Semaglutide’s Impact on Peripheral Artery Disease and Cardiovascular Risk

Semaglutide, a GLP-1 receptor agonist, is emerging as a valuable treatment option for individuals with type 2 diabetes and cardiovascular complications. Originally developed as an anti-diabetic medication, semaglutide is also used as an anti-obesity medication for long-term weight management [[3]]. Recent studies have explored its efficacy in improving outcomes for patients with obliterating arteriopathies of the lower limbs (AOMI) and those at high cardiovascular risk.

Improving Walking Distance in Diabetic AOMI Patients

A meaningful challenge in managing AOMI is the limited availability of treatments to enhance functional capacity and quality of life. The Multicenter Stride test evaluated the impact of semaglutide in this context.The study focused on 792 patients with type 2 diabetes and AOMI experiencing intermittent claudication.Participants were administered 1 mg of subcutaneous semaglutide weekly.

The primary outcome measured was the change in maximum walking distance.At the start of the trial, the average walking distance was 186 meters. After one year, patients treated with semaglutide showed an increase of 40 meters, which was 26 meters more than the placebo group, representing a 13% enhancement (p = 0.0004). Secondary outcomes further supported these findings, demonstrating significant improvements in quality of life, painless walking distance, and systolic pressure index. Post-hoc analysis indicated a notable reduction in revascularizations or deaths.

While gastrointestinal side effects were observed, aligning with the known profile of semaglutide, no unexpected serious adverse events occurred. Further research is warranted to elucidate the mechanisms behind these benefits and to assess the potential of semaglutide in non-diabetic AOMI patients.

Reducing cardiovascular Events in High-risk Diabetics

The Phase 3 SOUL trial investigated the effects of semaglutide in a high-risk population. The trial randomized 9,650 individuals over 50 years old with type 2 diabetes, atherosclerotic cardiovascular disease, and/or chronic renal cardiovascular disease. Participants had HbA1c levels between 6.5% and 10%.

The primary endpoint was the occurence of a major adverse cardiovascular event (MACE), including cardiovascular death, myocardial infarction (MI), or stroke. Over an average follow-up of 49.5 months, 12% of patients on semaglutide experienced a MACE, compared to 13.8% in the placebo group (HR = 0.86,p = 0.006). There were no significant differences in major renal complications between the two groups, and the safety profile was consistent, with similar rates of serious adverse events in both the semaglutide (47.9%) and placebo (50.3%) groups.

In diabetics with renal or cardiovascular pathologies, the oral semaglutide substantially reduces the risk of serious cardiovascular complications, without resulting in additional adverse events.
Dr.Darren McGuire (Dallas, Texas)

These findings suggest that oral semaglutide can effectively lower the risk of severe cardiovascular events in diabetic patients with existing renal or cardiovascular conditions, without increasing adverse events.

Dapagliflozin‘s Role in Post-TAVI Management

The Dapa-TAVI trial, a Spanish multicenter study, evaluated the use of dapagliflozin, an SGLT2 inhibitor, in patients following transcatheter aortic valve implantation (TAVI). The trial demonstrated a significant 28% reduction in the risk of death or heart failure.

The study included 1,222 patients with a median age of 82.4 years (49% women) who underwent TAVI for severe aortic stenosis.All patients had heart failure and were considered high-risk,exhibiting factors such as moderate renal failure,type 2 diabetes,or a left ventricular ejection fraction (LVEF) of ≤ 40%. Patients were randomized to receive 10 mg/day of dapagliflozin or standard treatment within 14 days of their TAVI procedure.

After one year, the primary composite outcome of all-cause mortality or worsening heart failure occurred in 15% of the dapagliflozin group versus 20.1% in the standard care group (HR = 0.72, p = 0.02). This benefit was primarily driven by a 37% reduction in the worsening of heart failure in the dapagliflozin group (9.4% vs 14.4%). Mortality rates were 7.8% and 8.9% in the dapagliflozin and standard care groups, respectively (HR = 0.87).

Dapagliflozin reduces the risk of death or heart failure after angioplasty by a third party.

while adverse events were common in both groups due to the advanced age and comorbidities of the participants, genital infections (1.8% vs 0.5%) and hypotension (6.6% vs 3.6%) were significantly more frequent in the dapagliflozin group.

It is significant to have been able to highlight that the ISGLT2 are beneficial in post-tavi in all sub-groups of patients, but also that thay are well tolerated by this fragile population, generally excluded from clinical trials.
Sert Serge Serge-Roubin (Vig, Spain)

These results suggest that SGLT2 inhibitors like dapagliflozin are beneficial and well-tolerated in the fragile post-TAVI population, often excluded from clinical trials.