Intraclass differences in the risk of hospitalization for heart failure among patients with type 2 diabetes initiating a dipeptidyl peptidase‐4 inhibitor or a sulphonylurea: <scp>R</scp>esults from the <scp>OsMed H</scp>ealth‐<scp>DB</scp> registry

Fadini, Gian Paolo; Saragoni, Stefania; Russo, Pierluigi; Esposti, Luca Degli; Kreutzenberg, Saula Vigili de; Melazzini, Mario; Avogaro, Angelo

doi:10.1111/dom.12979

Cited by 21 publications

(23 citation statements)

References 34 publications

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“…Different considerations can be made: (1) the clinical relevance of CV benefit in terms of HHF is not as large as expected from the risk reduction estimates when compared to MACE and all‐cause mortality; (2) the lowest (outstanding) NNTBs came from the EASEL study; this may be interpreted taking into consideration that the population was a high‐risk cohort; (3) the CVD‐REAL studies provided similar findings, with the Nordic cohort showing the best estimates, especially the sub‐study on dapagliflozin; the reasons are uncertain although the comparison with DPP4‐Is may play a role: all published CVOTs on DPP4‐Is demonstrate non‐inferiority versus placebo, and the relative effect on the risk of HHF remains uncertain, with ongoing controversy over the increased risk for saxagliptin39, 40, 41; (4) only the UK cohort in the THIN database showed no significant risk reduction for MACE (expressed as incident CVD); (5) the highest NNTBs emerged for canagliflozin in the US cohort compared with DPP4‐Is; and (6) overall, it appears that the NNTBs are roughly comparable with those derived from the UKPDS follow‐up42 (in the metformin group comparing intensive vs. conventional therapy, the NNTB for the endpoint death from any cause was 139).…”

Section: Clinical Insight Into Observational Researchmentioning

confidence: 97%

Observational research on sodium glucose co‐transporter‐2 inhibitors: A real breakthrough?

Raschi

Poluzzi

Fadini

et al. 2018

Diabetes Obesity Metabolism

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Sodium glucose co‐transporter‐2 inhibitors have attracted the interest of the scientific community following the results from dedicated cardiovascular outcome trials, which demonstrated remarkable reduction in all‐cause mortality and other cardiovascular (CV) endpoints with empagliflozin and canagliflozin. These impressive results raised further expectations on real world data from large observational cohort studies. They were designed to address the possible existence of a class effect, and the uncertainty on whether this benefit can be extended from secondary to primary CV prevention of patients with type 2 diabetes. In this review, we collated data from existing observational studies (including the celebrated CVD‐REAL cohorts) and critically appraised results and methodological issues with the aim of providing clinical insight, including unsettled aspects, and proposing a research agenda for future investigations.

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Section: Clinical Insight Into Observational Researchmentioning

confidence: 97%

Observational research on sodium glucose co‐transporter‐2 inhibitors: A real breakthrough?

Raschi

Poluzzi

Fadini

et al. 2018

Diabetes Obesity Metabolism

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“…Retrospective analysis found no increased risk of HF compared to use of sulfonylureas, while a retrospective study based on the national Italian registry including 127 555 T2DM patients actually reported a reduction in the risk of hospitalization for HF as compared to that with use of sulfonylureas . In the same population, no interclass difference was apparent for DPP4i with regard to the risk of hospitalization for HF . These results, along with the overall tolerability profile, make DPP4i an attractive and safe treatment in the early stage of the disease.…”

Section: Discussionmentioning

confidence: 88%

“…95 In the same population, no interclass difference was apparent for DPP4i with regard to the risk of hospitalization for HF. 107 These results, along with the overall tolerability profile, make DPP4i an attractive and safe treatment in the early stage of the disease. In patients with a longer duration of the disease and prior CV events, or with high CV risk, DPP4i have been proven to be safe in intervention trials, [66][67][68] as well as in population studies 108 and meta-analyses.…”

Section: Discussionmentioning

confidence: 99%

Practical strategies for improving outcomes in T2DM: The potential role of pioglitazone and DPP4 inhibitors

Prato

Chilton

2017

Diabetes Obesity Metabolism

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T2DM is a complex disease underlined by multiple pathogenic defects responsible for the development and progression of hyperglycaemia. Each of these factors can now be tackled in a more targeted manner thanks to glucose‐lowering drugs that have been made available in the past 2 to 3 decades. Recognition of the multiplicity of the mechanisms underlying hyperglycaemia calls for treatments that address more than 1 of these mechanisms, with more emphasis placed on the earlier use of combination therapies. Although chronic hyperglycaemia contributes to and amplifies cardiovascular risk, several trials have failed to show a marked effect from intensive glycaemic control. During the past 10 years, the effect of specific glucose‐lowering agents on cardiovascular risk has been explored with dedicated trials. Overall, the cardiovascular safety of the new glucose‐lowering agents has been proven with some of the trials summarized in this review, showing significant reduction of cardiovascular risk. Against this background, pioglitazone, in addition to exerting a sustained glucose‐lowering effect, also has ancillary metabolic actions of potential interest in addressing the cardiovascular risk of T2DM, such as preservation of beta‐cell mass and function. As such, it seems a logical agent to combine with other oral anti‐hyperglycaemic agents, including dipeptidyl peptidase‐4 inhibitors (DPP4i). DPP4i, which may also have a potential to preserve beta‐cell function, is available as a fixed‐dose combination with pioglitazone, and could, potentially, attenuate some of the side effects of pioglitazone, particularly if a lower dose of the thiazolidinedione is used. This review critically discusses the potential for early combination of pioglitazone and DPP4i.

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“…Monami et al [87] Increased risk of heart failure, without any clear evidence of differences among drugs of the class Fadini et al [98] No intraclass difference in the incidence rate of first and total hypertensive HF events between sitagliptin, saxagliptin, and vildagliptin.…”

Section: First Authors Findingsmentioning

confidence: 99%

The pleiotropic cardiovascular effects of dipeptidyl peptidase‐4 inhibitors

Avogaro

Fadini

2018

Brit J Clinical Pharma

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Patients with Type 2 diabetes have an excess risk for cardiovascular disease. One of the several approaches, included in the guidelines for the management of Type 2 diabetes, is based on dipeptidyl peptidase 4 (DPP-4; also termed CD26) inhibitors, also called gliptins. Gliptins inhibit the degradation of glucagon-like peptide-1 (GLP-1): this effect is associated with increased circulating insulin-to-glucagon ratio, and a consequent reduction of HbA1c. In addition to incretin hormones, there are several proteins that may be affected by DPP-4 and its inhibition: among these some are relevant for the cardiovascular system homeostasis such as SDF-1α and its receptor CXCR4, brain natriuretic peptides, neuropeptide Y and peptide YY. In this review, we will discuss the pathophysiological relevance of gliptin pleiotropism and its translational potential.

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Intraclass differences in the risk of hospitalization for heart failure among patients with type 2 diabetes initiating a dipeptidyl peptidase‐4 inhibitor or a sulphonylurea: Results from the OsMed Health‐DB registry

Abstract: In a cohort of patients with T2D taken from approximately one-third of the Italian population, no intraclass difference was noted for DPP-4 inhibitor and SU therapy with regard to HHF risk.

Cited by 21 publications

References 34 publications

Observational research on sodium glucose co‐transporter‐2 inhibitors: A real breakthrough?

Observational research on sodium glucose co‐transporter‐2 inhibitors: A real breakthrough?

Practical strategies for improving outcomes in T2DM: The potential role of pioglitazone and DPP4 inhibitors

The pleiotropic cardiovascular effects of dipeptidyl peptidase‐4 inhibitors

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