Diabetic Ulcers Medication
- Author: Vincent Lopez Rowe, MD; Chief Editor: Romesh Khardori, MD, PhD, FACP more...
Many medications may have a role in the treatment of diabetes, the complications of diabetes, and the etiologies of diabetic ulcer. For example, hemorheologic agents and antiplatelet agents are sometimes used in the management of underlying atherosclerotic disease.
Hemorheologic agents such as pentoxifylline (Trental) improve intermittent claudication in approximately 60% of patients after 3 months. Cilostazol (Pletal) is an alternative hemorheologic agent for patients who cannot tolerate pentoxifylline. Cilostazol is contraindicated in patients with congestive heart failure. However, there is no conclusive evidence of any direct beneficial effect of either pentoxifylline or cilostazol on the healing of diabetic foot ulcers.
Pentoxifylline is indicated to treat intermittent claudication. It may alter rheology of red blood cells, which in turn reduces blood viscosity. Two to eight weeks of therapy may be required before symptomatic improvement occurs, and only about 60% of patients respond to this drug.
Cilostazol is indicated to reduce symptoms of intermittent claudication, as indicated by an increased walking distance. It affects vascular beds and cardiovascular function and produces nonhomogeneous dilation of vascular beds, with greater dilation in femoral beds than in vertebral, carotid, or superior mesenteric arteries. Renal arteries were not found to be responsive to its effects. The mechanism of cilostazol involves inhibition of PDE, especially PDE III, and reversible inhibition of platelet aggregation. Patients may respond as early as 2-4 weeks after initiation of therapy, but treatment for as many as 12 weeks may be needed before a beneficial effect is experienced.
Antiplatelet therapy with aspirin or clopidogrel (Plavix) may be warranted in some cases for the prevention of the complications of atherosclerosis, although neither has a direct benefit in healing diabetic foot ulcers. Antiplatelet agents inhibit platelet function by blocking cyclooxygenase and subsequent platelet aggregation.
Clopidogrel selectively inhibits ADP binding to platelet receptor and subsequent ADP-mediated activation of glycoprotein GPIIb/IIIa complex, thereby inhibiting platelet aggregation. It is indicated as antiplatelet therapy in some patients with atherosclerotic disease.
Aspirin inhibits prostaglandin synthesis, preventing formation of platelet-aggregating thromboxane A2. It may be used in low dose to inhibit platelet aggregation and to improve complications of venous stases and thrombosis. The recommended dose varies with indication, and, often, the literature is unclear on the optimal dosing.
Wound Healing Agents
Topically applied platelet-derived growth factors (PDGF) such as becaplermin gel (Regranex) have a modestly beneficial effect in promoting wound healing.
Becaplermin gel 0.01% (Regranex), a recombinant human PDGF that is produced through genetic engineering, is approved by the US Food and Drug Administration (FDA) to promote healing of diabetic foot ulcers. Regranex is meant for a healthy, granulating wound, not one with a necrotic wound base, and it is contraindicated with known skin cancers at the site of application.
Amin N, Doupis J. Diabetic foot disease: From the evaluation of the "foot at risk" to the novel diabetic ulcer treatment modalities. World J Diabetes. 2016 Apr 10. 7 (7):153-64. [Medline]. [Full Text].
Naves CC. The Diabetic Foot: A Historical Overview and Gaps in Current Treatment. Adv Wound Care (New Rochelle). 2016 May 1. 5 (5):191-197. [Medline]. [Full Text].
Gentile AT, Berman SS, Reinke KR, Demas CP, Ihnat DH, Hughes JD, et al. A regional pedal ischemia scoring system for decision analysis in patients with heel ulceration. Am J Surg. 1998 Aug. 176(2):109-14. [Medline].
Beckert S, Witte M, Wicke C, Konigsrainer A, Coerper S. A new wound-based severity score for diabetic foot ulcers: A prospective analysis of 1,000 patients. Diabetes Care. 2006 May. 29(5):988-92. [Medline].
Oyibo SO, Jude EB, Tarawneh I, Nguyen HC, Harkless LB, Boulton AJ. A comparison of two diabetic foot ulcer classification systems: the Wagner and the University of Texas wound classification systems. Diabetes Care. 2001 Jan. 24(1):84-8. [Medline].
Robson MC, Hill DP, Woodske ME, Steed DL. Wound healing trajectories as predictors of effectiveness of therapeutic agents. Arch Surg. 2000 Jul. 135(7):773-7. [Medline].
Tomic-Canic M, Brem H. Gene array technology and pathogenesis of chronic wounds. Am J Surg. 2004 Jul. 188(1A Suppl):67-72. [Medline].
Boulton AJ, Kirsner RS, Vileikyte L. Clinical practice. Neuropathic diabetic foot ulcers. N Engl J Med. 2004 Jul 1. 351(1):48-55. [Medline].
Arora S, Pomposelli F, LoGerfo FW, Veves A. Cutaneous microcirculation in the neuropathic diabetic foot improves significantly but not completely after successful lower extremity revascularization. J Vasc Surg. 2002 Mar. 35(3):501-5. [Medline].
Boulton AJ. Pressure and the diabetic foot: clinical science and offloading techniques. Am J Surg. 2004 May. 187(5A):17S-24S. [Medline].
Jeffcoate WJ, Harding KG. Diabetic foot ulcers. Lancet. 2003 May 3. 361(9368):1545-51. [Medline].
Naemi R, Chatzistergos P, Sundar L, Chockalingam N, Ramachandran A. Differences in the mechanical characteristics of plantar soft tissue between ulcerated and non-ulcerated foot. J Diabetes Complications. 2016 Jun 8. [Medline].
Marshall MC Jr. Diabetes in African Americans. Postgrad Med J. 2005 Dec. 81(962):734-40. [Medline]. [Full Text].
Ramsey SD, Newton K, Blough D, McCulloch DK, Sandhu N, Reiber GE, et al. Incidence, outcomes, and cost of foot ulcers in patients with diabetes. Diabetes Care. 1999 Mar. 22(3):382-7. [Medline].
Reiber GE, Lipsky BA, Gibbons GW. The burden of diabetic foot ulcers. Am J Surg. 1998 Aug. 176(2A Suppl):5S-10S. [Medline].
Galkowska H, Olszewski WL, Wojewodzka U, Rosinski G, Karnafel W. Neurogenic factors in the impaired healing of diabetic foot ulcers. J Surg Res. 2006 Aug. 134(2):252-8. [Medline].
Chammas NK, Hill RL, Edmonds ME. Increased Mortality in Diabetic Foot Ulcer Patients: The Significance of Ulcer Type. J Diabetes Res. 2016. 2016:2879809. [Medline]. [Full Text].
Mayfield JA, Sugarman JR. The use of the Semmes-Weinstein monofilament and other threshold tests for preventing foot ulceration and amputation in persons with diabetes. J Fam Pract. 2000 Nov. 49(11 Suppl):S17-29. [Medline].
Teodorescu VJ, Chen C, Morrissey N, Faries PL, Marin ML, Hollier LH. Detailed protocol of ischemia and the use of noninvasive vascular laboratory testing in diabetic foot ulcers. Am J Surg. 2004 May. 187(5A):75S-80S. [Medline].
Christman AL, Selvin E, Margolis DJ, Lazarus GS, Garza LA. Hemoglobin a1c predicts healing rate in diabetic wounds. J Invest Dermatol. 2011 Oct. 131(10):2121-7. [Medline]. [Full Text].
Dutta P, Bhansali A, Mittal BR, Singh B, Masoodi SR. Instant 99mTc-ciprofloxacin scintigraphy for the diagnosis of osteomyelitis in the diabetic foot. Foot Ankle Int. 2006 Sep. 27(9):716-22. [Medline].
Edmonds M, Foster A. The use of antibiotics in the diabetic foot. Am J Surg. 2004 May. 187(5A):25S-28S. [Medline].
O'Meara SM, Cullum NA, Majid M, Sheldon TA. Systematic review of antimicrobial agents used for chronic wounds. Br J Surg. 2001 Jan. 88(1):4-21. [Medline].
Brem H, Balledux J, Bloom T, Kerstein MD, Hollier L. Healing of diabetic foot ulcers and pressure ulcers with human skin equivalent: a new paradigm in wound healing. Arch Surg. 2000 Jun. 135(6):627-34. [Medline].
Beuker BJ, van Deursen RW, Price P, Manning EA, van Baal JG, Harding KG. Plantar pressure in off-loading devices used in diabetic ulcer treatment. Wound Repair Regen. 2005 Nov-Dec. 13(6):537-42. [Medline].
Hilton JR, Williams DT, Beuker B, Miller DR, Harding KG. Wound dressings in diabetic foot disease. Clin Infect Dis. 2004 Aug 1. 39 Suppl 2:S100-3. [Medline].
Veves A, Falanga V, Armstrong DG, Sabolinski ML. Graftskin, a human skin equivalent, is effective in the management of noninfected neuropathic diabetic foot ulcers: a prospective randomized multicenter clinical trial. Diabetes Care. 2001 Feb. 24(2):290-5. [Medline].
Bennett SP, Griffiths GD, Schor AM, Leese GP, Schor SL. Growth factors in the treatment of diabetic foot ulcers. Br J Surg. 2003 Feb. 90(2):133-46. [Medline].
Guzman-Gardearzabal E, Leyva-Bohorquez G, Salas-Colín S, Paz-Janeiro JL, Alvarado-Ruiz R, García-Salazar R. Treatment of chronic ulcers in the lower extremities with topical becaplermin gel .01%: a multicenter open-label study. Adv Ther. 2000 Jul-Aug. 17(4):184-9. [Medline].
Platelet-derived growth factor for diabetic ulcers. Med Lett Drugs Ther. 1998 Jul 17. 40(1031):73-4. [Medline].
Jirkovska A, Boucek P, Woskova V, Bartos V, Skibova J. Identification of patients at risk for diabetic foot: a comparison of standardized noninvasive testing with routine practice at community diabetes clinics. J Diabetes Complications. 2001 Mar-Apr. 15(2):63-8. [Medline].
Muha J. Local wound care in diabetic foot complications. Aggressive risk management and ulcer treatment to avoid amputation. Postgrad Med. 1999 Jul. 106(1):97-102. [Medline].
Pinzur MS, Slovenkai MP, Trepman E, Shields NN. Guidelines for diabetic foot care: recommendations endorsed by the Diabetes Committee of the American Orthopaedic Foot and Ankle Society. Foot Ankle Int. 2005 Jan. 26(1):113-9. [Medline].
Edmonds M. Diabetic foot ulcers: practical treatment recommendations. Drugs. 2006. 66(7):913-29. [Medline].
Bello YM, Phillips TJ. Recent advances in wound healing. JAMA. 2000 Feb 9. 283(6):716-8. [Medline].
Frykberg RG, Armstrong DG, Giurini J, Edwards A, Kravette M, Kravitz S, et al. Diabetic foot disorders. A clinical practice guideline. For the American College of Foot and Ankle Surgeons and the American College of Foot and Ankle Orthopedics and Medicine. J Foot Ankle Surg. 2000. Suppl:1-60. [Medline].
Margolis DJ, Kantor J, Santanna J, Strom BL, Berlin JA. Risk factors for delayed healing of neuropathic diabetic foot ulcers: a pooled analysis. Arch Dermatol. 2000 Dec. 136(12):1531-5. [Medline].
Brem H, Sheehan P, Rosenberg HJ, Schneider JS, Boulton AJ. Evidence-based protocol for diabetic foot ulcers. Plast Reconstr Surg. 2006 Jun. 117(7 Suppl):193S-209S; discussion 210S-211S. [Medline].
Evans D, Land L. Topical negative pressure for treating chronic wounds: a systematic review. Br J Plast Surg. 2001 Apr. 54(3):238-42. [Medline].
Lipsky BA, Berendt AR, Deery HG, Embil JM, Joseph WS, Karchmer AW, et al. Diagnosis and treatment of diabetic foot infections. Plast Reconstr Surg. 2006 Jun. 117(7 Suppl):212S-238S. [Medline].
Wieman TJ, Mercke YK, Cerrito PB, Taber SW. Resection of the metatarsal head for diabetic foot ulcers. Am J Surg. 1998 Nov. 176(5):436-41. [Medline].
Faries PL, Teodorescu VJ, Morrissey NJ, Hollier LH, Marin ML. The role of surgical revascularization in the management of diabetic foot wounds. Am J Surg. 2004 May. 187(5A):34S-37S. [Medline].
Marston WA, Davies SW, Armstrong B, Farber MA, Mendes RC, Fulton JJ, et al. Natural history of limbs with arterial insufficiency and chronic ulceration treated without revascularization. J Vasc Surg. 2006 Jul. 44(1):108-114. [Medline].
Ehrenreich M, Ruszczak Z. Update on tissue-engineered biological dressings. Tissue Eng. 2006 Sep. 12(9):2407-24. [Medline].
Streit M, Braathen LR. Apligraf--a living human skin equivalent for the treatment of chronic wounds. Int J Artif Organs. 2000 Dec. 23(12):831-3. [Medline].
Demiri E, Foroglou P, Dionyssiou D, Antoniou A, Kakas P, Pavlidis L, et al. Our experience with the lateral supramalleolar island flap for reconstruction of the distal leg and foot: a review of 20 cases. Scand J Plast Reconstr Surg Hand Surg. 2006. 40(2):106-10. [Medline].
Strauss MB. Hyperbaric oxygen as an intervention for managing wound hypoxia: its role and usefulness in diabetic foot wounds. Foot Ankle Int. 2005 Jan. 26(1):15-8. [Medline].
Roeckl-Wiedmann I, Bennett M, Kranke P. Systematic review of hyperbaric oxygen in the management of chronic wounds. Br J Surg. 2005 Jan. 92(1):24-32. [Medline].
Löndahl M, Katzman P, Nilsson A, Hammarlund C. Hyperbaric oxygen therapy facilitates healing of chronic foot ulcers in patients with diabetes. Diabetes Care. 2010 May. 33(5):998-1003. [Medline]. [Full Text].
Kranke P, Bennett MH, Martyn-St James M, Schnabel A, Debus SE. Hyperbaric oxygen therapy for chronic wounds. Cochrane Database Syst Rev. 2012 Apr 18. 4:CD004123. [Medline].
Singh N, Armstrong DG, Lipsky BA. Preventing foot ulcers in patients with diabetes. JAMA. 2005 Jan 12. 293(2):217-28. [Medline].
The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med. 1993 Sep 30. 329(14):977-86. [Medline].
Hiatt WR, Money SR, Brass EP. Long-term safety of cilostazol in patients with peripheral artery disease: the CASTLE study (Cilostazol: A Study in Long-term Effects). J Vasc Surg. 2008 Feb. 47(2):330-336. [Medline].
[Guideline] Lipsky BA, Berendt AR, Deery HG, Embil JM, Joseph WS, Karchmer AW, et al. Diagnosis and treatment of diabetic foot infections. Clin Infect Dis. 2004 Oct 1. 39(7):885-910. [Medline].
Game FL, Apelqvist J, Attinger C, Hartemann A, Hinchliffe RJ, et al. Effectiveness of interventions to enhance healing of chronic ulcers of the foot in diabetes: a systematic review. Diabetes Metab Res Rev. 2015 Sep 7. [Medline].
van Netten JJ, Price PE, Lavery LA, Monteiro-Soares M, Rasmussen A, et al. Prevention of foot ulcers in the at-risk patient with diabetes: a systematic review. Diabetes Metab Res Rev. 2015 Sep 5. [Medline].
Bus SA, van Deursen RW, Armstrong DG, Lewis J, Caravaggi CF, et al. Footwear and offloading interventions to prevent and heal foot ulcers and reduce plantar pressure in patients with diabetes: a systematic review. Diabetes Metab Res Rev. 2015 Sep 5. [Medline].
|This seaweed extract contains guluronic and mannuronic acids that provide tensile strength and calcium and sodium alginates, which confer an absorptive capacity. Some of these can leave fibers in the wound if they are not thoroughly irrigated. These are secured with secondary coverage.||These are highly absorbent and useful for wounds having copious exudate. Alginate rope is particularly useful to pack exudative wound cavities or sinus tracts.|
|An absorptive textile fiber pad, also available as a ribbon for packing of deep wounds. This material is covered with a secondary dressing. The hydrofiber combines with wound exudate to produce a hydrophilic gel. Aquacel-Ag contains 1.2% ionic silver that has strong antimicrobial properties against many organisms, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus.||These are absorbent dressings used for exudative wounds.|
|Debriding agents||Hypergel (hypertonic saline gel)
Accuzyme (papain urea)
|Various products provide some degree of chemical or enzymatic debridement.||These are useful for necrotic wounds as an adjunct to surgical debridement.|
|Polyurethane foam has some absorptive capacity.||These are useful for cleaning granulating wounds having minimal exudate.|
Duoderm CGF Extra Thin
|These are made of microgranular suspension of natural or synthetic polymers, such as gelatin or pectin, in an adhesive matrix. The granules change from a semihydrated state to a gel as the wound exudate is absorbed.||They are useful for dry necrotic wounds, wounds having minimal exudate, and clean granulating wounds.|
|These are water-based or glycerin-based semipermeable hydrophilic polymers; cooling properties may decrease wound pain. These gels can lose or absorb water depending upon the state of hydration of the wound. They are secured with secondary covering.||These are useful for dry, sloughy, necrotic wounds (eschar).|
|These are various materials designed to remove easily without damaging underlying skin.||These are useful for acute minor wounds, such as skin tears, or as a final dressing for chronic wounds that have nearly healed.|
|These are highly conformable acrylic adhesive film having no absorptive capacity and little hydrating ability, and they may be vapor permeable or perforated.||These are useful for clean dry wounds having minimal exudate, and they also are used to secure an underlying absorptive material. They are used for protection of high-friction areas and areas that are difficult to bandage such as heels (also used to secure IV catheters).|