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Updated: Mar 8, 2026

A Zebrafish Model of Diabetes Mellitus and Metabolic Memory
Published on: February 28, 2013
[Type 2 diabetes treatment and cardiovascular risk: what can we learn from trials?]
Agostino Consoli1, Fabrizio Febo1
1Dipartimento di Medicina Interna e Scienze dell'Invecchiamento e Centro Scienze dell'Invecchiamento e Medicina Traslazionale, Università degli Studi "G. d'Annunzio", Chieti-Pescara.
Abstract:
Diabetes treatment should include drugs with absolutely no adverse effects toward cardiovascular risk. Indeed, it would be advisable to use drugs with intrinsic protective effect against the risk of cardiovascular events. Intervention trials aiming at demonstrating a protective cardiovascular effect of very tight glucose control have produced controversial results. It is commonly perceived, however, that early intervention with safe treatment strategies is likely to be beneficial. In regard to safety, in the attempt to firmly establish cardiovascular safety of new drugs for diabetes, Government Authorities have mandated that cardiovascular safety trials need to be performed for all new drugs registered for diabetes treatment. Several of such trials have already been performed and their results are available. These results support the cardiovascular safety of three dipeptidyl peptidase-4 inhibitors (sitagliptin, saxagliptin and alogliptin) and of a glucagon-like peptide-1 receptor agonist (GLP-1RA) (lixisenatide). These results, however, also document a plausible protective effect against cardiovascular risk associated with the use of a SGLT2 inhibitor (empagliflozin) and of two GLP-1RAs (liraglutide and semaglutide). Differences and similarities among the results of these cardiovascular safety trials as well as their potential implications will be discussed in this article.
Insights
New diabetes drugs require cardiovascular safety trials. Some drugs show safety, while SGLT2 inhibitors and GLP-1 receptor agonists may offer cardiovascular protection.
Area of Science:
- Cardiology
- Endocrinology
- Pharmacology
Background:
- Diabetes treatment necessitates drugs with no adverse cardiovascular effects, ideally with protective benefits.
- Mandated cardiovascular safety trials for new diabetes medications aim to establish drug safety profiles.
- Controversial results exist regarding tight glucose control's cardiovascular impact.
Purpose of the Study:
- To review cardiovascular safety trial results for recently approved diabetes medications.
- To identify diabetes drugs with established cardiovascular safety or potential protective effects.
Main Methods:
- Analysis of available cardiovascular safety trial data for various diabetes drug classes.
- Comparison of safety and efficacy outcomes across different drug classes, including DPP-4 inhibitors, GLP-1 RAs, and SGLT2 inhibitors.
Main Results:
- Cardiovascular safety is supported for three dipeptidyl peptidase-4 inhibitors (sitagliptin, saxagliptin, alogliptin) and one GLP-1 receptor agonist (lixisenatide).
- A plausible protective cardiovascular effect is suggested for an SGLT2 inhibitor (empagliflozin) and two GLP-1 receptor agonists (liraglutide, semaglutide).
Conclusions:
- Recent trials confirm the cardiovascular safety of certain DPP-4 inhibitors and a GLP-1 RA.
- Emerging evidence suggests potential cardiovascular benefits from SGLT2 inhibitors and other GLP-1 RAs, warranting further investigation.
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