From the Guidelines
Semaglutide has been shown to have a beneficial effect on microvascular disease in patients with diabetes, with studies suggesting it can help prevent or slow the progression of microvascular complications. This GLP-1 receptor agonist works beyond glucose control by improving endothelial function, reducing inflammation, and decreasing oxidative stress—all factors that contribute to microvascular complications 1. The SUSTAIN-6 trial, which studied the effects of semaglutide on cardiovascular outcomes, found that semaglutide reduced the risk of major adverse cardiovascular events, including cardiovascular death, nonfatal MI, or nonfatal stroke, by 26% compared to placebo 1.
Key points to consider when prescribing semaglutide for patients with diabetes at risk for or already experiencing microvascular complications include:
- Starting doses of 0.25 mg weekly for Ozempic or 3 mg daily for oral Rybelsus, gradually increasing to therapeutic doses of 0.5-2.0 mg weekly or 7-14 mg daily, respectively
- Using the medication alongside standard preventive care including regular eye exams, kidney function monitoring, and foot examinations
- Informing patients that while semaglutide primarily targets blood glucose, its beneficial effects on blood vessels occur through multiple mechanisms including improved vascular tone, reduced inflammation, and enhanced nitric oxide production 1
- Monitoring patients for potential adverse effects, mainly gastrointestinal, which may lead to treatment discontinuation 1
The beneficial effects of semaglutide on microvascular disease are thought to occur through several mechanisms, including:
- Improved endothelial function
- Reduced inflammation
- Decreased oxidative stress
- Enhanced nitric oxide production
- Improved vascular tone 1. Overall, semaglutide has been shown to be a valuable addition to the treatment regimen for patients with diabetes at risk for or already experiencing microvascular complications, and its use should be considered in conjunction with standard preventive care and regular monitoring.
From the Research
Relationship between Semaglutide and Microvascular Disease
The relationship between semaglutide, a glucagon-like peptide-1 receptor agonist, and microvascular disease is complex and has been investigated in several studies 2, 3, 4, 5, 6.
- Microvascular Complications: An unexpected increase in diabetes-related retinopathy was observed in the SUSTAIN 6 trial, a cardiovascular outcome trial for semaglutide 3. However, the reason for this increase is not fully understood and may be due to a rapid decrease in glycemic parameters in patients with preexisting retinopathy.
- Impact on Cardiovascular Outcomes: The LEADER and SUSTAIN 6 clinical trials showed that patients with microvascular disease at baseline had an increased risk of major adverse cardiovascular events compared to those without microvascular disease 4. However, semaglutide consistently reduced cardiovascular risk in patients with and without microvascular disease.
- Effect on Atherosclerosis: A real-world study found that injectable semaglutide reduced carotid intima-media thickness, a marker of subclinical atherosclerosis, and improved glycemic control in patients with type 2 diabetes 5. This suggests that semaglutide may have a protective effect on atherosclerosis, a key mechanism for cardiovascular protection.
- Cardiovascular Safety: The PIONEER programme demonstrated the cardiovascular safety of oral semaglutide in patients with type 2 diabetes at high cardiovascular risk 6. Oral semaglutide was found to be well-tolerated and effective in reducing glycated hemoglobin and body weight, with a safety profile consistent with the known effects of glucagon-like peptide-1 receptor agonists.
Key Findings
- Semaglutide may increase the risk of diabetes-related retinopathy, particularly in patients with preexisting retinopathy 3.
- Semaglutide reduces cardiovascular risk in patients with and without microvascular disease 4.
- Semaglutide has a protective effect on atherosclerosis, a key mechanism for cardiovascular protection 5.
- Oral semaglutide is well-tolerated and effective in reducing glycated hemoglobin and body weight, with a safety profile consistent with the known effects of glucagon-like peptide-1 receptor agonists 6.