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in licensed indications or safety perceptions/misunderstandings associated with historical data that have since been superseded by robust clinical evidence and long-term pharmacovigilance reporting.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

Assessing opinion on lower LDL-cholesterol lowering, and the role of newer lipid-reducing treatment options.

While statins are the gold standard for lipid-lowering therapies, newer therapies, such as PCSK9 inhibitors, have also demonstrated low-density lipoprotein cholesterol (LDL-C) reduction, but with a similar or better safety profile. Conflicting guidance has contributed to a low uptake. More up-to-date, evidence-led guidance supports greater use of newer therapies, particularly in combination with statins, to reduce LDL-C to levels shown to be effective in trials. The aim of this study was to determine how such guidance can be implemented more effectively in the UK. Using a modified Delphi approach, a panel of healthcare professionals with an interest in the management of dyslipidaemia developed 27 statements across four key themes. These were used to form an online survey that was distributed to healthcare professionals working in cardiovascular care across the UK. Stopping criteria included 100 responses received, a seven-month window for response (September 2021 to March 2022), and 90% of statements passing the predefined consensus threshold of 75%. A total of 109 responses were analysed with 23 statements achieving consensus (four statements <75%). Variance was observed across respondent role, and by UK region. From the high degree of consensus, seven recommendations were established as to how evidence-based guidance can be delivered, including a call for personalised therapy strategies and simplification of LDL-C goals, which should be achieved within as short a time as possible.

The Place and Value of Sodium-Glucose Cotransporter 2 Inhibitors in the Evolving Treatment Paradigm for Type 2 Diabetes Mellitus: A Narrative Review.

Over recent years, the expanding evidence base for sodium-glucose cotransporter-2 inhibitor (SGLT2i) therapies has revealed benefits beyond their glucose-lowering efficacy in the treatment of Type 2 diabetes mellitus (T2DM), resulting in their recognition as cardiorenal medicines. While SGLT2is continue to be recommended among the second-line therapies for the treatment of hyperglycaemia, their true value now extends to the prevention of debilitating and costly cardiovascular and renal events for high-risk individuals, with particular benefit shown in reducing major adverse cardiac events and heart failure (HF) and slowing the progression of chronic kidney disease. However, SGLT2i usage is still suboptimal among groups considered to be at greatest risk of cardiorenal complications. The ongoing coronavirus disease 2019 (COVID-19) pandemic has intensified financial pressures on healthcare systems, which may hamper further investment in newer effective medicines. Emerging evidence indicates that glycaemic control should be prioritised for people with T2DM in the era of COVID-19 and practical advice on the use of T2DM medications during periods of acute illness remains important, particularly for healthcare professionals working in primary care who face multiple competing priorities. This article provides the latest update from the Improving Diabetes Steering Committee, including perspectives on the value of SGLT2is as cost-effective therapies within the T2DM treatment paradigm, with particular focus on the latest published evidence relating to the prevention or slowing of cardiorenal complications. The implications for ongoing and future approaches to diabetes care are considered in the light of the continuing coronavirus pandemic, and relevant aspects of international treatment guidelines are highlighted with practical advice on the appropriate use of SGLT2is in commonly occurring T2DM clinical scenarios. The 'SGLT2i Prescribing Tool for T2DM Management', previously published by the Steering Committee, has been updated to reflect the latest evidence and is provided in the Supplementary Materials to help support clinicians delivering T2DM care.

The impact of the COVID pandemic on primary care diabetes services in the UK: A cross-sectional national survey of views of health professionals delivering diabetes care.

BACKGROUND: Healthcare systems worldwide have been adversely affected by the Coronavirus disease 2019 (COVID-19) pandemic. There has been a substantial decrease in admissions for acute medical conditions with longer delays between the onset of the symptoms and hospital treatment compared to the pre-pandemic period. The impact of the COVID pandemic on primary care services is uncertain. AIM: Using an online survey, we examined the impact of the COVID pandemic on primary care diabetes services in the UK. METHODS: An online survey was developed by the Primary Care Diabetes Society research group and administered to healthcare and allied health professionals delivering diabetes care in the UK from January to May 2021. Descriptive statistics and odds ratios (ORs) with 95% confidence intervals (CIs) were estimated. RESULTS: Of the 1070 professionals surveyed, 975 (91.1%) completed the questionnaire. Most respondents were nurses or nurse practitioners (59.7%) and doctors (32.9%). The mean age of respondents was 52 years and 79% were female. The majority of respondents felt overloaded with work (71.2%) or emotionally drained at the end of a working day (79.1%) compared with the pre-pandemic period. Being a doctor and worried about infecting a family member with the Coronavirus were each associated with an increased odds of being substantially overworked or emotionally drained: (OR = 2.52; 95% CI, 1.25-5.07) and (OR = 2.05; 95% CI, 1.24-3.39), respectively. The most common consultation method used to provide diabetes care during the pandemic was telephone consultation (92.0%). Overall 79.1% of respondents felt the COVID-19 pandemic had had moderate to significant impact on their practice's ability to provide routine diabetes care; 70.6% of respondents felt the COVID-19 pandemic had had moderate to significant impact on their practice's ability to provide routine health checks or screening for type 2 diabetes and approximately half of respondents (48.3%) reported encountering mental health concerns in people with diabetes. CONCLUSIONS: COVID-19 pandemic has had significant impact on the ability of healthcare professionals and their practices to deliver routine diabetes care. Failure to restore primary care provision urgently and safely to at least pre-pandemic levels in a sustainable manner may lead to emotionally drained and overworked workforce in primary care, place additional burden on the already overburdened healthcare system and worse outcomes for patients.

Risk Factors and Outcomes of Acute Cardio-renal Syndrome in a Tertiary Care Setting in South India.

AIMS AND OBJECTIVES: To study the incidence,risk factors and in hospital mortality of Type I Cardiorenal syndrome(CRS1). To study the incidence of hyperkalemia in patients receiving Acei, ARB's or MRA Materials and Methods: Prospective observational cohort study done between June and December 2015 in Madras Medical Mission, Chennai. Consecutive patients admitted with ACS/ADHF were studied and clinical, biochemical and laboratory data was collected. The development of CRS1 was determined by KDIGO criteria. Statistical analysis was done using IBM SPSS version 21. RESULTS: Among 460 patients studied, 153 (34%) developed CRS 1 according to KDIGO criteria. The number of diabetics and patients with pre-existing CKD was significantly higher in the CRS 1 group (p=0.00). Mortality was significantly higher in the CRS 1 group (20.2% vs. 7.8% p=0.00). The presence of CKD, Diabetes mellitus, inotropic requirement and eGFR, 60 ml/min/1.73 m2 were significant predictors of CRS 1. Among patients with CRS1, 55 patients (23.5%) needed renal replacement therapy (15.6 % acute peritoneal dialysis, 20.2% SLED). There was no significant difference in the incidence of hyperkalemia in patients who were on prior Acei, ARBs and MRA. CONCLUSION: There is a high incidence of CRS 1 in our setting and the mortality is significantly higher in this group of patients. Early nephrology referral and prompt stoppage of nephrotoxic agents can significantly reduce the incidence and risk of CRS1.

Glucagon-Like Peptide 1 Receptor Agonist Usage in Type 2 Diabetes in Primary Care for the UK and Beyond: A Narrative Review.

The scientific landscape of treatments for type 2 diabetes (T2D) has changed rapidly in the last decade with newer treatments becoming available. However, a large proportion of people with T2D are not able to achieve glycaemic goals because of clinical inertia. The majority of T2D management is in primary care, where clinicians (medical, nursing and pharmacist staff) play an important role in addressing patient needs and achieving treatment goals. However, management of T2D is challenging because of the heterogeneity of T2D and complexity of comorbidity, time constraints, guidance overload and the evolving treatments. Additionally, the current coronavirus disease pandemic poses additional challenges to the management of chronic diseases such as T2D, including routine access to patients for monitoring and communication. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are a class of agents that have evolved rapidly in recent years. These agents act in a glucose-dependent manner to promote insulin secretion and inhibit glucagon secretion, as well as enhancing satiety and reducing hunger. As a result, they are effective treatment options for people with T2D, achieving glycated haemoglobin reductions, weight loss and potential cardiovascular benefit, as monotherapy or as add-on to other glucose-lowering therapies. However, given the complexity of managing T2D, it is important to equip primary care clinicians with clear information regarding efficacy, safety and appropriate positioning of GLP-1 RA therapies in clinical practice. This review provides a summary of clinical and real-world evidence along with practical guidance, with the aim of aiding primary care clinicians in the initiation and monitoring of GLP-1 RAs to help ensure that desired outcomes are realised. Furthermore, a benefit/risk tool has been developed on the basis of current available evidence and guidelines to support primary care clinicians in selecting individuals who are most likely to benefit from GLP-1 RA therapies, in addition to indicating clinical situations where caution is needed.

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.

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.

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 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.

Therapeutic inertia amongst general practitioners with interest in diabetes.

INTRODUCTION: As the therapeutic options in the management of type 2 diabetes increase, there is an increase confusion among health care professionals, thus leading to the phenomenon of therapeutic inertia. This is the failure to escalate or de-escalate treatment when the clinical need for this is required. It has been studied extensively in various settings, however, it has never been reported in any studies focusing solely on primary care physicians with an interest in diabetes. This group is increasingly becoming the focus of managing complex diabetes care in the community, albeit with the support from specialists. METHODS: In this retrospective audit, we assessed the prevalence of the phenomenon of therapeutic inertia amongst primary care physicians with an interest in diabetes in UK. We also assessed the predictive abilities of various patient level characteristics on therapeutic inertia amongst this group of clinicians. RESULTS: Out of the 240 patients reported on, therapeutic inertia was judged to have occurred in 53 (22.1%) of patients. The full model containing all the selected variables was not statistically significant, p=0.59. So the model was not able to distinguish between situations in which therapeutic inertia occurred and when it did not occur. None of the patient level characteristics on its own was predictive of therapeutic inertia. CONCLUSION: Therapeutic inertia was present only in about a fifth of patient patients with diabetes being managed by primary care physicians with an interest in diabetes.

Major placenta praevia should not preclude out-patient management.

OBJECTIVE: To review current management of women with major and minor placenta praevia in view of the recommendations made in the RCOG guideline 2001. To assess whether out-patient care was detrimental to pregnancy outcome. STUDY DESIGN: Retrospective observational study at the Simpson Memorial Maternity Pavilion, Edinburgh (a tertiary referral centre). One hundred and sixty-one women with major and minor placenta praevia between 1994 and 2000 were separated into those who experienced bleeding (antepartum haemorrhage (APH)) and those who had no bleeding during pregnancy (non-APH). Statistical analysis was carried out using SPSS. RESULTS: There were 129 women (80%) in the APH group. Forty-three were out-patients at the time of delivery and 63% had a major degree of praevia. Thirty-two women were in the non-APH group. Sixty-eight were managed as out-patients and 50% had a major degree of praevia. Women with a major degree of praevia were not significantly more likely to experience bleeding. Women with APH were significantly more likely to be delivered early, by emergency caesarean section (C/S), of lower birthweight babies who required neonatal admission than the non-APH group. CONCLUSION: There is a place for out-patient management of women with placenta praevia. Caution is required with increasing number of bleeds but not degree of praevia.