Impact of BMI and comorbidities on efficacy of once-weekly semaglutide: Post hoc analyses of the STEP 1 randomized trial.

OBJECTIVE: This study assessed the effects of semaglutide on body weight, cardiometabolic risk factors, and glycemic status in individuals categorized by baseline BMI with or without additional obesity-related comorbidities, including prediabetes and high risk of cardiovascular disease (CVD). METHODS: This was a post hoc exploratory subgroup analysis of the Semaglutide Treatment Effect in People with Obesity (STEP) 1 trial (NCT03548935), in which participants without diabetes and BMI ≥30 kg/m2 , or BMI ≥27 kg/m2 with ≥1 weight-related comorbidity, were randomized to once-weekly subcutaneous semaglutide 2.4 mg or placebo for 68 weeks. For this analysis, individuals were categorized into subgroups based on baseline BMI <35 versus ≥35 kg/m2 (with no additional criteria, with ≥1 comorbidity, with prediabetes, and with prediabetes and high risk of CVD). RESULTS: Mean changes in body weight from baseline to week 68 with semaglutide were -16.2% and -14.0% in the subgroups with baseline BMI <35 and ≥35 kg/m2 , respectively (both p < 0.0001 vs. placebo). Similar changes were observed in individuals with comorbidities, with prediabetes, and with prediabetes plus high CVD risk. The beneficial effects of semaglutide on cardiometabolic risk factors were consistent across all subgroups. CONCLUSIONS: This subgroup analysis confirms that semaglutide is effective in individuals with baseline BMI <35 and ≥35 kg/m2 , including in those with comorbidities.

Effect of once-weekly subcutaneous semaglutide 2.4 mg on weight- and health-related quality of life in an East Asian population: Patient-reported outcomes from the STEP 6 trial.

We assessed the effect of semaglutide 2.4 and 1.7 mg versus placebo on weight-related quality of life (WRQOL) and health-related quality of life (HRQOL) in the STEP 6 trial. Adults from East Asia (body mass index [BMI] ≥27.0 kg/m2 with ≥2 weight-related comorbidities, or ≥35.0 kg/m2 with ≥1 weight-related comorbidity) were randomized 4:1:2:1 to once-weekly subcutaneous semaglutide 2.4 mg or placebo, or semaglutide 1.7 mg or placebo, plus lifestyle intervention for 68 weeks. WRQOL and HRQOL were assessed from baseline to Week 68 using the Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQOL-Lite-CT) and the 36-Item-Short-Form-Survey-version-2.0 acute (SF-36v2), with changes in scores by categories of baseline BMI (

Disutility of injectable therapies in obesity and type 2 diabetes mellitus: general population preferences in the UK, Canada, and China.

INTRODUCTION: Once-daily and once-weekly injectable glucagon-like peptide-1 receptor agonist therapies (GLP-1 RAs) are established in obesity and type 2 diabetes mellitus (T2DM). In T2DM, both once-daily and once-weekly insulin are expected to be available. This study elicited utilities associated with these treatment regimens from members of the general public in the UK, Canada, and China, to quantify administration-related disutility of more-frequent injectable treatment, and allow economic modelling. METHODS: Two anchor states (no pharmacological treatment), and seven treatment states (daily oral tablet and generic injectable regimens of variable frequency), with identical outcomes were tested A broadly representative sample of the general public in each country participated (excluding individuals with diabetes or pharmacologically treated obesity). An adapted Measurement and Valuation of Health protocol was administered 1:1 in web-enabled interviews by trained moderators: visual analogue scale (VAS) as a "warm-up", and time trade-off (TTO) using a 20-year time horizon for utility elicitation. RESULTS: A total of 310 individuals participated. The average disutility of once-daily versus once-weekly GLP-1 RA was - 0.048 in obesity and - 0.033 in T2DM; the corresponding average disutility for insulin was - 0.064. Disutilities were substantially greater in China, relative to UK and Canada. DISCUSSION: Within obesity and T2DM, more-frequent treatment health states had lower utility. Scores by VAS also followed a logical order. The generated utility values are suitable for use in modelling injectable therapy regimens in obesity and T2DM, due to the use of generic descriptions and assumption of equal efficacy. Future research could examine the reasons for greater administration-related disutility in China.

The public economic burden of suboptimal type 2 diabetes control upon taxpayers in Sweden: Looking beyond health costs.

AIM: To estimate the fiscal burden for taxpayers in Sweden associated with type 2 diabetes (T2D) attributed to diabetes-related complications in patients failing to meet HbA1c targets. MATERIAL AND METHODS: We developed a public economic framework to assess how changes in diabetes-related complications influenced projected tax contributions and government disability payments for people with T2D. The analysis applied accepted disease-modelling practices to estimate different rates of diabetes-related complications based on an HbA1c of 6.9% (52 mmol/mol) and of 6.0% (42 mmol/mol). We adjusted the employment activity rates for those experiencing T2D-related events, applying age-specific earnings to estimate lifetime tax losses. Furthermore, the likelihood of receiving payments for health-related employment inactivity was estimated. Direct healthcare costs are excluded from this analysis. RESULTS: The estimated per person earnings loss for immediate and delayed HbA1c control was Swedish krona (SEK) 42 299 and SEK 44 157, respectively, over 10 years. The lost employment activity of people with T2D translates to lost tax revenues of SEK 23 265 and SEK 24 287 for immediate and delayed control, respectively. The estimated difference in disability payments was SEK 538. Combining the tax revenue loss and excess disability payments defines the broader fiscal costs, where we observe combined fiscal losses that favour immediate and sustained control by SEK 1560 over 10 years. CONCLUSIONS: We show that conducting fiscal analysis of diabetes interventions offers an enriched perspective capturing a range of costs that fall on government in relation to lost tax revenue and disability payments. Tax-financed health systems may benefit from broadening the consideration of costs and benefits when evaluating new interventions and treatment practices.

An Indirect Treatment Comparison of Semaglutide 2.0 mg vs Dulaglutide 3.0 mg and 4.5 mg Using Multilevel Network Meta-regression.

AIMS: Currently, no head-to-head data are available comparing semaglutide 2.0 mg with dulaglutide 3.0 mg or 4.5 mg. We conducted an indirect treatment comparison (ITC) of their effects on glycated hemoglobin (HbA1c) and body weight in patients with type 2 diabetes. MATERIALS AND METHODS: Multilevel network meta-regression was conducted, based on a connected evidence network of published results from the A Study of the Efficacy and Safety of Dulaglutide (LY2189265) in Participants With Type 2 Diabetes 11 trial and individual patient data from the A Research Study to Compare Two Doses of Semaglutide Taken Once Weekly in People With Type 2 Diabetes (SUSTAIN) and SUSTAIN 7 trials. RESULTS: Semaglutide 2.0 mg significantly reduced HbA1c vs dulaglutide 3.0 mg and 4.5 mg, with estimated treatment differences (ETDs) of -0.44% points (95% credible interval [CrI], -0.68 to -0.19) and -0.28% points (95% CrI, -0.52 to -0.03), respectively. Semaglutide 2.0 mg also significantly reduced body weight vs dulaglutide 3.0 mg and 4.5 mg with ETDs of -3.29 kg (95% CrI, -4.62 to -1.96) and -2.57 kg (95% CrI, -3.90 to -1.24), respectively. Odds of achieving HbA1c < 7.0% were significantly greater for semaglutide 2.0 vs dulaglutide 3.0 mg (odds ratio [OR]: 2.23 [95% CrI, 1.15-3.90]), whereas this did not reach significance for semaglutide 2.0 mg vs dulaglutide 4.5 mg (OR: 1.58 [95% CrI, 0.82-2.78]). Sensitivity analyses supported the main analysis findings. CONCLUSIONS: This ITC demonstrated significantly greater reductions from baseline in HbA1c and body weight with semaglutide 2.0 mg vs dulaglutide 3.0 mg and 4.5 mg. The findings of this study provide important comparative effectiveness information until randomized head-to-head studies become available.

Evaluating the Cost-Effectiveness of Once-Weekly Semaglutide 1 mg Versus Empagliflozin 25 mg for Treatment of Patients with Type 2 Diabetes in the UK Setting.

INTRODUCTION: Type 2 diabetes represents a continuing healthcare challenge, and choosing cost-effective treatments is crucial to ensure that healthcare resources are used efficiently. The present analysis assessed the cost-effectiveness of once-weekly semaglutide 1 mg versus empagliflozin 25 mg for the treatment of patients with type 2 diabetes mellitus with inadequate glycaemic control on metformin monotherapy from a healthcare payer perspective in the UK. METHODS: Outcomes were projected over patient lifetimes using the IQVIA CORE Diabetes Model. Baseline cohort characteristics and treatment effects of initiation of once-weekly semaglutide 1 mg and empagliflozin 25 mg were based on an indirect comparison conducted using patient-level data, as there is currently no head-to-head clinical trial comparing these therapies. Modelled patients received treatments until glycated haemoglobin exceeded 7.5% (58 mmol/mol), at which point patients initiated basal insulin. The analysis captured pharmacy costs and costs of diabetes-related complications, expressed in 2019 pounds sterling (GBP). Projected outcomes were discounted at 3.5% annually. Scenario analyses were prepared to assess uncertainty around projected outcomes. RESULTS: Once-weekly semaglutide 1 mg was associated with increases in life expectancy and quality-adjusted life expectancy of 0.12 years and 0.23 quality-adjusted life years (QALYs), respectively, compared with empagliflozin 25 mg. Projected improvements in quality and duration of life resulted from a reduced cumulative incidence and a delayed time to onset of diabetes-related complications. Once-weekly semaglutide was associated with increased pharmacy costs, but this was partially offset by avoided costs of treating complications. Once-weekly semaglutide was associated with an increase in costs of GBP 1017 per patient, leading to an incremental cost-effectiveness ratio of GBP 4439 per QALY gained. CONCLUSION: Once-weekly semaglutide 1 mg was projected to be a cost-effective treatment option from a healthcare payer perspective compared with empagliflozin 25 mg for the treatment of patients with type 2 diabetes in the UK setting.

The Economic Burden of Insulin-Related Hypoglycemia in Adults with Diabetes: An Analysis from the Perspective of the Italian Healthcare System.

INTRODUCTION: The aim of this analysis was to estimate the cost of insulin-related hypoglycemia in adult patients with diabetes in Italy using the Local Impact of Hypoglycemia Tool (LIHT), and to explore the effect of different hypoglycemia rates on budget impact. METHODS: Direct costs and healthcare resource utilization were estimated for severe and non-severe hypoglycemic episodes in Italy and applied to the population of adults with type 1 diabetes (T1DM) and type 2 diabetes (T2DM) and their corresponding hypoglycemia episode rates (0.49 severe and 53.3 non-severe episodes per year for T1DM, and 0.09 severe and 9.3 non-severe episodes per year for T2DM). Uncertainty around model inputs was explored through sensitivity and scenario analyses. RESULTS: The direct cost of insulin-related hypoglycemia in Italy is estimated at €144.7 million per year, with €65 million attributable to severe episodes and €79.6 million due to non-severe episodes. The total cost of hypoglycemia is approximately 1.7-fold higher for T2DM (€91.7 million) than for T1DM (€53 million). The cost of a hypoglycemic episode ranges from €4.59 for a non-severe event where additional self-monitoring of blood glucose (SMBG) testing is the only cost incurred, to €5790.59 for a severe event that also requires an ambulance, A&E, hospitalization, and a visit to a diabetes specialist. A reduction in hypoglycemia event rates could result in substantial cost savings; for example, a 20% reduction in severe and non-severe hypoglycemia rates could result in a saving of €47,769 per general population of 100,000 people. CONCLUSIONS: The LIHT highlights the substantial economic burden of insulin-related hypoglycemia in Italy, particularly with regards to non-severe hypoglycemia, an aspect of hypoglycemia that is often overlooked. This analysis may aid healthcare decision-making by allowing the costs of insulin therapies or diabetes self-management programs to be balanced with the savings provided by reductions in hypoglycemia. FUNDING: Novo Nordisk, UK.

The Economic Burden of Insulin-Related Hypoglycemia in Spain.

INTRODUCTION: An analysis was conducted to estimate the economic burden of insulin-related hypoglycemia in adults in Spain, derived from a novel concept developed for the UK known as the Local Impact of Hypoglycemia Tool. METHODS: Costs per severe and non-severe hypoglycemic episode were calculated for patients with type 1 diabetes (T1DM) and type 2 diabetes (T2DM). The costs per episode were applied to the population of adults with T1DM and T2DM using insulin in Spain according to the number of severe and non-severe episodes experienced per year. Costs were calculated using Spanish-specific resource costs and published values for resource utilization, including ambulance, accident and emergency (A&E) department, hospitalization, healthcare professional visits, and extra self-monitoring of blood glucose (SMBG) tests used in the week following the episode. A one-way sensitivity analysis on all model inputs was then performed. RESULTS: The cost of insulin-related hypoglycemia in Spain is estimated as €662.0 m per year, €292.6 m of which is due to severe episodes and €369.4 m to non-severe episodes. The cost per episode varies from €1.25 for patients with T1DM and €1.48 for patients with T2DM for a non-severe episode where extra SMBG testing after the episode is the only action taken, to €4378.22 for T1DM and €3005.74 for T2DM for a severe episode that was treated in hospital and requires an ambulance, A&E visit, hospitalization, and a diabetes specialist visit. A reduction in severe and non-severe hypoglycemia rates of just 20% could lead to considerable cost savings of €284,925 per 100,000 general population. CONCLUSION: This analysis highlights the substantial economic burden of hypoglycemia in Spain, and gives budget holders the ability to assess the costs of new treatments or patient education programs in relation to the potential cost savings due to lower hypoglycemia rates.