The legacy effect of hyperglycemia and early use of SGLT-2 inhibitors: a cohort study with newly-diagnosed people with type 2 diabetes

Ceriello, Antonio; Lucisano, Giuseppe; Prattichizzo, Francesco; Grotta, Rosalba La; Frigé, Chiara; Cosmo, Salvatore De; Bartolo, Paolo Di; Cianni, Graziano Di; Fioretto, Paola; Giorda, Carlo; Pontremoli, Roberto; Russo, Giuseppina; Viazzi, Francesca; Nicolucci, Antonio

doi:10.1016/j.lanepe.2023.100666

Cited by 14 publications

(11 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ceriello et al. also found that compared to non-users, patients using SGLT-2i during the early exposure period had a lower HR for the association between high level of HbA1c in early stage of T2D and increased later CVD risk, which was also consistent with our findings ( 12 ).…”

Section: Discussionsupporting

confidence: 92%

“…Another study based on population from the United Kingdom showed that patients with HbA1c consistently above 7% within 1 year of diabetes diagnosis had significantly higher CVD rates compared to those with HbA1c <7% ( 7 ). Additionally, in the study by Ceriello et al., researchers observed a significant trend toward an increasing risk of subsequent CVDs with progressively higher levels of mean HbA1c in the early 0–1, 0–2, and 0–3 years after diabetes diagnosis ( 12 ). Ceriello et al.…”

Section: Discussionmentioning

confidence: 99%

“…Based on prior study and the available sample size, early exposure of novel anti-hyperglycemic was defined in two ways: within one and two years after T2D diagnosis ( 12 ). The early exposure period started from the date of T2D diagnosis and ended at 1 or 2 years after diagnosis.…”

Section: Methodsmentioning

confidence: 99%

“…Regarding this phenomenon, Ceriello et al. recently reported that sodium-glucose transport protein 2 inhibitors (SGLT-2i), a novel class of anti-hyperglycemic agents that significantly reduce cardiovascular risk ( 9 – 11 ), can attenuate the legacy effect of poor glycemic control when used early in patients with T2D ( 12 ). According to their results, when using SGLT-2i in the first two years after diagnosis, the association between a high level of HbA1c in early stage of T2D and an increased subsequent risk of CVDs was no longer evident.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Influence of early use of sodium-glucose transport protein 2 inhibitors, glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors on the legacy effect of hyperglycemia

Deng,

Zhao,

Chai

et al. 2024

Front. Endocrinol.

View full text Add to dashboard Cite

BackgroundA phenomenon known as legacy effect was observed that poor glycemic control at early stage of patients with newly-diagnosed type 2 diabetes (T2D) increases the risk of subsequent cardiovascular diseases (CVD). Early use of some novel anti-hyperglycemic agents, such as sodium-glucose transport protein 2 inhibitors (SGLT-2i), may attenuate this effect, but the evidence is limited.MethodsTwo retrospective cohorts of newly diagnosed T2D patients from 2010–2023 were assembled using the Yinzhou Regional Health Care Database (YRHCD) with different definitions of the early exposure period - the 1-year exposure cohort and 2-year exposure cohort, which were comprised of subjects who had HbA1c measurement data within 1 year and 2 years after their T2D diagnosis, respectively. Using Cox proportional hazards models, we examined the association between high HbA1c level (HbA1c>7%) during the early exposure period and the risk of subsequent CVD. This analysis was performed in the overall cohort and three subpopulations with different treatments during the early exposure period, including patients initiating SGLT-2i or glucagon-like peptide-1 receptor agonists (GLP-1RA), patients using dipeptidyl peptidase-4 inhibitors (DPP-4i), and patients without using SGLT-2i, GLP-1RA, and DPP-4i. Besides, subgroup analyses were performed by stratifying patients into age <55 and ≥55 years.ResultsA total of 21,477 and 22,493 patients with newly diagnosed T2D were included in the two final cohorts. Compared with patients with mean HbA1c ≤ 7% during the early exposure period, those with HbA1c>7% had higher risks of incident CVD, with a HR of 1.165 (95%CI, 1.056–1.285) and 1.143 (95%CI, 1.044–1.252) in 1-year and 2-year exposure period cohort. Compared to non-users, in patients initiating SGLT-2i/GLP-1RA within 1 or 2 years after T2D diagnosis, higher HbA1c level at baseline was not associated with CVD in both two cohorts. In subgroup analyses, results were generally consistent with the main analysis.ConclusionsPoor glycemic control in the early stage of T2D increased later CVD risk in Chinese adults with newly diagnosed T2D. Compared to non-users, this association was smaller and non-significant in patients receiving SGLT-2i/GLP-1RA during the early stage of T2D, indicating early use of these drugs may have the potential to mitigate legacy effects of hyperglycemia.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Influence of early use of sodium-glucose transport protein 2 inhibitors, glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors on the legacy effect of hyperglycemia

Deng,

Zhao,

Chai

et al. 2024

Front. Endocrinol.

View full text Add to dashboard Cite

show abstract

“…While the UKPDS trial was focused on intervention with metformin, sulphonylureas (SUs)/insulin or conventional diet approaches, the results from the 44-year follow-up revealed the important legacy effect of early intensive blood-glucose management in the reduction of microvascular complications and the improvement in clinical outcomes [ 13 , 14 ]. Recently published registry data from Italy examining the associated risk of CVD in 251,339 people with T2DM and no CVD at baseline showed poor glycaemic outcomes (> 64 mmol/mol or HbA1c > 8%) during the first 3 years after diabetes diagnosis to be predictive of increased subsequent CVD risk, compared with having HbA1c < 53 mmol/mol (< 7%) [ 48 ]. Introduction of SGLT2i therapy during the initial 2 years appeared to remove the association between glycaemic management and CVD risk and early intervention seemed to be critical in achieving those outcomes [ 48 ].…”

Section: Back To Basics In T2dm Management: Improving Quantity and Qu...mentioning

confidence: 99%

SGLT2 Inhibitors – The New Standard of Care for Cardiovascular, Renal and Metabolic Protection in Type 2 Diabetes: A Narrative Review

Seidu,

Alabraba,

Davies

et al. 2024

Diabetes Ther

View full text Add to dashboard Cite

A substantial evidence base supports the use of sodium-glucose cotransporter-2 inhibitors (SGLT2is) in the treatment of type 2 diabetes mellitus (T2DM). This class of medicines has demonstrated important benefits that extend beyond glucose-lowering efficacy to protective mechanisms capable of slowing or preventing the onset of long-term cardiovascular, renal and metabolic (CVRM) complications, making their use highly applicable for organ protection and the maintenance of long-term health outcomes. SGLT2is have shown cost-effectiveness in T2DM management and economic savings over other glucose-lowering therapies due to reduced incidence of cardiovascular and renal events. National and international guidelines advocate SGLT2i use early in the T2DM management pathway, based upon a plethora of supporting data from large-scale cardiovascular outcome trials, renal outcomes trials and real-world studies. While most people with T2DM would benefit from CVRM protection through SGLT2i use, prescribing hesitancy remains, potentially due to confusion concerning their place in the complex therapeutic paradigm, variation in licensed indications or safety perceptions/misunderstandings associated with historical data that have since been superseded by robust clinical evidence and long-term pharmacovigilance reporting. This latest narrative review developed by the Improving Diabetes Steering Committee (IDSC) outlines the place of SGLT2is within current evidence-informed guidelines, examines their potential as the standard of care for the majority of newly diagnosed people with T2DM and sets into context the perceived risks and proven advantages of SGLT2is in terms of sustained health outcomes. The authors discuss the cost-effectiveness case for SGLT2is and provide user-friendly tools to support healthcare professionals in the correct application of these medicines in T2DM management. The previously published IDSC SGLT2i Prescribing Tool for T2DM Management has undergone updates and reformatting and is now available as a Decision Tool in an interactive pdf format as well as an abbreviated printable A4 poster/wall chart. Supplementary Information The online version contains supplementary material available at 10.1007/s13300-024-01550-5.

show abstract

Is glycaemic control still central in the hierarchy of priorities in type 2 diabetes management? The way forward is to combine glucose control and the prevention of cardiorenal complications

Ceriello,

Prattichizzo,

Berra

2024

Diabetologia

View full text Add to dashboard Cite

The legacy effect of hyperglycemia and early use of SGLT-2 inhibitors: a cohort study with newly-diagnosed people with type 2 diabetes

Cited by 14 publications

References 37 publications

Influence of early use of sodium-glucose transport protein 2 inhibitors, glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors on the legacy effect of hyperglycemia

Influence of early use of sodium-glucose transport protein 2 inhibitors, glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors on the legacy effect of hyperglycemia

SGLT2 Inhibitors – The New Standard of Care for Cardiovascular, Renal and Metabolic Protection in Type 2 Diabetes: A Narrative Review

Is glycaemic control still central in the hierarchy of priorities in type 2 diabetes management? The way forward is to combine glucose control and the prevention of cardiorenal complications

Contact Info

Product

Resources

About