Novel oral glucose‐lowering drugs are associated with lower risk of all‐cause mortality, cardiovascular events and severe hypoglycaemia compared with insulin in patients with type 2 diabetes

Nyström, Thomas; Bodegård, Johan; Thuresson, Marcus; Norhammar, Anna; Eriksson, Jan W.

doi:10.1111/dom.12889

Cited by 75 publications

(75 citation statements)

References 45 publications

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“…In parallel with CVD‐REAL cohorts, additional population‐based studies investigated CV outcomes with SGLT2‐Is from US (vs. non‐gliflozin agents),14, 15 UK Health Improvement Network (vs. other glucose‐lowering drugs)16 and Swedish (DPP4‐Is or SGLT2‐Is compared with insulin)17 databases. Although definitions of outcomes as well as patients' characteristics vary across different studies, all consistently highlighted a significantly reduced risk of MACE and other CV endpoints, except for the US cohort on canagliflozin (Table 1).…”

Section: Overview Of Resultsmentioning

confidence: 99%

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: Overview Of Resultsmentioning

confidence: 99%

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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“…Consistent with the observations in EMPA-REG OUTCOME and CANVAS, the broad impact of SGLT2 inhibition on CV outcomes has been observed in several “real-world” studies such as CVD-REAL, which reported significant benefits on mortality and hospitalization for HF risk with several SGLT2 inhibitor agents in an analysis of administrative data from 6 countries 33 . Separate analyses examining dapagliflozin vs. other glucose lowering therapies revealed similar beneficial CV effects 34, 35 , and an additional analysis demonstrated a 56% decreased risk of all-cause mortality and CVD with SGLT2 inhibition in a general practice cohort in the Sweden 36 .…”

Section: Anti-hyperglycemic Agents and Cardiovascular Safety Trialsmentioning

confidence: 93%

Sodium Glucose Cotransporter-2 Inhibition in Heart Failure

et al. 2017

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Despite current established therapy, heart failure (HF) remains a leading cause of hospitalization and mortality worldwide. Novel therapeutic targets are therefore needed to improve the prognosis of patients with HF. The EMPA-REG OUTCOME trial demonstrated significant reductions in mortality and HF hospitalization risk in patients with type 2 diabetes (T2D) and cardiovascular disease with the antihyperglycemic agent, empagliflozin – a sodium glucose co-transporter 2 (SGLT2) inhibitor. The CANVAS trial subsequently reported a reduction in 3-point MACE (major adverse cardiovascular events) and HF hospitalization risk. While SGLT2 inhibition may have potential application beyond T2D, including HF, the mechanisms responsible for the cardioprotective effects of SGLT2 inhibitors remain incompletely understood. SGLT2 inhibition promotes natriuresis and osmotic diuresis, leading to plasma volume contraction and reduced preload, as well as decreases in blood pressure, arterial stiffness and afterload, thereby improving subendocardial blood flow in patients with HF. SGLT2 inhibition is also associated with preservation of renal function. Based on data from mechanistic studies and clinical trials, large clinical trials with SGLT2 inhibitors are now investigating the potential use of SGLT2 inhibition in patients with HF with and without T2D. Accordingly, in this review, we summarize key pharmacodynamic effects of SGLT2 inhibitors and the clinical evidence which support the rationale for the use of SGLT2 inhibitors in HF patients with T2D. Since presumably these favorable effects occur independent of blood-glucose lowering, we also explore the potential use of SGLT2 inhibition in patients without T2D with HF or at risk of HF, such as in patients with coronary artery disease or hypertension. Finally, we provide a detailed overview and summary of ongoing cardiovascular outcome trials with SGLT2 inhibitors.

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“…13,28 The higher use of statin in Denmark despite the least prevalent CVD population might also reflect the differences in organization and attitudes on CV prevention in T2D across countries. Overall, the regional use of older GLDs displayed opposite differences to the above as ex- commonly have trained staff available to handle initiation of insulin therapy.…”

Section: Regional Differences In Second-line Treatment Within Swedenmentioning

confidence: 99%

Different patterns of second‐line treatment in type 2 diabetes after metformin monotherapy in Denmark, Finland, Norway and Sweden (D360 Nordic): A multinational observational study

Persson

Bodegård

Lahtela

et al. 2018

Endocrino Diabet & Metabol

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Summary Aims The understanding of second‐line use of glucose‐lowering drugs (GLDs) in the general population with type 2 diabetes (T2D) treatment is important as recent results have shown cardiovascular benefits with sodium‐glucose cotransporter‐2 inhibitors (SGLT‐2i) and glucagon‐like peptide‐1 receptor agonists (GLP‐1RA). Our aim was to describe second‐line GLD treatment patterns in four Nordic countries. Methods All T2D patients treated with GLD between 2006 and 2015 were identified in prescribed drug registries in Denmark, Finland, Norway and Sweden, and linked with National Patient and Cause of Death Registries. Second‐line treatment was defined as a prescription of a second GLD class following ≥6 months of metformin monotherapy. Index was the date of first dispense of the second‐line drug. Results A rapid uptake of newer GLDs (GLP‐1RA, DPP‐4i and SGLT‐2i) over the 10‐year observation period was seen in Denmark, Finland and Norway, while slower in Sweden. In 2015, 33,880 (3.1%) of 1,078,692 T2D patients initiated second‐line treatment, and newer GLDs were more commonly used in Finland (92%), Norway (71%) and Denmark (70%) vs Sweden (44%). In 2015, the use of older GLDs (insulin and sulphonylureas) was 7‐fold greater in Sweden compared to Finland (49% vs 7%), and 1.6‐fold greater compared with Denmark and Norway (49% vs 30% and 29%, respectively). Conclusions Despite comparable demography and healthcare systems in four neighbouring countries, surprisingly large differences in second‐line use of newer GLDs were found. With recent evidence of potential cardiovascular benefits with newer GLDs, such differences may have an important impact on cardiovascular outcomes.

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Novel oral glucose‐lowering drugs are associated with lower risk of all‐cause mortality, cardiovascular events and severe hypoglycaemia compared with insulin in patients with type 2 diabetes

Cited by 75 publications

References 45 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?

Sodium Glucose Cotransporter-2 Inhibition in Heart Failure

Different patterns of second‐line treatment in type 2 diabetes after metformin monotherapy in Denmark, Finland, Norway and Sweden (D360 Nordic): A multinational observational study

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