Promoting an increased awareness and standardized approaches in diagnosing and treating peripheral artery disease

PERIPHERAL ARTERY DISEASE (PAD)

Medical Therapy – Special Considerations for PAD Patients with Diabetes

The next step is to determine if the patient has diabetes according to current guidelines. Treatment for patients with diabetes should be guided by diabetes guidelines but some considerations extend to patients with PAD.

Patients with diabetes should have glucose-lowering therapy to reduce their risk of microvascular complications including renal disease and retinopathy. In addition, newer target-specific therapies have shown benefits in patients with cardiovascular disease. The GLP-1 agonist liraglutide was shown to reduce ischemic MACE in patients with diabetes. Inhibitors of SGLT2 have been shown to reduce cardiovascular death and heart failure in patients with atherosclerosis including PAD. These therapies should be considered as recommended by current guidelines. Partnering with a local diabetes specialist may be helpful in targeting intensive therapies for the complex and high-risk population with PAD and diabetes.

Specific consideration should be given when prescribing an SGLT2 inhibitor. The agent, canagliflozin, was shown to be associated with an increased risk of amputation with the greatest risk in those with PAD and particularly those with prior amputation. Until these data and the related mechanisms are better understood, caution should be exercised when prescribing canagliflozin to this population and if using an SGLT2 inhibitor, an agent that has not been shown to have this risk would be preferred.

References

Zinman B, Lachin JM, Inzucchi SE. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2016; 374: 1094

Verma S, Mazer CD, Al-Omran M, Inzucchi SE, Fitchett D, Hehnke U, George JT, Zinman B. Cardiovascular Outcomes and Safety of Empagliflozin in Patients With Type 2 Diabetes Mellitus and Peripheral Artery Disease: A Subanalysis of EMPA-REG OUTCOME. Circulation. 2017;

Inzucchi SE, Iliev H, Pfarr E, Zinman B. Empagliflozin and Assessment of Lower-Limb Amputations in the EMPA-REG OUTCOME Trial. Diabetes Care. 2018; 41: e4-e5.

Neal B, Perkovic V, Matthews DR. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med. 2017; 377: 2099.

Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JF, Nauck MA, Nissen SE, Pocock S, Poulter NR, Ravn LS, Steinberg WM, Stockner M, Zinman B, Bergenstal RM, Buse JB, LEADER Steering Committee, LEADER Trial Investigators. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2016; 375: 311-322.

Dhatariya K1,2, Bain SC3, Buse JB4, Simpson R5, Tarnow L6, Kaltoft MS7, Stellfeld M7, Tornøe K7, Pratley RE8; LEADER Publication Committee on behalf of the LEADER Trial Investigators. The Impact of Liraglutide on Diabetes-Related Foot Ulceration and Associated Complications in Patients With Type 2 Diabetes at High Risk for Cardiovascular Events: Results From the LEADER Trial. Diabetes Care. 2018 Oct;41(10):2229-2235. doi: 10.2337/dc18-1094. Epub 2018 Aug 2.

Wiviott SD, Raz I, Bonaca MP, Mosenzon O, Kato ET, Cahn A, Silverman MG, Zelniker TA, Kuder JF, Murphy SA, Bhatt DL, Leiter LA, McGuire DK, Wilding JPH, Ruff CT, Gause-Nilsson IAM, Fredriksson M, Johansson PA, Langkilde AM, Sabatine MS; DECLARE–TIMI 58 Investigators. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2019 Jan 24;380(4):347-357. doi: 10.1056/NEJMoa1812389. Epub 2018 Nov 10.

Singh S, Armstrong EJ, Sherif W, Alvandi B, Westin GG, Singh GD, Amsterdam EA, Laird JR. Association of elevated fasting glucose with lower patency and increased major adverse limb events among patients with diabetes undergoing infrapopliteal balloon angioplasty. Vasc Med. 2014; .