Recent advancements in antidiabetic therapies have introduced new drugs that not only manage blood sugar levels but also show promise in reducing stroke risk. Unlike traditional therapies, these newer medications offer cardiovascular benefits independent of tight glycemic control.


Understanding the Mechanism Beyond Glycemic Control

Dr. Larry B. Goldstein, Chair of Neurology at the University of Kentucky College of Medicine, highlights that these benefits are not directly tied to glycemic control. “They are not working through glycemic control per se,” he explains, emphasizing the need for further research to understand the underlying mechanisms.

Previous large-scale randomized trials, such as the ACCORD trial, demonstrated that tighter glycemic control did not significantly reduce stroke risk. The 2011 long-term results from ACCORD revealed an odds ratio of 0.97 for fatal or nonfatal stroke with tight glycemic control, which was not statistically significant (95% CI, 0.77-1.33; P = .85). These findings were consistent across various studies and meta-analyses, as presented by Dr. Goldstein.


Stroke Prevention with Newer Antidiabetic Agents

Newer antidiabetic drugs, such as sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA), have demonstrated significant reductions in cardiovascular events. However, their impact on stroke prevention varies.

Dr. Goldstein noted that GLP-1RA shows the most robust evidence for stroke risk reduction. A meta-analysis of eight randomized studies indicated a 15% risk reduction in both fatal and nonfatal strokes, with highly significant results (P = .0002 and P < .001, respectively). Conversely, SGLT2 inhibitors have shown weaker effects on stroke prevention. Analysis of large cardiovascular trials revealed significant stroke risk reduction only for GLP-1RA (P < .001) and pioglitazone (P = .025), but not for SGLT2i (P = .88) or dipeptidyl peptidase-4 inhibitors (DPP4i) (P = .5).


The Role of Weight Loss

Weight loss is a potential mechanism for the cardiovascular benefits of these newer drugs. Dr. Gordon Kelley of AdventHealth Medical Group suggests that weight loss may contribute to stroke risk reduction. Both SGLT2i and GLP-1RA are known for their weight loss effects, beyond glucose control.

However, Dr. Goldstein argues that weight loss alone may not explain the stroke prevention benefits. Studies indicate that SGLT2i generally lead to greater weight loss compared to GLP-1RA, yet GLP-1RA consistently show stronger stroke risk reduction.


Clinical Guidelines and Recommendations

The 2019 American College of Cardiology/American Heart Association guidelines for the primary prevention of cardiovascular disease recommend GLP-1RA or SGLT2i after metformin for glycemic control in T2DM patients with atherosclerotic cardiovascular disease (ASCVD) risk factors. While these guidelines focus on reducing ASCVD events, they do not isolate stroke risk specifically.

For patients with T2DM and a high risk of cardiovascular events, Dr. Goldstein suggests using the ASCVD risk calculator to determine the 10-year risk. For those with a risk greater than 10%, he recommends considering GLP-1RA for stroke prevention, based on available data and guidelines.

Newer antidiabetic drugs offer promising benefits for stroke prevention, but further research is needed to fully understand the mechanisms behind these effects. Clinicians should consider both glycemic control and cardiovascular risk factors when selecting antidiabetic therapies for their patients.

It’s important to remember that while these newer antidiabetic medications show promising benefits, individual health needs vary. Always consult with your healthcare provider to discuss the best treatment options for your specific condition and to tailor a plan that addresses your overall health and risk factors.


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