Duloxetine, Amitriptyline, Nortriptyline, Venlafaxine	Good effect against the neuropathic pain. Effects similar to gabapentin and pregabalin.	Sleep disturbances, depression, and have muscarinic effects.	[46,47]
	Analgesics: Tapentadol, Tramadol, Acetaminophen, Oxycodone	Reduce pain in diabetic polyneuropathy.	Confusion and sedation; opioids can be used inappropriately.	[11,46]
	Alpha-lipoic acid	Delay or reverse damages to peripheral nerves.	There is no evidence evaluating long-term treatment.	[48]
	Mesenchymal stem cells	Neuroprotective effects. It can be easily isolated from adipose tissue; has cell plasticity.	The number of transplanted cells that reach and are integrated into the functioning of the organ is low. The therapies are expensive.	[49]
	Interleukin 6	Regenerates peripheral nerve fibers.	High doses can cause inflammation.	[50]
Ischemic Ulcer:(a) Endovascular therapy	Angiosomas	Increases arterial flow to the ischemic limb. Get at least one pulsatile flow. Improves the healing of ischemic ulcer. Improves or eliminates pain at rest Reduce the level of amputation. Reduce the duration and number of hospitalizations. Improve mobility. Improves quality of life. Improves survival.	Variability in infrapopliteal arterial distribution. Differences between extension and borders of angiosomes. Difficulties in identifying affected angiosoma. Many lesions depend on several angiosomes. Objective diagnostic angiographic pattern not described. Optimal angiographic end point post endovascular therapy is not known. Differences in collateralization. Very long arterial segments. Diffuse, calcified, and multiple lesions. Small arterial caliber. Slow flow of distal beds. Poor run-off. Instrument handling. Technical difficulties.	[53,54,55]
	Percutaneous transluminal angioplasty	Technical feasibility reduces the number of complications, and increases the rate of recovery of the limb useful in elderly patient.	Limited scientific evidence. Not suitable for young patients. Requires adjuvant treatment to prevent restenosis with platelet inhibitors or vitamin antagonists K.	[55,56]
	Stents	Improves blood flow.	The permeability of the arteries after an angioplasty is the same if this is placed than if it is omitted.	[57,58]
	Angioplasty	Increases the primary permeability of the vessel. Revascularization of the target lesion.	High percentage of restenosis. Does not decrease the risk of amputation High cost.	[59]
	Bypass: autologous human umbilical vein and synthetic materials with or without heparin	Improve primary permeability. Preservation of the foot.	Lack of scientific evidence.	[60,61]
(b) Anticoagulant Therapy	Plaquetary inhibitors. Antagonists of vitamin K.	Adjuvant after angioplasty.	Hemorrhages. Hypersensitivity. Gastrointestinal disorders.	[62]
	Ginkgo biloba	Improves intermittent claudication.	Lack of scientific evidence.	[63]
	Vitamin E	Improves blood flow. Increases the body’s ability to repair. No adverse effects. Low cost.	Lack of documented scientific evidence.	[64]
	Levocarnitine	Improves walking tolerance. Greater effectiveness intravenously. Severe claudication better results.	There are not enough studies documenting their effectiveness in these patients. No dose has been established, and duration of treatment for patient safety.	[65,66]
	Beta-blockers	Its use does not affect walking distance, blood flow, the vascular resistance of the leg, or skin temperature.	Lack of scientific evidence.	[67]
	Cilostazol	Improve walking distance.	Presents mild and treatable side effects. Lack of scientific evidence.	[68]
	Hyperbaric oxygen therapy/ozone	Improves symptoms. Decreases ulcer area. Shorter duration of hospitalization.	The studies found are small, and there is a high risk of bias. It requires adjuvants with antibiotics.	[69,70]
	Stimulation of the spinal cord	Decreased pain. Greater limb preservation rate. Regression of the ischemic limb state (Fontaine). Improves the quality of life.	High cost, the risk of complications, such as implantation problems, infections that will eventually require reoperation.	[71,72]
Infection	Antibiotics	Selective. Low cost. Mechanism of specific action. Established doses. Multiple administration routes.	Drug interactions, high resistance potential hypersensitivity.	[73]
	Antimicrobial peptides of mammals	Multiple mechanisms of action. Broad-spectrum antimicrobial. Low resistance potential. Antiviral, antifungal, antibacterial, antitumor activity.	Its toxicity is unknown; it can only be administered topically. Embryotoxic and paralyzing activity for sperm. Short half-life, for the degradation of proteases, high price.	[73,74]