exenatide and Peripheral-Arterial-Disease

Recent trials have identified anti-diabetes mellitus agents that lower major adverse cardiovascular event (MACE) rates, although some increase rates of lower-extremity amputation (LEA). Patients with peripheral artery disease (PAD) have greater incidence of diabetes mellitus and risk for LEA, prompting this investigation of clinical outcomes in patients with diabetes mellitus and PAD in the EXSCEL trial (Exenatide Study of Cardiovascular Event Lowering).. EXSCEL evaluated the effects of once-weekly exenatide (a GLP-1 [glucagon-like peptide-1] receptor agonist) versus placebo on the rates of the primary composite MACE end point (cardiovascular death, myocardial infarction, or stroke) among patients with type 2 diabetes mellitus. In this post hoc analysis, we assessed the association of baseline PAD with rates of MACE, LEA, and the effects of exenatide versus placebo in patients with and without PAD.. EXSCEL included 2800 patients with PAD (19% of the trial population). These individuals had higher unadjusted and adjusted rates of MACE compared with patients without PAD (13.6% versus 11.4%, respectively) as well as a higher adjusted hazard ratio (adjusted hazard ratio, 1.13 [95% CI, 1.00-1.27];. EXSCEL participants with PAD had higher rates of all-cause mortality and LEA compared with those without PAD. There were no differences in MACE or LEA rates with exenatide versus placebo. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT01144338.

Topics: Aged; Cause of Death; Diabetes Mellitus, Type 2; Double-Blind Method; Exenatide; Female; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Incretins; Male; Middle Aged; Myocardial Infarction; Peripheral Arterial Disease; Risk Assessment; Risk Factors; Stroke; Time Factors; Treatment Outcome

Although models exist to predict amputation among people with type 2 diabetes with foot ulceration or infection, we aimed to develop a prediction model for a broader range of major adverse limb events (MALE)-including gangrene, revascularization and amputation-among individuals with type 2 diabetes.. In a post-hoc analysis of data from the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) trial, we compared participants who experienced MALE with those who did not. A multivariable model was constructed and translated into a risk score.. Among the 14,752 participants with type 2 diabetes in EXSCEL, 3.6% experienced MALE. Characteristics associated with increased risk of MALE were peripheral artery disease (PAD) (HR. The majority of MALE occurred among participants with PAD, but participants without a history of PAD also experienced MALE. A risk score with good performance was generated. Although it requires validation in an external dataset, this risk score may be valuable in identifying patients requiring more intensive care and closer follow-up.

Topics: Aged; Amputation, Surgical; Cardiovascular Diseases; Cohort Studies; Diabetes Mellitus, Type 2; Diabetic Foot; Exenatide; Female; Gangrene; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Male; Middle Aged; Peripheral Arterial Disease; Randomized Controlled Trials as Topic; Risk Factors; Sex Factors; Vascular Surgical Procedures