Injectable Glucagon-like Peptide-1 Research Articles

The Effect of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists on the Lipid Profile of Diabetic Patients Using Statins: A Retrospective Cohort Study in the Diabetic Center of King Salman Bin Abdulaziz Hospital, Saudi Arabia.

Background Dyslipidemia is a common complication of type 2 diabetes mellitus (T2DM), which is the leading cause of morbidity and mortality in developed countries, including Saudi Arabia. Injectable glucagon-like peptide-1 receptor agonists (GLP-1RA) are recent therapies found to be effective in treating dyslipidemia in diabetic patients by acting similarly to the body's internal glucagon peptide hormone, regulating blood sugar levels and reducing triglycerides and low-density lipoprotein (LDL) levels. Aim of the study This retrospective cohort study aimed to investigate the effect of GLP-1RA on the lipid profile of dyslipidemia diabetic patients who were not controlled using statins. Methods Data were collected from the medical records of male and female diabetic patients with dyslipidemia (uncontrolled by statins) who were administered to the diabetic center of King Salman Bin Abdulaziz Hospital in Riyadh, Saudi Arabia, and received GLP-1RA (dulaglutide) from June 2023 to August 2023. The primary endpoint was the change in triglycerides and LDL-C levels after three months of using dulaglutide, and the secondary endpoints included the change in body weight, BMI, and HbA1c%. Descriptive analysis was conducted to present numerical and categorical data. The Wilcoxon signed-ranktest was used to compare numerical data before and after using dulaglutide. Ethical considerations were taken into account by ensuring anonymous data collection and obtaining IRB approval before data collection. Results The study included 102 patients with a median (interquartile range (IQR)) age of 59 (14) years. Females constituted 55.2% of the population. Obesity (96.1%), hypertension (71.6%), and retinopathy (13.7%) were the most commonly reported comorbidities. The study showed a significant reduction in body weight, BMI, HbA1c, hemoglobin, mean corpuscular volume (MCV), serum LDL-C, and triglyceride concentrations after three months of using dulaglutide (p<0.001). Conclusion Our study results confirm the positive effect of the GLP-1RA (dulaglutide) on the lipid profile of diabetic patients with dyslipidemia uncontrolled by statins.

Hemiplegic Migraines Exacerbated using an Injectable GLP-1 Agonist for Weight Loss.

The widespread adoption of Glucagon-like peptide-1 (GLP-1) receptor agonists for the treatment of obesity and diabetes has raised concerns about their potential adverse effects, including the induction of depression and suicide ideation. We report on a male patient in his early 50s with a complex medical history, including adult Attention-Deficit/Hyperactive Disorder, narcolepsy with cataplexy, and major depressive disorder in remission, who experienced exacerbated hemiplegic migraines after initiating treatment with an injectable GLP-1 agonist (Saxenda) for weight loss. Despite a previous history of experiencing hemiplegic migraines once or twice a year, the patient reported daily occurrences of migraines, many of which were hemiplegic, during the 60 days of GLP-1 agonist treatment. The migraines abated only upon discontinuation of the medication. This case underscores the need to carefully consider patient history and potential genetic predispositions when prescribing GLP-1 agonists, highlighting the complex interactions between these medications, existing comorbidities, and the dopaminergic and calcitonin gene-related peptide pathways. Our findings suggest that GLP-1 agonists, while beneficial for some, may pose significant risks for patients with specific genetic backgrounds or neurological conditions, calling for personalized approaches to treatment and increased awareness of potential adverse effects.

A new indication for semaglutide (Wegovy).

The injectable glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide (Wegovy) has been approved by the FDA to reduce the risk of major adverse cardiovascular events (MACE) in adults with established cardiovascular disease (CVD) and either obesity or overweight.

Prevalence Patterns of Body Contouring Procedures Among Injectable Glucagon-like Peptide-1 Receptor Agonist Users.

The introduction of injectable glucagon-like peptide-1 (GLP-1) receptor agonists such as Ozempic (Novo Nordisk, Plainsboro, NJ) and Wegovy (Novo Nordisk Inc.) has transformed weight loss in plastic surgery patients, often leading to excess skin and soft tissue amenable to body contouring procedures. The aim of this study was to examine the relationship between injectable GLP-1 receptor agonist use and the growing need for body contouring surgeries, focusing on trunk and extremity procedures. A retrospective analysis of the PearlDiver database (PearlDiver, Inc., Colorado Springs, CO) was conducted, examining prescription data for Ozempic, Wegovy, and liraglutide, and correlating these with body contouring procedures across 30 US states from 2011 to 2022. Multimodal statistics were used to compare surgery rates and assess dosage and time interval patterns among GLP-1 receptor agonist users and nonusers. Significant correlations between GLP-1 receptor agonist use (881 Ozempic, 59 Wegovy, and 4655 liraglutide users) and increased body contouring surgeries were found. Ozempic showed weak correlations with brachioplasty (r = 0.23) and panniculectomy (r = 0.21), and Wegovy with breast procedures (r = 0.28), while liraglutide showed consistent correlations across surgeries. Time to surgery varied from 87 days (Wegovy) to 1018 days (liraglutide), with higher surgery rates among users (P < .01) and dose-related differences, especially in Ozempic and Wegovy users. This study demonstrates a dose-dependent link between the use of GLP-1 receptor agonists and an increase in subsequent aesthetic body contouring surgeries, highlighting the need for surgeons to adapt to the merging of medicinal body transformation and aesthetic plastic surgery.

Tirzepatide 10 and 15 mg vs semaglutide 2.0 mg: A long-term cost-effectiveness analysis in patients with type 2 diabetes in the United States.

Tirzepatide is a novel glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist approved for type 2 diabetes (T2D) treatment. To compare the long-term cost-effectiveness of tirzepatide 10 mg and 15 mg vs semaglutide 2.0 mg, an injectable glucagon-like peptide-1 receptor agonist, in patients with T2D from a US health care payer perspective. The PRIME T2D Model was used to project clinical and cost outcomes over a 50-year time horizon. Baseline cohort characteristics and treatment effects were sourced from a published adjusted indirect treatment comparison that used data from the SURPASS-2 and SUSTAIN FORTE trials. Patients were assumed to intensify to insulin therapy at a hemoglobin A1c of greater than 7.5%. Costs and health state utilities were derived from published sources. Future costs and clinical benefits were discounted at 3% annually. Tirzepatide 10 mg and 15 mg were associated with improved quality-adjusted life-expectancy (10 mg: 0.085 quality-adjusted life-years [QALYs], 15 mg: 0.121 QALYs), higher direct costs (10 mg: USD 5,990, 15 mg: USD 6,617), and incremental cost-effectiveness ratios of USD 70,147 and 54,699 per QALY gained, respectively, vs semaglutide 2.0 mg. Both doses of tirzepatide remained cost-effective vs semaglutide 2.0 mg over a range of sensitivity analyses. Long-term projections using the PRIME T2D model and based on treatment effects from an adjusted indirect treatment comparison indicate that tirzepatide 10 mg and 15 mg are likely to be cost-effective vs semaglutide 2.0 mg for the treatment of T2D in the United States.

Impact on Knowledge, Competence, and Performance of a Faculty-Led Web-Based Educational Activity for Type 2 Diabetes and Obesity: Questionnaire Study Among Health Care Professionals and Analysis of Anonymized Patient Records.

Strategies for managing type 2 diabetes (T2D) and obesity are evolving with the introduction of targeted therapies, including incretin-based dual agonists and growing knowledge of the importance of multidisciplinary care. Accessible, effective continuing medical education (CME) activities are required to ensure that health care professionals (HCPs) understand and can implement the most recent data to optimize patient outcomes. We aimed to measure changes in knowledge, competence, and self-reported performance and quantitatively evaluate changes in performance using anonymized patient data following participation in a web-based educational activity. The faculty-led CME-accredited activity was based on incretin-based dual agonists and patient education on T2D and obesity. The remaining educational gaps in this field were also identified. A CME-accredited, web-based, multidisciplinary (touchMDT) educational activity titled "The future for glycemic control and weight loss in T2D and obesity: Incretin-based dual-agonists and optimizing patient education" was developed. HCP knowledge, competence, and performance were assessed before and after the activity against Moore's expanded outcomes framework (levels 1-5), using self-reported questionnaires and by analyzing anonymized patient record data. For evaluating knowledge and competence (50 respondents before and 50 learners after the activity), the mean number of correctly answered questions was significantly higher post activity (median 5.0, IQR 4.0-6.0 to 6.0, IQR 5.0-7.0; mean 4.98, SD 1.22 to 5.78, SD 1.13; P<.001). Modest, nonsignificant improvements in self-reported performance (N=50 respondents preactivity; N=50 learners postactivity) from before to after the activity were observed (median 4.0, IQR 3.25-4.0 to 4.0, IQR 4.0-4.0; mean 3.64, SD 0.69 to 3.76, SD 0.48; P=.32). PPatient data analysis indicated that patients were being treated more intensively postactivity: before the activity, the most commonly used treatment regimens were metformin monotherapy (13/50, 26%) and dual therapy with metformin plus injectable glucagon-like peptide-1 (GLP-1) receptor agonist (RA; 11/50, 22%); post activity, this changed to dual therapy with metformin plus injectable GLP-1 RA (12/50, 24%) and triple therapy with metformin plus injectable GLP-1 RA plus sodium-glucose cotransporter-2 inhibitor (SGLT2i; 10/50, 20%). In addition, there was an increased number of referrals to a combination of specialists (physicians referred 27%, 8/30 of patients to ≥2 specialists before the activity and 36%, 10/28 to ≥2 specialists post activity). The remaining educational gaps included understanding the biology and psychology of obesity, efficacy and safety data for incretin-based dual agonists, and the role of the diabetes educator or diabetes care and education specialist in managing T2D and obesity. This short, web-based CME activity on the management of T2D and obesity led to improvements in HCP knowledge, competence, and performance. Several remaining unmet needs were identified, which can be used to inform the content of future educational activities in this disease area.

Efficacy and safety of oral orforglipron in patients with type 2 diabetes: a multicentre, randomised, dose-response, phase 2 study

Orforglipron, an oral, non-peptide glucagon-like peptide-1 (GLP-1) receptor agonist, is in development for type 2 diabetes and obesity. We assessed the efficacy and safety of orforglipron versus placebo or dulaglutide in participants with type 2 diabetes. In this 26-week, phase 2, double-blind, randomised, multicentre study, participants were recruited from 45 centres (private clinics, hospitals, and research centers) in the USA, Hungary, Poland, and Slovakia. Adult participants aged 18 years or older with type 2 diabetes treated with diet and exercise, with or without metformin, and with a glycated haemoglobin (HbA1c) of 7·0-10·5%, and stable BMI of 23 kg/m2 or more, were randomly assigned (5:5:5:5:5:3:3:3:3) via an interactive web-response system to placebo, dulaglutide 1·5 mg once per week, or orforglipron 3 mg, 12 mg, 24 mg, 36 mg (group 1), 36 mg (group 2), 45 mg (group 1), or 45 mg (group 2) once per day with no food or water restrictions. Two different dose escalation regimens were evaluated for each of the 36 mg and 45 mg cohorts. Participants were masked to the study drug, dulaglutide, and placebo. The primary efficacy outcome The primary efficacy outcome was mean change in HbA1c from baseline with orforglipron versus placebo at week 26. Efficacy was analysed in all randomly assigned participants who received at least one dose of study drug and excluded data after the permanent discontinuation of study drug or initiation of rescue medication. Safety was analysed in all participants who received at least one dose of study treatment. This trial is registered at ClinicalTrials.gov (NCT05048719) and is completed. Between Sept 15, 2021, and Sept 30, 2022, 569 participants were screened and 383 were enrolled and randomly assigned to a group. 352 (92%) completed the study and 303 (79%) completed 26 weeks of treatment. At baseline, the mean age was 58·9 years, HbA1c was 8·1%, BMI was 35·2 kg/m2, 226 (59%) were men, and 157 (41%) were women. At week 26, mean change in HbA1c with orforglipron was up to -2·10% (-1·67% placebo adjusted), versus -0·43% with placebo and -1·10% with dulaglutide. HbA1c reduction was statistically superior with orforglipron versus placebo (estimated treatment difference -0·8% to -1·7%). Change in mean bodyweight at week 26 was up to -10·1 kg (95% CI -11·5 to -8·7; 7·9 kg placebo adjusted [-9·9 to -5·9]) with orforglipron versus -2·2 kg (-3·6 to -0·7) for placebo and -3·9 kg (-5·3 to -2·4) for dulaglutide. The incidence of treatment-emergent adverse events ranged from 61·8% to 88·9% in orforglipron-treated participants, compared with 61·8% with placebo and 56·0% with dulaglutide. The majority were gastrointestinal events (44·1% to 70·4% with orforglipron, 18·2% with placebo, and 34·0% with dulaglutide) of mild to moderate severity. Three participants receiving orforglipron and one participant receiving dulaglutide had clinically significant (<54 mg/dL [<3 mmol/L]) hypoglycaemia and no participants had severe hypoglycaemia. One death occurred in the placebo group and was not related to study treatment. In this phase 2 trial the novel, oral, non-peptide GLP-1 receptor agonist orforglipron at doses of 12 mg or greater showed significant reductions in HbA1c and bodyweight compared with placebo or dulaglutide. The adverse event profile was similar to other GLP-1 receptor agonists in similar stage of development. Orforglipron might provide an alternative to injectable GLP-1 receptor agonists and oral semaglutide, with the prospect of less burdensome administration to achieve treatment goals in people with type 2 diabetes. Eli Lilly and Company.

Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity

BackgroundObesity is a major risk factor for many leading causes of illness and death worldwide. Data are needed regarding the efficacy and safety of the nonpeptide glucagon-like peptide-1 (GLP-1) receptor agonist orforglipron as a once-daily oral therapy for weight reduction in adults with obesity.MethodsIn this phase 2, randomized, double-blind trial, we enrolled adults with obesity, or with overweight plus at least one weight-related coexisting condition, and without diabetes. Participants were randomly assigned to receive orforglipron at one of four doses (12, 24, 36, or 45 mg) or placebo once daily for 36 weeks. The percentage change from baseline in body weight was assessed at week 26 (primary end point) and at week 36 (secondary end point).ResultsA total of 272 participants underwent randomization. At baseline, the mean body weight was 108.7 kg, and the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 37.9. At week 26, the mean change from baseline in body weight ranged from −8.6% to −12.6% across the orforglipron dose cohorts and was −2.0% in the placebo group. At week 36, the mean change ranged from −9.4% to −14.7% with orforglipron and was −2.3% with placebo. A weight reduction of at least 10% by week 36 occurred in 46 to 75% of the participants who received orforglipron, as compared with 9% who received placebo. The use of orforglipron led to improvement in all prespecified weight-related and cardiometabolic measures. The most common adverse events reported with orforglipron were gastrointestinal events, which were mild to moderate, occurred primarily during dose escalation, and led to discontinuation of orforglipron in 10 to 17% of participants across dose cohorts. The safety profile of orforglipron was consistent with that of the GLP-1 receptor agonist class.ConclusionsDaily oral orforglipron, a nonpeptide GLP-1 receptor agonist, was associated with weight reduction. Adverse events reported with orforglipron were similar to those with injectable GLP-1 receptor agonists. (Funded by Eli Lilly; GZGI ClinicalTrials.gov number, NCT05051579.)

RWD78 Characterization of Patients Treated with Semaglutide 2.4MG for Chronic Weight Management: A Retrospective Cohort Study

Semaglutide 2.4 mg is an injectable glucagon-like peptide-1 receptor agonist used for chronic weight management. There is limited published evidence on characteristics of patients treated with semaglutide 2.4 mg in a real-world setting. Our objective was to characterize US patients with obesity initiating semaglutide 2.4 mg compared with patients treated with other branded antiobesity medications (bAOMs) or without bAOM treatment using linked claims and electronic medical record databases.

The Impact of Substantial Improvements in HbA1c and Weight Loss on the Medication Preferences of People with Type 2 Diabetes.

To quantify the preferences of people with type 2 diabetes (T2D) for treatment attributes of a glucose-dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonist (RA) versus an injectable GLP-1 RA medication profile. Injection-naive people taking oral medications for T2D in the US and UK completed a web survey including a discrete choice experiment to quantify patients' preferences for five treatment attributes: delivery system, frequency of nausea, frequency of hypoglycemia, HbA1c reduction, and weight reduction. Attributes and levels were based on head-to-head clinical trial data of tirzepatide 5mg, 10mg, and 15mg versus semaglutide 1mg. Preference data were analyzed separately by country using multinomial mixed logit (MXL) models. MXL parameters were used to estimate the predicted preference for each tirzepatide dose versus semaglutide 1mg. Direct preferences for each dose of tirzepatide versus semaglutide 1mg were elicited. Participants (N=620) in the US(N=301) and UK(N=319) were 50.8% and 50.5% female with mean ages of 60.7 years and 58.9 years, respectively. The order and magnitude of relative attribute importance (RAI) scores differed between countries. HbA1c reduction (26.3%) had the greatest impact on US participants' preferences, and hypoglycemia (32.8%) did among UK participants. Attribute-level marginal utility results indicated preferences for greater HbA1c improvements, the single-use pre-filled pen, lower hypoglycemia, greater weight reductions, and lower frequency of nausea. Assuming the availability of only tirzepatide or semaglutide 1mg, the predicted preference for tirzepatide (5, 10, and 15mg) in the US is 95.6% (vs 4.4% for semaglutide 1mg) and in the UK was 86.3% (vs 13.7% for semaglutide 1mg). HbA1c reduction, frequency of hypoglycemia, and weight reduction are key drivers of preferences among people with T2D when considering medication options. Overall, people with T2D are likely to prefer the tirzepatide over the semaglutide 1mg medication profiles.

In brief: Semaglutide (Wegovy) for weight loss in children.

The injectable glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide (Wegovy), which was approved by the FDA in 2021 for chronic weight management in adults,1 has now been approved for chronic weight management in children ≥12 years old with an initial BMI in the ≥95th percentile for age and sex.Semaglutide is also available as Ozempic and Rybelsus for treatment of type 2 diabetes in adults.

Long-term cost-effectiveness analysis of tirzepatide versus semaglutide 1.0 mg for the management of type 2 diabetes in the United States.

To evaluate the long-term cost-effectiveness of tirzepatide (5, 10 and 15 mg doses), a novel glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, versus semaglutide 1.0 mg, an injectable glucagon-like peptide-1 receptor agonist, based on the results of the head-to-head SURPASS-2 trial, from a US healthcare payer perspective. The PRIME Type 2 Diabetes Model was used to make projections of clinical and cost outcomes over a 50-year time horizon. Baseline cohort characteristics, treatment effects and adverse event rates were derived from the 40-week SURPASS-2 trial. Intensification to insulin therapy occurred when HbA1c reached 7.5%, in line with American Diabetes Association recommendations. Direct costs in 2021 US dollars (US$) and health state utilities were derived from published sources. Future costs and clinical benefits were discounted at 3% annually. All three doses of tirzepatide were associated with lower diabetes-related complication rates, improved life expectancy, improved quality-adjusted life expectancy and higher direct costs versus semaglutide. This resulted in incremental cost-effectiveness ratios of US$ 75 803, 58 908 and 48 785 per quality-adjusted life year gained for tirzepatide 5, 10 and 15 mg, respectively, versus semaglutide. Tirzepatide remained cost-effective versus semaglutide over a range of sensitivity analyses. Long-term projections based on the SURPASS-2 trial results indicate that 5, 10 and 15 mg doses of tirzepatide are likely to be cost-effective versus semaglutide 1.0 mg for the treatment of type 2 diabetes in the United States.

Therapeutic inertia related to the injectable glucagon-like peptide-1 receptor agonists dulaglutide and semaglutide in patients with type 2 diabetes in UK primary care.

To determine the extent of therapeutic inertia related to the weekly injectable glucagon-like peptide-1 receptor agonists dulaglutide and semaglutide in patients with type 2 diabetes (T2D) in the United Kingdom. Adults with T2D who received their first primary care prescription of dulaglutide or semaglutide between January and July 2019 were identified from the UK Clinical Practice Research Datalink GOLD primary care database. Doses prescribed, glycated haemoglobin (HbA1c), body mass index (BMI) and concomitant T2D medications were assessed at first prescription and at 3, 6 and 9months. Of the patients prescribed dulaglutide (N=748; mean [SD] age 59.0 [11.2] years) and semaglutide (N=437; mean [SD] age 58.4 [10.6] years), 93.0% and 89.0%, respectively, had an HbA1c level ≥7.5%(≥58.46mmol/mol), and 56.4% and 54.9%, respectively, had an HbA1c level ≥9.0%(≥74.86mmol/mol), at first prescription. At 6 to 9 months, 75.0% of those on dulaglutide 0.75 mg and 57.6% of those on semaglutide 0.25 mg or 0.5 mg had an HbA1c level ≥7.5%(≥58.46mmol/mol). At 9 months, 21.9% of the dulaglutide cohort were on the suboptimal dose of 0.75 mg, and 46.1% of the semaglutide cohort were on the suboptimal doses of 0.25 mg or 0.5mg. Multiple examples of therapeutic inertia were identified, including first prescription at HbA1c levels considerably above target and failure to escalate to optimal doses even with evidence of suboptimal metabolic control. A substantial proportion of patients therefore did not achieve optimal HbA1c targets.

First-Line Therapy for Type 2 Diabetes With Sodium-Glucose Cotransporter-2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists : A Cost-Effectiveness Study.

Guidelines recommend sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP1) receptor agonists as second-line therapy for patients with type 2 diabetes. Expanding their use as first-line therapy has been proposed but the clinical benefits may not outweigh their costs. To evaluate the lifetime cost-effectiveness of a strategy of first-line SGLT2 inhibitors or GLP1 receptor agonists. Individual-level Monte Carlo-based Markov model. Randomized trials, Centers for Disease Control and Prevention databases, RED BOOK, and the National Health and Nutrition Examination Survey. Drug-naive U.S. patients with type 2 diabetes. Lifetime. Health care sector. First-line SGLT2 inhibitors or GLP1 receptor agonists. Life expectancy, lifetime costs, incremental cost-effectiveness ratios (ICERs). First-line SGLT2 inhibitors and GLP1 receptor agonists had lower lifetime rates of congestive heart failure, ischemic heart disease, myocardial infarction, and stroke compared with metformin. First-line SGLT2 inhibitors cost $43000 more and added 1.8 quality-adjusted months versus first-line metformin ($478000 per quality-adjusted life-year [QALY]). First-line injectable GLP1 receptor agonists cost more and reduced QALYs compared with metformin. By removing injection disutility, first-line GLP1 receptor agonists were no longer dominated (ICER, $327000 per QALY). Oral GLP1 receptor agonists were not cost-effective (ICER, $823000 per QALY). To be cost-effective at under $150000 per QALY, costs for SGLT2 inhibitors would need to be under $5 per day and under $6 per day for oral GLP1 receptor agonists. U.S. population and costs not generalizable internationally. As first-line agents, SGLT2 inhibitors and GLP1 receptor agonists would improve type 2 diabetes outcomes, but their costs would need to fall by at least 70% to be cost-effective. American Diabetes Association.

Real-world usage of sulphonylureas in Asian patients with type 2 diabetes using the Joint Asia Diabetes Evaluation (JADE) register.

To explore the patterns of use of oral glucose-lowering drugs (OGLDs) in Asian patients with type 2 diabetes (T2D), focusing on sulphonylureas (SUs), and to describe patient profiles according to treatment regimen. We conducted a cross-sectional analysis of data from adults with T2D from 11 Asian countries/regions with structured assessment enrolled in the prospective Joint Asia Diabetes Evaluation (JADE) register between November 2007 and December 2019. Patients receiving insulin and/or injectable glucagon-like peptide-1 receptor agonists were excluded. Amongst 62 512 patients (mean ± standard deviation age: 57.3 ± 11.8 years; 53.6% men), 54 783 (87.6%) were treated with OGLDs at enrolment. Most received one (37.5%) or two (44.2%) OGLDs. In the entire cohort, 59.4% of treated patients received SU-based therapy with variations amongst countries/regions. Overall, 79.5% of SU regimens were based on SUs plus metformin, and 22.1% on SUs plus dipeptidyl peptidase-4 inhibitors. Among SU users, gliclazide was most commonly prescribed (46.7%), followed by glimepiride (40.0%) and glibenclamide (8.1%). More gliclazide users entered the cohort with glycated haemoglobin levels <53 mmol/mol (7%) than non-gliclazide SU users (odds ratio [OR] 1.09, 95% CI 1.02-1.17), with less frequent self-reported hypoglycaemia in the 3 months before registration (OR 0.81, 95% CI 0.72-0.92; adjusted for sociodemographic factors, cardiometabolic risk factors, complications, use of other OGLDs, country/region and year of registration). In Asia, SUs are a popular OGLD class, often combined with metformin. Good glycaemic control and safety profiles associated with the use of SUs, including gliclazide, support their position as a key treatment option in patients with T2D.

738-P: The Real-World Observational Prospective Study of Health Outcomes with Dulaglutide and Liraglutide in Type 2 Diabetes Patients (TROPHIES) : Final 24-Month Patient-Reported Outcomes

Data on patient-reported outcome (PRO) measures in people living with T2D who initiate injectable glucagon-like peptide-1 receptor agonist (GLP-1 RA) medication in routine clinical practice are limited. Here we present final PRO data from the TROPHIES 24-month, prospective, non-comparative, observational study of adult patients with T2D in France, Germany and Italy who started their first injectable GLP-1 RA with either once-weekly dulaglutide (DU) or once-daily liraglutide (LIRA) . Patients’ scores on PRO questionnaires were assessed every 6 months. We present scores at 24 months compared with baseline values before starting DU or LIRA treatment. For each PRO measure, higher scores reflect better outcomes. Baseline characteristics (previously published) for patients prescribed DU (N=1,014) or LIRA (N=991) were similar between groups. Mean changes from baseline to 24 months in PRO scores indicate improvements in health outcomes in patients initiating DU or LIRA (Table) . In summary, among those patients still evaluable at 24 months we observed improvements in PRO scores from baseline in both groups, but with a more pronounced trend of improvement in the DU cohort for EQ-5D-5L VAS, IW-SP, DTSQs total, and DPM life and work productivity scores. Disclosure M.Fuechtenbusch: Advisory Panel; Berlin-Chemie AG, Consultant; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Speaker's Bureau; AstraZeneca, Novo Nordisk. K.Boye: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. B.Guerci: Advisory Panel; Amgen Inc., Medtronic, Board Member; Abbott Diagnostics, AstraZeneca, Bayer AG, Eli Lilly and Company, Novartis Pharmaceuticals Corporation, Consultant; Boehringer Ingelheim International GmbH, Intercept Pharmaceuticals, Inc., Novo Nordisk. F.Giorgino: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk, Consultant; Lilly Diabetes, Sanofi, Research Support; Lilly Diabetes, Roche Diabetes Care, Takeda Pharmaceutical Company Limited. L.Garcia-perez: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. E.Heitmann: None. J.Lebrec: Consultant; Eli Lilly and Company. A.Barrett: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. A.Dib: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. M.Orsini federici: Employee; Eli Lilly and Company.

The Cost-Effectiveness of Oral Semaglutide in Spain: A Long-Term Health Economic Analysis Based on the PIONEER Clinical Trials.

Novel glucagon-like peptide-1 (GLP-1) receptor agonist oral semaglutide has demonstrated greater improvements in glycated hemoglobin (HbA1c) and body weight versus oral medications empagliflozin and sitagliptin, and injectable GLP-1 analog liraglutide, in the PIONEER clinical trial program. Based on these data, the present analysis aimed to evaluate the long-term cost-effectiveness of oral semaglutide versus empagliflozin, sitagliptin and liraglutide in Spain. Outcomes were projected over patients' lifetimes using the IQVIA CORE Diabetes Model (v9.0), discounted at 3.0% annually. Cohort characteristics and treatment effects were sourced from PIONEER 2 and 4 for the comparisons of oral semaglutide 14mg versus empagliflozin 25mg and liraglutide 1.8mg, respectively, and PIONEER 3 for oral semaglutide 7 and 14mg versus sitagliptin 100mg. Costs were accounted from a healthcare payer perspective in 2020 euros (EUR). Patients were assumed to receive initial therapies until HbA1c exceeded 7.5% and then treatment-intensified to basal insulin. Oral semaglutide 14mg was associated with improvements in quality-adjusted life expectancy of 0.13, 0.19 and 0.06 quality-adjusted life years (QALYs) versus empagliflozin 25mg, sitagliptin 100mg and liraglutide 1.8mg, respectively, with direct costs EUR168 higher versus empagliflozin and EUR236 and 1415 lower versus sitagliptin and liraglutide, respectively. Oral semaglutide 14mg was associated with an incremental cost-effectiveness ratio (ICER) of EUR1339 per QALY gained versus empagliflozin and was considered dominant (clinically superior and cost saving) versus sitagliptin and liraglutide. Additional analyses demonstrated that oral semaglutide 7mg was associated with improvements of 0.11QALYs and increased costs of EUR226 versus sitagliptin and was therefore associated with an ICER of EUR2011 per QALY gained. Oral semaglutide 14mg was dominant versus sitagliptin and liraglutide, and cost-effective versus empagliflozin, for the treatment of type 2 diabetes in Spain.

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

IntroductionOnce-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.MethodsTwo 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.ResultsA 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.DiscussionWithin 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 long-term cost-effectiveness of oral semaglutide versus empagliflozin and dulaglutide in Portugal

BackgroundOral semaglutide is a novel glucagon-like peptide-1 (GLP-1) analog that has been associated with improvements in glycated hemoglobin (HbA1c) and body weight versus sodium-glucose cotransporter-2 inhibitor empagliflozin and injectable GLP-1 receptor agonist dulaglutide in the PIONEER 2 clinical trial and in a recent network meta-analysis (NMA), respectively. The aim of the present study was to evaluate the long-term cost-effectiveness of oral semaglutide 14 mg versus empagliflozin 25 mg and dulaglutide 1.5 mg for the treatment of type 2 diabetes from a healthcare payer perspective in Portugal.MethodsIn two separate analyses, outcomes were projected over patients’ lifetimes using the IQVIA CORE Diabetes Model (v9.0), discounted at 4% per annum. Clinical data were sourced from the PIONEER 2 trial and the NMA for the comparisons versus empagliflozin and dulaglutide, respectively. Patients were assumed to receive initial therapies until HbA1c exceeded 7.5%, then treatment-intensified to solely basal insulin therapy. Costs were accounted from a National Healthcare Service perspective in Portugal and expressed in 2021 euros (EUR). Utilities were taken from published sources.ResultsOral semaglutide 14 mg was associated with improvements in life expectancy of 0.10 and 0.03 years, and quality-adjusted life expectancy of 0.11 and 0.03 quality-adjusted life years (QALYs), versus empagliflozin 25 mg and dulaglutide 1.5 mg, respectively. Improved clinical outcomes were due to a reduced cumulative incidence and increased time to onset of diabetes-related complications with oral semaglutide. Total costs were projected to be EUR 2548 and EUR 814 higher with oral semaglutide versus empagliflozin and dulaglutide, with higher acquisition costs partially offset by cost savings from avoidance of diabetes-related complications. Oral semaglutide 14 mg was therefore associated with incremental cost-effectiveness ratios of EUR 23,571 and EUR 23,927 per QALY gained versus empagliflozin 25 mg and dulaglutide 1.5 mg, respectively.ConclusionsBased on a willingness-to-pay threshold of EUR 30,000 per QALY gained, oral semaglutide 14 mg was considered cost-effective versus empagliflozin 25 mg and dulaglutide 1.5 mg for the treatment of type 2 diabetes in Portugal.

POSC359 The Real-World Observational Prospective Study of Health Outcomes with Dulaglutide & Liraglutide in Type 2 Diabetes Patients (TROPHIES): Patient Reported Outcomes at 12-Months

Patient-reported outcome (PRO) measures provide information that complement clinical data. Studies assessing PRO measures in people living with T2D who initiate injectable glucagon-like peptide-1 receptor agonist (GLP-1 RA) medication in routine clinical practice are limited. To better understand the perspectives of people living with T2D regarding their overall health, treatment/device satisfaction, and quality of life and work, here we describe perspectives of participants at the 12-month time-point of TROPHIES.