Sodium-glucose transporter 2 inhibition and cardiovascular events in patients with diabetes: information from clinical trials and observational real-world data

Cardiovascular (CV) disease (CVD) is the main cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Despite optimal glycaemic control, standard antihyperglycaemic therapy failed to impact CV events in intervention trials; therefore, the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) issued a guidance to the pharmaceutical industry to specifically assess the CV outcomes and safety of new glucose-lowering drugs. Amongst them, sodium-glucose transporter 2 (SGLT2) inhibitors proved to not only provide good tolerance, few adverse effects, and good glycometabolic control, but also striking reduction in the risk of CV events. In this review, data from the main randomised controlled trials are presented, including post-hoc analyses looking into several aspects of CV protection. Moreover, the main findings from observational real-world studies to date are described, overall reassuring as regards to CV safety and efficacy of SGLT2 inhibitors. Finally, several mechanisms which might contribute to the cardioprotective effect of SGLT2 inhibition are depicted, including findings from recent mechanistic studies.

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The Value of Real-World Data in Understanding Prostate Cancer Risk and Improving Clinical Care: Examples from Swedish Registries

Cancers ◽

10.3390/cancers13040875 ◽

2021 ◽

Vol 13 (4) ◽

pp. 875

Author(s):

Kerri Beckmann ◽

Hans Garmo ◽

Ingela Franck Lissbrant ◽

Pär Stattin

Keyword(s):

Prostate Cancer ◽

Real World ◽

Clinical Care ◽

Prostate Cancer Risk ◽

Real World Data ◽

Level Of Evidence ◽

World Data ◽

Cancer Data ◽

Using Data ◽

Randomised Controlled

Real-world data (RWD), that is, data from sources other than controlled clinical trials, play an increasingly important role in medical research. The development of quality clinical registers, increasing access to administrative data sources, growing computing power and data linkage capacities have contributed to greater availability of RWD. Evidence derived from RWD increases our understanding of prostate cancer (PCa) aetiology, natural history and effective management. While randomised controlled trials offer the best level of evidence for establishing the efficacy of medical interventions and making causal inferences, studies using RWD offer complementary evidence about the effectiveness, long-term outcomes and safety of interventions in real-world settings. RWD provide the only means of addressing questions about risk factors and exposures that cannot be “controlled”, or when assessing rare outcomes. This review provides examples of the value of RWD for generating evidence about PCa, focusing on studies using data from a quality clinical register, namely the National Prostate Cancer Register (NPCR) Sweden, with longitudinal data on advanced PCa in Patient-overview Prostate Cancer (PPC) and data linkages to other sources in Prostate Cancer data Base Sweden (PCBaSe).

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Quality criteria for Real-World Data in pharmaceutical research and healthcare decision making. An Austrian Expert Consensus (Preprint)

10.2196/preprints.34204 ◽

2021 ◽

Author(s):

Peter Klimek ◽

Dejan Baltic ◽

Martin Brunner ◽

Alexander Degelsegger-Marquez ◽

Gerhard Garhöfer ◽

...

Keyword(s):

Decision Making ◽

Medical Research ◽

Real World ◽

Pharmaceutical Medicine ◽

Pharmaceutical Research ◽

Quality Criteria ◽

Clinical Decision ◽

European Medicines Agency ◽

Real World Data ◽

World Data

UNSTRUCTURED Real-world data (RWD) collected in routine healthcare processes and transformed to real-world evidence (RWE) has become increasingly interesting within research and medical communities to enhance medical research and support regulatory decision making. Despite numerous European initiatives, there is still no cross-border consensus or guideline determining which quality RWD must meet in order to be acceptable for decision making within regulatory or routine clinical decision support. An Austrian expert group led by GPMed (Gesellschaft für Pharmazeutische Medizin, Austrian Society for Pharmaceutical Medicine) reviewed drafted guidelines, published recommendations or viewpoints to derive a consensus statement on quality criteria for RWD to be used more effectively for medical research purposes beyond registry-based studies discussed in the European Medicines Agency (EMA) guideline for registry-based studies

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The Emerging Role of SGLT2 Inhibitors in the Treatment of Type 2 Diabetes. Focus on Dapagliflozin

Romanian Journal of Diabetes Nutrition and Metabolic Diseases ◽

10.1515/rjdnmd-2016-0014 ◽

2016 ◽

Vol 23 (1) ◽

pp. 113-120

Author(s):

Bogdan Timar ◽

Cristian Serafinceanu ◽

Adrian Vlad ◽

Romulus Timar

Keyword(s):

Type 2 Diabetes ◽

Glucose Transporter ◽

Diabetes Management ◽

Treatment Strategies ◽

Signs And Symptoms ◽

Sglt2 Inhibitors ◽

Glucose Transporter 2 ◽

Target Blood Glucose ◽

Attractive Therapeutic Target

AbstractType 2 diabetes is a progressive metabolic disorder, accounting for more than 90% of all cases of diabetes. Treatment strategies target blood glucose reduction and non-glycemic effects that can reduce long-term complications, such as cardiovascular disease. Although metformin is often initially effective as monotherapy, the progressive nature of diabetes frequently requires additional therapies. Sodium-glucose transporter 2 (SGLT2) became a very attractive therapeutic target in diabetes management. The mechanism of action of SGLT2 inhibitors is not dependent on insulin, thus making them attractive options anytime over the course of the disease. Dapagliflozin is a stable and highly selective inhibitor of SGLT2. The reductions in fasting plasma glucose concentration and bodyweight recorded during the first week of treatment in the dapagliflozin groups continued over weeks and years of treatment. Early weight loss with dapagliflozin might be partly due to a mild osmotic diuresis, while the gradual progressive reduction in bodyweight is consistent with a reduction of fat mass. Although dapagliflozin is well tolerated, signs and symptoms suggestive for urinary and/or genital infections were reported during clinical trials in more patients assigned to the drug than in placebo groups.

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Protocol for data extraction: how real-world data have been used in the National Institute for Health and Care Excellence appraisals of cancer therapy

BMJ Open ◽

10.1136/bmjopen-2021-055985 ◽

2022 ◽

Vol 12 (1) ◽

pp. e055985

Author(s):

Jiyeon Kang ◽

John Cairns

Keyword(s):

Real World ◽

Data Extraction ◽

Systematic Research ◽

London School ◽

Real World Data ◽

World Data ◽

Data Extraction Tool ◽

Potential Benefits ◽

Critical Components ◽

Randomised Controlled

IntroductionDue to the limitations of relying on randomised controlled trials, the potential benefits of real-world data (RWD) in enriching evidence for health technology assessment (HTA) are highlighted. Despite increased interest in RWD, there is limited systematic research investigating how RWD have been used in HTA. The main purpose of this protocol is to extract relevant data from National Institute for Health and Care Excellence (NICE) appraisals in a transparent and reproducible manner in order to determine how NICE has incorporated a broader range of evidence in the appraisal of oncology medicines.Methods and analysisThe appraisals issued between January 2011 and May 2021 are included following inclusion criteria. The data extraction tool newly developed for this research includes the critical components of economic evaluation. The information is extracted from identified appraisals in accordance with extraction rules. The data extraction tool will be validated by a second researcher independently. The extracted data will be analysed quantitatively to investigate to what extent RWD have been used in appraisals. This is the first protocol to enable data to be extracted comprehensively and systematically in order to review the use of RWD.Ethics and disseminationThis study is approved by the Ethics Committee of the London School of Hygiene and Tropical Medicine on 14 November 2019 (17315). Results will be published in peer-reviewed journals.

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88-LB: Kidney and Metabolic Benefits by Adding GLP-1 Agonists and/or SGLT2 Inhibitors on Metformin in Obese Type 2 Diabetes (T2DM) Patients: 24-Month Real-World Data from Both Urban and Rural Clinics

Diabetes ◽

10.2337/db21-88-lb ◽

2021 ◽

Vol 70 (Supplement 1) ◽

pp. 88-LB

Author(s):

IOANNIS ZOUPAS ◽

ATHANASIA PAPAZAFIROPOULOU ◽

MARIA XENOU ◽

DIMITRIOS LYGNOS ◽

EVANGELOS FOUSTERIS

Keyword(s):

Type 2 Diabetes ◽

Real World ◽

Sglt2 Inhibitors ◽

Real World Data ◽

World Data ◽

Rural Clinics

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Pharmacoeconomic evaluation of sodium-glucose transporter-2 (SGLT2) inhibitors for the treatment of type 2 diabetes

Expert Opinion on Pharmacotherapy ◽

10.1080/14656566.2018.1543408 ◽

2018 ◽

Vol 20 (2) ◽

pp. 151-161 ◽

Cited By ~ 6

Author(s):

Wedad Rahman ◽

Paul Joseph Solinsky ◽

Kashif M. Munir ◽

Elizabeth M. Lamos

Keyword(s):

Type 2 Diabetes ◽

Glucose Transporter ◽

Pharmacoeconomic Evaluation ◽

Sglt2 Inhibitors ◽

Glucose Transporter 2

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Use of Healthcare Services Following Severe Hypoglycemia in Patients with Diabetes: Analysis of Real-World Data

Diabetes Therapy ◽

10.1007/s13300-016-0169-8 ◽

2016 ◽

Vol 7 (2) ◽

pp. 295-308 ◽

Cited By ~ 9

Author(s):

Dalit Goldstein ◽

Gabriel Chodick ◽

Varda Shalev ◽

Brian L. Thorsted ◽

Lisa Elliott ◽

...

Keyword(s):

Real World ◽

Severe Hypoglycemia ◽

Healthcare Services ◽

Real World Data ◽

World Data ◽

Patients With Diabetes

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What type of clinical evidence is needed to assess medical devices?

European Respiratory Review ◽

10.1183/16000617.0016-2016 ◽

2016 ◽

Vol 25 (141) ◽

pp. 259-265 ◽

Cited By ~ 17

Author(s):

Rosanna Tarricone ◽

Paola Roberta Boscolo ◽

Patrizio Armeni

Keyword(s):

Medical Therapy ◽

Real World ◽

Clinical Evidence ◽

Experimental Studies ◽

Bias Reduction ◽

Economic Evaluations ◽

Real World Data ◽

Relevant Evidence ◽

Randomised Controlled ◽

Matching Techniques

The objective of this mini-review is to discuss the role of real-world studies as a source of clinical evidence when experimental studies, such as randomised controlled trials (RCTs), are not available. Waiting for RCT evidence when the technology is diffusing could be anti-economical, inefficient from the policy perspective and methodologically questionable.We explain how real-world studies could provide relevant evidence to decision makers. Matching techniques are discussed as a viable solution for bias reduction.We describe a case study concerning a cost-effectiveness analysis based on real-world data of a technology already in use: Mitraclip combined with medical therapy versus medical therapy alone in patients with moderate-to-severe mitral regurgitation. The CEA has encountered the scepticism of most reviewers, due not to the statistical methodology but to the fact that the study was observational and not experimental. Editors and reviewers converged in considering real-world economic evaluations premature in the absence of a RCT, even if in the meantime the technology had been implanted >30 000 times. We believe there is a need to acknowledge the importance of real-world studies, and engage the scientific community in the promotion and use of clinical evidence produced through observational studies.

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