Frontiers in Clinical Diabetes and Healthcare, Год журнала: 2024, Номер 5
Опубликована: Ноя. 26, 2024
1 IntroductionPeripheral artery disease (PAD) is the third leading cause of atherosclerosis-related morbidity, after coronary and cerebrovascular diseases. Approximations its prevalence are 10–26% in general adult population increase with age. PAD bears burden functional decline major adverse limb events (MALE), consisting chronic limb-threatening ischemia, acute amputations. Chronic ischemia associated 20% mortality amputations one year. The lifetime risk varies based on traditional factors, including diabetes, smoking, dyslipidaemia, hypertension, a sedentary lifestyle. inflammation, metals, air pollution, depression also seem to play role. Furthermore, albuminuria related leg retinopathy PAD, regardless duration diabetes haemoglobin A1c (HbA1c) levels (1). has an increased propensity not only for MALE, but significant cardiovascular (MACE). Coronary prevalent 30–50% patients while presence polyvascular further increases susceptibility MACE (2).Diabetes significantly affecting 20–28% people diabetes. crucial factor diabetic foot ulcers, 50% those ulcers have PAD. diagnosis ischaemia challenging due atypical symptoms, particularly absence intermittent claudication rest pain attributed peripheral neuropathy, medial calcification that affects precision non-invasive diagnostic tests. In progression differs from individuals without manifesting itself more distal arteries, multiple bilateral arterial segments, reducing collateral growth, thus increasing amputation. leads worse outcomes, non-healing gangrene, amputation, disease. Approximately 70% non-traumatic lower extremity United States can be this disproportional overall 12% (2, 3). Post-amputation severe, dying 5 years, comparable many cancers (4).As MALE MACE, comprehensive multidisciplinary management highest importance, comprising non-pharmacologic intervention (lifestyle modification: smoking cessation, supervised exercise therapy, Mediterranean diet, weight loss), pharmacologic (antihypertensive lipid lowering antithrombotic glucose therapy) invasive therapy (endovascular surgical revascularization) 5). Revascularization procedures performed improve local conditions; however, who undergone these still face higher compared their counterparts such (2). 2 New antidiabetic therapies diseaseNew consist mainly sodium-glucose cotransporter-2 inhibitors (SGLT2i) glucagon-like peptide 1-receptor agonists (GLP1-RA). Representatives drug classes been reduction type (6). However, main outcome trials, most enrolled had concomitant disease, were underrepresented Even though, proven risk, which goes beyond mere glycaemic control, drugs both benefit recommended by 2023 ESC Guidelines treatment 2024 aortic diseases as choice reduce independent baseline or target HbA1c (5, 7). SGLT2i effectively kidney heart failure patients, common comorbidities seen yet meta-analysis 20 trials did find impact incidence contrast, US databases linked 1.65-fold GLP-1RA. A similar signal was observed 1.97-fold canagliflozin. It should emphasized amputation canagliflozin CANVAS trial, confirmed CREDENCE trial. post hoc analysis trial revealed majority minor infection, dose Instead, primarily previous established factors despite specific identified etiological mechanism. anticipated number less than averted (8). Additionally, conducted Lin et al. showed treated exhibited modest use SGLT2i. This greater loss cohort, addition diastolic pressure pronounced reductions systolic blood pressures, all potential markers volume depletion (9). Thus, underlying mechanism contributes elevated diuretic-induced hypovolemia, provoked SGLT2i, resulting reduced perfusion extremities. hypoperfusion initiate tissue necrosis, subsequently diuretic effect question likely during initial phase (10). mentioned probably specifical (canagliflozin) class effect, there no other obvious (11). International Working Group Diabetic Foot advises against starting any drug-naïve gangrene suggests stopping until healing occurs, carefully balancing individual risk-benefit ratio (3). GLP-1RA within two years following commencement, decreased (12). finding aligns various putative anti-atherosclerotic mechanisms, enhancement systemic microcirculation, inflammation oxidative stress, well improvements endothelial function vasodilation (13). Some expected shed additionally (14). recent LEADER SUSTAIN-6 liraglutide semaglutide demonstrated consistent efficacy Consequently, it appears show evident superiority medications respect PAD-related (15). could emerge even obesity since SELECT 2,4 mg. included 8.6% (16). terms current emerging therapies, great anticipation SOUL event-driven, double-blind, placebo-controlled evaluated first oral GLP1-RA, (14 mg once daily) placebo, atherosclerotic and/or Among individuals, 15.7% symptomatic category mutually exclusive territories (17). Recent announcement 14% (18). tirzepatide, dual GIP/GLP-1 receptor agonist, being SURPASS-CVOT designed randomized, active-controlled outcomes People (25.3% PAD) subjected weekly subcutaneous injection tirzepatide up 15 1.5 dulaglutide. noninferiority time dulaglutide will confirm safety tirzepatied placebo determine whether produces active comparator (demonstrating superiority) (19). And analysing mostly indirect data, STARDUST daily 1.8 6 months directly detected transcutaneous oxygen (TcPO2) confirming prevention clinical (20). results STRIDE eagerly 52-week week would maximum walking distance constant load treadmill median pain-free 114 m (maximum 186 m). Secondary include quality life cardiometabolic parameters (21). ongoing objective evaluating (NCT04146155) 24 weeks distance.3 DiscussionThe field sufficiently explored demonstrate possible favourable benefits new therapies. Although shown definitive data come, effects validated. On contrary, wide range conditions populations exists lack direct evaluate effectiveness With certain negative indicators, may never occur, casting pessimistic outlook demographic patients. advent personalized medicine underscores importance tailoring approaches each patient. Therefore, imperative meticulously assess balance risks ensure beneficial does exclude patient much gain use.
Язык: Английский