Real-World Clinical Experience of Oral Semaglutide in a Secondary Diabetes Clinic in the UK: A Retrospective Observational Study.

INTRODUCTION: Oral semaglutide improves cardiovascular risk factors in people with type 2 diabetes (T2D) in clinical trials, though real-world evidence is limited. We aimed to determine the real-world impact of oral semaglutide on routinely collected clinical data in our practice. METHODS: People with T2D initiated on oral semaglutide in secondary care diabetes clinics at two hospital sites in Wales (United Kingdom) were included. Data were collected on reasons for oral semaglutide initiation and changes in bodyweight, blood pressure, glycemic control, and lipid profiles over follow-up at 3-6 months, and at 6-12 months. Data were collected to determine the safety of oral semaglutide. RESULTS: Seventy-six patients were included, with a median age 59.3 [51.4-67.6] years, and 38 (50.0%) patients were female. The most common reasons for oral semaglutide were need for weight loss and improved glycemia (69.8%), and improved glycemia alone (25.0%). Oral semaglutide associated with significantly reduced bodyweight (- 3.3 kg), body mass index (BMI) (- 0.9 kg/m2), glycated hemoglobin (HbA1c) (- 11 mmol/mol), and total cholesterol (- 0.4 mmol/l) by 3-6 months follow-up. At 6-12 months, there was a significant reduction in systolic blood pressure (- 7.0 mmHg), in addition to sustained reductions in other metabolic parameters. By 12 months, 18 (23.6%) patients had discontinued the drug, largely resulting from gastrointestinal disturbance, but there were no serious events in this cohort. CONCLUSIONS: Oral semaglutide was effective in improving cardiovascular risk factors in this real-world population living with T2D, and no serious events were identified related to oral semaglutide in this patient group.

Using Artificial Intelligence to Improve the Accuracy of a Wrist-Worn, Noninvasive Glucose Monitor: A Pilot Study.

BACKGROUND: Self-monitoring of glucose is important to the successful management of diabetes; however, existing monitoring methods require a degree of invasive measurement which can be unpleasant for users. This study investigates the accuracy of a noninvasive glucose monitoring system that analyses spectral variations in microwave signals. METHODS: An open-label, pilot design study was conducted with four cohorts (N = 5/cohort). In each session, a dial-resonating sensor (DRS) attached to the wrist automatically collected data every 60 seconds, with a novel artificial intelligence (AI) model converting signal resonance output to a glucose prediction. Plasma glucose was measured in venous blood samples every 5 minutes for Cohorts 1 to 3 and every 10 minutes for Cohort 4. Accuracy was evaluated by calculating the mean absolute relative difference (MARD) between the DRS and plasma glucose values. RESULTS: Accurate plasma glucose predictions were obtained across all four cohorts using a random sampling procedure applied to the full four-cohort data set, with an average MARD of 10.3%. A statistical analysis demonstrates the quality of these predictions, with a surveillance error grid (SEG) plot indicating no data pairs falling into the high-risk zones. CONCLUSIONS: These findings show that MARD values approaching accuracies comparable to current commercial alternatives can be obtained from a multiparticipant pilot study with the application of AI. Microwave biosensors and AI models show promise for improving the accuracy and convenience of glucose monitoring systems for people with diabetes.

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.

Real-World Use of Oral and Subcutaneous Semaglutide in Routine Clinical Practice in the UK: A Single-Centre, Retrospective Observational Study.

INTRODUCTION: Semaglutide, the only glucagon-like peptide-1 receptor agonist (GLP-1 RA) available in subcutaneous and oral formulation for treatment of type 2 diabetes (T2D), has demonstrated clinically significant improvements in glycaemic control and weight in clinical trials. This study aimed to gain insights into the use of both formulations and evaluate their clinical effectiveness in a secondary care clinic in Wales. METHODS: This was a retrospective observational analysis of adults with T2D initiated on oral or subcutaneous semaglutide. Changes from baseline in glycated haemoglobin (HbA1c), weight and other metabolic parameters were evaluated. RESULTS: At baseline, participants (n = 103) had a mean age of 57.3 years, mean HbA1c of 79.1 mmol/mol (9.38%), mean weight of 111.8 kg and body mass index (BMI) of 39.6 kg/m2 (no statistically significant differences between oral and subcutaneous groups). At 6-month follow-up, statistically significant improvements in HbA1c (- 19.3 mmol/mol [- 1.77%] and - 20.8 mmol/mol [- 1.90%]), body weight (- 9.0 kg and - 7.2 kg), and BMI (- 3.3 kg/m2 and - 2.5 kg/m2) were observed for oral and subcutaneous semaglutide, respectively. No statistically significant differences between the formulations were observed, and safety profiles were comparable. CONCLUSIONS: Both formulations of semaglutide provided clinically and statistically significant reductions in HbA1c and weight in real-world practice. Oral GLP-1 RA may offer a practical and effective option for the management of T2D.

Early use of oral semaglutide in the UK: A cost-effectiveness analysis versus continuing metformin and SGLT-2 inhibitor therapy.

OBJECTIVES: Many people with type 2 diabetes experience clinical inertia, remaining in poor glycaemic control on oral glucose-lowering medications rather than intensifying treatment with a glucagon-like peptide-1 receptor agonist, despite an efficacious, orally administered option, oral semaglutide, being available. The present study evaluated the long-term cost-effectiveness of initiating oral semaglutide versus continuing metformin plus sodium-glucose cotransporter-2 (SGLT-2) inhibitor therapy in the UK. DESIGN: Outcomes were projected over patients' lifetimes using the IQVIA Core Diabetes Model (V.9.0). Clinical data were taken from the oral semaglutide and placebo arms of the patient subgroup receiving metformin plus an SGLT-2 inhibitor in PIONEER 4. Costs, expressed in 2021 Pounds sterling (GBP), were accounted from a healthcare payer perspective. INTERVENTIONS: Modelled patients received oral semaglutide immediately (in the first year of the analysis) or after a 2-year delay, after which all physiological parameters were brought to values observed in the immediate therapy arm. During the simulation, patients intensified with the addition of basal insulin and, subsequently, by switching to basal-bolus insulin. RESULTS: Immediate oral semaglutide therapy was associated with improvements in life expectancy of 0.17 (95% CIs 0.16 to 0.19) years, and quality-adjusted life expectancy of 0.15 (0.14 to 0.16) quality-adjusted life years (QALYs), versus a 2-year delay. Benefits were due to a reduced incidence of diabetes-related complications. Direct costs were estimated to be GBP 1423 (1349 to 1496) higher with immediate oral semaglutide therapy versus a 2-year delay, with higher treatment costs partially offset by cost savings from avoidance of diabetes-related complications. Immediate oral semaglutide therapy was therefore associated with an incremental cost-effectiveness ratio of GBP 9404 (8380 to 10 538) per QALY gained versus a 2-year delay. CONCLUSIONS: Immediate oral semaglutide is likely to represent a cost-effective treatment in people with type 2 diabetes with inadequate glycaemic control on metformin plus an SGLT-2 inhibitor in the UK. TRIAL REGISTRATION NUMBER: NCT02863419.

Effect of semaglutide on major adverse cardiovascular events by baseline kidney parameters in participants with type 2 diabetes and at high risk of cardiovascular disease: SUSTAIN 6 and PIONEER 6 post hoc pooled analysis.

BACKGROUND: Semaglutide is a glucose-lowering treatment for type 2 diabetes (T2D) with demonstrated cardiovascular benefits; semaglutide may also have kidney-protective effects. This post hoc analysis investigated the association between major adverse cardiovascular events (MACE) and baseline kidney parameters and whether the effect of semaglutide on MACE risk was impacted by baseline kidney parameters in people with T2D at high cardiovascular risk. METHODS: Participants from the SUSTAIN 6 and PIONEER 6 trials, receiving semaglutide or placebo, were categorised according to baseline kidney function (estimated glomerular filtration rate [eGFR] < 45 and ≥ 45-<60 versus ≥ 60 mL/min/1.73 m2) or damage (urine albumin:creatinine ratio [UACR] ≥ 30-≤300 and > 300 versus < 30 mg/g). Relative risk of first MACE by baseline kidney parameters was evaluated using a Cox proportional hazards model. The same model, adjusted with inverse probability weighting, and a quadratic spline regression were applied to evaluate the effect of semaglutide on risk and event rate of first MACE across subgroups. The semaglutide effects on glycated haemoglobin (HbA1c), body weight (BW) and serious adverse events (SAEs) across subgroups were also evaluated. RESULTS: Independently of treatment, participants with reduced kidney function (eGFR ≥ 45-<60 and < 45 mL/min/1.73 m2: hazard ratio [95% confidence interval]; 1.36 [1.04;1.76] and 1.52 [1.15;1.99]) and increased albuminuria (UACR ≥ 30-≤300 and > 300 mg/g: 1.53 [1.14;2.04] and 2.52 [1.84;3.42]) had an increased MACE risk versus those without. Semaglutide consistently reduced MACE risk versus placebo across all eGFR and UACR subgroups (interaction p value [pINT] > 0.05). Semaglutide reduced HbA1c regardless of baseline eGFR and UACR (pINT>0.05); reductions in BW were affected by baseline eGFR (pINT<0.001) but not UACR (pINT>0.05). More participants in the lower eGFR or higher UACR subgroups experienced SAEs versus participants in reference groups; the number of SAEs was similar between semaglutide and placebo arms in each subgroup. CONCLUSIONS: MACE risk was greater for participants with kidney impairment or damage than for those without. Semaglutide consistently reduced MACE risk across eGFR and UACR subgroups, indicating that semaglutide provides cardiovascular benefits in people with T2D and at high cardiovascular risk across a broad spectrum of kidney function and damage. TRIAL REGISTRATIONS: NCT01720446; NCT02692716.

Weekly Icodec versus Daily Glargine U100 in Type 2 Diabetes without Previous Insulin.

BACKGROUND: Insulin icodec is an investigational once-weekly basal insulin analogue for diabetes management. METHODS: We conducted a 78-week randomized, open-label, treat-to-target phase 3a trial (including a 52-week main phase and a 26-week extension phase, plus a 5-week follow-up period) involving adults with type 2 diabetes (glycated hemoglobin level, 7 to 11%) who had not previously received insulin. Participants were randomly assigned in a 1:1 ratio to receive once-weekly insulin icodec or once-daily insulin glargine U100. The primary end point was the change in the glycated hemoglobin level from baseline to week 52; the confirmatory secondary end point was the percentage of time spent in the glycemic range of 70 to 180 mg per deciliter (3.9 to 10.0 mmol per liter) in weeks 48 to 52. Hypoglycemic episodes (from baseline to weeks 52 and 83) were recorded. RESULTS: Each group included 492 participants. Baseline characteristics were similar in the two groups. The mean reduction in the glycated hemoglobin level at 52 weeks was greater with icodec than with glargine U100 (from 8.50% to 6.93% with icodec [mean change, -1.55 percentage points] and from 8.44% to 7.12% with glargine U100 [mean change, -1.35 percentage points]); the estimated between-group difference (-0.19 percentage points; 95% confidence interval [CI], -0.36 to -0.03) confirmed the noninferiority (P<0.001) and superiority (P = 0.02) of icodec. The percentage of time spent in the glycemic range of 70 to 180 mg per deciliter was significantly higher with icodec than with glargine U100 (71.9% vs. 66.9%; estimated between-group difference, 4.27 percentage points [95% CI, 1.92 to 6.62]; P<0.001), which confirmed superiority. Rates of combined clinically significant or severe hypoglycemia were 0.30 events per person-year of exposure with icodec and 0.16 events per person-year of exposure with glargine U100 at week 52 (estimated rate ratio, 1.64; 95% CI, 0.98 to 2.75) and 0.30 and 0.16 events per person-year of exposure, respectively, at week 83 (estimated rate ratio, 1.63; 95% CI, 1.02 to 2.61). No new safety signals were identified, and incidences of adverse events were similar in the two groups. CONCLUSIONS: Glycemic control was significantly better with once-weekly insulin icodec than with once-daily insulin glargine U100. (Funded by Novo Nordisk; ONWARDS 1 ClinicalTrials.gov number, NCT04460885.).

Impact of severe hypoglycaemia requiring hospitalization on mortality in people with type 1 diabetes: A national retrospective observational cohort study.

AIMS: To assess if the risk of all-cause mortality increases in people with type 1 diabetes (T1D) with increasing number of severe hypoglycaemia episodes requiring hospitalization. MATERIALS AND METHODS: We conducted a national retrospective observational cohort study in people with T1D (diagnosed between 2000 and 2018). Clinical, comorbidity and demographic variables were assessed for impact on mortality for people with no, one, two and three or more episodes of severe hypoglycaemia requiring hospitalization. The time to death (all-cause mortality) from the timepoint of the last episode of severe hypoglycaemia was modelled using a parametric survival model. RESULTS: A total of 8224 people had a T1D diagnosis in Wales during the study period. The mortality rate (95% confidence interval [CI]) was 6.9 (6.1-7.8) deaths/ 1000 person-years (crude) and 15.31 (13.3-17.63) deaths/ 1000 person-years (age-adjusted) for those with no occurrence of severe hypoglycaemia requiring hospitalization. For those with one episode of severe hypoglycaemia requiring hospitalization the mortality rate (95% CI) was 24.9 (21.0-29.6; crude) and 53.8 (44.6-64.7) deaths/ 1000 person-years (age-adjusted), for those with two episodes of severe hypoglycaemia requiring hospitalization it was 28.0 (23.1-34.0; crude) and 72.8 (59.2-89.5) deaths/ 1000 person-years (age-adjusted), and for those with three or more episodes of severe hypoglycaemia requiring hospitalization it was 33.5 (30.0-37.3; crude) and 86.3 (71.7-103.9) deaths/ 1000 person years (age-adjusted; P < 0.001). A parametric survival model showed that having two episodes of severe hypoglycaemia requiring hospitalization was the strongest predictor for time to death (accelerated failure time coefficient 0.073 [95% CI 0.009-0.565]), followed by having one episode of severe hypoglycaemia requiring hospitalization (0.126 [0.036-0.438]) and age at most recent episode of severe hypoglycaemia requiring hospitalization (0.917 [0.885-0.951]). CONCLUSIONS: The strongest predictor for time to death was having two or more episodes of severe hypoglycaemia requiring hospitalization.

Automated Insulin Delivery Around Exercise in Adults with Type 1 Diabetes: A Pilot Randomized Controlled Study.

Aim: To assess the effectiveness of an automated insulin delivery (AID) system around exercise in adults with type 1 diabetes (T1D). Methods: This was a three-period, randomized, crossover trial involving 10 adults with T1D (hemoglobin A1C; HbA1c: 8.3% ± 0.6% [67 ± 6 mmol/mol]) using an AID system (MiniMed 780G; Medtronic USA). Participants performed 45 min of moderate intensity continuous exercise 90 min after consuming a carbohydrate-based meal using three strategies: (1) a 100% dose of bolus insulin with exercise announcement immediately at exercise onset "spontaneous exercise" (SE) or a 25% reduced dose of bolus insulin with exercise announcement either (2) 90 min (AE90) or (3) 45 min (AE45) before exercise. Venous-derived plasma glucose (PG) taken in 5 and 15 min intervals over a 3 h collection period was stratified into the percentage of time spent below (TBR [<3.9 mmol/L]), time in range (TIR [3.9-10 mmol/L]), and time above range (TAR [ > 10 mmol/L]). In instances of hypoglycemia, PG data were carried forward for the remainder of the visit. Results: Overall, TBR was greatest during SE (SE: 22.9 ± 22.2, AE90: 1.1 ± 1.9, AE45: 7.8% ± 10.3%, P = 0.029). Hypoglycemia during exercise occurred in four participants in SE but one in both AE90 and AE45 (ꭓ2 [2] = 3.600, P = 0.165). In the 1 h postexercise period, AE90 was associated with higher TIR (SE: 43.8 ± 49.6, AE90: 97.9 ± 5.9, AE45: 66.7% ± 34.5%, P = 0.033), lower TBR (SE: 56.3 ± 49.6, AE90: 2.1 ± 5.9, AE45: 29.2% ± 36.5%, P = 0.041) with the greatest source of discrepancy observed relative to SE. Conclusion: In adults using an AID system and undertaking postprandial exercise, a strategy involving both bolus insulin dose reduction and exercise announcement 90 min before commencing the activity may be most effective in minimizing dysglycemia. The study was registered as a clinical trial (Clinical Trials Register; NCT05134025).

Emerging drugs for the treatment of type 1 diabetes mellitus: a review of phase 2 clinical trials.

INTRODUCTION: Despite therapeutic advances in the field of diabetes management since the discovery of insulin 100 years ago, there are still unmet clinical needs for people with type 1 diabetes mellitus (T1DM). AREAS COVERED: Genetic testing and islet autoantibodies testing allow researchers to design prevention studies. This review discusses the emerging therapy for prevention of T1DM, disease modification therapy in early course of T1DM, and therapies and technologies for established T1DM. We focus on phase 2 clinical trials with promising results, thus avoiding the exhausted list of every new therapy for T1DM. EXPERT OPINION: Teplizumab has demonstrated potential as a preventative agent for individuals at risk prior to the onset of overt dysglycemia. However, these agents are not without side effects, and there are uncertainties on long-term safety. Technological advances have led a substantial influence on quality of life of people suffering from T1DM. There remains variation in uptake of new technologies across the globe. Novel insulins (ultra-long acting), oral insulin, and inhaled insulin attempt to narrow the gap of unmet needs. Islet cell transplant is another exciting field, and stem cell therapy might have potential to provide unlimited supply of islet cells.

Glucagon-Like Peptide 1 Therapy: From Discovery to Type 2 Diabetes and Beyond.

The therapeutic benefits of the incretin hormone, glucagon-like peptide 1 (GLP1), for people with type 2 diabetes and/or obesity, are now firmly established. The evidence-base arising from head-to-head comparative effectiveness studies in people with type 2 diabetes, as well as the recommendations by professional guidelines suggest that GLP1 receptor agonists should replace more traditional treatment options such as sulfonylureas and dipeptidyl-peptidase 4 (DPP4) inhibitors. Furthermore, their benefits in reducing cardiovascular events in people with type 2 diabetes beyond improvements in glycaemic control has led to numerous clinical trials seeking to translate this benefit beyond type 2 diabetes. Following early trial results their therapeutic benefit is currently being tested in other conditions including fatty liver disease, kidney disease, and Alzheimer's disease.

Post hoc analysis of SUSTAIN 6 and PIONEER 6 trials suggests that people with type 2 diabetes at high cardiovascular risk treated with semaglutide experience more stable kidney function compared with placebo.

Glucagon-like peptide-1 receptor agonists reduce albuminuria and may stabilize the estimated glomerular filtration rate (eGFR) in people with type 2 diabetes (T2D). In this post hoc analysis of the SUSTAIN 6/PIONEER 6 trials encompassing 6480 participants at high cardiovascular risk (semaglutide, 3239 participants; placebo, 3241 participants), we investigated the effects of semaglutide versus placebo on eGFR decline. Pooled data by treatment were evaluated for annual eGFR change (total annual eGFR slope in ml/min per 1.73 m2) from baseline to end of treatment and time to persistent eGFR reductions of 30%, 40%, 50% and 57% or more, including subgroup analyses by baseline eGFR (30 to under 60 or 60 and over ml/min per 1.73 m2). In the overall population, the estimated treatment difference (ETD; semaglutide versus placebo) in annual eGFR slope was significant at 0.59 ml/min per 1.73 m2 (95% confidence interval 0.29; 0.89). The ETD was numerically largest in the 30 to under 60 ml/min per 1.73 m2 eGFR subgroup, 1.06 ml/min per 1.73 m2 (0.45; 1.67), but no significant interaction was observed for treatment effect by subgroup. Hazard ratios (semaglutide versus placebo) for time to persistent eGFR decline were under 1.0 for all eGFR thresholds in the overall population; and were numerically lower in the baseline eGFR 30 to under 60 ml/min per 1.73 m2 subgroup versus the overall population, although no significant interaction was observed for treatment effect by subgroup. Thus, pooled analyses of clinical trial data in patients with T2D suggest that semaglutide may reduce the rate of eGFR decline.

Glycemia Around Exercise in Adults with Type 1 Diabetes Using Automated and Nonautomated Insulin Delivery Pumps: A Switch Pilot Trial.

In an in-patient switch study, 10 adults with type 1 diabetes (T1D) performed 45 min of moderate-intensity exercise on 2 occasions: (1) when using their usual insulin pump (UP) and (2) after transitioning to automated insulin delivery (AID) treatment (MiniMed™ 780G). Consensus glucose management guidelines for performing exercise were applied. Plasma glucose concentrations measured over a 3-h monitoring period were stratified into time below range (TBR, <3.9 mmol/L), time in range (TIR, 3.9-10.0 mmol/L), and time above range (TAR, >10.0 mmol/L). Overall, TBR (UP: 11 ± 21 vs. AID: 3% ± 10%, P = 0.413), TIR (UP: 53 ± 27 vs. AID: 66% ± 39%, P = 0.320), and TAR (UP: 37 ± 34 vs. AID: 31% ± 41%, P = 0.604) were similar between arms. A proportionately low number of people experienced exercise-induced hypoglycemia (UP: n = 2 vs. AID: n = 1, P = 1.00). In conclusion, switching to AID therapy did not alter patterns of glycemia around sustained moderate-intensity exercise in adults with T1D. Clinical Trial Registration number: NCT05133765.

The long-term cost-effectiveness of once-weekly semaglutide 1 mg vs. dulaglutide 3 mg and 4.5 mg in the UK.

AIMS: Once-weekly semaglutide and dulaglutide represent two highly efficacious treatment options for type 2 diabetes. A recent indirect treatment comparison (ITC) has associated semaglutide 1 mg with similar and greater improvements in glycated haemoglobin (HbA1c) and body weight, respectively, vs. dulaglutide 3 mg and 4.5 mg. The present study aimed to evaluate the long-term cost-effectiveness of semaglutide 1 mg vs. dulaglutide 3 mg and 4.5 mg in the UK. MATERIALS AND METHODS: The IQVIA CORE Diabetes Model (v9.0) was used to project outcomes over patients' lifetimes. Baseline cohort characteristics were sourced from SUSTAIN 7, with changes in HbA1c and body mass index applied as per the ITC. Modelled patients received semaglutide or dulaglutide for 3 years, after which treatment was intensified to basal insulin. Costs (expressed in 2020 pounds sterling [GBP]) were accounted from a healthcare payer perspective. RESULTS: Semaglutide 1 mg was associated with improvements in quality-adjusted life expectancy of 0.05 and 0.04 quality-adjusted life years (QALYs) vs. dulaglutide 3 mg and 4.5 mg, respectively, due to a reduced incidence of diabetes-related complications with semaglutide. Direct costs were estimated to be GBP 76 lower and GBP 8 higher in the comparisons with dulaglutide 3 mg and 4.5 mg, respectively. Overall outcomes were similar, but favoured semaglutide, and based on modelled mean outcomes it was considered dominant vs. dulaglutide 3 mg and associated with an incremental cost-effectiveness ratio of GBP 228 per QALY gained vs. dulaglutide 4.5 mg. CONCLUSIONS: Semaglutide 1 mg represents a cost-effective treatment vs. dulaglutide 3 mg and 4.5 mg for type 2 diabetes from a healthcare payer perspective in the UK.

Metabolic and physiological responses to graded exercise testing in individuals with type 1 diabetes using insulin pump therapy.

AIMS: To profile acute glycaemic dynamics during graded exercise testing (GXT) and explore the influence of glycaemic indicators on the physiological responses to GXT in adults with type 1 diabetes using insulin pump therapy. METHODS: This was a retrospective analysis of pooled data from four clinical trials with identical GXT protocols. Data were obtained from 45 adults with type 1 diabetes using insulin pumps [(30 females); haemoglobin A1c 59.5 ± 0.5 mmol/mol (7.6 ± 1.0%); age 49.7 ± 13.0 years; diabetes duration 31.2 ± 13.5 years; V̇O2peak 29.5 ± 8.0 ml/min/kg]. Integrated cardiopulmonary variables were collected continuously via spiroergometry. Plasma glucose was obtained every 3 min during GXT as well as the point of volitional exhaustion. Data were assessed via general linear modelling techniques with age and gender adjustment. Significance was accepted at p ≤ .05. RESULTS: Despite increasing duration and intensity, plasma glucose concentrations remained similar to rest values (8.8 ± 2.3 mmol/L) throughout exercise (p = .419) with an overall change of +0.3 ± 1.1 mmol/L. Starting glycaemia bore no influence on subsequent GXT responses. Per 1% increment in haemoglobin A1c there was an associated decrease in V̇O2peak of 3.8 ml/min/kg (p < .001) and powerpeak of 0.33 W/kg (p < .001) concomitant with attenuations in indices of peripheral oxygen extraction [(O2 pulse) -1.2 ml/beat, p = .023]. CONCLUSION: In adults with long-standing type 1 diabetes using insulin pump therapy, circulating glucose remains stable during a graded incremental cycle test to volitional exhaustion. Glycaemic indicators are inversely associated with aerobic rate, oxygen economy and mechanical output across the exercise intensity spectrum. An appreciation of these nexuses may help guide appropriate decision making for optimal exercise management strategies.