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US-20260124280-A1 - SEMAGLUTIDE IN THE TREATMENT OF PERIPHERAL ARTERIAL DISEASE

US20260124280A1US 20260124280 A1US20260124280 A1US 20260124280A1US-20260124280-A1

Abstract

Disclosed herein is a further medical use of semaglutide, namely semaglutide in the treatment of intermittent claudication in a human subject with diabetes and peripheral arterial disease. Semaglutide is shown to have a positive impact on symptoms of intermittent claudication and therefore the functional limb capacity and quality of life of patients with type 2 diabetes and peripheral arterial disease.

Inventors

  • Andrei-Mircea Catarig
  • Diana Mathilde Roepcke
  • Anders Gaarsdal HOLST

Assignees

  • NOVO NORDISK A/S

Dates

Publication Date
20260507
Application Date
20251104
Priority Date
20241115

Claims (20)

  1. 1 . A method for the improvement of intermittent claudication in a subject in need thereof, comprising administering semaglutide to the subject, wherein the subject has type 2 diabetes and peripheral arterial disease (PAD).
  2. 2 . The method according to claim 1 , wherein the subject has intermittent claudication corresponding to Fontaine stage IIA.
  3. 3 . The method according to claim 1 , wherein the subject has an ankle-brachial index (ABI) equal or less than 0.90.
  4. 4 . The method according to claim 3 , wherein the subject has an ABI equal to or more than 0.40.
  5. 5 . The method according to claim 1 , wherein the subject has a toe-brachial index (TBI) equal to or less than 0.70.
  6. 6 . The method according to claim 1 , wherein the subject has an ankle-brachial index (ABI) equal or less than 0.90 and a toe-brachial index (TBI) equal to or less than 0.70.
  7. 7 . The method according to claim 6 , wherein the ABI is equal to or more than 0.40.
  8. 8 . The method according to claim 1 , wherein the treatment increases the maximum distance that the subject is capable of walking.
  9. 9 . The method according to claim 1 , wherein the treatment increases the distance that the subject is capable of walking without feeling pain.
  10. 10 . The method according to claim 1 , wherein the treatment increases the ankle-brachial index (ABI) of the subject.
  11. 11 . The method according to claim 1 , wherein the treatment increases the toe-brachial index (TBI) of the subject.
  12. 12 . The method according to claim 1 , wherein the semaglutide is administered in an amount of 0.2-50 mg.
  13. 13 . The method according to claim 1 , wherein the semaglutide is administered in a liquid formulation.
  14. 14 . The method according to claim 13 , wherein the liquid formulation comprises 0.25-22 mg/ml semaglutide.
  15. 15 . The method according to claim 13 , wherein the semaglutide is administered in an amount of about 0.25 mg.
  16. 16 . The method according to claim 13 , wherein the semaglutide is administered in an amount of about 0.5 mg.
  17. 17 . The method according to claim 13 , wherein the semaglutide is administered in an amount of about 1.0 mg.
  18. 18 . The method according to claim 13 , wherein the semaglutide is administered in an amount of about 1.7 mg.
  19. 19 . The method according to claim 13 , wherein the semaglutide is administered in an amount of about 2.0 mg.
  20. 20 . The method according to claim 13 , wherein the semaglutide is administered in an amount of about 2.4 mg.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority under 35 U.S.C. § 119 to U.S. Provisional Application 63/716,349, filed Nov. 5, 2024 and European Patent Applications 24213241.3, filed Nov. 15, 2024 and 25167042.8, filed Mar. 28, 2025; the contents of which are incorporated herein by reference. The present invention relates to semaglutide in the improvement or treatment of intermittent claudication in a subject with peripheral arterial disease and diabetes. BACKGROUND Peripheral arterial disease (PAD) affecting the lower extremities is a major cause of disability in older men and women, affecting more than 230 million people worldwide. The earliest, most common, and most disabling manifestation is functional decline and disability. In PAD, atherosclerotic plaque builds up slowly on the inside of arteries. In the early stages of PAD, the arteries compensate for plaque buildup by dilating to preserve flow through the affected artery. Eventually, the artery cannot dilate any further, and the atherosclerotic plaque starts to narrow the arterial lumen. Blood flow restriction caused by atherosclerosis represents the hallmark of PAD. The muscles of the lower extremity require increased blood flow during ambulation (walking), to meet their increased energy demand. When walking, patients with PAD reach a point at which collateral blood flow to affected tissues has been maximized and cannot compensate for the reduced perfusion to the lower extremity muscles caused by PAD. The supply-demand mismatch causes temporary ischemia of the muscles which manifests as pain, cramping or fatigue and ultimately makes the patient with PAD slow down or stop walking. Lowering the energy demands of the muscle (by slowing or stopping) allows the blood supply to “catch up,” and the ischemic symptoms resolve. The most characteristic ischemic symptoms of PAD—pain, cramping or fatigue in leg muscles which are brought on by walking and relieved with rest—are referred to as claudication. Primarily when walking, symptoms occur in the muscle group distal to the artery that is narrowed or blocked. Patients with aortoiliac artery occlusive disease, therefore, have symptoms in the thigh and buttock muscles, whilst patients with femoropopliteal PAD have symptoms in their calf muscles. The walking distance at which symptoms occur depends on multiple factors, including disease severity, walking pace, terrain, and incline. The cycle of blood flow restriction, increased energy demand and temporary muscle ischemia describes the pathophysiology of intermittent claudication due to PAD, which is stable or slowly progressive. PAD can, however, become progressively more severe, such that the blood flow cannot even meet the resting metabolic demands of the lower extremity. Non-healing wounds and ischemic ulcers manifest due to poor blood flow. In the most severe of cases, the toes or entire forefoot can become black and mummified as gangrene develops. Risk factors include smoking, diabetes, obesity, high blood pressure, high cholesterol, increasing age, a family history of PAD, heart disease or stroke. Type 2 diabetes and smoking are the two leading causes of PAD, approximately one third (⅓) of all PAD patients having type 2 diabetes. Current medical guidelines indicate that patients with symptomatic PAD should be treated with antiplatelet and antithrombotic therapy, cardiovascular risk reduction therapy (lipid lowering therapy, antihypertensive therapy and diabetes management), structured exercise and cilostazol (for chronic symptomatic PAD). Additionally, preventative foot care, influenza vaccination and SARS-CoV-2 vaccination are recommended. Cilostazol, currently the only guideline-recommended medical therapy of PAD in the USA, is infrequently used due to side-effects that lead to treatment discontinuation in up to half of all treated patients, black box warnings for heart failure and a lack of other benefits. Ultimately, PAD is associated with life and limb-threatening complications. Despite many advances in endovascular surgery, amputations of digits and limbs are not uncommon. Critical limb ischemia necessitating limb amputation is more common amongst PAD patients with T2D, compared to PAD patients without T2D. Thus, there is a significant unmet medical need for a means of improving outcomes, such as walking ability, in patients with PAD. SUMMARY Disclosed herein is a further medical use of semaglutide; namely, semaglutide for use in the treatment of intermittent claudication in a human subject with peripheral arterial disease. The subject may have diabetes, such as type 2 diabetes. DESCRIPTION Semaglutide is a glucagon-like peptide 1 (GLP-1) receptor agonist and is the active pharmaceutical ingredient in Ozempic®, Rybelsus® and Wegovy®. Ozempic® is used as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus;to reduce the risk of major adverse cardiovascular events in adults with