SEMAGLUTIDE AND PERIPHERAL ARTERIAL DISEASE (PAD)

The brand names for the generic GLP-1RA, semaglutide, are Ozempic, Wegovy, and Rybelsus. They all are indicated primarily for the treatment and control of elevated blood sugar in Type 2 Diabetes (T2D) and for the prevention of cardiovascular complications in diabetic patients. Secondarily, however, semaglutide was found to cause as much as a 20% loss of body weight in obese patients, whether diabetic or not, so it, and it’s sister tirzepatide, have become very popular with obese Americans. Ozempic and Wegovy are injectable drugs while Rybelsus is oral. 

“The most common initial manifestation of cardiovascular disease in Type 2 Diabetes is Peripheral Arterial Disease, PAD.” That’s means that circulatory problems in the legs and feet are the first complications that many T2D patients develop. PAD is gradually progressive and  worsens faster in diabetics than in non-diabetics. Poor circulation ultimately leads to limitations (pain) in walking and the fear of amputation of the toes, feet, or lower legs. By the time most patients begin having pain with walking, they already have advanced arteriosclerotic disease that threatens loss of limb.

Enter semaglutide. A study in The Lancet “explored the impact of subcutaneous [weekly] injections of semaglutide……on walking capacity in patients with T2D and symptomatic PAD.” Diabetics with early PAD were chosen based on the results of Ankle-Brachial Index circulation testing (ABI). After 52 weeks of weekly semaglutide, ABI testing was repeated and results were compared to baseline. “Subcutaneous semaglutide was associated with a significantly increased maximum walking distance……[and] significantly improved symptoms and quality of life.” 

A later study in Diabetes Care “confirmed that the effect of semaglutide on maximum walking distance was consistent irrespective of……diabetes duration, BMI, HbA1C, or the use of insulin.” These results were better than those of any other drug treatment studied for comparison. 

So, semaglutide advocates are saying that the recognized improvement in “walking capacity, quality of life, and disease progression for patients with T2D and PAD….position[s] semaglutide as a foundational therapy to improve quality and quantity of life.” Once again, semaglutide has been found to have another major use for which it can be recommended. Now, along with controlling T2D, causing weight loss, decreasing cardiovascular events, and increasing exercise tolerance, semaglutide’s anti-inflammatory effect actually reduces the progression of atherosclerosis—or so they think.

Reference: Fernando K. Semaglutide has found its STRIDE. Medscape 2025 July 3.