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A Zebrafish Model of Diabetes Mellitus and Metabolic Memory
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Redefining diabetes mellitus treatments according to different mechanisms beyond hypoglycaemic effect

Savina Nodari1, Francesco Fioretti2, Francesco Barilla3

  • 1Department of Medical and Surgical Specialities, Radiological Sciences and Public Health, University and Spedali Civili of Brescia, Brescia, Italy. savina.nodari@unibs.it.

Heart Failure Reviews
|February 8, 2022
PubMed

Insights

Aggressively lowering blood glucose in diabetes may worsen outcomes. Newer therapies like SGLT2 inhibitors offer benefits beyond glucose control, marking a new era in diabetes and heart failure treatment.

Area of Science:

  • Cardiology
  • Endocrinology
  • Pharmacology

Background:

  • Early diabetes research focused on achieving near-normal glucose (euglycaemia) to prevent complications.
  • Intensive glucose control strategies, while lowering HbA1c, were associated with adverse outcomes and increased hypoglycemia risk.

Purpose of the Study:

  • To review the paradigm shift in diabetes treatment beyond solely focusing on glycaemic control.
  • To highlight the cardiovascular and mortality benefits of newer diabetes medications.
  • To discuss the expanding role of SGLT2 inhibitors in heart failure, irrespective of diabetes status.

Main Methods:

  • Review of recent clinical trial data and treatment guidelines.
  • Analysis of mechanisms of action for GLP-1 receptor agonists (GLP-1RAs) and SGLT2 inhibitors (SGLT2i).
  • Examination of evidence supporting the use of SGLT2i in heart failure (HF).

Main Results:

  • GLP-1RAs and SGLT2i demonstrate significant benefits in mortality and cardiovascular events, independent of their glucose-lowering effects.
  • SGLT2 inhibitors are now recognized for treating heart failure in both diabetic and non-diabetic patients, as per ESC/HFA guidelines.

Conclusions:

  • Diabetes treatment is shifting from exclusive glycaemic control to a broader approach addressing cardiovascular and other mechanisms.
  • SGLT2 inhibitors represent a major advancement, expanding therapeutic possibilities for cardiovascular disease and heart failure.
Keywords:
Cardiovascular riskDiabetes mellitusGLP-1RAsHyperglicemiaMetabolic syndromeSGLT2i

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