Reassessing SGLT2 Inhibitors: Cardiovascular Concerns and the Promise of Phytocannabinoids

SGLT2 inhibitors have transformed glycemic control in type 2 diabetes but emerging evidence points to an underrecognized cardiovascular risk that demands careful reassessment in patients with established heart disease.

The dual demands of glycemic management and cardiovascular protection place clinicians at a crossroads. While SGLT2 inhibitors are hailed for reducing hospitalizations in heart failure and improving renal outcomes, a large retrospective cohort from Mass General Brigham revealed a higher incidence of myocardial infarction and arrhythmias compared with other diabetes medication classes, as documented in the study’s findings on heart-related conditions. This insight necessitates a critical appraisal of SGLT2 inhibitor therapy in patients with preexisting cardiovascular disease.

To broaden the therapeutic armamentarium, recent work on phytocannabinoids suggests these natural compounds may modulate the SLC5A2 transporter through multi-target pharmacology, offering glucose-lowering effects alongside anti-inflammatory and vasodilatory benefits. Such a strategy could mitigate the cardiovascular risk associated with traditional SGLT2 inhibitors and introduce a novel adjunctive or alternative avenue for high-risk patients.

Pharmacogenetic insights add another layer of complexity: variation in genes such as SLC5A2 correlates with divergent responses to dapagliflozin in patients with heart failure with reduced ejection fraction (HFrEF). A recent research on pharmacogenetic variations demonstrated that certain allelic profiles predict greater improvements in ejection fraction and fewer adverse events among individuals receiving standard doses, highlighting the potential of genotyping to personalize SGLT2 inhibitor therapy. Earlier findings on phytocannabinoid modulation reinforce the concept that individual biology can reshape treatment outcomes.

Balancing the cardiometabolic benefits of SGLT2 inhibitors with their emerging risk profile demands a nuanced approach. Integrating pharmacogenetic profiling into clinical practice and exploring innovative modulators such as phytocannabinoids can help tailor therapy, maximizing efficacy while minimizing cardiovascular harm.

Key Takeaways:

• SGLT2 inhibitors play a dual role in glucose management and cardiovascular risk, requiring careful therapeutic consideration.
• Emerging evidence supports the potential of phytocannabinoids to modulate glucose and reduce cardiovascular complications.
• Pharmacogenetic profiling could optimize the use of SGLT2 inhibitors by tailoring treatments to individual genetic profiles.