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Objectives: Recent trials of glucose-lowering drugs (GLDs) have drawn attention to renal outcomes. Our goal was to understand how patients with diabetic kidney disease (DKD) are treated in general practices in the United States., Study Design: Retrospective cohort study using a national-level claims data set and electronic health records., Methods: Patients (≥ 18 years) with type 2 diabetes, whose estimated glomerular filtration rates (eGFRs) were between 15 and 89 mL/min/1.73 m2 between 2016 and 2018, were selected. Use of different GLDs during a 12-month period was examined across all eGFR levels., Results: Of the 25,486 sample patients, 69.2%, 18.9%, 9.6%, and 2.3% had an eGFR in the ranges of 60 to 89, 45 to 59, 30 to 44, and 15 to 29 mL/min/1.73 m2, respectively. Metformin was used by nearly 33% of patients with an eGFR of 30 to 44 mL/min/1.73 m2 and by 10% of patients with an eGFR less than 30 mL/min/1.73 m2. Less than 10% (across all eGFR levels) of patients used glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors. Use of insulin was more frequent among patients with a lower eGFR (P < .05). The findings were similar in subgroups with different hemoglobin A1c levels (< 7% and ≥ 7%)., Conclusions: Real-world treatment of DKD in the United States is suboptimal. Inappropriate use of some GLD classes, especially in advanced DKD stages, was found along with lower than expected use of modern agents that are considered safe and effective to treat glycemic outcomes. Efforts may be needed to improve understanding of safety, glycemic efficacy, and overall clinical value of GLDs across DKD stages.

Purpose: To estimate the incremental cost-utility ratio of oral semaglutide (14 mg once daily) vs other glucagon-like peptide 1 receptor agonist treatments among adults with type 2 diabetes that was inadequately controlled with 1 to 2 oral antidiabetic drugs from a US payer perspective., Methods: A state-transition model with a competing risk approach was developed for diabetic complications and risk of cardiovascular events based on the UK Prospective Diabetes Study Outcomes Model 1 equations. Baseline population characteristics reflect the PIONEER 4 trial (Efficacy and Safety of Oral Semaglutide Versus Liraglutide and Versus Placebo in Subjects With Type 2 Diabetes Mellitus) of oral semaglutide. Model comparators included subcutaneous semaglutide, dulaglutide, and liraglutide. Treatment effects (change in glycosylated hemoglobin, weight, and systolic blood pressure) were estimated by network meta-analysis. Drug, management, and event costs (in 2019 US dollars), survival after nonfatal events, and utilities were obtained from the literature. Costs and quality-adjusted life-year (QALY) outcomes were discounted at 3% annually over a lifetime horizon. Probabilistic and 1-way sensitivity analyses were performed., Findings: Total estimated costs and QALYs were $144,065 and 12.98 for oral semaglutide, $145,721 and 12.96 for dulaglutide, $145,833 and 12.99 for SC semaglutide, and $149,428 and 12.97 for liraglutide, respectively. Oral semaglutide was less costly and more effective than dulaglutide and liraglutide but less costly than subcutaneous semaglutide with similar effectiveness. Oral semaglutide was favored versus subcutaneous semaglutide in 52.10% of model replications at a willingness-to-pay of $150,000 per QALY., Implications: Oral semaglutide is predicted to offer health benefits similar to subcutaneous semaglutide and ahead of dulaglutide and liraglutide. Oral semaglutide is a cost-effective glucagon-like peptide 1 receptor agonist treatment option., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: Patients managing type 2 diabetes mellitus (T2DM) often require combination therapy to meet their blood glucose control targets. With limited real-world evidence focused on the use of glucagon-like peptide 1 receptor agonist (GLP-1RA) therapies, the objective of this study was to describe the association between semaglutide once weekly (OW) initiation and changes in hemoglobin A 1c (A 1c ) levels., Methods: This retrospective, descriptive cohort study used the HealthCore Integrated Research Environment (HIRE) to examine commercially insured and Medicare Advantage patients who had T2DM while taking semaglutide OW from December 1, 2017, to April 30, 2019. The first semaglutide OW prescription fill was defined as the study index date. Changes in mean A 1c levels and A 1c target attainment were evaluated among an intention-to-treat (ITT) population (overall group). Furthermore, a persistent population (PP) analysis on the same outcomes was performed that was limited to ITT patients who were observed to continue to use semaglutide OW at the time of the postindex A 1c measurement. In addition, these outcomes were explored in patients stratified based on prior use of GLP-1RA therapy (experienced vs naive) and baseline A 1c values >9% (75 mmol/mol)., Findings: A total of 1888 patients were identified in the overall ITT group. The mean change in the overall ITT group between preindex and postindex A 1c values was -0.9% percentage points (-9.8 mmol/mol) (mean preindex A 1c , 8.2% [66.1 mmol/mol]) and -1.1 percentage points (-12.0 mmol/mol) (mean preindex A 1c , 8.2% [66.1 mmol/mol]) in the PP subgroup (all P < 0.001). Among the subgroup of patients with a baseline A 1c value >9% (75 mmol/mol), percentage point changes in A 1c were -2.2 (-24.0 mmol/mol) and -2.4 (-26.2 mmol/mol) (all P < 0.001). When accounting for prior GLP-1RA use, the GLP-1RA-naive stratum had double the mean reduction in A 1c compared with the GLP-1RA-experienced stratum (-1.2 [-13.1 mmol/mol] vs -0.6 [-6.6 mmol/mol] percentage points)., Implications: Semaglutide OW is associated with clinically and statistically significant A 1C reduction and increases in reaching A 1 targets using real-world data, even in GLP-1RA-experienced patients, despite more frequent use of insulin or sodium glucose transport protein 2 inhibitors in this group. Target A 1c attainment significantly increased overall and within all subgroups and strata, with approximately half of all patients attaining an A 1c value <7% (53 mmol/mol) and three-quarters attaining an A 1c value <8% (64 mmol/mol)., Competing Interests: Disclosures Chioma Uzoigwe, Caroline Swift, Tam Dang-Tan, and Yurek Paprocki report being employees of Novo Nordisk during the conduct of this study. In addition, Chioma Uzoigwe and Yurek Paprocki report being stockholders with Novo Nordisk. Jay Visaria and Vincent Willey report being employees of HealthCore, Inc during the conduct of this study. Authors from NovoNordisk contributed to the study by participating in study design, data analysis and interpretation, manuscript writing and revisions, and approval for publication. HealthCore Inc receives funding from numerous external entities to perform research projects. The authors have indicated that they have no other conflicts of interest regarding the content of this article., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: The efficacy and safety of oral semaglutide, the first glucagon-like peptide-1 (GLP-1) receptor agonist developed for oral administration for the treatment of type 2 diabetes, was evaluated in the PIONEER clinical trial program, and a recently published network meta-analysis allowed comparison with further injectable GLP-1 receptor agonists. The present study aimed to assess the short-term cost- effectiveness of oral semaglutide 14 mg versus subcutaneous once-weekly dulaglutide 1.5 mg, once-weekly exenatide 2 mg, twice-daily exenatide 10 µg, once-daily liraglutide 1.8 mg, once-daily lixisenatide 20 µg, and once-weekly semaglutide 1 mg, in terms of the cost per patient achieving glycated hemoglobin (HbA1c) targets (cost of control). Materials and methods: Cost of control was calculated by dividing the annual treatment costs associated with an intervention by the proportion of patients achieving the treatment target with an intervention, with outcomes calculated for targets of HbA1c ≤6.5% and HbA1c <7.0% for all included GLP-1 receptor agonists. Annual treatment costs were accounted in 2019 United States dollars (USD), based on 2019 wholesale acquisition cost. Results: For the treatment target of HbA1c ≤6.5%, once-weekly semaglutide 1 mg and oral semaglutide 14 mg were associated with the lowest costs of control, at USD 15,430 and USD 17,383 per patient achieving target, respectively. Similarly, the cost of control was lowest with once-weekly semaglutide 1 mg at USD 12,627 per patient achieving target, followed by oral semaglutide 14 mg at USD 13,493 per patient achieving target for the target of HbA1c <7.0%. All other interventions were associated with higher cost of control values for both targets. Conclusions: Oral semaglutide 14 mg is likely to be cost-effective versus dulaglutide, exenatide (once weekly and twice daily), liraglutide, and lixisenatide in terms of bringing people with type 2 diabetes to glycemic control targets of HbA1c ≤6.5% and HbA1c <7.0% in the US.

Introduction: Therapeutic inertia refers to the failure to initiate or intensify treatment in a timely manner and is widespread in type 2 diabetes (T2D) despite the well-established importance of maintaining good glycemic control. The aim of this analysis was to quantify the clinical and economic burden associated with poor glycemic control due to therapeutic inertia in patients with T2D in the USA., Methods: The IQVIA CORE Diabetes Model was used to simulate life expectancy, costs associated with diabetes-related complications, and lost workplace productivity in US patients. Baseline glycated hemoglobin (HbA1c) levels were 7.0% (53 mmol/mol), 9.0% (75 mmol/mol), 11.0% (97 mmol/mol) 13.0% (119 mmol/mol), or 15.0% (140 mmol/mol), with targets of 6.5% (48 mmol/mol), 7.0% (53 mmol/mol), 8.0% (64 mmol/mol), or 9.0% (75 mmol/mol) depending on baseline HbA1c, across several delayed intensification scenarios (values above target were defined as poor control). The burden associated with intensification delays of 1, 2, 3, 5, and 7 years was estimated over time horizons of 1-30 years. Future costs and clinical benefits were discounted at 3% annually., Results: In a population of 13.4 million patients with T2D and baseline HbA1c of 9.0% (75 mmol/mol), delaying intensification of therapy by 1 year was associated with a loss of approximately 13,390 life-years and increased total costs of US dollars (USD) 7.3 billion (1-year time horizon). Longer delays in intensification were associated with a greater economic burden. Delaying intensification by 7 years was projected to cost approximately 3 million life-years and USD 223 billion over a 30-year time horizon., Conclusion: Therapeutic inertia is common in routine clinical practice and makes a substantial contribution to the burden associated with type 2 diabetes in the USA. Initiatives and interventions aimed at preventing therapeutic inertia are needed to improve clinical outcomes and avoid excess costs.

Introduction: Oral semaglutide is the first orally administered glucagon-like peptide-1 receptor agonist for the treatment of type 2 diabetes, and has been evaluated in the PIONEER clinical trial program. These trials assessed the proportions of patients achieving single and composite endpoints, encompassing glycemic control [defined in terms of glycated hemoglobin (HbA1c)], weight loss, and hypoglycemia. The present study assessed the cost of control with oral semaglutide versus empagliflozin, sitagliptin, and liraglutide in the US., Methods: Four endpoints were evaluated: (1) HbA1c ≤ 6.5%; (2) HbA1c < 7.0%; (3) ≥ 1.0%-point HbA1c reduction and weight loss ≥ 3.0%; and (4) HbA1c < 7.0% without hypoglycemia and without weight gain. The proportions of patients achieving each endpoint were sourced from the PIONEER 2, 3 and 4 trials. Treatment costs were accounted over an annual time-period in 2019 US dollars (USD), based on wholesale acquisition cost. Cost of control was calculated by dividing treatment costs by the proportion of patients achieving each target., Results: Oral semaglutide was consistently associated with the lowest cost of control for all four endpoints. For the targets of HbA1c ≤ 6.5% and HbA1c < 7.0%, oral semaglutide 14 mg was associated with lower cost of control than empagliflozin 25 mg, sitagliptin 100 mg and liraglutide 1.8 mg by USD 15,036, 14,697, and 6996, respectively, and USD 931, 346 and 4497, respectively. For the double composite endpoint, cost of control was lower with oral semaglutide 14 mg by USD 525, 32,277 and 13,011, respectively versus empagliflozin 25 mg, sitagliptin 100 mg and liraglutide 1.8 mg. For the triple composite endpoint, cost of control was lower with oral semaglutide 14 mg by USD 1255, 7510 and 5774, respectively., Conclusion: Oral semaglutide was associated with lower cost of bringing patients with type 2 diabetes to four clinically-relevant treatment targets versus empagliflozin, sitagliptin, and liraglutide in the US., Funding: Novo Nordisk A/S.

Background: Previous studies report weight loss to be associated with significantly lower total health care costs among patients with type 2 diabetes mellitus (T2DM). The effect of weight change on health care costs, independent of glycemic control and after controlling for time-varying covariates among T2DM patients, remains unknown., Objective: To evaluate the effect of weight change, independent of glycemic control, on all-cause and T2DM-related health care resource utilization (HCRU) and costs among T2DM patients in the United States., Methods: A retrospective cohort study was conducted using a linked data extract composed of IQVIA's RWI Data Adjudicated Claims-US and Ambulatory Electronic Medical Record data. Adults (aged ≥ 18 years) with T2DM receiving ≥ 1 oral antidiabetic drug (OAD) medication, glucagon-like peptide-1 receptor agonist (GLP-1RA), and/or short- or long-acting insulin between January 1, 2010, and December 31, 2014 were included (the date of the first observed medical claim with a diagnosis code or medication prescription claim was the index date). Baseline characteristics were evaluated in the 6-month pre-index period. Weight loss (3%, 5%, or 7% from baseline) was evaluated over two 6-month periods (months 1-6 and 7-12) following the index date. Covariates included time-varying weight, hemoglobin A1c (A1c), costs, and HCRU within each 6-month period. Outcomes of interest (all-cause and T2DM-related HCRU and costs) were evaluated in the 6-month (months 13-18) and 12-month (months 13-24) periods following the initial 1- to 6-month and 7- to 12-month post-index periods. Structural nested mean models were used to evaluate the effect of weight change on these outcomes, independent of glycemic control., Results: 1,407 patients were included (mean age = 55 years; 55% male), with a mean baseline weight of 102.2 kg (median = 99.7 kg) and a mean baseline A1c of 7.4% (median = 6.9%). In adjusted analysis, weight loss was associated with significantly lower all-cause and T2DM-related annual total health care costs. Compared with those showing no weight change, a 3%, 5%, and 7% weight loss resulted in approximately $500, $800, and $1,100 in savings, respectively, in all-cause annual total health care costs per patient in the year following the weight loss. Similarly, compared with those with no weight change, a 3%, 5%, and 7% weight loss resulted in approximately $200, $300, and $400 in savings, respectively, in T2DM-related annual total health care costs per patient in the following year. Even greater savings (up to ~$2,000 and ~$800 in all-cause and T2DM-related annual costs per patient, respectively) were experienced by those who lost weight compared with those who gained weight., Conclusions: After accounting for glycemic control, this study found that weight loss was associated with additional significant reductions in all-cause and T2DM-related annual total health care costs. Understanding the role of weight loss in T2DM may provide useful evidence for decision makers as they evaluate therapy options for T2DM., Disclosures: This study was funded by Novo Nordisk. Dang-Tan, Smolarz, and Iyer are employees of Novo Nordisk. Karkare and DeKoven (employees of IQVIA) and Fridman (employed by AMF Consulting) were contracted by Novo Nordisk to conduct this study. Fridman also reports personal fees from Shire, GSK, and CSL Behring, outside of the submitted work. Lu, an employee of IQVIA, accessed the database and conducted the statistical analysis for this study.

Introduction: The SUSTAIN 3 and 7 clinical trials compared the efficacy and safety of once-weekly semaglutide relative to exenatide extended-release (ER) and dulaglutide, respectively, in the treatment of patients with type 2 diabetes (T2D). The trials included a series of clinically relevant single and composite endpoints focused on improving glycemic control and reducing body weight, while avoiding hypoglycemia. The present study combined SUSTAIN 3 and 7 outcomes with short-term treatment costs to evaluate the relative cost of control of once-weekly semaglutide versus exenatide ER and dulaglutide., Methods: Proportions of patients reaching three endpoints were taken from SUSTAIN 3 and 7 for comparisons with exenatide ER and dulaglutide, respectively. The endpoints investigated were HbA1c < 7.0%, HbA1c < 7.0% without hypoglycemia or weight gain, and a ≥ 1.0% HbA1c reduction with ≥ 5.0% weight loss. Annual per patient treatment costs were based on US wholesale acquisition costs from July 2018. Relative cost of control was calculated by plotting the ratio of the treatment costs and the ratio of the proportions of patients reaching each endpoint on the cost-efficacy plane., Results: Once-weekly semaglutide 0.5 mg and 1.0 mg were most effective at bringing patients to each of the three endpoints across both SUSTAIN trials. The efficacy-to-cost ratios for once-weekly semaglutide 0.5 mg and 1.0 mg were also superior to all comparators when assessing both the single endpoint of HbA1c < 7.0% and the two composite endpoints including weight loss and hypoglycemia., Conclusions: The present study showed that once-weekly semaglutide 0.5 mg and 1.0 mg offer superior cost of control versus exenatide ER and dulaglutide in terms of achieving single and composite endpoints, based on an analysis of retrieved dropout data. Once-weekly semaglutide 0.5 mg and 1.0 mg would therefore represent good value for money in the USA, particularly in the attainment of multi-model T2D treatment goals., Funding: Novo Nordisk A/S.

Aims: Bringing patients with type 2 diabetes to recommended glycated hemoglobin (HbA1c) treatment targets can reduce the risk of developing diabetes-related complications. The aim of the present analysis was to evaluate the short-term cost-effectiveness of once-daily liraglutide 1.8 mg vs once-daily lixisenatide 20 μg as an add-on to metformin for treatment of type 2 diabetes in the US by assessing the cost per patient achieving HbA1c-focused and composite treatment targets., Materials and Methods: Percentages of patients achieving recommended targets were obtained from the LIRA-LIXI trial, which compared the efficacy and safety of once-daily liraglutide 1.8 mg and once-daily lixisenatide 20 μg as an add-on to metformin in patients with type 2 diabetes failing to achieve glycemic control with metformin. Annual costs were estimated from a healthcare payer perspective. An economic model was developed to evaluate the annual cost per patient achieving target (cost of control) with liraglutide 1.8 mg vs lixisenatide 20 μg for five end-points., Results: Annual treatment costs were higher with liraglutide 1.8 mg than lixisenatide 20 μg, but this was offset by greater clinical efficacy, and the cost of control was lower with liraglutide 1.8 mg than lixisenatide 20 μg for all five end-points. The annual cost of control was USD 3,850, USD 11,404, USD 3,807, USD 4,299, and USD 6,901 lower for liraglutide 1.8 mg than lixisenatide 20 μg for targets of HbA1c < 7.0%, HbA1c ≤ 6.5%, HbA1c < 7.0% and no weight gain, HbA1c < 7.0% with no weight gain and no confirmed hypoglycemia, and HbA1c < 7.0% with no weight gain and systolic blood pressure <140 mmHg, respectively., Conclusions: Once-daily liraglutide 1.8 mg was associated with greater clinical efficacy than once-daily lixisenatide 20 μg, which resulted in a lower annual cost of control for HbA1c-focused and composite treatment targets.