Similar risk of exercise-related hypoglycaemia for insulin degludec to that for insulin glargine in patients with type 1 diabetes: a randomized cross-over trial

We compared changes in blood glucose (BG) and risk of hypoglycaemia during and after exercise in 40 patients with type 1 diabetes (T1D) treated with insulin degludec (IDeg) or insulin glargine (IGlar) in a randomized, open-label, two-period, crossover trial. After individual titration and a steady-state period, patients performed 30 min of moderate-intensity cycle ergometer exercise (65% peak rate of oxygen uptake). BG, counter-regulatory hormones and hypoglycaemic episodes were measured frequently during and for 24 h after exercise. BG changes during exercise were similar with IDeg and IGlar [estimated treatment difference (ETD) for maximum BG decrease: 0.14 mmol/l; 95% confidence interval (CI) -0.15, 0.42; p = 0.34], as was mean BG (ETD -0.16 mmol/l; 95% CI -0.36, 0.05; p = 0.13). No hypoglycaemic episodes occurred during exercise. Post-exercise mean BG, counter-regulatory hormone response and number of hypoglycaemic episodes in 24 h after starting exercise were similar with IDeg (18 events in 13 patients) and IGlar (23 events in 15 patients). This clinical trial showed that, in patients with T1D treated with a basal-bolus regimen, the risk of hypoglycaemia induced by moderate-intensity exercise was low with IDeg and similar to that with IGlar

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

Current management of chronic kidney disease in type‐2 diabetes—A tiered approach: An overview of the joint Association of British Clinical Diabetologists and UK Kidney association ( ABCD ‐ UKKA ) guidelines

A growing and significant number of people with diabetes develop chronic kidney disease (CKD). Diabetes‐related CKD is a leading cause of end‐stage kidney disease (ESKD) and people with diabetes and CKD have high morbidity and mortality, predominantly related to cardiovascular disease (CVD). Despite advances in care over the recent decades, most people with CKD and type 2 diabetes are likely to die of CVD before developing ESKD. Hyperglycaemia and hypertension are modifiable risk factors to prevent onset and progression of CKD and related CVD. People with type 2 diabetes often have dyslipidaemia and CKD per se is an independent risk factor for CVD, therefore people with CKD and type 2 diabetes require intensive lipid lowering to reduce burden of CVD. Recent clinical trials of people with type 2 diabetes and CKD have demonstrated a reduction in composite kidney end point events (significant decline in kidney function, need for kidney replacement therapy and kidney death) with sodium‐glucose co‐transporter‐2 (SGLT‐2) inhibitors, non‐steroidal mineralocorticoid receptor antagonist finerenone and glucagon‐like peptide 1 receptor agonists. The Association of British Clinical Diabetologists (ABCD) and UK Kidney Association (UKKA) Diabetic Kidney Disease Clinical Speciality Group have previously undertaken a narrative review and critical appraisal of the available evidence to inform clinical practice guidelines for the management of hyperglycaemia, hyperlipidaemia and hypertension in adults with type 2 diabetes and CKD. This 2024 abbreviated updated guidance summarises the recommendations and the implications for clinical practice for healthcare professionals who treat people with diabetes and CKD in primary, community and secondary care settings

Efficacy and safety of oral semaglutide monotherapy vs placebo in a predominantly Chinese population with type 2 diabetes (PIONEER 11): a double-blind, Phase IIIa, randomised trial

Aims/hypothesis: The aim of this study was to evaluate the efficacy and safety of oral semaglutide monotherapy vs placebo in a predominantly Chinese population with type 2 diabetes insufficiently controlled with diet and exercise alone. Methods: The Peptide Innovation for Early Diabetes Treatment (PIONEER) 11 trial was a double-blind, randomised, Phase IIIa trial conducted across 52 sites in the China region (mainland China and Taiwan), Hungary, Serbia and Ukraine. Eligible participants were ≥18 years (≥20 years in Taiwan), had a diagnosis of type 2 diabetes with HbA1c 53–86 mmol/mol (7.0–10.0%) and were not receiving any glucose-lowering drugs. After a 4-week run-in period in which participants were treated with diet and exercise alone, those who fulfilled the randomisation criteria were randomised (1:1:1:1) using a web-based randomisation system to receive once-daily oral semaglutide 3 mg, 7 mg or 14 mg or placebo for 26 weeks (using a 4-week dose-escalation regimen for the higher doses). Randomisation was stratified according to whether participants were from the China region or elsewhere. The primary and confirmatory secondary endpoints were change from baseline to week 26 in HbA1c and body weight (kg), respectively. Safety was assessed in all participants exposed to at least one dose of the trial product. Results: Between October 2019 and October 2021, a total of 774 participants were screened and 521 participants were randomised to oral semaglutide 3 mg (n=130), 7 mg (n=130), 14 mg (n=130) or placebo (n=131); most participants (92.5%, n=482) completed the trial, with 39 participants prematurely discontinuing treatment. The number of participants contributing to the trial analyses was based on the total number of participants who were randomised at the beginning of the trial. The majority of participants were male (63.7%), and the mean age of participants was 52 years. At baseline, mean HbA1c and body weight were 63 mmol/mol (8.0%) and 79.6 kg, respectively. Oral semaglutide resulted in significantly greater reductions in HbA1c than placebo at week 26 (p<0.001 for all doses). The estimated treatment differences (ETDs [95% CIs]) for oral semaglutide 3 mg, 7 mg and 14 mg vs placebo were –11 (–13, –9) mmol/mol, –16 (–18, –13) mmol/mol and –17 (–19, –15) mmol/mol, respectively. The corresponding ETDs in percentage points (95% CI) vs placebo were –1.0 (–1.2, –0.8), –1.4 (–1.6, –1.2) and –1.5 (–1.8, –1.3), respectively. Significantly greater reductions in body weight were also observed for oral semaglutide 7 mg and 14 mg than for placebo at week 26 (ETD [95% CI] –1.2 kg [–2.0 kg, –0.4 kg; p<0.01] and –2.0 kg [–2.8 kg, –1.2 kg; p<0.001], respectively), but not for oral semaglutide 3 mg (ETD [95% CI] –0.0 kg [–0.9 kg, 0.8 kg; not significant]). Similar reductions in HbA1c and body weight were observed in the Chinese subpopulation, which represented 74.9% of participants in the overall population. Adverse events (AEs) occurred in between 65.4% and 72.3% of participants receiving oral semaglutide (for all doses) and 57.3% of participants with placebo. Most AEs were mild to moderate in severity, with few serious AEs reported; the most commonly reported AEs were gastrointestinal-related and were more frequent with semaglutide (all doses) than with placebo. The proportion of AEs was slightly higher in the Chinese subpopulation. Conclusions/interpretation: Oral semaglutide resulted in significantly greater reductions in HbA1c across all doses and in significant body weight reductions for the 7 mg and 14 mg doses when compared with placebo in predominantly Chinese participants with type 2 diabetes insufficiently controlled by diet and exercise alone. Oral semaglutide was generally well tolerated, with a safety profile consistent with that seen in the global PIONEER trials. Trial registration: ClinicalTrials.gov NCT04109547. Funding: Novo Nordisk A/S. Graphical Abstract

Effect of the Glucagon-Like Peptide-1 Receptor Agonists Semaglutide and Liraglutide on Kidney Outcomes in Patients With Type 2 Diabetes: Pooled Analysis of SUSTAIN 6 and LEADER

We assessed the effect of once-weekly semaglutide and once-daily liraglutide on kidney outcomes in type 2 diabetes (T2D). Pooled (N=12,637) and by-trial data from SUSTAIN 6 (N=3297) and LEADER (N=9340) were assessed for albuminuria change, annual slope of estimated glomerular filtration rate (eGFR) change, and time to persistent eGFR reduction (30%, 40%, 50%, and 57%) from baseline. The median follow-up durations were 2.1 and 3.8 years for SUSTAIN 6 and LEADER, respectively. In the pooled analysis, semaglutide/liraglutide lowered albuminuria from baseline to 2 years post-randomization by 24% versus placebo (95% confidence interval [CI] [20%,27% ], <0.001). Significant reductions were also observed in by-trial data analyses ( <0.001 for all), the largest being with semaglutide 1.0 mg: 33% (95% CI [24%,40% ], <0.001) at 2 years. With semaglutide 1.0 mg and liraglutide, eGFR slope decline was significantly slowed by 0.87 and 0.26 mL/min/1.73 m /year ( <0.0001 and <0.001), respectively, versus placebo. Effects appeared larger in those with baseline eGFR <60 versus ≥60 mL/min/1.73m ( =0.06 and 0.008 for semaglutide 1.0 mg and liraglutide, respectively). Semaglutide/liraglutide significantly lowered risk of persistent 40% and 50% eGFR reductions versus placebo (hazard ratio [HR] 0.86, 95% CI [0.75,0.99], =0.039, and HR 0.80, 95% CI [0.66,0.97], =0.023, respectively). Similar, non-significant, directional results were observed for 30% and 57% eGFR reductions (HR 0.92, 95% CI [0.84, 1.02], =0.10, and HR 0.89, 95% CI [0.69, 1.13], =0.34). In those with baseline eGFR 30-<60mL/min/1.73m , the likelihood of persistent reduction for all thresholds was increased, ranging from a HR 0.71 for 30% reduction (95% CI [0.59,0.85], =0.0003, pinteraction=0.017) to 0.54 for 57% reduction (95% CI [0.36,0.81], =0.003, pinteraction=0.035). In patients with T2D, semaglutide/liraglutide offered kidney-protective effects, which appeared more pronounced in those with pre-existing chronic kidney disease