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Why have SGLT2 Inhibitors Failed to Achieve the Desired Success in COVID-19?

Medine Cumhur Cure1, Erkan Cure2

  • 1Medilab Laboratory and Imaging Center, Department of Biochemistry, Sisli, Istanbul, Turkey.

Current Pharmaceutical Design
|April 3, 2024
PubMed

Insights

Sodium-glucose transport protein 2 (SGLT2) inhibitors showed promise for treating COVID-19 in diabetic patients but were not effective. This review explores potential reasons for their failure, including drug interactions and physiological effects.

Area of Science:

  • Infectious Diseases
  • Endocrinology
  • Pharmacology

Background:

  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic, leading to COVID-19, a disease with complex pathophysiology including cellular toxicity, inflammation, and renin-angiotensin system (RAS) activation.
  • Sodium-glucose transport protein 2 (SGLT2) inhibitors (SGLT2i) offer benefits like weight loss, improved glycemic control, and enhanced vascular function, raising hopes for their use in diabetic patients with COVID-19.
  • Existing literature presents conflicting data and confusion regarding the efficacy of SGLT2i in managing COVID-19 patients with diabetes.

Purpose of the Study:

  • To investigate and clarify the reasons behind the ineffectiveness of SGLT2 inhibitors in treating COVID-19 patients with diabetes.
  • To analyze the potential detrimental effects and interactions of SGLT2 inhibitors in the context of SARS-CoV-2 infection.
  • To reconcile conflicting findings in the literature concerning SGLT2 inhibitors and COVID-19.

Main Methods:

  • Review of existing scientific literature on SARS-CoV-2, COVID-19, SGLT2 inhibitors, and their interactions.
  • Analysis of physiological effects of SGLT2 inhibitors, including impacts on glucose transport, erythropoiesis, and the renin-angiotensin system.
  • Exploration of potential confounding factors such as drug co-administration, ketoacidosis risk, and electrolyte imbalances.

Main Results:

  • Current data indicate that SGLT2 inhibitors are not highly effective in treating COVID-19, even in diabetic patients.
  • Several factors may have contributed to the lack of efficacy, including increased SGLT1 activity, absence of angiotensin receptor blocker co-administration, and potential for adverse events like ketoacidosis and kidney injury.
  • The duration of SGLT2 inhibitor use and their influence on erythropoiesis, blood viscosity, and lipid profiles may also have impacted outcomes.

Conclusions:

  • SGLT2 inhibitors failed to demonstrate significant therapeutic benefit in COVID-19 patients with diabetes due to a combination of pharmacological and physiological factors.
  • Further research is needed to fully understand the complex interplay between SGLT2 inhibition and SARS-CoV-2 infection to guide future therapeutic strategies.
  • The findings highlight the importance of considering drug-specific mechanisms and patient-specific conditions when evaluating treatment efficacy during pandemics.
Keywords:
COVID-19SARS-CoV-2SGLT2 inhibitorsangiotensin-converting enzyme 2 (ACE2)cellular toxicity.sodium-glucose transport protein 2 inhibitors

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