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

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in licensed indications or safety perceptions/misunderstandings associated with historical data that have since been superseded by robust clinical evidence and long-term pharmacovigilance reporting.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.

Digital Interventions Supporting Self-care in People With Type 2 Diabetes Across Greater Manchester (Greater Manchester Diabetes My Way): Protocol for a Mixed Methods Evaluation.

BACKGROUND: Type 2 Diabetes (T2D) is common, with a prevalence of approximately 7% of the population in the United Kingdom. The quality of T2D care is inconsistent across the United Kingdom, and Greater Manchester (GM) does not currently achieve the National Institute for Health and Care Excellence treatment targets. Barriers to delivery of care include low attendance and poor engagement with local T2D interventions, which tend to consist of programs of education delivered in traditional, face-to-face clinical settings. Thus, a flexible approach to T2D management that is accessible to people from different backgrounds and communities is needed. Diabetes My Way (DMW) is a digital platform that offers a comprehensive self-management and educational program that should be accessible to a wide range of people through mobile apps and websites. Building on evidence generated by a Scotland-wide pilot study, DMW is being rolled out and tested across GM. OBJECTIVE: The overarching objectives are to assess whether DMW improves outcomes for patients with T2D in the GM area, to explore the acceptability of the DMW intervention to stakeholders, and to assess the cost-effectiveness of the intervention. METHODS: A mixed methods approach will be used. We will take a census approach to recruitment in that all eligible participants in GM will be invited to participate. The primary outcomes will be intervention-related changes compared with changes observed in a matched group of controls, and the secondary outcomes will be within-person intervention-related changes. The cost-effectiveness analysis will focus on obtaining reliable estimates of how each intervention affects risk factors such as HbA1c and costs across population groups. Qualitative data will be collected via semistructured interviews and focus groups and organized using template analysis. RESULTS: As of May 10, 2021, a total of 316 participants have been recruited for the quantitative study and have successfully enrolled. A total of 278 participants attempted to register but did not have appropriate permissions set by the general practitioners to gain access to their data. In total, 10 participants have been recruited for the qualitative study (7 practitioners and 3 patients). An extension to recruitment has been granted for the quantitative element of the research, and analysis should be complete by December 2022. Recruitment and analysis for the qualitative study should be complete by December 2021. CONCLUSIONS: The findings from this study can be used both to develop the DMW system and improve accessibility and usability in more deprived populations generally, thus improving equity in access to support for T2D self-management. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/26237.

Impact of COVID-19 restrictions on diabetes health checks and prescribing for people with type 2 diabetes: a UK-wide cohort study involving 618 161 people in primary care.

OBJECTIVE: To compare rates of performing National Institute for Health and Care Excellence-recommended health checks and prescribing in people with type 2 diabetes (T2D), before and after the first COVID-19 peak in March 2020, and to assess whether trends varied by age, sex, ethnicity and deprivation. METHODS: We studied 618 161 people with T2D followed between March and December 2020 from 1744 UK general practices registered with the Clinical Practice Research Datalink. We focused on six health checks: haemoglobin A1c, serum creatinine, cholesterol, urinary albumin excretion, blood pressure and body mass index assessment. Regression models compared observed rates in April 2020 and between March and December 2020 with trend-adjusted expected rates derived from 10-year historical data. RESULTS: In April 2020, in English practices, rates of performing health checks were reduced by 76%-88% when compared with 10-year historical trends, with older people from deprived areas experiencing the greatest reductions. Between May and December 2020, the reduced rates recovered gradually but overall remained 28%-47% lower, with similar findings in other UK nations. Extrapolated to the UK population, there were ~7.4 million fewer care processes undertaken March-December 2020. In England, rates for new medication fell during April with reductions varying from 10% (95% CI: 4% to 16%) for antiplatelet agents to 60% (95% CI: 58% to 62%) for antidiabetic medications. Overall, between March and December 2020, the rate of prescribing new diabetes medications fell by 19% (95% CI: 15% to 22%) and new antihypertensive medication prescribing fell by 22% (95% CI: 18% to 26%), but prescribing of new lipid-lowering or antiplatelet therapy was unchanged. Similar trends were observed across the UK, except for a reduction in new lipid-lowering therapy prescribing in the other UK nations (reduction: 16% (95% CI: 10% to 21%)). Extrapolated to the UK population, between March and December 2020, there were ~31 800 fewer people with T2D prescribed a new type of diabetes medication and ~14 600 fewer prescribed a new type of antihypertensive medication. CONCLUSIONS: Over the coming months, healthcare services will need to manage this backlog of testing and prescribing. We recommend effective communications to ensure patient engagement with diabetes services, monitoring and opportunities for prescribing, and when appropriate use of home monitoring, remote consultations and other innovations in care.

SGLT2 Inhibitors: Slowing of Chronic Kidney Disease Progression in Type 2 Diabetes.

Diabetic kidney disease (DKD) is a topic of increasing concern among clinicians involved in the management of type 2 diabetes mellitus (T2DM). It is a progressive and costly complication associated with increased risk of adverse cardiovascular (CV) and renal outcomes and mortality. Ongoing monitoring of the estimated glomerular filtration (eGFR) rate alongside the urine albumin:creatinine ratio (ACR) is recommended during regular T2DM reviews to enable a prompt DKD diagnosis or to assess disease progression, providing an understanding of adverse risk for each individual. Many people with DKD will progress to end-stage kidney disease (ESKD), requiring renal replacement therapy (RRT), typically haemodialysis or kidney transplantation. A range of lifestyle and pharmacological interventions is recommended to help lower CV risk, slow the advancement of DKD and prevent or delay the need for RRT. Emerging evidence concerning sodium-glucose co-transporter-2 inhibitor (SGLT2i) agents suggests a role for these medicines in slowing eGFR decline, enabling regression of albuminuria and reducing progression to ESKD. Improvements in renal end points observed in SGLT2i CV outcome trials (CVOTs) highlighted the possible impact of these agents in the management of DKD. Data from the canagliflozin CREDENCE trial (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) have since demonstrated the effectiveness of this medicine in reducing the risk of kidney failure and CV events in a population comprising individuals with T2DM and renal disease. CREDENCE was the first SGLT2i study to examine renal outcomes as the primary end point. Real-world studies have reaffirmed these outcomes in routine clinical practice. This article summarises the evidence regarding the use of SGLT2i medicines in slowing the progression of DKD and examines the possible mechanisms underpinning the renoprotective effects of these agents. The relevant national and international guidance for monitoring and treatment of DKD is also highlighted to help clinicians working to support this vulnerable group.

Correction to: SGLT2 Inhibitors: Cardiovascular Benefits Beyond HbA1c-Translating Evidence into Practice.

In the original publication, Table 2 note was incorrectly published as "SGLT2i therapies may be initiated in people with eGFR 60 mL/min/1.73 m2. Individuals already treated with canagliflozin or empagliflozin who demonstrate renal decline may continue treatment until eGFR reaches < 45 mL/min/1.73 m2".

SGLT2 Inhibitors: Cardiovascular Benefits Beyond HbA1c-Translating Evidence into Practice.

Cardiovascular disease (CVD), including heart failure (HF), is a leading cause of morbidity and mortality in people with type 2 diabetes mellitus (T2DM). CVD and T2DM share common risk factors for development and progression, and there is significant overlap between the conditions in terms of worsening outcomes. In assessing the cardiovascular (CV) safety profiles of anti-diabetic drugs, sodium-glucose co-transporter-2 inhibitor (SGLT2i) therapies have emerged with robust evidence for reducing the risk of adverse CVD outcomes in people with T2DM who have either established CVD or are at risk of developing CVD. A previous consensus document from the Improving Diabetes Steering Committee has examined the potential role of SGLT2is in T2DM management and considered the risk-benefit profile of the class and the appropriate place for these medicines within the T2DM pathway. This paper builds on these findings and presents practical guidance for maximising the pleiotropic benefits of this class of medicines in people with T2DM in terms of reducing adverse CVD outcomes. The Improving Diabetes Steering Committee aims to offer evidence-based practical guidance for the use of SGLT2i therapies in people with T2DM stratified by CVD risk. This is of particular importance currently because some treatment guidelines have not been updated to reflect recent evidence from cardiovascular outcomes trials (CVOTs) and real-world studies that complement the CVOTs. The Improving Diabetes Steering Committee seeks to support healthcare professionals (HCPs) in appropriate treatment selection for people with T2DM who are at risk of developing or have established CVD and examines the role of SGLT2i therapy for these people.Funding: Napp Pharmaceuticals Limited.

SGLT2 Inhibitors in Type 2 Diabetes Management: Key Evidence and Implications for Clinical Practice.

Management of type 2 diabetes mellitus (T2DM) is complex and challenging, particularly for clinicians working in primary care who are faced with many competing clinical priorities. The range of available T2DM treatments has diversified significantly in recent years, generating a busy and data-rich environment in which evidence is rapidly evolving. Sodium-glucose cotransporter-2 inhibitor (SGLT2i) agents are a relatively new class of oral glucose-lowering therapy that have been available in the UK for approximately 5 years. These agents reduce the reabsorption of glucose in the kidney and increase its excretion via the urine. Conflicting messages and opinions within the clinical community have led to misconceptions concerning the efficacy, safety and appropriate position of SGLT2i therapies within the T2DM treatment pathway. To help address some of these concerns and provide advice regarding the appropriate place of these medicines in clinical practice, the Improving Diabetes Steering Committee was formed. The Committee worked together to develop this review article, providing a summary of relevant data regarding the use of SGLT2i medicines and focusing on specific considerations for appropriate prescribing within the T2DM management pathway. In addition, a benefit/risk tool has been provided (see Fig. 3) that summarises many of the aspects discussed in this review. The tool aims to support clinicians in identifying the people most likely to benefit from SGLT2i treatments, as well as situations where caution may be required. FUNDING: Napp Pharmaceuticals Limited.

Contour and volume assessment of repairing mandibular osteoperiosteal continuity defects in sheep using recombinant human osteogenic protein 1.

BACKGROUND: This study describes the contour and volume of reconstructed mandibles using recombinant human osteogenic protein 1. MATERIAL AND METHODS: The investigation was conducted on six adult sheep, where a unilateral 35 mm parasymphyseal osteoperiosteal continuity defect of the mandible was created. Recombinant human osteogenic protein 1 and type-I collagen (as carrier) were applied to the defects. Radiographic and ultrasonographic examinations were carried out at day 1 of the surgery and 2, 4, 8, and 12 weeks following the surgery. The animals were then sacrificed 3 months after the operation. Postmortem CT-scan was performed for volumetric, cross-sectional area, height and width measurements. RESULTS: Ultrasound was more efficient than radiographs in demonstrating early callus formation at 2 weeks, while radiographic evidence of bone formation was consistently detectable only after 4 weeks. Using the combination of recombinant human osteogenic protein type 1 and type-I collagen resulted in twice the volume, cross-sectional surface area, and height when compared with those of the corresponding region of the contra-lateral non-operated side of the mandible. CONCLUSION: Within 3 months, recombinant human osteogenic protein type 1 on type-I collagen carrier failed to restore the original contour and volume of mandibular osteoperiosteal continuity defects.