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in licensed indications or safety perceptions/misunderstandings associated with historical data that have since been superseded by robust clinical evidence and long-term pharmacovigilance reporting.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

Risk of Stroke in Real-World US Individuals with Type 2 Diabetes Receiving Semaglutide or a Dipeptidyl Peptidase 4 Inhibitor.

INTRODUCTION: People with type 2 diabetes (T2D) have a higher risk of stroke and worse outcomes than those without T2D. Pooled data from randomized controlled trials indicate that the glucagon-like peptide 1 receptor agonist semaglutide is associated with stroke risk reduction in people with T2D at high cardiovascular risk. We compared real-world stroke risk in people with T2D or T2D plus atherosclerotic cardiovascular disease (ASCVD) initiating either semaglutide or a dipeptidyl peptidase 4 inhibitor (DPP4i). METHODS: Adults (≥ 18 years old) in a US claims database with a claim indicating initiation of either semaglutide or a DPP4i (index date) during the index period (1 January 2018-30 September 2020), a diagnosis code for T2D on or before the index date and at least 12 months' continuous enrolment in the database pre-index were included and propensity score matched 1:1 on baseline demographic and clinical characteristics. The primary outcome was time to first stroke event during follow-up. Healthcare resource utilization was also compared between groups. RESULTS: The analysis included 17,920 matched pairs with T2D and 4234 matched pairs with T2D and ASCVD. The groups were well matched on baseline characteristics. People initiating semaglutide had a lower risk of stroke over short-term follow-up than those initiating a DPP4i (T2D: hazard ratio 0.63 [95% confidence interval 0.41-0.95], p = 0.029; T2D plus ASCVD: 0.45 [0.24-0.86], p = 0.015). Semaglutide was also associated with a lower rate of inpatient, outpatient and emergency room visits compared with a DPP4i. CONCLUSION: This proof-of-concept analysis indicates that semaglutide has the potential to reduce the risk of stroke in people with T2D when prescribed in clinical practice.

Cardiovascular and renal outcomes of GLP-1 receptor agonists vs. DPP-4 inhibitors and basal insulin in type 2 diabetes mellitus: A systematic review and meta-analysis.

OBJECTIVE: To compare the cardiovascular and renal outcomes of GLP-1 RA versus DPP4i and basal insulin in the management of T2DM. METHODS: Data from 22 studies involving over 200,000 participants were pooled using the inverse variance method and random-effects meta-analysis. The review was reported in accordance with PRISMA. RESULTS: Compared with DPP4i, treatment with GLP-1 RA was associated with a greater benefit on composite cardiovascular outcomes (HR:0.77, 95% CI:0.69-0.87), myocardial infarction (HR:0.82, 95% CI:0.69-0.97), stroke (HR:0.83, 95% CI: 0.74-0.93), cardiovascular mortality (HR:0.76, 95% CI:0.68-0.85) and all-cause mortality (HR:0.65, 95% CI:0.48-0.90). There was no difference in effect on heart failure (HR:0.97, 95% CI:0.82-1.15). Compared with basal insulin, GLP-1 RA was associated with better effects on composite cardiovascular outcomes (HR:0.62, 95% CI:0.48-0.79), heart failure (HR:0.57, 95% CI:0.35-0.92), myocardial infarction (HR:0.70, 95% CI:0.58-0.85), stroke (HR:0.50, 95% CI:0.40-0.63) and all-cause mortality (HR:0.31, 95% CI:0.20-0.48). Evidence from a small number of studies suggests that GLP-1 RA had better effects on composite and individual renal outcomes, such as eGFR, compared with either DPP4i and basal insulin. CONCLUSION: Available evidence suggests that treating T2DM with GLP-1 RA can yield better benefits on composite and specific cardiorenal outcomes than with DPP4i and basal insulin. PROSPERO REGISTRATION NUMBER: CRD42022335504.

Real-world costs of obesity-related complications over eight years: a US retrospective cohort study in 28,500 individuals.

BACKGROUND: Obesity-related complications (ORCs) are associated with high costs for healthcare systems. We assessed the relationship between comorbidity burden, represented by both number and type of 14 specific ORCs, and total healthcare costs over time in people with obesity in the USA. METHODS: Adults (≥ 18 years old) identified from linked electronic medical records and administrative claims databases, with a body mass index measurement of 30-< 70 kg/m2 between 1 January 2007 and 31 March 2012 (earliest measurement: index date), and with continuous enrolment for ≥ 1 year pre index (baseline year) and ≥ 8 years post index, were included. Individuals were grouped by type and number of ORCs during the pre-index baseline year. The primary outcome was annual total adjusted direct per-person healthcare costs. RESULTS: Of 28,583 included individuals, 12,686 had no ORCs, 7242 had one ORC, 4180 had two ORCs and 4475 had three or more ORCs in the baseline year. Annual adjusted direct healthcare costs increased with the number of ORCs and over the 8-year follow-up. Outpatient costs were the greatest contributor to baseline annual direct costs, irrespective of the number of ORCs. For specific ORCs, costs generally increased gradually over the follow-up; the largest percentage increases from year 1 to year 8 were observed for chronic kidney disease (+ 78.8%) and type 2 diabetes (+ 47.8%). CONCLUSIONS: In a US real-world setting, the number of ORCs appears to be a cost driver in people with obesity, from the time of initial obesity classification and for at least the following 8 years.

Obesity-related complications, healthcare resource use and weight loss strategies in six European countries: the RESOURCE survey.

BACKGROUND: Obesity-related complications (ORCs), such as type 2 diabetes (T2D) and cardiovascular disease, contribute considerably to the clinical and economic impacts of obesity. To obtain a holistic overview of health and weight management attempts for people with obesity in Europe, we designed the cross-sectional RESOURCE survey to collect data on comorbidities, healthcare resource use (HCRU) and weight loss strategies from people with obesity in France, Germany, Italy, Spain, Sweden and the UK. METHODS: Adults (≥18 years old) with self-reported body mass index (BMI) ≥30 kg/m2 who reported interacting with primary or secondary healthcare services in the past 12 months, but had not been pregnant during this time, were recruited from an existing consumer research panel. All data were self-reported via an online survey (May-June 2021). Weight changes over the past year were calculated from participants' estimated weights. RESULTS: Of the 1850 participants in the survey, 26.3% reported that they had ≥3 ORCs from a set of 15 conditions of interest. The most frequently reported ORCs were hypertension (39.3% of participants), dyslipidaemia (22.8%) and T2D (17.5%). Participants in obesity class III (BMI 40 to <70 kg/m2) were more likely to report multiple ORCs than those in lower obesity classes. The presence of multiple ORCs was linked to various types of HCRU, including a significantly increased chance of reporting hospitalization in the past year. Most participants (78.6%) had attempted to lose weight in the past year, but of those who also reported estimated weight changes, 73.4% had not experienced clinically meaningful weight loss of ≥5%. CONCLUSIONS: ORCs are common in people with obesity, and are linked to increased HCRU. Together with the low reported success rate of weight loss attempts, this highlights an unmet need in Europe for enhanced weight management support for people with obesity.

Evaluating the Long-Term Cost-Effectiveness of Once-Weekly Semaglutide 1 mg Versus Liraglutide 1.8 mg: A Health Economic Analysis in the UK.

INTRODUCTION: Glucagon-like peptide-1 (GLP-1) receptor agonists represent highly efficacious treatment options for type 2 diabetes. Liraglutide was amongst the first authorised for use in 2010, but once-weekly semaglutide represents the most efficacious GLP-1 analogue currently available for type 2 diabetes. The aim of the present analysis was therefore to evaluate the long-term cost-effectiveness of once-weekly semaglutide 1 mg versus liraglutide 1.8 mg with a lowered acquisition cost in the UK, as potentially lower cost liraglutide formulations may soon be developed. METHODS: Outcomes were projected over patients' lifetimes using the IQVIA Core Diabetes Model (v9.0). Baseline cohort characteristics were sourced from SUSTAIN 2, with changes in HbA1c, blood pressure and body mass index applied from a network meta-analysis, in which SUSTAIN 2 was used to inform the semaglutide arm. Modelled patients received semaglutide or liraglutide for 3 years, after which treatment was intensified to basal insulin. Costs were accounted from a healthcare payer perspective and expressed in 2021 pounds sterling (GBP). The acquisition cost of liraglutide was reduced by 33% compared with the currently marketed formulation. RESULTS: Life expectancy and quality-adjusted life expectancy were projected to improve with once-weekly semaglutide 1 mg, by 0.05 years and 0.06 quality-adjusted life years, respectively, versus liraglutide 1.8 mg. Clinical benefits were due to a reduced incidence of diabetes-related complications with semaglutide. Direct costs were estimated to be GBP 280 lower with semaglutide, entirely because of avoidance of diabetes-related complications versus liraglutide. Semaglutide 1 mg was therefore considered dominant versus liraglutide 1.8 mg, even with the liraglutide price reduced by 33%. CONCLUSION: Once-weekly semaglutide 1 mg is likely to represent a dominant treatment option versus liraglutide 1.8 mg for the treatment of type 2 diabetes in the UK, even with the liraglutide price reduced by 33%.

Estimating the value of sodium-glucose cotransporter-2 inhibitors within the context of contemporary guidelines and the totality of evidence.

AIMS: To comprehensively estimate the cost-effectiveness of sodium glucose cotransporter-2 (SGLT2) inhibitor usage in the management of type 2 diabetes mellitus (T2DM) at established clinical review points, incorporating the totality of proven health benefits. MATERIALS AND METHODS: This study considered the cardio- and reno-protective effects of SGLT2 inhibitors using the Cardiff type 2 diabetes model. Conventional cost-effectiveness evaluations were undertaken for eligible populations at relevant intensification points reflecting the 2022 guidelines versus the 2015 National Institute of Health and Care Excellence (NICE) guidelines; incremental cost-effectiveness ratio lifetime trajectories and timepoints for complete cost-offset were estimated for each pathway. Treatment effects, utility decrements and costs (applied additively and discounted at 3.5%) were sourced from the published literature. RESULTS: For all subpopulations on treatment pathways reflecting the NG28-2022 guidelines, SGLT2 inhibitor introduction was cost-effective, becoming cost-saving between 2 and 16 years post-initiation. Despite increases in pharmacy costs, predicted lifetime costs were lower than for pathways reflecting the NG28-2015 guidelines, driven by a reduction in heart failure hospitalization and chronic kidney disease costs. Incremental gains in quality-adjusted life years (ranging from 0.58-1.12) resulted in dominance for the updated NG28-2022 guidance in all scenarios. CONCLUSIONS: Our results show that SGLT2 inhibitors have the potential to lower healthcare costs while improving health outcomes in eligible patient subpopulations.

Stroke Prevention and Treatment in People With Type 2 Diabetes: Is There a Role for GLP-1 (Glucagon-Like Peptide-1) Analogues?

Stroke is a leading cause of disability and death, and people with type 2 diabetes (T2D) have a greater risk of stroke and death or disability from stroke. The underlying pathophysiology associating stroke and T2D is complicated by the association of risk factors for stroke frequently seen in people with T2D. Treatments to reduce the excess risk of new-onset stroke or to improve outcomes in people with T2D following stroke would be of major clinical interest. In practice, the focus of care in people with T2D remains treating risk factors for stroke, such as lifestyle and pharmacological interventions for hypertension, dyslipidemia, obesity, and glycemic control. More recently, cardiovascular outcome trials primarily designed to assess the cardiovascular safety of GLP-1RAs (glucagon-like peptide-1 receptor analogues) have consistently observed a reduced stroke risk in people with T2D. This is supported by several meta-analyses of cardiovascular outcome trials observing clinically important risk reductions in stroke. Moreover, phase II trials have described reductions in poststroke hyperglycemia in people with acute ischemic stroke suggestive of improved outcomes following admission to hospital with acute stroke. In this review, we discuss the increased risk of stroke in people with T2D and outline the key associated mechanisms responsible. We discuss the evidence from cardiovascular outcome trials exploring GLP-1RA use and highlight areas of potential interest for future work in this rapidly developing area of clinical research.

Eight-year trends in obesity-related complications and health care cost progression in a US population with obesity: A retrospective cohort study.

AIMS: Obesity-related complications (ORCs) impose a substantial health burden on affected individuals, and economic costs to health care systems. We examined ORCs and the progression of direct health care costs over 8 years, stratified by obesity class. MATERIALS AND METHODS: Adults with obesity were identified in linked US medical records and administrative claims databases. The index date was the first body mass index measurement of 30 to <70 kg/m2 between 1 January 2007 and 31 March 2012; a ≥8-year continuous enrolment post-index was required for inclusion. Diagnosis codes for five specific ORCs and total health care costs were recorded in each year of follow-up. Costs adjusted for clinical and demographic factors were also estimated. RESULTS: Of 28 583 eligible individuals, 17 892 had class I obesity, 6550 had class II obesity and 4141 had class III obesity. From baseline to year 8, the presence of type 2 diabetes and knee osteoarthritis doubled in all obesity classes, with even larger increases for chronic kidney disease and heart failure. Observed and adjusted total health care costs generally increased from the baseline year to year 8. The difference in costs between obesity classes increased over time: at year 1, individuals with class III obesity had 26.8% higher costs than those in class I, but at year 8, this difference was 40.7%. Outpatient costs constituted half of the total observed costs across obesity classes. CONCLUSIONS: ORC rates and health care costs increase over time, and are greater in higher obesity classes. This could be mitigated by approaches that limit obesity progression.

Once-weekly semaglutide versus insulin aspart for the treatment of type 2 diabetes in the UK: A long-term cost-effectiveness analysis based on SUSTAIN 11.

AIM: To evaluate the long-term cost-effectiveness of once-weekly semaglutide 1 mg versus insulin aspart in the UK. MATERIALS AND METHODS: Long-term outcomes were projected over patients' lifetimes using the IQVIA CORE Diabetes Model (vers 9.0). SUSTAIN 11 was used to inform baseline cohort characteristics and treatment effects. Patients were modelled to receive once-weekly semaglutide plus basal insulin for 3 years before intensifying to basal-bolus insulin, compared with basal-bolus insulin for lifetimes in the aspart arm. Costs were accounted from a healthcare payer perspective in the UK, expressed in 2021 pounds sterling (GBP). RESULTS: Once-weekly semaglutide 1 mg was associated with improvements in quality-adjusted life expectancy of 0.18 quality-adjusted life years (QALYs) versus insulin aspart, due to a reduced incidence and delayed time to onset of diabetes-related complications. Direct costs were estimated to be GBP 800 higher with semaglutide, with higher treatment costs partially offset by cost savings from avoidance of diabetes-related complications. Once-weekly semaglutide 1 mg was therefore associated with an incremental cost-effectiveness ratio of GBP 4457 per QALY gained versus insulin aspart. CONCLUSIONS: Based on a willingness-to-pay threshold of GBP 20 000 per QALY gained, once-weekly semaglutide 1 mg was projected to be highly cost-effective versus insulin aspart for the treatment of type 2 diabetes in the UK.

The challenges and pitfalls of incorporating evidence from cardiovascular outcomes trials in health economic modelling of type 2 diabetes.

The clinical evidence base for evaluating modern type 2 diabetes interventions has expanded greatly in recent years, with numerous efficacious treatment options available (including dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors). The cardiovascular safety of these interventions has been assessed individually versus placebo in numerous cardiovascular outcomes trials (CVOTs), statistically powered to detect differences in a composite endpoint of major adverse cardiovascular events. There have been growing calls to incorporate these data in the long-term modelling of type 2 diabetes interventions because current diabetes models were developed prior to the conduct of the CVOTs and therefore rely on risk equations developed in the absence of these data. However, there are numerous challenges and pitfalls to avoid when using data from CVOTs. The primary concerns are around the heterogeneity of the trials, which have different study durations, inclusion criteria, rescue medication protocols and endpoint definitions; this results in significant uncertainty when comparing two or more interventions evaluated in separate CVOTs, as robust adjustment for these differences is difficult. Analyses using CVOT data inappropriately can dilute clear evidence from head-to-head clinical trials, and blur healthcare decision making. Calibration of existing models may represent an approach to incorporating CVOT data into diabetes modelling, but this can only offer a valid comparison of one intervention versus placebo based on a single CVOT. Ideally, model development should utilize patient-level data from CVOTs to prepare novel risk equations that can better model modern therapies for type 2 diabetes.

The role of sodium-glucose co-transporter-2 inhibitors in frail older adults with or without type 2 diabetes mellitus.

Sodium-glucose co-transporter-2 (SGLT2) inhibitors offer significant outcome benefits beyond glucose lowering, including reduced risk of cardiovascular death, all-cause mortality, major adverse cardiovascular events, hospitalisations for heart failure and progression of renal disease. Considering these therapeutic effects, minimal incremental risk for hypoglycaemia and simplicity of administration, this drug class appears to be an attractive therapeutic option for older adults, and post hoc analysis of trial data provides support for the use of SGLT2 inhibitors in this population. Nevertheless, despite favourable clinical trial data, there has been some hesitance in clinical practice prescribing these drugs to older frail adults due to the limited therapeutic experience in this population and insufficient long-term safety data. In this review article, we evaluate the risk-benefit profile for the use of SGLT2 inhibitors in this population and suggest that rather than being a treatment to avoid, SGLT2 inhibitors should be considered a valid therapeutic option for older frail adults with or without diabetes.

Healthcare costs and hospitalizations in US patients with type 2 diabetes and cardiovascular disease: A retrospective database study (OFFSET).

AIM: To investigate the budget implications of treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) versus other glucose-lowering treatment (here termed 'standard of care' [SoC]) during 2012-2019. MATERIALS AND METHODS: GLP-1 RA-naïve adults with type 2 diabetes (T2D) in the IBM MarketScan database with at least one glucose-lowering medication claim within 6 months after their first cardiovascular disease (CVD) hospitalization were included (index date was the date of first claim for a GLP-1 RA for the GLP-1 RA group, and the date of the first claim, independent of medication type, for the SoC group). Monthly healthcare costs and hospitalization risk over 12 months postindex date were compared for those who initiated a GLP-1 RA posthospitalization versus those with a claim for any other glucose-lowering medication. RESULTS: Postindex date, mean observed total costs were lower for patients receiving a GLP-1 RA compared with SoC ($3853 vs. $4288). In adjusted analysis, both groups had similar total healthcare costs (P = .56). This was driven by significantly lower inpatient and outpatient costs and higher drug costs in the GLP-1 RA group compared with SoC (P < .001). Risks of all-cause (adjusted hazard ratio: 0.85) and CVD-related hospitalization (0.76) were significantly lower in the GLP-1 RA group compared with SoC (P < .001). Similar results were observed in a subgroup with atherosclerotic CVD. CONCLUSIONS: These findings suggest that, in US patients with T2D and a CVD-related hospitalization, the added medical cost of treatment with GLP-1 RAs is offset by lower inpatient and outpatient care costs, resulting in budget neutrality against SoC.

Serum potassium variability as a predictor of clinical outcomes in patients with cardiorenal disease or diabetes: a retrospective UK database study.

Background: Hyperkalaemia is an electrolyte abnormality associated with adverse clinical outcomes; however, few studies have investigated the relationship with patterns of hyperkalaemia over time. This study explored the impact of time spent in a hyperkalaemic state and variability of serum potassium (sK+) on major adverse cardiovascular events (MACE) and all-cause mortality in patients with chronic kidney disease (CKD), resistant hypertension, heart failure and diabetes. Methods: Cohorts comprised adult patients diagnosed with CKD stage 3+, resistant hypertension, heart failure or diabetes, and/or renin-angiotensin-aldosterone system inhibitor prescription, between 1 January 2003 and 30 June 2018, from the UK Clinical Practice Research Datalink. Associations between percentage of follow-up spent in a hyperkalaemic state (sK+ ≥5.0 mmol/L, ≥5.5 mmol/L, ≥6.0 mmol/L) or sK+ variability (standard deviation above or below median standard deviation) and all-cause mortality or MACE were investigated. Results: For sK+ ≥5.0 mmol/L, time spent in a hyperkalaemic state was associated with reduced risk of all-cause mortality across all cohorts. For higher sK+ thresholds, this trend was attenuated or reversed; for time spent in a hyperkalaemic state at sK+ ≥6.0 mmol/L, an increased risk of mortality was seen in the overall cohort and for patients with diabetes, resistant hypertension or prescribed renin-angiotensin-aldosterone system inhibitors, with no consistent association seen for patients with CKD or heart failure. Risk of MACE in the overall cohort and in patients with CKD, diabetes or resistant hypertension increased with time spent in a hyperkalaemic state at all sK+ thresholds; however, no correlation was seen in patients with heart failure or those receiving dialysis. High sK+ variability was associated with a higher risk of MACE compared with low sK+ variability across most sK+ categories in the overall population and in all disease cohorts, except patients on dialysis; however, no association between sK+ variability and all-cause mortality was observed. Conclusions: Patterns of hyperkalaemia, including time spent in hyperkalaemia and sK+ variability, are associated with adverse clinical outcomes. Regular monitoring of sK+ in high-risk populations in broader community, primary care and outpatient settings may enable guideline-recommended management of hyperkalaemia and help avoid adverse events.

Defining the Role of SGLT2 Inhibitors in Primary Care: Time to Think Differently.

Disease burden in people with diabetes is mainly driven by long-term complications such as cardiovascular disease, heart failure and chronic kidney disease. This is a consequence of the interconnection between the cardiovascular, renal and metabolic systems, through a continuous chain of events referred to as 'the cardiorenal metabolic continuum'. Increasing evidence suggests that sodium-glucose cotransporter 2 inhibitors (SGLT2is) have beneficial effects across all stages of the cardiorenal metabolic continuum, reducing morbidity and mortality in a wide range of individuals, from those with diabetes and multiple risk factors to those with established heart failure and chronic kidney disease, regardless of the presence of diabetes. Despite this robust evidence base, the complexity of label indications and misconceptions concerning potential side effects have resulted in a lack of clear understanding in primary care regarding the implementation of SGLT2is in clinical practice. With this in mind, we provide an overview of the clinical and economic benefits of SGLT2is across the cardiorenal metabolic continuum together with practical considerations in order to help address some of these concerns and clearly define the role of SGLT2is in primary care as a holistic outcomes-driven treatment with the potential to reduce disease burden across the cardiorenal metabolic spectrum.

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 Population-Wide Risk-Benefit Profile of Extending the Primary COVID-19 Vaccine Course Compared with an mRNA Booster Dose Program.

The vaccination program is reducing the burden of COVID-19. However, recently, COVID-19 infections have been increasing across Europe, providing evidence that vaccine efficacy is waning. Consequently, booster doses are required to restore immunity levels. However, the relative risk-benefit ratio of boosters, compared to pursuing a primary course in the unvaccinated population, remains uncertain. In this study, a susceptible-exposed-infectious-recovered (SEIR) transmission model of SARS-CoV-2 was used to investigate the impact of COVID-19 vaccine waning on disease burden, the benefit of a booster vaccine program compared to targeting the unvaccinated population, and the population-wide risk-benefit profile of vaccination. Our data demonstrates that the rate of vaccine efficacy waning has a significant impact on COVID-19 hospitalisations with the greatest effect in populations with lower vaccination coverage. There was greater benefit associated with a booster vaccination strategy compared to targeting the unvaccinated population, once >50% of the population had received their primary vaccination course. The population benefits of vaccination (reduced hospitalisations, long-COVID and deaths) outweighed the risks of myocarditis/pericarditis by an order of magnitude. Vaccination is important in ending the COVID-19 pandemic sooner, and the reduction in hospitalisations, death and long-COVID associated with vaccination significantly outweigh any risks. Despite these obvious benefits some people are vaccine reluctant, and as such remain unvaccinated. However, when most of a population have been vaccinated, a focus on a booster vaccine strategy for this group is likely to offer greater value, than targeting the proportion of the population who choose to remain unvaccinated.

Emerging Horizons in Heart Failure with Preserved Ejection Fraction: The Role of SGLT2 Inhibitors.

Heart failure with preserved ejection fraction (HFpEF) is a condition with increasing disease burden. Prevalence of HFpEF is increasing, reflecting an increasingly elderly and comorbid population, as well as reinforcing the need for more treatments for this disease. The pathophysiology of HFpEF is complex. Some inflammatory processes seen in HFpEF are shared with diabetes mellitus (DM) and there is an association seen between the two conditions. It is therefore no wonder that treatments for diabetes may have some effect on heart failure outcomes. Current treatment strategies in HFpEF are limited, with treatments focusing on symptom control rather than morbidity or mortality benefit. However, there are now promising results from the EMPEROR-Preserved study that show significantly reduced cardiovascular death or hospitalisation for heart failure (HHF) in patients taking empagliflozin, compared to those taking placebo. These results indicate a promising future for sodium-glucose co-transporter 2 (SGLT2) inhibitors in HFpEF. The ongoing DELIVER trial (investigating the use of dapagliflozin in HFpEF) is awaited but could provide further evidence of support for SGLT2 inhibitors in HFpEF. With hospital admissions for HFpEF increasing in the UK, the economic impact of treatments that reduce HHF is vast. The European Society of Cardiology (ESC) recently added SGLT2 inhibitors to their guidelines for treatment of heart failure with reduced ejection fraction (HFrEF) following DAPA-HF and EMPEROR-Reduced trials and we suggest that similar changes be made to guidelines to support the use of SGLT2 inhibitors in the management of HFpEF in upcoming months.

Meeting the Challenge of Virtual Diabetes Care: A Consensus Viewpoint on the Positioning and Value of Oral Semaglutide in Routine Clinical Practice.

While glucagon-like peptide-1 receptor agonists (GLP-1 RAs), such as semaglutide, are among the most effective drugs for treating people with type 2 diabetes (T2D), they are clinically under-utilised. Until recently, the only route for semaglutide administration was via subcutaneous injection. However, an oral formulation of semaglutide was recently licensed, with the potential to address therapy inertia and increase patient adherence to treatment, which is essential in controlling blood glucose and reducing complications. The availability of oral semaglutide provides a new option for both clinicians and patients who are reluctant to use an injectable agent. This has been of particular importance in addressing the challenge of virtual diabetes care during the COVID-19 pandemic, circumventing the logistical problems that are often associated with subcutaneous medication administration. However, there remains limited awareness of the clinical and economic value of oral semaglutide in routine clinical practice. In this article, we present our consensus opinion on the role of oral semaglutide in routine clinical practice and discuss its value in reducing the burden of delivering diabetes care in the post-COVID-19 pandemic period of chronic disease management.