Clinical practice guideline for the management of lipids in adults with diabetic kidney disease: abbreviated summary of the Joint Association of British Clinical Diabetologists and UK Kidney Association (ABCD-UKKA) Guideline 2024.

The contribution of chronic kidney disease (CKD) towards the risk of developing cardiovascular disease (CVD) is magnified with co-existing type 1 or type 2 diabetes. Lipids are a modifiable risk factor and good lipid management offers improved outcomes for people with diabetic kidney disease (DKD).The primary purpose of this guideline, written by the Association of British Clinical Diabetologists (ABCD) and UK Kidney Association (UKKA) working group, is to provide practical recommendations on lipid management for members of the multidisciplinary team involved in the care of adults with DKD.

Cardiovascular events and all-cause mortality associated with sulphonylureas compared with other antihyperglycaemic drugs: A Bayesian meta-analysis of survival data.

AIM: To conduct a systematic review and meta-analysis to determine the risk of cardiovascular events and all-cause mortality associated with sulphonylureas (SUs) vs other glucose lowering drugs in patients with T2DM (T2DM). MATERIALS AND METHODS: A systematic review of Medline, Embase, Cochrane and clinicaltrials.gov was conducted for studies comparing SUs with placebo or other antihyperglycaemic drugs in patients with T2DM. A cloglog model was used in the Bayesian framework to obtain comparative hazard ratios (HRs) for the different interventions. For the analysis of observational data, conventional fixed-effect pairwise meta-analyses were used. RESULTS: The systematic review identified 82 randomized controlled trials (RCTs) and 26 observational studies. Meta-analyses of RCT data showed an increased risk of all-cause mortality and cardiovascular-related mortality for SUs compared with all other treatments combined (HR 1.26, 95% confidence interval [CI] 1.10-1.44 and HR 1.46, 95% CI 1.21-1.77, respectively). The risk of myocardial infarction was significantly higher for SUs compared with dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium-glucose co-transporter-2 inhibitors (HR 2.54, 95% CI 1.14-6.57 and HR 41.80, 95% CI 1.64-360.4, respectively). The risk of stroke was significantly higher for SUs than for DPP-4 inhibitors, glucagon-like peptide-1 agonists, thiazolidinediones and insulin. CONCLUSIONS: The present meta-analysis showed an association between SU therapy and a higher risk of major cardiovascular disease-related events compared with other glucose lowering drugs. Results of ongoing RCTs, which should be available in 2018, will provide definitive results on the risk of cardiovascular events and all-cause mortality associated with SUs vs other antihyperglycaemic drugs.

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.

Narrative Review of Glycemic Management in People With Diabetes on Peritoneal Dialysis.

There is an increasing number of people with diabetes on peritoneal dialysis (PD) worldwide. However, there is a lack of guidelines and clinical recommendations for managing glucose control in people with diabetes on PD. The aim of this review is to provide a summary of the relevant literature and highlight key clinical considerations with practical aspects in the management of diabetes in people undergoing PD. A formal systematic review was not conducted because of the lack of sufficient and suitable clinical studies. A literature search was performed using PubMed, MEDLINE, Central, Google Scholar and ClinicalTrials.gov., from 1980 through February 2022. The search was limited to publications in English. This narrative review and related guidance have been developed jointly by diabetologists and nephrologists, who reviewed all available current global evidence regarding the management of diabetes in people on PD.We focus on the importance of individualized care for people with diabetes on PD, the burden of hypoglycemia, glycemic variability in the context of PD and treatment choices for optimizing glucose control. In this review, we have summarized the clinical considerations to guide and inform clinicians providing care for people with diabetes on PD.

Safety of injectable semaglutide for type 2 diabetes.

INTRODUCTION: Semaglutide is the most recently approved injectable glucagon-like peptide-1 receptor agonist (GLP-1RA) for people with type 2 diabetes (T2DM). It is one of the three currently marketed GLP-1RAs that can be administered once weekly. AREAS COVERED: This review focusses on the safety of injectable semaglutide. Semaglutide has been assessed in the SUSTAIN phase 3 clinical trial programme, which included patients across the disease spectrum, i.e. treatment-naïve to those receiving insulin. The authors have looked at all published literature on safety considerations of once weekly GLP-1RA with particular reference to semaglutide. EXPERT OPINION: Semaglutide is the most powerful injectable GLP-1RA. The cardiovascular (CV) outcome trial (SUSTAIN 6) showed CV superiority and its adverse event profile is as expected for the GLP-1RA class with predominantly gastrointestinal side-effects. Concerns about the thyroid and pancreatic safety have not been substantiated. There is no indication of renal or liver harm for semaglutide. Data consistent with reno-protection and benefit in liver disease is presented. There is a modest signal for increased gall bladder adverse events. An increase in diabetic retinopathy (DR) events in the SUSTAIN 6 trial is the most concerning safety signal. Caution regarding DR is needed when initiating semaglutide and recommendations are suggested.

The Effect of Glucagon-Like Peptide-1 Receptor Agonists on Renal Outcomes in Type 2 Diabetes.

This review examines the available literature on the effect of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on renal outcomes in type 2 diabetes mellitus. Diabetes is an important cause of end-stage renal disease requiring renal replacement therapy, and diabetic kidney disease is an independent risk factor for cardiovascular disease (CVD). GLP-1RAs are proven to be safe in terms of CVD, and some of them have been shown to have a beneficial effect on cardiovascular outcomes. The effect of GLP-1RAs on hard renal endpoints has yet to be established; to date, there have been no published GLP-1RA clinical trials with primary renal endpoints. In this review, we discuss the evidence for a renal protective role of GLP-1RAs, highlighting the secondary renal outcomes from recent cardiovascular outcome trials of this class of glucose-lowering therapies.

A Randomized Controlled, Treat-to-Target Study Evaluating the Efficacy and Safety of Insulin Glargine 300 U/mL (Gla-300) Administered Using Either Device-Supported or Routine Titration in People With Type 2 Diabetes.

BACKGROUND: The efficacy/safety of device-supported versus routine titration with Gla-300 in type 2 diabetes (T2DM) was evaluated. METHOD: AUTOMATIX was a 16-week, randomized, open-label, parallel-group, multicenter, noninferiority trial in insulin-treated or insulin-naïve people with T2DM. The fasting self-monitored plasma glucose (FSMPG) target was 90-130 mg/dL (5.0-7.2 mmol/L). Primary endpoint: proportion of participants achieving target FSMPG at week 16 without severe hypoglycemia. Secondary endpoints included: proportion reaching FSMPG target without confirmed (≤70 mg/dL [≤3.9 mmol/L]) or severe hypoglycemia; time to first achieve FSMPG target; mean FSMPG and HbA1c change (baseline to week 16). Safety endpoints included hypoglycemia and adverse events. Patient-reported outcomes (PROs) were also assessed. RESULTS: Participants were randomized to device-supported (n = 75) or routine titration (n = 76); 17 participants in the device-supported group discontinued device use. Noninferiority was achieved for the primary endpoint (device-supported: 45.9%, routine: 36.8%; weighted difference: 9.04 [95% CI: -6.75, 24.83]), but not superiority (P = .262). The proportion reaching FSMPG target range without confirmed (≤70 mg/dL [≤3.9 mmol/L]) or severe hypoglycemia was 34.3% vs 14.5%, respectively. The time at which 50% of the participants achieved the FSMPG target was less in the device-supported than routine titration arm (10 vs 13 weeks). Least squares mean HbA1c reduction, safety profiles, and PROs were similar in both arms. Mean "ease of use" score for the device, assessed by healthcare professionals and participants on a scale of 1-7, was ≥6. CONCLUSIONS: Device-supported self-titration had a good safety/efficacy profile, and was noninferior to routine titration and well accepted by diabetes specialists and patients.

Resistance Isn't Futile: The Physiological Basis of the Health Effects of Resistance Exercise in Individuals With Type 1 Diabetes.

The importance of regular exercise for glucose management in individuals with type 1 diabetes is magnified by its acknowledgment as a key adjunct to insulin therapy by several governmental, charitable, and healthcare organisations. However, although actively encouraged, exercise participation rates remain low, with glycaemic disturbances and poor cardiorespiratory fitness cited as barriers to long-term involvement. These fears are perhaps exacerbated by uncertainty in how different forms of exercise can considerably alter several acute and chronic physiological outcomes in those with type 1 diabetes. Thus, understanding the bodily responses to specific forms of exercise is important for the provision of practical guidelines that aim to overcome these exercise barriers. Currently, the majority of existing exercise research in type 1 diabetes has focused on moderate intensity continuous protocols with less work exploring predominately non-oxidative exercise modalities like resistance exercise. This is surprising, considering the known neuro-muscular, osteopathic, metabolic, and vascular benefits associated with resistance exercise in the wider population. Considering that individuals with type 1 diabetes have an elevated susceptibility for complications within these physiological systems, the wider health benefits associated with resistance exercise may help alleviate the prevalence and/or magnitude of pathological manifestation in this population group. This review outlines the health benefits of resistance exercise with reference to evidence in aiding some of the common complications associated with individuals with type 1 diabetes.

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

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

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

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

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

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