Significant Reduction In HbA1c Research Articles

Innovative Integrated Motivational Interviewing for Dual Management in Tuberculosis Patients with Diabetes (MID-DOT) in Malaysia

(1) Background: Achieving successful tuberculosis (TB) treatment outcomes among diabetic patients is a real challenge as TB complicates control of diabetes. This study aimed to evaluate the effectiveness of an integrated dual management educational module, MID-DOTS, which uses the mmotivational interviewing (MI) technique implemented within directly observed treatment as part of a short course (DOTS) program in TB patients with diabetes (TB/DM). A randomized controlled trial was conducted in the northeastern state of Malaysia. (2) Methods: One hundred and twenty-four TB patients with diabetes received educational intervention using a MID-DOT module that used the MI technique, which was repetitively applied by TB nurses throughout a 6-month DOTS program while another 122 patients were given standard health education. Study outcomes include the proportion of patients with successful TB treatment, and changes in HbA1c and diabetic self-care scores at 6 months. (3) Results: The successful TB treatment outcome was 88% in the intervention group versus 72% in the control group (RR = 1.24; 95%CI 1.16, 1.58). A significant reduction of HbA1c (mean difference 0.82%; 95%CI 0.66, 0.98) and significantly higher diabetes self-care score (mean difference 8.49; 95%CI 7.38, 9.59) were also shown in the intervention group. (4) Conclusions: A dual TB/DM educational strategy which integrates the MI technique applied repetitively within the DOTS program is effective in increasing successful TB treatment as well as improving diabetic outcomes.

Comparison of efficacy between canagliflozin and teneligliptin as add-on therapy to metformin and glimepiride on plasma glucose levels along with blood pressure and lipid levels in patients with type 2 diabetes mellitus

Abstract Background: Despite of several guidelines metformin and glimepiride remains the first prescribed drug in most people with diabetes. Very often canagliflozin and teneligliptin remain the third prescribed OHA. Efficacy of teneligliptin and canagliflozin as solo drug or in combination with other single OHA’s on glycaemic parameters, lipid profiles & blood pressure is already established. But their efficacy on above parameters when used as third drug next to metformin and sulfonylurea is still not investigated. Aims and objectives: Aim of this study is to compare glycaemic and non-glycemic effects of canagliflozin and teneligliptin as third line drug. Objective is to establish their multiple pleotropic effects at this position. Methods: Subjects with uncontrolled glycaemic parameters with hypertension and diabetic dyslipidaemia already on half maximal doses of metformin and glimepiride were enrolled in the study. Out of 87 selections, 45 were prescribed canagliflozin 100 mg/d and to 42 subjects, teneligliptin 20mg/d, each for 24 weeks. Effects over HbA1c, fasting and post prandial plasma glucose, systolic and diastolic blood pressures, HDL’c and triglycerides were observed pre and post intervention. Results: As a third drug both canagliflozin and teneligliptin show significant reduction in HbA1c (1.5 versus 1.6%), fasting (-20.2 versus -28.8 mg %), and post prandial (-39.9 versus – 58.5mg %). Effects over systolic (4 mmHg versus 1.1 mmHg) and diastolic BP (3.1 mmHg versus 0.2 mmHg) was clinically and statistically significant (p = 0.3 and 0.1) respectively in both groups. A statistically insignificant (9.6 versus 4.1 mg%; p =) reduction in Triglycerides but significant (7.6 versus 1.2; p <0.0001) increase in HDL’c was observed. Conclusion: Canagliflozin and teneligliptin, both retains their glycaemic and non-glycaemic benefits even when used as third OHA for diabetes management. Canagliflozin scores better for comorbid hypertension and diabetic dyslipidaemia.

Effectiveness of Oral Semaglutide in Weight Loss and Glycemic Control among Type 2 Diabetes Population: A Real-world Longitudinal Study

Abstract Background: Oral semaglutide is a drug belonging to the class of glucagon-like peptide-1 receptor agonists which is known for its ability to maintain glycemic levels while reducing weight and lowering the risk of cardiovascular events. This study aims to explore the effectiveness of oral semaglutide by using real-world data from South Asia (India). Materials and Methods: The study is a real-world longitudinal study, and the data for the study were extracted from electronic medical records of a comprehensive diabetes center in Kerala. The primary outcome variables were measured at the baseline and at 6 months. The subjects who had data from March 2022 to July 2023 were included in the study while those with no follow-up data were excluded. The sample size was calculated as 52 using the sample size formula for the comparison of two dependent groups with a quantitative outcome. All the analyses were carried out at a level of significance of 5% using R version 4.3.1. Results: The clinical characteristics such as weight, systolic blood pressure, estimated glomerular filtration rate, and serum glutamic-oxaloacetic transaminase/aspartate aminotransferase were found to have a significant difference between the baseline and endpoint (P < 0.05). The mean absolute difference between the baseline and endpoint hemoglobin A1c (HbA1c) was found to be 0.65% (P < 0.001), and for body mass index (BMI), it was found to be 1.69 kg/m2 (P < 0.001). The baseline HbA1c and BMI were found to be significantly associated with the change in HbA1c and BMI, respectively (P < 0.05). Conclusion: This study is one of the first real-world studies conducted in South Asia (India) that explores the effectiveness of oral semaglutide. The study showed that the usage of oral semaglutide induced a significant reduction of weight and HbA1c among people with type 2 diabetes. Addressing the limitations can bring new insights into the diabetes management paradigm.

Effectiveness and Tolerability of the Intensification of Canagliflozin Dose from 100 mg to 300 mg Daily in Patients with Type 2 Diabetes in Real Life: The INTENSIFY Study

Aim: This study aimed to evaluate the effectiveness and tolerability of intensifying the dose of canagliflozin from 100 mg/day (CANA100) to 300 mg/day (CANA300) in patients with type 2 diabetes (T2DM) and suboptimal metabolic control in a real-world setting. Methods: A multicenter observational study was conducted on adult patients with T2DM who initiated treatment with CANA100 and subsequently required intensification to CANA300. The primary outcome measures were changes in HbA1c and weight at 6 months after the switch and at the end of the follow-up period. Results: A total of 317 patients met the inclusion criteria (59.6% male, mean age 62.2 years, baseline HbA1c 7.55%, weight 88.6 kg, median duration of treatment with CANA100 9.9 months). Switching to CANA300 resulted in a significant reduction in HbA1c (6 months: −0.33%; last visit: −0.47%, both p < 0.0001) and weight (6 months: −1.8 kg; last visit: −2.9 kg, both p < 0.0001) over a median follow-up period of 20.8 months. The proportion of patients that achieved HbA1c < 7% increased from 26.7% with CANA100 to 51.6% with CANA300 (p < 0.0001). Among individuals with poor baseline glycemic control (HbA1c > 8%, mean 9.0%), HbA1c was significantly reduced by −1.24% (p < 0.0001). Furthermore, significant improvements were observed in fasting plasma glucose (FPG), blood pressure (BP), liver enzymes, and albuminuria. No unexpected adverse events were reported. Conclusions: Intensifying the treatment to CANA300 in a real-world setting resulted in further significant and clinically relevant reductions in FPG, HbA1c, weight, and BP in patients with T2DM. The switch was particularly effective in patients with higher baseline HbA1c levels.

761-P: Effect of Orforglipron vs. Placebo and Dulaglutide on Glycemic Control and Body Weight in Patients with Type 2 Diabetes

Orforglipron [OFG (LY3502970)] is an oral, non-peptide, glucagon-like peptide-1 receptor agonist (GLP-1 RA). The 26-week, randomized, double-blind, double placebo, phase 2 study enrolled 383 patients with type 2 diabetes (T2D) treated with diet, exercise, ± metformin. At baseline, mean age was 58.9 yr, HbA1c was 8.1%, and body weight (BW) was 100.3 kg. Patients were randomly assigned to OFG 3, 12, 24, 36, or 45 mg once daily, placebo (PBO), or dulaglutide 1.5 mg (dula). Protocols guided the initial OFG dose and escalation schemes. Primary endpoint was HbA1c change from baseline (CFB) at wk 26 for OFG vs PBO. Secondary endpoints included CFB at wk 26 in HbA1c for OFG vs dula, and CFB in fasting blood glucose (FBG) and body weight (BW) for OFG vs PBO and dula. OFG resulted in improvements in glycemic control and BW (table). At wk 26, HbA1c reduction with OFG ranged from 1.19 to 2.10% vs PBO 0.43% (P<0.001, all doses vs PBO). Significantly greater reductions in HbA1c were also noted with 12, 24, 36, and 45 mg OFG vs dula (p<0.001). Most adverse events (AE) were gastrointestinal (nausea: PBO 5.5%, OFG 30.6%, dula 18.0%) and mild or moderate in severity. OFG resulted in significant reductions in HbA1c, FBG, and BW with an AE profile consistent with other GLP-1RAs. OFG does not have food or water administration restrictions and may provide a safe, effective, and convenient oral treatment option for patients with T2D. Disclosure J.P.Frias: Advisory Panel; Becton, Dickinson and Company, Pfizer Inc., Sanofi, Consultant; Akero Therapeutics, Inc., 89bio, Inc., Aimmune, Boehringer Ingelheim Inc., Eli Lilly and Company, Carmot Therapeutics, Inc., Echosens, Merck & Co., Inc., Metacrine, Inc., Novo Nordisk, Pfizer Inc., Sanofi, Employee; Ionis Pharmaceuticals, Research Support; Akero Therapeutics, Inc., 89bio, Inc., Altimmune, Axcella Health Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Intercept Pharmaceuticals, Inc., Carmot Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Madrigal Pharmaceuticals, Inc., Merck & Co., Inc., Metacrine, Inc., Novo Nordisk, Oramed Pharmaceuticals, Novartis, Pfizer Inc., Sanofi, Speaker's Bureau; Eli Lilly and Company, Sanofi. A.Haupt: Employee; Lilly, Stock/Shareholder; Lilly. D.A.Robins: None. S.H.Hsia: Research Support; Eli Lilly and Company. S.Eyde: None. R.Liu: None. X.Ma: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. M.Konig: None. C.M.Kazda: Employee; Eli Lilly and Company. E.J.Pratt: Employee; Eli Lilly and Company. K.J.Mather: Employee; Eli Lilly and Company.

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.

1803-PUB: Effectiveness and Safety of the Insulin Degludec U100 vs. Glargine U300 in People with Type 1 diabetes—The IneoxPlus Real-World Study

Objective: The INEOX-Plus study aims to compare the efficacy and safety of Deg-U100 and Gla-U300 in people with T1d incorporated to the Flash Glucose Monitoring (FGM) technology for over 6 months. Materials and Methods: Cross-sectional study in 161 of the 260 T1D participants of the INEOX randomized study (NCT 03328845) who were initially randomized between 2017 and 2019 to receive Gla-U300 or Deg-U100 insulin and incorporated to FGM technology after. Participants were re-evaluated in the INEOX_Plus visit, at an average 2.8 years after the final INEOX visit. Sociodemographic variables, insulin dose, plasma HbA1c and episodes of severe hypoglycemia and ketosis in the previous year were collected together with data on Freestyle libre 2® system downloaded from the last 90 days: sensor use, number of daily scans, GMI, mean glucose, CV, TIR 70-180, TBR 69-54, TBR &amp;lt;54, TAR 181-250, TAR &amp;gt;250 and hypoglycemia events- number/90 days and rate/year-. Results: 90 men (56%) and 71 women (44%), mean age 44±11 years, with diabetes evolution of 23.5±10 years belonging to the INEOX study accepted to participate; 75 subjects (46%) used Gla-U300 and 86 (54%) Deg-U100. A significant reduction in HbA1c was observed between the final INEOX and INEOX-Plus visit (7.65±1.04% vs 7.43±0.84%, p= 0.002) regardless of the type and dose of second-generation long-acting insulin analogue used. There were no episodes of severe hypoglycemia or ketoacidosis reported. We did not find significant differences in insulin doses, HbA1c and FGM metrics except in the Hypoglycemia events incidence rate -213.65 vs 260.05 events/person/year; p=0.001 - for Gla-U300 vs Deg-U100 respectively. Conclusions: For people with T1D in routine clinical follow-up with FGM, Gla-U300 and Deg-U100 insulin have a similar effect on the efficacy and safety variables except for significantly lower incidence rate of yearly hypoglycemia events for Gla-U300 users. Disclosure M.S.Ruiz de adana: None. L.I.Navas vela: None. C.Maldonado-araque: None. G.Olveira: Other Relationship; Abbott Diabetes, Novo Nordisk, Speaker's Bureau; Lilly. G.Rojo martínez: None. M.E.Domínguez-lópez: None. M.Vallejo mora: None. N.Colomo: None. F.Linares: None. V.Morillas: Other Relationship; Boehringer Ingelheim and Eli Lilly Alliance. M.Vallejo herrera: None. S.Alonso gallardo: None. M.Padilla fuentes: None. Funding Instituto de Salud Carlos III (PI 17/00861)

1812-PUB: Safety and Effectiveness of Empagliflozin/Linagliptin FDC in Uncontrolled T2DM Patients with COVID-19 Infection

Background: COVID-19 infection prognosis is known to worsen in patients with various co-morbidities particularly with uncontrolled diabetes mellitus and is often associated with increased serum levels of various inflammatory markers such as CRP, IL-6, D-dimer, LDH etc. Hence optimal glycemic care is crucial for a good prognosis in type 2 Diabetes (T2D) patients with COVID-19 infection. Efficacy and safety of Empagliflozin/linagliptin fixed dose combination (FDC) in T2D patients is well known. In the present study, the safety and effectiveness of Empagliflozin/Linagliptin FDC was evaluated in T2D patients diagnosed with COVID-19 infection. Aim: To evaluate the safety, effectiveness of T2D patients with COVID-19 infection with empagliflozin/linagliptin FDC. Methods: A single center, retrospective observational study included T2D patients who were on Empagliflozin/Linagliptin (25/5 mg) at the time of COVID-19 diagnosis and were followed up for 6 months. Laboratory (HbA1c, Ferritin, LDH, IL-6, CRP, D-Dimer) and clinical assessments (need for oxygen support &amp; steroids) were done at baseline, 3rd, and 6th months. Repeated measures ANOVA was used to determine the mean difference at specified time intervals and any p-value &amp;lt; 0.05 was considered statistically significant. Results: A total of 50 T2D patients were included with mean age (SD) was 57.44 ± 9.88 years. Patients treated with Empagliflozin/Linagliptin FDC at 6 months showed significant reduction in HbA1c (6.87 ± 0.22 mg/dL from 10.2± 0.9 mg/dL), CRP (8.9 ± 2.79 mg/dL from 99.2 ± 4.00 mg/dL), LDH (288 ± 45.12U/L from 675 ± 95.41U/L), ferritin (408.4 ± 131.00 ng/mL from 1100± 216.2 ng/mL), IL-6 (8.97 ± 2.40 pg/mL from 95.56 ± 23.4 pg/mL). Also, the need for oxygen support and daily steroid dose requirement had become lesser over 6 months. Conclusion: Once daily Empagliflozin/Linagliptin (25/5 mg) FDC was found to be safe, effective, and well tolerated in non-critically ill T2D patients with COVID-19 infection. Disclosure A.Sengupta: None.

1801-PUB: Efficacy and Safety of Once-Weekly Semaglutide in People with Type 1 Diabetes in Real-World Practice

Introduction: Semaglutide has shown significant improvements in weight and HbA1c in T2D, but the data about the efficacy and safety in people with T1D (PWT1D) are scarce. Aims &amp; Methods: We conducted a retrospective study including adults with T1D and obesity who had initiated once weekly (OW) semaglutide adjunct to insulin, to evaluate its efficacy and safety. Results: Twenty-one subjects were included (52.4% female, mean age 44.2 ± 12.9 years, diabetes duration 19.1 ± 10.8 years, HbA1c 7.7 ± 0.8%, BMI 38.3 ± 5.9 kg/m2). Of them, 47.6% had hypertension, 52.4% dyslipidaemia, 23.8% cardiovascular disease, and 19% renal disease. Mean treatment duration was 30.4 weeks. Mean OW semaglutide dose was 0.8 ± 0.2 mg. Significant reductions in HbA1c (-0,6 ± 0.7%), weight (-8.1 ± 6.1 kg; -7.5 ± 5.8%) and daily insulin dose (-20.7 ± 18.9 U/day) were achieved. An HbA1c reduction of ≥ 0.4% was seen in 61.9% of subjects. Weight loss ≥ 5% and ≥ 10% were achieved in 57.1% and 33.3% of cases, respectively. Significant improvements in time in range (+8.8 ± 13.4%) and time in hyperglycemia &amp;gt;250 mg/dL (-5.3 ± 5.1%) were attained. Four subjects experienced gastrointestinal adverse events, and two of them discontinued treatment. Conclusions: Adjunct treatment with OW semaglutide in PWT1D in a real-life setting resulted in promising results in glycemic control, weight, and insulin requirements, in a safe and well-tolerated manner. Disclosure V.Bellido: None. N.Gros herguido: None. S.Amuedo: None. L.Baena ariza: None. S.M.Alfonso: None.

1813-PUB: Cardiorenal Effect of Dapagliflozin and Dapagliflozin-Saxagliptin Combination on CD34+ve Hematopoietic Stem Cells (HSCs) and Podocyte Specific Markers in Type 2 Diabetes Subjects

Introduction: Effect of Dapagliflozin (Dapa) and Dapagliflozin-Saxagliptin combination (Combo) was examined on peripheral blood derived CD34+ HSCs as a cellular CVD biomarker. Both Dapa (a SGLT2 receptor inhibitor) and Saxagliptin (a DPP4 enzyme inhibitor) are T2DM meds, but the combo has not been evaluated for cardio-renal risk. Hypothesis: We hypothesized that Dapa will improve the outcomes when compared to placebo and the Combo maybe even more beneficial. Methods: 15 subjects were enrolled in 16 weeks, double-blind, three-arm, randomized placebo matched trial, with 10mg Dapa + Saxa placebo (n=4), 10 mg Dapa + 5 mg Saxa (n=5) Combo, And Dapa placebo + Saxa placebo (n=6), Placebo groups. T2DM (30-70 yrs) with HbA1c of 7-10%, were included. CD34+ HSC number, migration, mRNA expression along with biochemistry and urine exosomes were measured. Data were collected at wks 0, 8, and 16. For stats, a mixed model regression analysis was used. Results: Significant HbA1c (p=0.0357) reduction was noted in Combo group vs Dapa alone and Placebo. hsCRP levels (P=0.0317) and IL-6, two important inflammatory molecules, were significantly reduced in both Dapa and Combo vs Placebo. Leptin levels decreased significantly in both Dapa alone (p=0.035) and Combo group (p=0.015), vs Placebo, however the Adiponectin levels were higher in Dapa alone group. EPC migration improved significantly in both Dapa alone (p=0.05) and Combo group (p=0.05) vs Placebo. Interestingly, urine exosome-based podocyte specific protein such as podocalyxin was actually higher in Combo vs Control. Conclusions: Several parameters showed significant improvement with both Dapa and Combo vs placebo. However, other than glycemic control Combo didn’t offer any further benefit over Dapa alone in terms of HSC and biochemistry. Moreover, the Combo may have deleterious effect on renal podocyte inflammation which needs to be examined in a larger study. Disclosure S.Nandula: None. S.Sen: None.

962-P: Impact of Digital Diabetes Solution on Glycemic Control in Adults with Type 2 Diabetes Mellitus in the United States—A Retrospective Cohort Study

Background: Dario Diabetes Solution (DDS) is a digital health application (app) that combines a blood glucose (BG) monitoring system with a smartphone app, allowing tracking of BG levels in real time. This study evaluated effectiveness of DDS on HbA1c between DDS users and matched nonusers. Methods: This retrospective cohort study included adults with type 2 diabetes mellitus (T2DM) with a baseline (BL) HbA1c ≥7% who used DDS (users) or received usual care (nonusers) between January 1, 2017, to October 31, 2021. BL period was 1 year before index date (first DDS registration [users] or first claim date in the quarter [nonusers]); follow-up period was 6 months. DDS user and nonuser cohorts were matched 1:3 using exact and propensity score matching. Primary endpoint was change in HbA1c from BL to 6 months, with subgroup analyses of patients (pts) with BL HbA1c &amp;gt;7.5%, &amp;gt;8%, &amp;gt;9%, and ≥1% drop from BL. Difference-in-difference results are reported using least squares (LS) means from linear models. Results: The study included 568 DDS users and 1699 nonusers. For all 2267 pts, mean ± SD age was 57.5±11.3 years and HbA1c was 9.14±1.83% at BL. At 6 months, LS mean difference between groups was −0.23% (mean HbA1c change vs BL: users, −1.02% [95% CI, −1.15, −0.89]; nonusers, −0.79% [−0.87, −0.71]; P=0.004). HbA1c drop ≥1% from BL to 6 months was achieved by 47% of users vs 37% nonusers (difference: 10%; P&amp;lt;0.001). Subgroup analysis at all BL HbA1c showed users achieved more significant HbA1c reductions vs nonusers (P&amp;lt;0.05). For pts with BL HbA1c &amp;gt;9%, the healthcare effectiveness data and information set performance measure, mean difference between groups was -0.47% (users, -2.25% [-2.50, -1.99]; nonusers, -1.78% [-1.92, -1.63]; P=0.002). Conclusions: Adults with uncontrolled T2DM using DDS had better outcomes at 6 months, with more significant HbA1c reductions than matched nonusers across various BL HbA1c levels, showing incremental improvements to usual care. Disclosure N.Thingalaya: None. F.Lee: Employee; Sanofi, Stock/Shareholder; Sanofi. D.Kerr: Consultant; Sanofi-Aventis U.S. P.Potukuchi: None. L.Wilson: Employee; Sanofi. K.C.Lee: Employee; Sanofi. E.K.Han-burgess: Employee; Sanofi. A.Edwards: Employee; Symphony Health, an ICON plc company, Other Relationship; Sanofi. X.Yu: None. A.Kennedy: None. Funding Sanofi

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

778-P: Efficacy and Safety of Supaglutide as Add-on to Metformin in Patients with Type 2 Diabetes

GLP-1 is an incretin hormone with broad pharmacological potential. GLP-1 receptor agonists (GLP-1RA) are successfully in clinical use for T2D and obesity. Several GLP-1-based therapies are in clinical evaluation for treating metabolic diseases. Supaglutide (supa), a novel GLP-1RA, is in late-stage clinical investigation for T2D. The efficacy and safety are being investigated in 340 patients with T2D inadequately controlled on metformin in this randomized, double-blind, placebo-controlled phase 3 clinical trial (NCT04998032). Supa 3 mg QW treatment resulted in a statistically significant reduction in HbA1c of -1.81% from baseline at week 24 (p&amp;lt;0.001). Body weight was decreased by 3.80% from baseline in supa 3 mg group, with a significant difference versus placebo group (p&amp;lt;0.001). Supa also significantly improved glucose excursion, and increased meal-stimulated insulin and C-peptide secretion as determined by MMTT, suggesting improved glucose tolerance and enhanced β-cell function. Overall TEAEs occurred in 66.7% and 73.4% with placebo and supa 3 mg, respectively. The most common TEAEs with supa were GI symptoms, such as nausea, vomiting, diarrhea and decreased appetite mostly in mild or moderate severity. Supa 3 mg improved glycemic and metabolic control and was well tolerated in T2D inadequately controlled on metformin, suggesting supa as a novel alternative therapy for T2D and metabolic disorders. Disclosure D.Anwar: None. X.Su: None. L.Li: None. H.Wang: None. Y.Wang: None. S.Li: None. Q.Li: None. X.Li: None. M.Liu: None. J.Sun: None. N.Zhao: None. Y.Bao: None. Y.Yang: None. J.Ma: None. Y.Li: None. Q.Wang: None. W.Jia: None. Y.Zhou: None. S.Chen: None. J.Zhou: None. L.Li: None. Z.Cheng: None. X.Dong: None. X.Shi: None.

972-P: Significant Weight Loss among People with Diabetes Despite Using Antidiabetic Medications Associated with Weight Gain after 90-Day Fitterfly Digital Therapeutics Program

Background and Aim: Majority of people with Diabetes (PWD) use insulin and sulfonylurea (SU) as a necessary part of treatment regimen for glycemic control. Weight gain associated with these medications becomes a major challenge in effectively managing diabetes. The study evaluates the real-world effectiveness of the Fitterfly Diabetes program for weight management in PWD using antidiabetic medications associated with weight gain and weight loss. Methods: Deidentified data of 79 participants (mean age: 45.4 ± 10.4 years, female: 54.4 %) with T2DM enrolled in the program was analyzed. Out of all participants, 28 people used antidiabetic medications associated with weight gain (thiazolidinediones, meglitinides, SU, and insulin) while 51 participants used antidiabetic medications associated with weight loss (biguanides, sodium-glucose cotransporter-2 inhibitors). Participants using medications from both groups or any other antidiabetic medications were excluded. Data has been shown as the median (IQR). Results: After 90 days, participants using antidiabetic medications associated with weight loss showed reduction in HbA1c, weight, and waist circumference by -0.5 (-1.0, 1.0) %, -3.5 (-6.0, -1.1) kg, -5.0 (-9.0, -1.5) cm from the pre-program baseline of 7.6 (7.1, 8.4) %, 81.0 (68.0, 92.0) kg, and 105.0 (97.0, 110.0) cm respectively (P&amp;lt;0.001 for all). Participants using antidiabetic medications associated with weight gain showed reduction in HbA1c, weight and waist circumference by -1.3 (-2.8, -0.02) %, -2.0 (-3.6, 0.9) kg, -2.0 (-4.7, 0.0) cm from the baseline of 9.6 (8.1, 10.7) %, 73.0 (66.2, 79.4) kg, and 99.0 (92.0, 105.8) cm respectively (P&amp;lt;0.05 for all). Conclusion: Significant reduction in weight, HbA1c, and anthropometric parameters was observed after 90 days on the program irrespective of the effect of antidiabetic medications on weight. PWD looking to lose weight are good candidates for such programs. Disclosure S.A.Patange: None. S.Joshi: Consultant; Fitterfly Health Tech Pvt. Ltd. A.K.Singal: Employee; Fitterfly Healthtech Pvt Ltd. R.Verma: Employee; Fitterfly Healthtech Pvt Ltd. C.Selvan: None. S.Kalra: Speaker's Bureau; Abbott, Bayer Inc., Novo Nordisk, Sanofi. M.H.Tiwaskar: None. V.Methil: None. B.V.Patil: None. F.Malde: None. V.Nair: None. Funding Fitterfly Healthtech Pvt. Ltd.

729-P: Metabolic Surgery for the Treatment of Type 2 Diabetes Mellitus in China—Five-Year Outcomes from a Prospective Multicenter Study

The prevalence of type 2 diabetes (T2D) among adults in China is 10.9%-13.2%. Multicenter, long-term, prospective studies evaluating bariatric/metabolic surgery in obese patients with T2D in China are limited. This prospective study evaluated the 5-year impact of laparoscopic Roux-en-Y gastric bypass (RYGB; n=76 subjects, mean [SD] age 36.4 [9.5], 52.6% women, mean [SD] BMI 34.6 [4.9] kg/m2, mean [SD] glycosylated hemoglobin A1c [HbA1c] 8.3% [1.7%], mean [SD] duration diabetes 3.7 [2.7]) and sleeve gastrectomy (SG; n=25 subjects, mean [SD] age 41.1 [10.8], 44.0% women, mean [SD] BMI 36.4 [6.0] kg/m2, mean [SD] HbA1c 7.5% [1.5%], mean [SD] duration diabetes 2.4 [2.4]) on T2D at six centers in China from August 2014-April 2021. According to the composite measure of glycemic control for metabolic surgeries as suggested by the American Society for Metabolic and Bariatric Surgery, among 62 subjects evaluable at five years (50 RYGB, 12 SG), complete remission occurred in 28.6% (27.5% RYGB, 33.3% SG), partial remission in 27.0% (29.4% RYGB, 16.7% SG), improvement in 30.2% (29.4% RYBG, 33.3% SG), no change in 9.5% (7.8% RYBG, 16.7% SG), and recurrence in 4.8% (5.9% RYGB). Significant 5-year reductions in HbA1c (RYGB -1.7±2.1%, SG -1.8±1.1%), body weight (RYGB -19.8±8.4 kg, SG -21.2±6.0 kg), and BMI (RYGB -7.1±3.1 kg/m2, SG -7.7±2.1 kg/m2) were observed (all p&amp;lt;0.001). Five-year improvements in triglycerides and high-density lipoprotein cholesterol were also observed. Procedure-related serious adverse events occurred in 8 RYGB subjects (7.9%). To our knowledge, this is the first prospective, multicenter, 5-year study of bariatric/metabolic surgery in subjects with T2D in China. These data demonstrate that RYGB and SG achieved clinically meaningful, sustained impacts on T2D remission in many subjects for up to five years. Bariatric/metabolic surgery has enormous potential to provide a safe and effective option for appropriately selected subjects with T2D in China. Disclosure Y.Bao: None. Y.Tu: None. S.Lin: None. H.Zhang: None. W.Yang: None. J.Yang: None. S.Chen: None. Q.Fan: None. Y.Ma: None. C.Ma: None. J.Waggoner: Employee; Ethicon, Inc., Janssen Research &amp; Development, LLC, Stock/Shareholder; Johnson &amp; Johnson. H.Liang: None. A.Tokarski: Employee; Ethicon, Inc. N.Edwards: Consultant; Boston Scientific Corporation, EMD Serono, Inc., Ethicon, Inc., Johnson &amp; Johnson, Becton, Dickinson and Company. T.Yang: None. R.Zhang: None. W.Jia: None. P.Zhang: None. C.Wang: None. T.Jiang: None. N.Zhang: None. J.Zhu: None. H.Yu: None. J.Han: None. Funding Ethicon, Inc.; Johnson &amp; Johnson

73-LB: Tirzepatide 5, 10, and 15 mg vs Injectable Semaglutide 0.5 mg for the Treatment of Type 2 Diabetes—An Indirect Treatment Comparison

Semaglutide (sema) 0.5 mg is part of type 2 diabetes (T2D) standard of care as initial maintenance dose. While there has been a study conducted on TZP and sema 1.0 mg, showing TZP superiority, currently there is no head-to-head study comparing TZP and sema 0.5 mg. Therefore, the objective of this analysis was to evaluate the efficacy and safety of TZP and sema 0.5 mg using adjusted indirect comparisons. Adjusted indirect comparisons were performed using the Bucher method to compare the relative efficacy and safety of TZP 5, 10, 15 mg and sema 0.5 mg via a common comparator (sema 1.0 mg) based on trial results from SURPASS-2 (TZP vs sema 1.0 mg) and SUSTAIN 7 (sema 0.5 and 1.0 mg vs dulaglutide 0.75 and 1.5 mg). All TZP doses showed statistically significant greater reductions in HbA1c, weight and BMI from baseline to week 40 compared to sema 0.5 mg (Figure). TZP demonstrated a comparative safety profile for adverse events (AEs) but patients had statistically significant greater odds of treatment discontinuations due to AEs for TZP 10 and 15 mg. All TZP doses demonstrated no statistically significant differences vs sema 0.5 mg in the odds or likelihood of gastrointestinal AEs. In these adjusted indirect comparisons the extent of differences between TZP and sema 0.5 mg regarding HbA1c and weight reductions provide insights on their comparative effectiveness in the absence of a head-to-head study. Disclosure K. M. Pantalone: Consultant; AstraZeneca, Bayer Inc., Corcept Therapeutics, Diasome, Eli Lilly and Company, Merck &amp; Co., Inc., Novo Nordisk, Sanofi, Research Support; Bayer Inc., Merck &amp; Co., Inc., Novo Nordisk, Twin Health, Speaker's Bureau; AstraZeneca, Corcept Therapeutics, Merck &amp; Co., Inc., Novo Nordisk. S. Tofe: Advisory Panel; Lilly, Novo Nordisk, Research Support; Lilly, Novo Nordisk, Speaker's Bureau; Lilly, Novo Nordisk. L. Fan: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. J. S. Paik: None. K. T. Ranta: Employee; Eli Lilly and Company. H. Sapin: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. B. Osumili: Employee; Eli Lilly and Company. Funding Eli Lilly and Company

755-P: A Phase 2 Evaluation of a Novel GLP-1 Analog Ecnoglutide (XW003) for Glycemic Control in Adults with Type 2 Diabetes

Ecnoglutide (XW003) is a novel, long-acting GLP-1 analog being developed for the treatment of type 2 diabetes mellitus (T2DM) and obesity. We conducted a Phase 2 randomized, double-blind, placebo-controlled study of ecnoglutide, which enrolled 145 adults at over 20 hospital-based sites in China. Eligible participants had T2DM that was inadequately controlled by lifestyle or a single oral hypoglycemic agent. Participants were randomized to receive 0.4, 0.8, or 1.2 mg ecnoglutide or placebo as once weekly injections for 20 weeks, including dose escalation. Change in mean HbA1c, body weight, and BMI, as well as safety and tolerability were evaluated. At baseline, participants had mean HbA1c of 8.55 ± 0.707 % and BMI of 26.27 ± 3.308 kg/m2. At the end of treatment, participants receiving ecnoglutide achieved significant HbA1c reductions of 1.81% to 2.39% from baseline (P&amp;lt;0.0001 for all cohorts vs placebo). At end of treatment, up to 67% of participants in the ecnoglutide cohorts achieved HbA1c levels ≤6.5% and up to 33% had body weight reductions ≥5% from baseline (Figure). Ecnoglutide was generally safe and well tolerated. There were no treatment-related ≥Grade 3 AEs and no treatment-related SAEs. The proportion of participants reporting any AE ranged from 72.2 to 78.4% for ecnoglutide and 58.3 % for placebo. The most frequently reported AEs were gastrointestinal, including diarrhea and nausea. Disclosure D.Zhu: None. S.Xu: Employee; Sciwind. M.K.Junaidi: None. H.H.Qin: Employee; Sciwind Biosciences, Sichuan Anerobic Biotech. Q.Zheng: Employee; Sciwind Biosciences. J.Ning: None. Z.Zhu: Employee; Sciwind Biosciences. G.Mengying: None. Y.Bu: Employee; Sciwind Biosciences. C.Jones: Employee; Sciwind Biosciences. M.Fenaux: Employee; Sciwind Biosciences, Stock/Shareholder; Terns Pharmaceuticals. Funding Sciwind Biosciences

1064-P: Pharm2Home Initiative—The Impact on Diabetes Management and Behavioral Changes

Objective: To evaluate whether the intervention program (telehealth and home visit) focusing on chronic disease management induces changes in clinical, psychological, and behavioral measures. Methods: This program evaluation utilizes a pre-and-post-intervention comparison design. For detecting whether differences exist between the baseline data and the follow-up data for the various measures, paired t-test (for parametric data) and Wilcoxon signed-rank test (for non-parametric data) are used. Results: Paired HbA1c data from 57 individuals (out of 122 enrolled participants) have been collected. 55% of the participants were non-White, and 88% were Medicaid recipients. The table below summarizes some of the evaluation measures (most data are collected at the end of the intervention period). Conclusion: Our preliminary analyses show that program participants have achieved a significant HbA1c reduction with a significant increase in perceived self-efficacy in chronic disease management. In addition, the available behavioral data with statistical significance reveal that participants have changed their behaviors during the intervention relating to diabetes management. The preliminary analyses show some early signals that our intervention program has the potential to help participants better manage diabetes. Disclosure C.F.Young: Other Relationship; Abbott Diabetes. S.Wong: None. C.Myung: None. Funding Sutter Health

Tolerability, safety and pharmacodynamics of oral, small-molecule glucagon-like peptide-1 receptor agonist danuglipron for type 2 diabetes: A 12-week, randomized, placebo-controlled, Phase 2 study comparing different dose-escalation schemes.

To evaluate the tolerability, safety and pharmacodynamics of different dose-escalation schemes of the oral small-molecule glucagon-like peptide-1 receptor (GLP-1R) agonist danuglipron. This Phase 2a, double-blind, placebo-controlled, parallel-group study randomly assigned adults with type 2 diabetes (T2D) treated with metformin to placebo or danuglipron (low [5-mg] or high [10-mg] starting dose, with 1- or 2-week dose-escalation steps, to target doses of 80, 120 or 200 mg twice daily [BID]) and adults with obesity without diabetes to placebo or danuglipron 200 mg BID. Participants with T2D (n = 123, mean glycated haemoglobin [HbA1c] 8.19%) or obesity without diabetes (n = 28, mean body mass index 37.3 kg/m2 ) were randomly assigned and treated. Discontinuation from study medication occurred in 27.3% to 72.7% of participants across danuglipron groups versus 16.7% to 18.8% for placebo, most often due to adverse events. Nausea (20.0%-47.6% of participants across danuglipron groups vs. 12.5% for placebo) and vomiting (18.2%-40.9% danuglipron vs. 12.5% placebo, respectively) were most commonly reported in participants with T2D. Gastrointestinal adverse events were generally related to danuglipron target dose and were not substantially affected by starting dose. In participants with T2D, least squares mean changes from baseline in HbA1c (-1.04% to -1.57% across danuglipron groups vs. -0.32% for placebo), fasting plasma glucose (-23.34 mg/dL to -53.94 mg/dL danuglipron vs. -13.09 mg/dL placebo) and body weight (-1.93 to -5.38 kg danuglipron vs. -0.42 kg placebo) at Week 12 were generally statistically significant for danuglipron compared with placebo (P < 0.05). Danuglipron resulted in statistically significant reductions in HbA1c, FPG and body weight over 12 weeks, in the setting of higher discontinuation rates and incidence of gastrointestinal adverse events with higher target doses. gov identifier: NCT04617275.

Metabolic bariatric surgery as a therapeutic option for patients with type 2 diabetes: A meta-analysis and network meta-analysis of randomized controlled trials.

To compare different types of metabolic surgery with non-surgical therapy for the treatment of type 2 diabetes (T2D). The present network meta-analysis (NMA) includes randomized clinical trials (duration ≥ 52 weeks) comparing different surgery techniques with non-surgical therapy in diabetes patients. The primary endpoints were endpoint HbA1c, body mass index (BMI) and diabetes remission. The secondary endpoints included fasting plasma glucose, lipid profile, blood pressure, arterial hypertension and dyslipidaemia remission, quality of life and surgical adverse events. Indirect comparisons of different types of surgery were performed by NMA. Mean and 95% confidence intervals for continuous variables, and the Mantel-Haenzel odds ratio for categorial variables, were calculated. The types of surgical procedure included laparoscopic adjustable gastric banding, Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), bilio-pancreatic diversion (BPD), greater curvature plication (GCP), one-anastomosis gastric bypass (OAGB) and Duodeno-Jejunal bypass. Thirty-six trials were included. Metabolic bariatric surgery (MBS) was associated with a significantly higher reduction of HbA1c, diabetes remission and BMI compared with medical therapy. In the NMA, a significant reduction of HbA1c was observed with OAGB and SG. Complete diabetes remission significantly increased with all surgical procedures in comparison with non-surgical therapy, except for GCP. In addition, only BPD, RYGB and OAGB were associated with a significant reduction of BMI. MBS is an effective option for the treatment of T2D in patients with obesity. Further long-term trials of appropriate quality are needed for assessing the risk-benefit ratio in some patient cohorts, such as those with a BMI of less than 35 kg/m2 and aged older than 65 years.