Injectable Glucagon-like Peptide-1 Receptor Agonists Research Articles

Engineering Supramolecular Nanofiber Depots from a Glucagon-Like Peptide-1 Therapeutic.

Diabetes and obesity have emerged as major global health concerns. Glucagon-like peptide-1 (GLP-1), a natural incretin hormone, stimulates insulin production and suppresses glucagon secretion to stabilize and reduce blood glucose levels and control appetite. The therapeutic use of GLP-1 receptor agonists (e.g., semaglutide) has transformed the standard of care in recent years for treating type 2 diabetes and reversing obesity. The native GLP-1 sequence has a very short half-life, and therapeutic advances have come from molecular engineering to alter the pharmacokinetic profile of synthetic GLP-1 receptor agonists to enable once-weekly administration, reduce the frequency of injection, and improve adherence. Efforts to further extend this profile would offer additional convenience or enable entirely different treatment modalities. Here, an injectable GLP-1 receptor agonist depot is engineered through integration of a prosthetic self-assembling peptide motif to enable supramolecular nanofiber formation and hydrogelation. This supramolecular GLP-1 receptor agonistic (PA-GLP1) offers sustained release in vitro for multiple weeks, supporting long-lasting therapy. Moreover, in a rat model of type 2 diabetes, a single injection of the supramolecular PA-GLP1 formulation achieved sustained serum concentrations for at least 40 days, with an overall reduction in blood glucose levels and reduced weight gain, comparing favorably to daily injections of semaglutide. The general and modular approach is also extensible to other next-generation peptide therapies. Accordingly, the formation of supramolecular nanofiber depots offers a more convenient and long-lasting therapeutic option to manage diabetes and treat metabolic disorders.

PIONEER REAL UK: A Multi-Centre, Prospective, Real-World Study of Once-Daily Oral Semaglutide Use in Adults with Type 2 Diabetes.

Oral semaglutide provides an alternative to injectable glucagon-like peptide-1 receptor agonists (GLP-1RAs) for treatment of type 2 diabetes (T2D). The PIONEER REAL studies evaluate clinical outcomes of oral semaglutide treatment of T2D in a real-world setting. PIONEER REAL UK focused on adults living with T2D in the UK. The multi-centre, prospective and non-interventional single-arm study enrolled 333 participants and followed them for 34-44 weeks. Participants were treated as part of routine clinical practice and had not been previously treated with injectable glucose-lowering medication. The primary endpoint was change in glycated haemoglobin (HbA1C) from baseline to end of study (EOS). Secondary endpoints included change in body weight, proportion of participants with HbA1C < 7% (53 mmol/mol) at EOS and proportion of participants with ≥ 1%-point HbA1C reduction and body weight reduction of ≥ 3% or ≥ 5% at EOS. Treatment satisfaction was assessed by Diabetes Treatment Satisfaction Questionnaire (DTSQ) status and change. Of 333 participants, 299 completed the study and 227 were on treatment at EOS. People treated with oral semaglutide experienced significantly reduced HbA1C by an estimated change of - 1.1%-points (95% CI - 1.27 to - 0.96; P < 0.0001) or - 12.2 mmol/mol (CI - 13.87 to - 10.47; P < 0.0001). Estimated change in body weight was - 4.8 kg (CI - 5.47 to - 4.12; P < 0.0001). At EOS, an HbA1C level < 7% (53 mmol/mol) was recorded in 46.3% of participants. A ≥ 1%-point reduction in HbA1C combined with a ≥ 3% reduction in body weight was observed in 36.4% of participants, and 27.1% had a ≥ 1%-point reduction in HbA1C and a ≥ 5% body weight reduction. Treatment satisfaction improved significantly during the study. No new safety concerns or cases of severe hypoglycaemia were reported. People living with T2D in the UK experienced a meaningful decrease in HbA1C and body weight after initiation of oral semaglutide treatment. No new safety issues were observed. ClinicalTrials.gov: NCT04862923. Graphical plain language summary available for this article.

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.

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.)

787-P: Glucose and Weight Outcomes Associated with Oral Semaglutide in the Real-World—Initial Results from the Association of British Clinical Diabetologists’ (ABCD) Audit

Semaglutide is the first glucagon like peptide-1 receptor agonist (GLP1-RA) available in an oral preparation. Weight and HbA1c outcomes with injectable semaglutide in the real-world are well established. The aim of this analysis is to assess weight and HbA1c response to oral semaglutide. Methods: Data were extracted from the secure online ABCD audit tool. Individuals were included if baseline and follow-up weight and/or HbA1c data were available. Change in HbA1c, body mass index (BMI) and weight from baseline was assessed using a multivariate linear regression model and change in the numbers achieving an endpoint HbA1c≤7.5% [58mmol/mol] were assessed using Chi2 tests in Stata 16. Results: Data were available for 350 individuals with baseline mean±SD HbA1c 9.2%±1.7 [76.6mmol/mol±18.3], weight 101.8kg±21.9, BMI 34.3kg/m2±6.9, median diabetes duration 11years (IQR 6-16) and age 59 years (IQR 51-68); 63.0% were male and 79.7% were white. Median follow-up was 0.5years (IQR 0.3-0.8). Significant reductions in HbA1c of 0.7% (95%CI 0.4, 0.9; P&amp;lt;0.001) [7.4mmol/mol; 95%CI 4.7, 10.0; P&amp;lt;0.001] were observed. Weight decreased by 3.3kg (95%CI 2.3, 4.3; P&amp;lt;0.001) and BMI fell by 1.1kg/m2 (95%CI 0.6, 1.6; P&amp;lt;0.001). Twice as many people achieved a HbA1c≤7.5% at follow-up compared to baseline (28.6% [52/182] vs 14.3% [26/182]) - this change was statistically significant (P&amp;lt;0.001). Conclusion: In the real-world, oral semaglutide is associated with statistically significant and clinically meaningful reductions in HbA1c, weight and BMI. The numbers achieving a HbA1c≤7.5% also increased. In the light of this, further data collection and analysis should be undertaken, including comparisons between oral and injectable GLP1-RAs and analysis of switches between them Disclosure T.S.J.Crabtree: Speaker's Bureau; Abbott Diabetes, Novo Nordisk, Lilly, Sanofi, Insulet Corporation. K.Adamson: None. S.Krishnasamy: Other Relationship; Novo Nordisk, Sanofi, Eli Lilly and Company, AstraZeneca. M.Khine: None. P.De: Speaker's Bureau; Novo Nordisk, AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Takeda Canada, Daiichi Sankyo, Napp Pharmaceuticals Limited, Lilly Diabetes. R.Peter: None. R.E.Ryder: Other Relationship; Novo Nordisk, Speaker's Bureau; GI Dynamics, BioQuest. Funding Novo Nordisk

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.

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.

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.

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.

ODP171 Choosing GLP-1RA Over Insulin for Patients with Type 2 Diabetes and Severe Hyperglycemia

Abstract Introduction Although insulin remains the recommended treatment in type 2 diabetes for hyperglycemia with catabolic symptoms, it is also the generally recommended treatment for persistent hyperglycemia or hemoglobin A1c (HbA1c) values above 10% 1 . Recent data has suggested that glucagon like peptide 1 receptor agonists (GLP-1RAs) are also powerful at glucose lowering while additionally offering extra-glycemic benefits such as weight loss with minimal risk of hypoglycemia. Unfortunately, data on initial use of GLP-1RA is limited in patients with very high hemoglobin A1cs. Our objective was to evaluate outcomes in patients with type 2 diabetes and a baseline HbA1c of 10% or greater treated with GLP-1RAs instead of insulin. Methods This study is a small retrospective case series of insulin-naïve patients with uncontrolled type 2 diabetes who were prescribed an injectable GLP-1RA. Patients included had a baseline hemoglobin A1c ≥ 10% without signs of catabolism (weight loss, ketosis, significant polyuria), a minimum of one follow-up visit after initiating GLP-1RA, and at least one HbA1c measurement within six months of initiating treatment. Patients were excluded if they had previously been on insulin or a GLP-1RA in the past 1 year. The primary endpoint was change in HbA1c after 3-6 months of GLP-1 RA use. Results Of the patients initially screened, 7 patients fulfilled criteria and were included in the final analysis. The age range was 45-73 with 4 female patients and 3 male patients. The number of years patients had been diagnosed with type 2 diabetes ranged from 0 to 13 with 1 patient having newly diagnosed diabetes not previously on medications. Of the 6 patients who were on medical treatment at baseline, 3 patients were on monotherapy with either metformin or a sulfonylurea and 3 patients were on 2-4 oral hypoglycemic agents. Patients were continued on their initial medication regimen with the exception of DPP-4 inhibitors which were stopped at the time of GLP-1RA initiation. Mean baseline HbA1c prior to initiation of GLP-1RA was 11.9%. Following 3-6 months of GLP-1RA use, mean HbA1c significantly improved to 7.5% (p value= 0. 0005). All patients showed improvement of HbA1c in response to GLP-1RA initiation (mean HbA1c reduction = 4.4, minimum = 1.9, maximum = 7.5). All patients remained on GLP-1RA without significant side effects. Conclusion In this limited case series of patients with HbA1c ≥ 10%, GLP-1RAs were well tolerated and resulted in significant improvement in HbA1c. Our results suggest that GLP-1RAs should be considered as an alternative treatment option to insulin in non-catabolic patients with very high hemoglobin A1cs.

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.

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.