Continuous glucose monitoring for the routine care of type 2 diabetes mellitus.

Although continuous glucose monitoring (CGM) devices are now considered the standard of care for people with type 1 diabetes mellitus, the uptake among people with type 2 diabetes mellitus (T2DM) has been slower and is focused on those receiving intensive insulin therapy. However, increasing evidence now supports the inclusion of CGM in the routine care of people with T2DM who are on basal insulin-only regimens or are managed with other medications. Expanding CGM to these groups could minimize hypoglycaemia while allowing efficient adaptation and escalation of therapies. Increasing evidence from randomized controlled trials and observational studies indicates that CGM is of clinical value in people with T2DM on non-intensive treatment regimens. If further studies confirm this finding, CGM could soon become a part of routine care for T2DM. In this Perspective we explore the potential benefits of widening the application of CGM in T2DM, along with the challenges that must be overcome for the evidence-based benefits of this technology to be delivered for all people with T2DM.

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.

Beliefs, practices, perceptions and motivations of healthcare professionals on medication deprescribing during end-of-life care: A systematic review.

AIM: Conduct a systematic review to investigate current beliefs, practices, perceptions, and motivations towards deprescribing practices from the healthcare professional perspective in older adults residing in long term care facilities with cardiometabolic conditions, using a narrative approach. METHODS: Studies were identified using a literature search of MEDLINE, CINAHL and Web of Science from inception to June 2023 Two reviewers (EH and AA) independently extracted data from each selected study using a standardised self-developed data extraction proforma. Studies reviewed included cross-sectional and observational studies. Data was extracted on baseline characteristics, motivations and beliefs and was discussed using a narrative approach. RESULTS: Eight studies were identified for inclusion. Deprescribing approaches included complete withdrawal, dose reduction, or switching to an alternative medication, for at least one preventive medication. Most healthcare professionals were willing to initiate deprescribing strategies and stated the importance of such interventions, however many felt inexperienced and lacked the required knowledge to feel comfortable doing so. CONCLUSION: Deprescribing is a key strategy when managing older people with cardiometabolic and multiple long term conditions (MLTC). Overall, HCPs including specialists, were happy to explore deprescribing strategies if provided with the relevant training and development to do so. Barriers that still exist include communication and consultation skills, a lack of evidence-based guidance and trust based policies, and a lack of MDT communications and involvement. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022335106.

Glycaemic control and macrovascular and microvascular outcomes: A systematic review and meta-analysis of trials investigating intensive glucose-lowering strategies in people with type 2 diabetes.

AIM: We aimed to determine the macrovascular and microvascular outcomes of intensive versus standard glucose-lowering strategies in type 2 diabetes (T2D) and investigate the relationships between these outcomes and trial arm glycated haemoglobin (HbA1c) reduction. MATERIALS AND METHODS: In this systematic review and meta-analysis, we identified relevant trials from MEDLINE, Embase, the Cochrane Library, and bibliographies up to August 2023. Macrovascular and microvascular outcomes, along with safety outcomes, were evaluated. Pooled study-specific hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated, and meta-regression was employed to analyse the relationships between outcomes and HbA1c reduction. RESULTS: We included 11 unique RCTs involving 51 469 patients with T2D (intensive therapy, N = 26 691; standard therapy, N = 24 778). Intensive versus standard therapy reduced the risk of non-fatal myocardial infarction (MI) (HR 0.84; 95% CI 0.75-0.94) with no difference in the risk of major adverse cardiovascular events (HR 0.97; 95% CI 0.92-1.03) and other adverse cardiovascular outcomes. Intensive versus standard therapy reduced the risk of retinopathy (HR 0.85; 0.78-0.93), nephropathy (HR 0.71; 0.58-0.87) and composite microvascular outcomes (HR 0.88; 0.77-1.00). Meta-regression analyses showed modest evidence of inverse linear relationships between HbA1c reduction and the outcomes of major adverse cardiovascular events, non-fatal MI, stroke and retinopathy, but these were not statistically significant. CONCLUSIONS: In people with T2D, intensive glucose control was associated with a reduced risk of non-fatal MI and several microvascular outcomes, particularly retinopathy and nephropathy. The lack of an effect of intensive glucose-lowering on most macrovascular outcomes calls for a more comprehensive approach to managing cardiovascular risk factors alongside glycaemic control.

Tertiary centre study highlights low inpatient deintensification and risks associated with adverse outcomes in frail people with diabetes.

INTRODUCTION: The community deintensification rates in older people with diabetes are low and hospital admission presents an opportunity for medication review. We audited the inpatient assessment and deintensification rate in people with diabetes and frailty. We also identified factors associated with adverse inpatient outcomes. METHODS: A retrospective review of electronic charts was conducted in all people with diabetes and clinical frailty score ≥6 who were discharged from the medical unit in 2022. Data on demographics, comorbidities and background glucose-lowering medications were collected. RESULTS: Six-hundred-and-sixty-five people with diabetes and moderate/severe frailty were included in our analysis. For people with no HbA1c in the last six months preceding admission, only 9.0% had it assessed during inpatient. Deintensification rates were 19.1%. Factors that were associated with adverse inpatient outcomes included inpatient hypoglycaemia, non-White ethnicity, and being overtreated (HbA1c <7.0% [53 mmol/mol] with any glucose-lowering medication). CONCLUSION: The assessment and deintensification rate in secondary care for people with diabetes and frailty is low. Inpatient hypoglycaemia, non-White ethnicity, and overtreatment are important factors in determining inpatient outcomes highlighting the importance of deintensification and the need for an evidence-based risk stratification tool.

Glycaemic control and macrovascular and microvascular outcomes in type 2 diabetes: Systematic review and meta-analysis of cardiovascular outcome trials of novel glucose-lowering agents.

AIM: Using a systematic review and meta-analysis of placebo-controlled cardiovascular outcome trials (CVOTs) of newer glucose-lowering agents [sodium-glucose cotransporter-2 inhibitors (SGLT-2is), glucagon-like peptide-1 receptor agonists (GLP-1RAs), and dipeptidyl peptidase-4 inhibitors (DPP-4is)] in type 2 diabetes (T2D), we aimed to determine the macrovascular and microvascular outcomes of these agents and clarify the relationships between glycated haemoglobin (HbA1c) reduction and risk of these outcomes. MATERIALS AND METHODS: Randomized controlled trials were identified from MEDLINE, Embase and the Cochrane Library until September 2023. Study-specific hazard ratios with 95% confidence intervals (CIs) were pooled, and meta-regression was used to assess the relationships between outcomes and between trial arm HbA1c reductions. RESULTS: Twenty unique CVOTs (six SGLT-2is, nine GLP-1RAs, five DPP-4is), based on 169 513 participants with T2D, were eligible. Comparing SGLT-2is, GLP-1RAs and DPP-4is with placebo, the hazard ratios (95% CIs) for 3-point major adverse cardiovascular events were 0.88 (0.82-0.94), 0.85 (0.79-0.92) and 1.00 (0.94-1.06), respectively. SGLT-2is and GLP-1RAs consistently reduced the risk of several macrovascular and microvascular complications, particularly kidney events. DPP-4is showed no macrovascular benefits. There was potential evidence of an inverse linear relationship between HbA1c reduction and 3-point major adverse cardiovascular event risk (estimated risk per 1% reduction in HbA1c: 0.84, 95% CI 0.67-1.06; p = .14; R2 = 14.2%), which was driven by the component of non-fatal stroke (R2 = 100.0%; p = .094). There were non-significant inverse linear relationships between HbA1c reduction and the risk of several vascular outcomes. CONCLUSIONS: SGLT-2is and GLP-1RAs showed consistent risk reductions in macrovascular and microvascular outcomes. The vascular benefits of SGLT-2is and GLP-1RAs in patients with T2D extend beyond mere glycaemic control.

Baseline and usual triglyceride-glucose index and the risk of chronic kidney disease: a prospective cohort study.

Triglyceride-glucose (TyG) index is an emerging marker of adverse cardiometabolic conditions such as cardiovascular disease and type 2 diabetes. The long-term relevance of TyG index to chronic kidney disease (CKD) is uncertain. We aimed to assess the association of TyG index with CKD risk and its utility in risk prediction in a prospective study. The TyG index was calculated using fasting triglycerides and fasting plasma glucose (FPG) levels measured in 2362 men aged 42-61 years with normal kidney function using the formula: Ln (fasting triglycerides [mg/dL] × FPG [mg/dL]/2). Multivariable adjusted hazard ratios (HRs) (95% confidence intervals, CIs) were estimated for CKD. Correction for within-person variability was made using data from repeat measurements of triglycerides and FPG taken 11 years after baseline. Over a median follow-up duration of 17.5 years, 223 CKD cases were recorded. The age-adjusted regression dilution ratio for the TyG index was 0.54 (95% CI, 0.48-0.60). The risk of CKD increased continuously with increasing TyG index across the range 9.3 to 11.6 (p value for nonlinearity<.001). In analysis adjusted for established risk factors, a unit higher TyG index was associated with an increased risk of CKD (HR 1.59, 95% CI 1.24-2.05). Comparing extreme tertiles of the TyG index, the corresponding adjusted HR (95% CI) for CKD was 1.61 (1.15-2.27). Addition of the TyG index to a CKD risk prediction model containing established risk factors improved risk discrimination and reclassification (p value for difference in -2 log likelihood<.001; NRI=47.66%, p=.014; IDI=0.0164, p<.001). Higher TyG index is associated with an increased risk of CKD and improves the prediction and classification of CKD beyond established risk factors. Using single baseline estimations of the TyG index to investigate its association with CKD risk could considerably under-estimate the true association.

Deintensification of potentially inappropriate medications amongst older frail people with type 2 diabetes: Protocol for a cluster randomised controlled trial (D-MED study).

AIMS: Amongst elderly people with type 2 diabetes (T2D) over prescribing can result in emergency ambulance call-outs, falls and fractures and increased mortality, particularly in frail patients. Current clinical guidelines, however, remain focused on medication intensification rather than deintensification where appropriate. This study aims to evaluate the effectiveness of an electronic decision-support system and training for the deintensification of potentially inappropriate medications amongst older frail people with T2D, when compared to 'usual' care at 12-months. METHODS: This study is an open-label, multi-site, two-armed pragmatic cluster-randomised trial. GP practices randomised to the 'enhanced care' group have an electronic decision support system installed and receive training on the tool and de-intensification of diabetes medications. The system flags eligible patients for possible deintensification of diabetes medications, linking the health care professional to a clinical algorithm. The primary outcome will be the number of patients at 12-months who have had potentially inappropriate diabetes medications de-intensified. RESULTS: Study recruitment commenced in June 2022. Data collection commenced in January 2023. Baseline data have been extracted from 40 practices (3145 patients). CONCLUSIONS: Digital technology, involving computer decision systems, may have the potential to reduce inappropriate medications and aid the process of de-intensification. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number: ISRCTN53221378. Available at: https://www.isrctn.com/ISRCTN53221378.

Blood pressure levels and adverse cardiovascular outcomes in heart failure: A systematic review and meta-analysis.

AIM: Existing data on the association between blood pressure levels and adverse cardiovascular outcomes in patients with heart failure (HF) are inconsistent. The optimal blood pressure targets for patients with HF remain uncertain. This study sought to assess the associations between blood pressure (systolic [SBP] and diastolic blood pressure [DBP]) levels and adverse cardiovascular disease (CVD) outcomes in patients with HF. METHODS AND RESULTS: A systematic review and meta-analysis were conducted using MEDLINE, Embase, the Cochrane Library, and Web of Science databases up to 5 May 2023. The outcomes of interest included adverse cardiovascular events and all-cause mortality. Pooled relative risks (RRs) with corresponding 95% confidence intervals (CIs) were calculated. Forty-three unique observational cohort studies, comprising 120 643 participants with HF, were included. The pooled RRs (95% CIs) for SBP thresholds of ≥140 mmHg versus <140 mmHg were 0.92 (0.83-1.01) for all-cause mortality, 0.83 (0.67-1.04) for CVD death, and 0.98 (0.80-1.21) for HF hospitalization. The pooled RR (95% CI) for SBP thresholds of ≥160 mmHg versus <160 mmHg and all-cause mortality was 0.67 (0.62-0.74). SBP levels below <130, <120, and <110 mmHg were each associated with an increased risk of various cardiovascular endpoints and all-cause mortality. The pooled RR (95% CI) for DBP thresholds of ≥80 mmHg versus <80 mmHg and all-cause mortality was 0.86 (0.67-1.10). A 10 mmHg increase in SBP or DBP was associated with a reduction in all-cause mortality and other cardiovascular endpoints. CONCLUSIONS: The findings suggest that lower and normal baseline SBP levels (<130, <120, and <110 mmHg) may be associated with future risk of worse outcomes in patients with HF. Optimal baseline blood pressure levels for these patients may lie within the range of ≥140 mmHg for SBP. In the absence of observational studies with repeated blood pressure measurements or definitive trials evaluating optimal blood pressure targets, individualized blood pressure targets based on patients' unique circumstances are warranted in HF management.

The impact of the COVID-19 pandemic and associated disruptions in health-care provision on clinical outcomes in people with diabetes: a systematic review.

The COVID-19 pandemic triggered disruptions to health care and lifestyles that could conceivably impact diabetes management. We set out to identify the impact of disruptions caused by COVID-19 on clinical outcomes in people with diabetes. We performed a systematic review of the available literature in the MEDLINE and OVID databases from Jan 1, 2020, to June 7, 2023, and included 138 studies (n>1 000 000 people). All but five studies were judged to be at some risk of bias. All studies compared prepandemic with pandemic periods. All-cause mortality (six studies) and diabetes-related mortality (13 studies) showed consistent increases, and most studies indicated increases in sight loss (six studies). In adult and mixed samples, data generally suggested no difference in diabetic ketoacidosis frequency or severity, whereas in children and adolescents most studies showed increases with some due to new-onset diabetes (69 studies). Data suggested decreases in hospital admissions in adults but increases in diabetes-related admissions to paediatric intensive care units (35 studies). Data were equivocal on diabetic foot ulcer presentations (nine studies), emergency department admissions (nine studies), and overall amputation rates (20 studies). No studies investigated renal failure. Where reported, the impact was most pronounced for females, younger people, and racial and ethnic minority groups. Further studies are needed to investigate the longer-term impact of the pandemic and the on potential differential impacts, which risk further exacerbating existing inequalities within people with diabetes.

A Podcast on the Use of CGM in Optimizing Type 2 Diabetes Management with Non-intensive Insulin Treatment in the Primary Care Setting.

INTRODUCTION: Type 2 diabetes is a widespread health concern with significant implications for patient well-being. Poor glycaemic control can lead to long-term complications, hypoglycaemia and glycaemic variability, highlighting the importance of setting treatment goals. This podcast, "The use of CGM in optimizing type 2 diabetes management with non-intensive insulin treatment in the primary care setting", introduces non-intensive insulin treatment and continuous glucose monitoring (CGM) as crucial tools in achieving these goals. OBJECTIVES AND RATIONALE: The advantages of CGM over blood glucose monitoring (BGM) are explored, emphasizing its real-time glucose data provision and how it empowers patients to make informed treatment decisions. Drawing on randomized controlled trials (RCTs), the compelling evidence of CGM's effectiveness in patients with type 2 diabetes on basal insulin treatment are discussed. Additionally, the real-world evidence, comparing outcomes between insulin-treated and non-insulin-treated patients are also addressed. The podcast examines the link between glycaemic control and acute complications requiring hospitalizations and how CGM contributes to a better quality of life for patients with type 2 diabetes. Empowering patients is central to this podcast, with a focus on education, engagement and strategies for integrating CGM data into treatment plans. The pivotal role of healthcare providers in supporting patients on non-intensive insulin treatment and CGM in the primary care setting is addressed. Addressing challenges and barriers in CGM adoption, including cost considerations, technology accessibility and patient concerns, is vital to its widespread use. There is also a consideration of the cost-effectiveness of CGM in type 2 diabetes management. The podcast provides insights into when to consider CGM, including intermittent use and data integration with other health technologies. It emphasizes the potential for improved patient outcomes and a reduced burden of type 2 diabetes. Practical tips for interpreting the Ambulatory Glucose Profile (AGP) report are shared, benefitting primary care healthcare professionals new to CGM. CONCLUSION: The podcast "The use of CGM in optimizing type 2 diabetes management with non-intensive insulin treatment in the primary care setting" highlights the transformative potential of CGM in type 2 diabetes care. It encourages patients and healthcare providers to consider CGM as an integral part of treatment plans, ultimately improving the lives of those living with type 2 diabetes. Podcast Video (MP4 261831 KB).

Effect of delay in treatment intensification in people with type 2 diabetes and suboptimal glycaemia after basal insulin initiation: A real-world observational study.

AIM: Despite global recommendations for type 2 diabetes mellitus treatment to maintain optimal glycaemic targets, a significant proportion of people remain in suboptimal glycaemic control. Our objective was to investigate the impact of intensification delay after basal insulin (BI) initiation on long-term complications in people with suboptimal glycaemia. MATERIALS AND METHODS: We conducted a retrospective cohort study in individuals with type 2 diabetes mellitus initiated on BI. Those with suboptimal glycaemia (glycated haemoglobin ≥7% or ≥53 mmol/mol) within 12 months of BI initiation were divided into early (treatment intensified within 5 years), or late (≥5 years) intensification groups. We estimated the age-stratified risks of micro- and macrovascular complications among these groups compared with those with optimal glycaemia (glycated haemoglobin <7%). RESULTS: Of the 13 916 people with suboptimal glycaemia, 52.5% (n = 7304) did not receive any treatment intensification. In those aged <65 years, compared with the optimal glycaemia group late intensification was associated with a 56% higher risk of macrovascular complications (adjusted hazard ratio 1.56; 95% confidence intervals 1.08, 2.26). In elderly people (≥65 years), late intensification was associated with a higher risk of cardiovascular-related death (1.62; 1.03, 2.54) and a lower risk of microvascular complications (0.26; 0.08, 0.83). CONCLUSIONS: Those who had late intensification were at an increased risk of cardiovascular death if they were ≥65 years and an increased risk of macrovascular complications if they were <65 years. These findings highlight the critical need for earlier intensification of treatment and adopting personalized treatment strategies to improve patient outcomes.

Efficacy and Safety of Continuous Glucose Monitoring and Intermittently Scanned Continuous Glucose Monitoring in Patients With Type 2 Diabetes: A Systematic Review and Meta-analysis of Interventional Evidence.

BACKGROUND: Traditional diabetes self-monitoring of blood glucose (SMBG) involves inconvenient finger pricks. Continuous glucose monitoring (CGM) and intermittently scanned CGM (isCGM) systems offer CGM, enhancing type 2 diabetes (T2D) management with convenient, comprehensive data. PURPOSE: To assess the benefits and potential harms of CGM and isCGM compared with usual care or SMBG in individuals with T2D. DATA SOURCES: We conducted a comprehensive search of MEDLINE, Embase, the Cochrane Library, Web of Science, and bibliographies up to August 2023. STUDY SELECTION: We analyzed studies meeting these criteria: randomized controlled trials (RCT) with comparison of at least two interventions for ≥8 weeks in T2D patients, including CGM in real-time/retrospective mode, short-/long-term CGM, isCGM, and SMBG, reporting glycemic and relevant data. DATA EXTRACTION: We used a standardized data collection form, extracting details including author, year, study design, baseline characteristics, intervention, and outcomes. DATA SYNTHESIS: We included 26 RCTs (17 CGM and 9 isCGM) involving 2,783 patients with T2D (CGM 632 vs. usual care/SMBG 514 and isCGM 871 vs. usual care/SMBG 766). CGM reduced HbA1c (mean difference -0.19% [95% CI -0.34, -0.04]) and glycemic medication effect score (-0.67 [-1.20 to -0.13]), reduced user satisfaction (-0.54 [-0.98, -0.11]), and increased the risk of adverse events (relative risk [RR] 1.22 [95% CI 1.01, 1.47]). isCGM reduced HbA1c by -0.31% (-0.46, -0.17), increased user satisfaction (0.44 [0.29, 0.59]), improved CGM metrics, and increased the risk of adverse events (RR 1.30 [0.05, 1.62]). Neither CGM nor isCGM had a significant impact on body composition, blood pressure, or lipid levels. LIMITATIONS: Limitations include small samples, single-study outcomes, population variations, and uncertainty for younger adults. Additionally, inclusion of <10 studies for most end points restricted comprehensive analysis, and technological advancements over time need to be considered. CONCLUSIONS: Both CGM and isCGM demonstrated a reduction in HbA1c levels in individuals with T2D, and unlike CGM, isCGM use was associated with improved user satisfaction. The impact of these devices on body composition, blood pressure, and lipid levels remains unclear, while both CGM and isCGM use were associated with increased risk of adverse events.

Associations of blood pressure with cardiovascular and mortality outcomes in over 2 million older persons with or without diabetes mellitus: A systematic review and meta-analysis of 45 cohort studies.

BACKGROUND: The impact of blood pressure on cardiovascular disease (CVD) and mortality outcomes in older people with diabetes mellitus (DM) is not well quantified. Using a systematic review and meta-analysis of observational cohort studies, we aimed to compare the associations of blood pressure levels with cardiovascular and mortality outcomes in older people aged ≥ 65 years with or without DM. METHODS: Studies were identified from MEDLINE, Embase, Web of Science, and search of bibliographies to July 2022. Study-specific risk ratios (RRs) with 95% confidence intervals (CIs) were pooled. RESULTS: Forty-five unique observational cohort studies (n = 2305,189 participants) assessing the associations of systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) levels with adverse cardiovascular outcomes were included. In the general population, the pooled RRs (95% CIs) of SBP ≥ 140 vs < 140 mmHg and per 10 mmHg increase for composite CVD/MACE were 1.26 (0.96-1.64) and 1.15 (1.08-1.23), respectively. The respective estimates were 1.56 (1.04-2.34) and 1.10 (1.04-1.18) for patients with DM. SBP ≥ 130 vs < 130 mmHg was not associated with an increased risk of adverse cardiovascular outcomes in both populations. SBP < 120 vs ≥ 120 mmHg was associated with an increased risk of all cause-mortality in the general population (n = 10 studies). DBP ≥ 90 mmHg was associated with an increased risk of some adverse cardiovascular outcomes in both populations. Interaction analyses suggested similar risk of outcomes in both populations. CONCLUSIONS: Observational evidence suggests SBP and DBP confer similar cardiovascular and mortality risk in older adults in the general population and those with DM. A blood pressure target range of > 130/80 to < 140/90 mmHg may be optimal for patients ≥ 65 years with DM, but specific targets may need to be individualised based on patients' unique circumstances. Furthermore, findings do not support stringent blood pressure control in this population group. Definitive RCTs are needed to support these observational findings.

Racial, ethnic and regional differences in the effect of sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide 1 receptor agonists on cardiovascular and renal outcomes: a systematic review and meta-analysis of cardiovascular outcome trials.

OBJECTIVES: The cardiorenal protective effects of sodium-glucose co-transporter 2 inhibitors (SGLT2-Is) and glucagon-like peptide 1 receptor agonists (GLP1-RAs) across racial and ethnic groups are not well defined. By conducting a systematic review and meta-analysis of all randomised, placebo-controlled, cardiovascular disease (CVD) outcomes trials (CVOTs), we aimed to compare racial/ethnic as well as regional patterns in the effects of SGLT2-Is and GLP1-RAs on cardiovascular and renal outcomes in patients with type 2 diabetes (T2D). DESIGN: Trials were identified from MEDLINE, Embase, the Cochrane Library, and search of bibliographies to 7 July 2023. Setting North America, South/Central America, Europe (Eastern and Western), Asia, Australia-New Zealand (Pacific), Asia/Pacific, and Africa. SETTING: North America, South/Central America, Europe (Eastern and Western), Asia, Australia-New Zealand (Pacific), Asia/Pacific, and Africa. PARTICIPANTS: people with type 2 diabetes enrolled in cardiovascular outcome trials of SGLT2-Is and GLP1-RAs. MAIN OUTCOME MEASURES: Outcomes were (i) major adverse cardiovascular events (MACE), (ii) composite CVD death/heart failure (HF) hospitalization; (iii) composite renal outcome; and (iv) their components. Study-specific hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled. RESULTS: In total, 14 unique CVOTs (7 comparing SGLT2-Is vs placebo and 7 comparing GLP1-RAs vs placebo) were eligible. The proportion of participants enrolled in the trials ranged from 66.6-93.2% for White populations, 1.2-21.6% for Asian populations, 2.4-8.3% for Black populations and 0.9-23.1% for Other populations. The HR (95% CI) for MACE comparing SGLT2-Is vs placebo was 0.92 (0.86-0.98), 0.69 (0.53-0.92) and 0.70 (0.54-0.91) for White, Asian and Hispanic/Latino populations, respectively. Comparing GLP1-RAs vs placebo, the corresponding HR (95% CI) was 0.88 (0.80-0.97), 0.76 (0.63-0.93) and 0.82 (0.70-0.95), respectively. SGLT2-Is reduced the risk of all other cardiorenal outcomes in White and Asian populations, except for HF hospitalizations in Asians. No effects were observed in Black populations except for a reduced risk of HF hospitalizations by SGLT2-I. SGLT1-Is reduced the risk of composite CVD death/HF hospitalization in North America and Europe, whereas GLP1-RAs reduced the risk of MACE in Europe. GRADE certainty of evidence ranged from moderate to high. CONCLUSIONS: There appears to be substantial racial/ethnic differences in the cardiorenal effects of SGLT2-Is and GLP1-RAs in patients with T2D, with consistent benefits observed among White and Asian populations and consistent lack of benefits in Black populations. Whether the differences are due to issues with under-representation of Black populations and low statistical power or racial/ethnic variations in the pharmacokinetics, pharmacodynamics and safety of SGLT2-Is and GLP1-RAs need further investigation.PROSPERO Registration: CRD42023401734.

Factors associated with therapeutic inertia in individuals with type 2 diabetes mellitus started on basal insulin.

AIM: In this study we aim to identify the factors associated with treatment inertia in patients with type 2 diabetes mellitus (T2DM) who have been recently started on basal insulin (BI). METHODS: Using UK CPRD GOLD, we identified adults with T2DM with suboptimal glycaemia (HbA1c within 12 months of BI ≥ 7% (≥53 mmol/mol)). We used multivariable Cox regression model to describe the association between patient characteristics and the time to treatment intensification. RESULTS: A total of 12,556 patients were analysed. Compared to individuals aged < 65 years, those aged ≥ 65 years had lower risk of treatment intensification (HR: 0.69; 95% CI: 0.64-0.73). Other factors included being female (0.93, 0.89-0.99), longer T2DM duration (0.99, 0.98-0.99), living in the most deprived areas (0.90, 0.83-0.98), being a current smoker (0.91, 0.84-0.98), having one (0.91, 0.85-0.97) or more than one comorbidity (0.88, 0.82-0.94), and patients who were on metformin (0.71, 0.63-0.80), or 2nd generation sulphonylureas (0.85; 0.79-0.92) or DPP4 inhibitors (0.87, 0.82-0.93) compared to those who were not. CONCLUSION: Therapeutic inertia still remains a major barrier, with multiple factors associated with delay in intensification. Interventions to overcome therapeutic inertia need to be implemented at both patient and health care professional level.

Deprescribing in cardiometabolic conditions in older patients: a systematic review.

We conduct a systematic review to investigate current deprescribing practices and evaluate outcomes and adverse events with deprescribing of preventive medications in older patients with either an end-of-life designation or residing in long-term care facilities with cardiometabolic conditions. Studies were identified using a literature search of MEDLINE, EMBASE, Web of Science, clinicaltrials.gov.uk, CINAHLS, and the Cochrane Register from inception to March 2022. Studies reviewed included observational studies and randomised control trials (RCTs). Data was extracted on baseline characteristics, deprescribing rates, adverse events and outcomes, and quality of life indicators, and was discussed using a narrative approach. Thirteen studies were identified for inclusion. Deprescribing approaches included complete withdrawal, dose reduction or tapering, or switching to an alternative medication, for at least one preventive medication. Deprescribing success rates ranged from 27 to 94.7%. The studies reported no significant changes in laboratory values or adverse outcomes but did find mixed outcomes for hospitalisations and a slight increase in mortality rates when comparing the intervention and control groups. Lack of good-quality randomised control trials suggests that deprescribing in the older population residing in long-term care facilities with cardiometabolic conditions and multimorbidity is feasible when controlled and regularly monitored by an appropriate healthcare clinician, and that the benefits outweigh the potential harm in this cohort of patients. Due to the limited evidence and the heterogeneity of studies, a meta-analysis was not performed and as such further research is required to assess the benefits of deprescribing in this patient population. Systematic review registration: PROSPERO CRD42021291061.