bluuebunny/crossref_metadata_2025 huggingface dataset:
79-LB: An Open-Label, Active-Controlled Phase 2 Evaluation of Novel GLP-1 Analog Ecnoglutide in Adults with Obesity
Authors: ZHU ZHIYI , LI YAO , ZHENG QING , ADEGBITE ERIC , ROSS STEPHEN , TELUSCA LIBNIR , JONES CATHERINE L. , FENAUX MARTIJN , XU SUSAN , JUNAIDI MOHAMMED K.
Published: June 2023

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 multi-center, open-label, active-controlled Phase 2b study in adults with a body mass index (BMI) ≥30 to ≤40 kg/m2. The trial was conducted at nine sites in Australia and New Zealand, with 206 participants enrolled. Participants were randomized to receive target doses of ecnoglutide at 1.2, 1.8, or 2.4 mg as once weekly SC injections or liraglutide (Saxenda®) at 3.0 mg as once daily injections for 26 weeks. Doses were increased by titration for up to 14 weeks before reaching the target dose. Safety and tolerability were assessed, along with efficacy parameters including change in body weight. At baseline, participants had a mean body weight of 100.67 ± 13.54 kg and BMI of 35.29 ± 2.76 kg/m2. After 26 weeks of dosing, participants receiving 1.2, 1.8, or 2.4 mg ecnoglutide weekly achieved a least square mean (LSM) body weight reduction from baseline of -11.5%, -11.2%, and -14.7%, respectively, compared to -8.8% for those receiving 3.0 mg liraglutide daily injections. Participants receiving 2.4 mg ecnoglutide showed significantly more pronounced body weight reduction compared to liraglutide (LSM difference -5.9, 95% confidence interval -10.4, -1.5; p<0.001). Overall, treatment with ecnoglutide was safe and well tolerated. Treatment emergent AEs were reported in 93.5% of participants in the ecnoglutide groups and 98.0% in the liraglutide group. Gastrointestinal disorders were reported in 81.9% of ecnoglutide-treated participants and 80.4% of those receiving liraglutide, most of which were mild to moderate and most occurred during the dose escalation period. Two SAEs related to the study drug were reported. Both were cases of acute cholecystitis, one in a participant receiving 1.2 mg ecnoglutide and one in the liraglutide group.

Disclosure

Z. Zhu: Employee; Sciwind Biosciences. M. K. Junaidi: None. Y. Li: Employee; Sciwind Biosciences. Q. Zheng: Employee; Sciwind Biosciences. E. Adegbite: Employee; Sciwind Biosciences. S. Ross: None. L. Telusca: None. C. L. Jones: Employee; Sciwind Biosciences. M. Fenaux: Employee; Sciwind Biosciences, Stock/Shareholder; Terns Pharmaceuticals. S. Xu: Employee; Sciwind.

Funding

Sciwind Biosciences Co., Ltd.
797-P: Safety Profile of Once-Weekly Subcutaneous Semaglutide in a Real-World Adult Population with T2D
Authors: YALE JEAN-FRANÇOIS , MAJOR-PEDERSEN ATHELINE , CATARIG ANDREI-MIRCEA , JAIN RASHMI , MENZEN MARKUS , HOLMES PATRICK
Published: June 2023

Real-world (RW) drug safety studies complement safety information from randomized clinical trials. This post hoc analysis of pooled data from nine global non-interventional studies (SURE program: 10 countries, ~30 weeks duration) investigated the safety and prescription patterns of once-weekly (OW) semaglutide in 3,505 adults with T2D in routine practice, overall and by patient subgroup and medical specialty stratification. All safety data reported by site physicians were collected and presented using descriptive statistics. Results: Tables 1 and 2. A two-fold increase in level-2 hypoglycemia was associated with insulin use and microvasculopathy. No new safety concerns were observed with OW semaglutide in this large, diverse, RW population with T2D; the safety profile was in line with that of phase 3 trials of semaglutide.

Disclosure

J.Yale: Advisory Panel; Sanofi, Novo Nordisk Canada Inc., Eli Lilly and Company, Bayer Inc., Boehringer Ingelheim (Canada) Ltd., Abbott, Mylan, Research Support; Sanofi, Novo Nordisk Canada Inc., Bayer Inc., Speaker's Bureau; Sanofi, Novo Nordisk Canada Inc., Eli Lilly and Company, Bayer Inc., AstraZeneca, Merck & Co., Inc., Boehringer Ingelheim (Canada) Ltd., Janssen Pharmaceuticals, Inc., Abbott, Dexcom, Inc. A.Major-pedersen: Employee; Novo Nordisk A/S. A.Catarig: Employee; Novo Nordisk, Stock/Shareholder; Novo Nordisk. R.Jain: Employee; Novo Nordisk Global Business Services, Stock/Shareholder; Novo Nordisk Global Business Services. M.Menzen: Advisory Panel; Boehringer Ingelheim Pharma GmbH&Co.KG, Novo Nordisk A/S, Ascensia Diabetes Care, Eli Lilly and Company, Novartis, Speaker's Bureau; Abbott Diabetes, AstraZeneca, Santis, Boehringer Ingelheim Pharma GmbH&Co.KG, Novo Nordisk A/S, Bayer Inc., Eli Lilly and Company, Novartis. P.Holmes: Advisory Panel; Boehringer-Ingelheim, Sanofi, Research Support; Novo Nordisk, Roche Diagnostics, Speaker's Bureau; Novo Nordisk, AstraZeneca, Eli Lilly and Company, Bayer Inc.

Funding

Novo Nordisk A/S
802-P: Beneficial Effects of a Functionally Selective Insulin on Vascular Function and Liver Triglycerides
Authors: OLSEN GRITH S. , PEDERSEN THOMAS A. , SLAABY RITA , HANSEN BO F. , GLENDORF TINE , DEMOZAY DAMIEN , HVID HENNING , NISHIMURA ERICA , BRANDT JAKOB , POVLEN GRO
Published: June 2023

Selective insulin resistance, where insulin's ability to lower blood glucose via the Akt signaling pathway gradually decreases while retaining its effectiveness in activating other signaling pathways (e.g. MAPK), is a key pathophysiological mechanism underlying the hyperglycemia, dyslipidemia and vascular dysfunction in type 2 diabetes (T2D). Here we hypothesize that a selective signaling insulin analog that activates Akt signaling but has a considerably reduced effect on MAPK should counteract selective insulin resistance and provide effective glucose lowering with improved vascular function, reduced hepatic lipid accumulation and generally alleviate insulin resistance over time compared to human insulin (HI). NNC-965, a basal insulin analog with 4 amino acid modifications and a C18 fatty diacid, was designed as a functionally selective insulin, with greater Akt than MAPK activation in several cellular systems and in vivo. NNC-965 fully activates glucose regulating pathways, including inhibition of glucose output, glycogen accumulation and inhibition of gluconeogenic mRNAs in rat hepatocytes as well as stimulation of glucose uptake and inhibition of lipolysis in rat adipocytes. In contrast, NNC-965 displayed reduced induction of lipogenic mRNA and de novo lipogenesis in rat liver cells compared to HI. In a mouse model of T2D, treatment with NNC-965 for 6 weeks to the same glucose level as insulin 700 (an insulin degludec-like analog) resulted in 35% less liver triglycerides and improved acetylcholine mediated vasodilation in ex vivo studies using mesenteric arterioles. In conclusion, NNC-965 is a novel functionally selective insulin analog that can potentially improve insulin resistance and eventually reduce cardiovascular risk by restoring balanced insulin signaling.

Disclosure

G.S.Olsen: Employee; Novo Nordisk A/S. G.Povlen: Employee; Novo Nordisk. T.A.Pedersen: Employee; Novo Nordisk A/S. R.Slaaby: Employee; Novo Nordisk, Stock/Shareholder; Novo Nordisk. B.F.Hansen: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. T.Glendorf: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. D.Demozay: None. H.Hvid: Employee; Novo Nordisk A/S. E.Nishimura: Employee; Novo Nordisk A/S. J.Brandt: Employee; Novo Nordisk A/S.
805-P: Double-Blind Crossover Study of Ultra-Rapid AT247 Compared with NovoLog and Fiasp during Continuous Subcutaneous Infusion (CSII) Assessed by a Hyperinsulinemic Euglycemic Clamp
Authors: HOMPESCH MARCUS , LAWRENCE FIONA J. , JEZEK JAN , GERRING DAVID J. , PIEBER THOMAS
Published: June 2023

Background: AT247 is a novel insulin aspart formulation designed for ultra rapid absorption following subcutaneous injection to achieve optimal postprandial glycemic control.

Method: Adults (29) with T1DM were randomized to 6 treatment sequences of AT247, Novolog (N), and Fiasp (F). Bolus (0.15 U/kg) and basal (0.02 U/kg/h) doses of insulin were administered via CSII for 3 days. PK and PD were assessed using euglycemic clamps on days (D) 1 and 3.

Results: A higher early insulin exposure (AUCIns 0-30min mU/L/h) was observed for AT247 (16.7) vs N (6.3*) or F (13.0**) on D1, Fig 1A. The difference for AT247 was maintained on D3 (20.8) vs N (10.5*) but not vs F (19.2). A higher early glucose lowering effect (AUCGIR 0-60 mins mg/kg) was observed for AT247 (144.4) vs N (70.4*) but not vs F (145.8) on D1 only, Fig 1B. Time to early 50% Cmax insulin (h) occurred earlier for AT247 (0.18) compared to N (0.43*) and F (0.28**) on D1 and D3 (AT247 0.17; N 0.33**; F 0.22**). Statistical significance was p<0.05* or p<0.01**. AT247 was well tolerated with no significant adverse effects.

Conclusions: The faster absorption of AT247 resulted in higher early insulin exposure than for F or N following bolus dose delivery during CSII. The demonstrated PK profile of AT247 supports further investigation into its potential to further improve automated insulin delivery.

Disclosure

M.Hompesch: Board Member; ProSciento, Consultant; Wiley-Blackwell, Employee; ProSciento, Stock/Shareholder; ProSciento. F.J.Lawrence: None. J.Jezek: None. D.J.Gerring: Employee; Arecor. T.Pieber: Advisory Panel; Arecor, Novo Nordisk A/S, Consultant; Lilly, Research Support; AstraZeneca, Novo Nordisk A/S, Sanofi, Speaker's Bureau; Roche Diagnostics.
806-P: Once Weekly (QW) Basal Insulin Fc (BIF) and Daily Degludec (DEG) Achieve Comparable Glycemic Control in Three Patient Populations Studied during Phase 2—Clinical Insights from CGM Assessments
Authors: KAZDA CHRISTOF M. , BUE-VALLESKEY JULIANA M. , ZHANG QIANYI , HAUPT AXEL , FRIAS JUAN P. , DAHL DOMINIK
Published: June 2023

BIF is a fusion protein combining a novel single chain insulin variant with a human IgG Fc domain.

Three randomized, open-label, treat-to-target phase 2 studies of 26 or 32 week duration assessed 912 people with T2D previously treated with basal insulin (T2D-Switch) or new to insulin therapy (T2D-Naïve), or T1D on multiple daily injections (T1D). Studies assessed QW BIF vs once daily DEG. Key results were previously disclosed and met the primary endpoint of non-inferiority in HbA1c change from baseline (non-inferiority margin=0.4%). Two studies had CGM during entire study and T2D-Naïve had blinded, intermittent CGM using 14-day sessions.

Patients had baseline HbA1c of 8.1, 8.0, and 7.5% for T2D-Switch, T2D-Naïve, and T1D respectively. Figure shows average hourly mean glucose at endpoint and time in range (inset). Glucose profiles appeared comparable between treatments with 24-hour average glucose for BIF vs DEG in T2D-Naïve: 137 vs 127 mg/dL p=.042 and T1D: 175 vs 169 p=.075 (T2D-Switch not available). Average duration of hypoglycemia, <70mg/dL (min) per patient for BIF vs DEG: T2D-Switch 31 vs 35 p=NS, T2D-Naïve 51 vs 91 p<.001, and T1D 35 vs 35 p=NS.

QW BIF achieved similar glycemic control vs DEG as seen in several CGM derived measures providing useful and reassuring insights into the use of QW BIF in these patient populations.

Disclosure

C.M.Kazda: Employee; Eli Lilly and Company. J.M.Bue-valleskey: Employee; Eli Lilly and Company. Q.Zhang: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. A.Haupt: Employee; Lilly, Stock/Shareholder; Lilly. 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. D.Dahl: Research Support; Lilly, Novo Nordisk, Eli Lilly and Company, Boehringer Ingelheim Inc., Amgen Inc.

Funding

Eli Lilly and Company
807-P: Patient and Health Care Provider Experiences of Suboptimal Insulin Dosing in the United States
Authors: DAVIDSON MICHAEL B. , GELSEY FELICIA , BOWER JULIE , ARTIME ESTHER , SPAEPEN ERIK , NEWSON RACHEL
Published: June 2023

Objectives: This study described the frequency of suboptimal insulin dosing (missed and mistimed doses) and the factors underlying this behavior from the perspective of people with diabetes (PwD) and healthcare professionals (HCPs.)

Methods: For this cross-sectional, multinational non-interventional study, 640 HCPs and 1150 PwD (300 with type 1 diabetes, 850 with type 2 diabetes) completed an online survey. A research vendor recruited adult PwD currently using a non-connected insulin pen (400 from US) and eligible HCPs (160 from US) via validated panels, referrals, list acquisition, and custom methods. Results are presented for US data.

Results: Overall, 42% and 61% of PwD reported missing basal and bolus insulin doses in the past 30 days. The average number of missed basal and bolus doses were 3.1 (SD=3.81) and 5.0 (SD=10.30), respectively. PwD reported forgetting, being too busy/distracted, and out of my normal routine as key reasons for missed doses. Overall, 37% and 49% of PwD reported mistiming basal and bolus doses, respectively, in the past 30 days. This corresponded to an average of 3.1 (SD=3.29) mistimed basal and 4.9 (SD=6.28) mistimed bolus doses. Key reasons PwD reported for mistimed doses included being too busy/distracted, forgot or having an unexpected or earlier/later-than-expected meal. Conversely, the majority of HCPs reported ≤20% of their PwD missed/skipped a dose in the past 30 days. HCPs reported dosing reminders (90%), automatically recorded insulin doses and timing (92%) and having insulin and glucose data in one place (94%) as identified solutions.

Conclusions: PwD are missing, skipping, or delaying their insulin doses, largely for preventable reasons. HCPs perceive PwD dosing adherence greater than PwD self-reported behaviors. Digital health solutions, such as connected insulin pens, may help PwD reduce missed and mistimed doses as well as help close the perception gap to further optimize insulin management.

Disclosure

M.B.Davidson: Employee; Eli Lilly and Company. F.Gelsey: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. J.Bower: None. E.Artime: None. E.Spaepen: Consultant; Eli Lilly and Company. R.Newson: Employee; Eli Lilly and Company.

Funding

Eli Lilly and Company
81-OR: The Rnf20 Ubiquitin Ligase Is Required for Beta-Cell Identity and Function
Authors: PIERRE TANYA , LIU YANPING , HUNTER CHAD S.
Published: June 2023

Type 1 and Type 2 Diabetes are characterized by a loss of functional β-cell mass. With the incidence of diabetes rising globally, a better understanding of the gene regulatory mechanisms maintaining β-cell functional identity is imperative to improve diabetes therapies. Islet 1 (Isl1) is a LIM-homeodomain class transcription factor that is essential for β-cell maturation and function. Our previous Isl1 studies revealed that it interacts with the histone ubiquitin ligases Ring Finger 20 (Rnf20) and Rnf40 in mouse β-cells, mouse islets, and human islets. Rnf20 and Rnf40 act as homo- or heterodimeric complexes wherein they monoubiquitinate histone 2B to regulate transcription. In mouse β-cell lines, we demonstrated that Rnf20 and Rnf40 are important for β-cell gene expression and insulin secretion, perhaps mediated by their occupancy of Slc2a2 and MafA. Additionally, using proximity ligation assay we showed a robust increase in Isl1 and Rnf20 interactions under high glucose conditions. Based on these findings, we hypothesized that at least Rnf20 is required for β-cell function in adult islets. To evaluate the contribution of Rnf complexes to β-cell maintenance, we developed an adult-inducible Rnf20 β-cell-specific knockout mouse model, termed Rnf20Δβ-cell. By 8 weeks of age (2 weeks after tamoxifen induction) male and female Rnf20Δβ-cell mice became hyperglycemic, severely glucose intolerant, and had reduced plasma insulin levels following a glucose challenge. Additionally, Rnf20Δβ-cell mice had reduced β-cell mass, in parallel with dysregulated expression of glucose-stimulated insulin secretion and β-cell identity mRNAs including Ins I, Slc2a2, Ucn3, Ngn3, and Aldh1a3. Our in vivo findings resemble those observed in adult Isl1 knockout mice. Paired with similar changes in gene expression in the Rnf20 and Isl1 models, and the glucose-responsive interaction between Isl1 and Rnf20 in vitro, our data support the hypothesis that Isl1-Rnf complexes are critical regulators of β-cell function.

Disclosure

T.Pierre: None. Y.Liu: None. C.S.Hunter: None.

Funding

National Institutes of Health (DK111483, DK128132)
812-P: Tight vs. Standard Inpatient Glycemic Targets in Non–Critical Care Settings—A Propensity Scored–Matched Analysis of Insulin-Treated Patients with Type 2 Diabetes
Authors: SALING JARROD , MIGDAL ALEXANDRA L. , URRUTIA MARIA A. , ZABALA ZOHYRA , MOAZZAMI BOBAK , GALINDO RODOLFO J. , FAYFMAN MAYA , RASHIED AMMAR A. , UMPIERREZ GUILLERMO
Published: June 2023

Differing blood glucose (BG) targets are recommended by professional organizations in noncritical care settings. Previous Endocrine Society and ADA guidelines recommended a target BG of 70-140 and 140-180 mg/dl; however, the 2023 ADA Standards of Care recommends a target of 100-180 mg/dl. The lack of consensus is due to the lack of randomized clinical trials (RTC) to support a tight vs relaxed BG target. We performed a post-hoc analysis on 9 RCTs to assess hospital outcomes in non-critically ill insulin-treated subjects with T2D targeting BG 70-140 mg/dL vs. 140-180 mg/dL. Among 1446 patients, 640 were treated to a target of 70-140 mg/dl and 806 to a target of 140-180 mg/dL. Propensity score matching was used to reduce the bias including sex, HbA1c, and home insulin use, for a final count of 1,146 patients (573 subjects in each target group). Patients in the tight BG target group had lower mean BG (163.73±39.79 vs 170.15±39.94 mg/dL, p=0.004), less hyperglycemia (BG >180: 86% vs 92%, p=0.003; BG >240: 51% vs 62%, p<.001), similar rates of hypoglycemia (BG <70: 12% vs 15%, p=0.11; BG <54: 2.5% vs 4.0%, p=0.14). The intensive target resulted in a shorter length of stay (4.0 vs 6.0 days, p<.001) and lower composite of complication rate (acute kidney injury, infection, myocardial infarction, respiratory failure and stroke) (3.7% vs 6.8%, p=0.02) than the relaxed BG target, with similar mortality rates (0.9% vs 0.3%, p=0.36). There were no differences in glycemic variability (GV) between groups with greater GV in those experiencing hypoglycemia <70 mg/dL or hyperglycemia >200 mg/dL. Our results indicate that lower BG target of 70-140 mg/dl leads to lower mean daily BG, less severe hyperglycemia events, similar rates of hypoglycemia and glycemic variability, and lower length of stay and complication rates compared to a higher target of 140-180 mg/dl. RCTs are indicated to elucidate optimal glycemic targets in hospitalized patients with T2D.

Disclosure

J.Saling: None. A.L.Migdal: None. M.A.Urrutia: None. Z.Zabala: None. B.Moazzami: None. R.J.Galindo: Consultant; Novo Nordisk, Eli Lilly and Company, Sanofi, Pfizer Inc., Bayer Inc., WW (Weight Watchers), Research Support; Novo Nordisk, Eli Lilly and Company, Dexcom, Inc. M.Fayfman: None. A.A.Rashied: None. G.Umpierrez: Research Support; Abbott, Dexcom, Inc., Baxter.

Funding

Jacob Family Funds
813-P: Bridging Dose of U-100 Glargine with First Dose of Insulin Degludec Improves Glycemia in the 48 Hours after Transition In Twice-Daily Glargine Users
Authors: THIRUMALAI ARTHI , CHAO JING H. , KALERU THANMAI , DONG XIAOFU , MANDAVA PATALI , KHAKPOUR DORI , HIRSCH IRL B.
Published: June 2023

Background: Degludec (D), a once-daily basal insulin, takes 2-3 days to achieve steady state. When transitioning from insulin glargine (G) to D, 1:1 conversion is recommended. We studied the off-label effects of a bridging dose of G with the first dose of D in type 1 diabetes (T1D) patients using a continuous glucose monitor (CGM) 48 hours before and after the transition.

Methods: Patients with T1D on a stable G regimen and A1C <9% were randomized (double-blind) to a dose of placebo or G with first dose of D. Patients transitioned to D at 80% of total baseline G dose, based on result of SWITCH 1 clinical trial of transition to D. Bridging dose of G was 50% of total daily G dose for patients on once daily (QD) regimen at baseline and 50% of evening G dose in those on twice daily (BID) G and was taken with only the first dose of D. All participants wore a study CGM (Dexcom G6) and were instructed to manage their diabetes as usual except for not administering correctional doses of insulin unless glucose was greater than 250 mg/dL in the 48 hours before and after first dose of D.

Results: Forty participants were randomized and 37 completed the study. The study population was 65% male with mean age of 47 years, 22 years duration of T1D, BMI 26 kg/m2, A1C of 6.8% and total daily insulin dose of 0.7 units/kg body weight. Nineteen patients (12 QD, 7 BID) received a bridging dose of G with their first dose of D; 18 patients (12 QD, 6 BID) received placebo. Among the BID users, patients bridged with G had a mean 9% increase in time in range (70-180 mg/dL) on CGM, while placebo patients had a mean 12% decrease (p=0.003). Time above range (180-250 mg/dL) also showed a mean 11.4% decrease in the BID users bridged with G, contrasted with an 11.5% increase in BID users on placebo (p=0.002). There were no significant differences in time below ranges (<70 mg/dL, <54 mg/dL).

Conclusions: Well-controlled twice-daily G users transitioning to D may benefit from a 50% bridging dose of evening G with first dose of D.

Disclosure

A.Thirumalai: Research Support; Novo Nordisk, Fractyl Health, Inc. J.H.Chao: None. T.Kaleru: None. X.Dong: None. P.Mandava: None. D.Khakpour: None. I.B.Hirsch: Consultant; Abbott Diabetes, Lifecare, Inc., Hagar, Research Support; Beta Bionics, Inc., Insulet Corporation, Dexcom, Inc.

Funding

Novo Nordisk (ISS001250)
818-P: Glycemic Control in Naïve Users of Second-Generation Basal Insulins with T2D and CKD—A Nationwide Register-Based Cohort Study
Authors: KOSJERINA VANJA , CARSTENSEN BENDIX , AMADID HANAN , VISTISEN DORTE
Published: June 2023

Objective: We aimed to compare the effectiveness and safety of second-generation basal insulins, insulin glargine 300 U/mL (Gla-300) and insulin degludec 100 U/mL (Deg-100), in terms of change in HbA1c, hospitalization for hypoglycemia and all-cause mortality.

Methods: In this register-based cohort study, using real-word data on the entire Danish diabetes population in the period 2013-2020, we included 6519 naïve users of Gla-300 or Deg-100 with T2D and chronic kidney disease (CKD). Change in HbA1c, from initiation of either study drugs to end of follow-up, was modeled with mixed-effect models while rates of hospitalization for hypoglycemia and all-cause mortality were modeled in separate Poisson models.

Results: Mean HbA1c levels were reduced by 13-14 mmol/mol over a four-year period in both groups with no significant difference (Figure). The rate of hospitalization for hypoglycemia was slightly but not significantly higher in the Deg-100 group (rate-ratio 1.03 (CI 95%: 0.71, 1.49) while the all-cause mortality rate was slightly but not significantly lower in the Deg-100 group (0.97 (0.83, 1.14)).

Conclusion: We found no difference in HbA1c reduction, hospitalization for hypoglycemia or all-cause mortality between Gla-300 and Deg-100, in a real-world population of naïve users with T2D and CKD.

Disclosure

V.Kosjerina: Research Support; Sanofi-Aventis Deutschland GmbH. B.Carstensen: Stock/Shareholder; Novo Nordisk. H.Amadid: Employee; Novo Nordisk A/S. D.Vistisen: Research Support; Bayer Inc., Sanofi, Boehringer-Ingelheim, Stock/Shareholder; Novo Nordisk A/S.

Funding

Sanofi-Aventis Deutschland GmbH
821-P: Treatment and Outcomes of Nonemergent Hyperglycemia in the Emergency Department
Authors: MURPHY KRISTA , LACY MARY E. , HEIER KORY , CLAAS STEVEN A. , KECK JAMES
Published: June 2023

Background: Patients with hyperglycemia often seek care in the emergency department (ED). Hyperglycemia is associated with longer hospital stays and increased risk of mortality.

Methods: Using electronic health record data from patients ≥18 seen at an academic medical center ED (11/1/2015-12/31/2020), we described presentation of non-emergent hyperglycemia (blood glucose (BG) 180-600mg/dL) and examined associations between insulin receipt in ED and in-hospital mortality and hospitalization. We excluded patients with initial BG >600mg/dl, decompensated diabetes, stroke, myocardial infarction, pregnancy, or sepsis, and calculated National Early Warning Score to control for illness severity. We examined associations between insulin receipt and hospitalization and mortality in patients with BG 180-600mg/dL using logistic regression, and stratified analyses by diabetes diagnosis and BG value to assess for effect modification.

Results: Of 177,176 eligible patients, 10.9% (19,378) had BG 180-600mg/dL (mean (SD) age=54.6 (15); 52.5% male). Of these patients, 6.8% (1,312) received insulin, 41.8% (8,097) were hospitalized, and 0.3% (278) died. Regression results appear in Figure 1.

Conclusions: Hyperglycemia in the ED was common. Treatment with insulin, though uncommon, yielded lower odds of mortality but not hospitalization. Diabetes diagnosis and severity of hyperglycemia modified this association.

Disclosure

K.Murphy: None. M.E.Lacy: None. K.Heier: None. S.A.Claas: None. J.Keck: None.

Funding

National Institutes of Health (UL1TR001998)
822-P: Machine Learning Guided Interpretation of Point-of-Care Ultrasound to Diagnose Lipohypertrophy
Authors: MADDEN KENNETH M. , BANDARI ELA , HABASHY LARA , RAZA JAVAIRIA , KAPELUTO JORDANNA E. , MENEILLY GRAYDON S.
Published: June 2023

Objective: Using a supervised machine learning convolutional neural network (CNN) we developed a model to detect lipohypertrophy (LH) using point-of-care ultrasound (PoCUS) images.

Research Designs and Methods: Using a PoCUS ultrasound machine (GE LOGIQe, 5-18 MHz probe), images were obtained by a single, blinded technician. We then split the data set into training (70%), validation (15%) and testing (15%) splits. To improve the generalizability of the model, we used image augmentation techniques (randomly changing contrast, brightness, etc). We considered recall and accuracy of our models when testing the various architectures on our testing dataset. An YOLOv5m object detection model was used to place bounding boxes around LH lesions.

Results: The learning architectures investigated were VGG16, ResNet50, DenseNet169, and InceptionV3. The highest recall (76%) and accuracy (76%) was found using the DenseNet CNN architecture. As shown in the figure, YOLOv5m was able to identify LH locations with a F1 score of 0.78 and a confidence value of 0.41.

Conclusions: We were able to use a DenseNet CNN architecture to automatically detect the presence of LH lesions on PoCUS images obtained at the bedside.

Disclosure

K.M.Madden: None. E.Bandari: None. L.Habashy: None. J.Raza: None. J.E.Kapeluto: None. G.S.Meneilly: None.

Funding

Allan M. McGavin Foundation
823-P: GLY-200, a Pharmacologic Duodenal Exclusion Therapy, Improved Metabolic Parameters in the DIO Rat
Authors: NIMGAONKAR ASHISH , BRYANT CHRISTINE , HABEGGER KIRK M. , COLBERT KEVIN , CARLSON TAYLOR , POLOMOSCANIK STEVEN , PETERSEN JOHN S. , JOZEFIAK THOMAS H. , FINEMAN MARK
Published: June 2023

Non-invasive alternatives to metabolic surgery or duodenal exclusion devices for type 2 diabetes (T2D) and obesity are lacking. We developed an orally administered therapeutic polymer, GLY-200, designed to create a barrier in duodenum by complexing with mucin. In healthy subjects, 5 days treatment resulted in significant reductions in postprandial glucose and insulin and increases in bile acids and gut hormones. To evaluate the chronic effects of GLY-200, we conducted an 8-week study in the diet-induced obesity (DIO) rat model.

Methods: DIO rats (60% kcal fat diet) were gavaged once daily following a 3-hour fast with GLY-200 (120 mg/rat) or saline (n=12/group). Metabolic assessments included body weight, mesenteric fat mass, skeletal muscle mass (gastrocnemius), glycemic responses to an oral glucose tolerance test (oGTT), and gut hormones from fasted samples at study termination.

Results: At 8 weeks, GLY-200 treated rats had a significant reduction in % body weight gain (5%, p < 0.05), lower mesenteric fat mass (p < 0.01), and a significant reduction in incremental glucose AUC0-120 min following the oGTT on Day 51 (p < 0.05) compared to control. These metabolic benefits were associated with a significantly higher fasting active GLP-1 level compared to control (p < 0.01). Trends for increased PYY were also observed as compared to control. There was no difference in skeletal muscle mass.

Conclusions: In the DIO rat, chronic (8-weeks) once-daily treatment with GLY-200 resulted in significant improvements in metabolic parameters compared to saline control consistent with a duodenal exclusion MOA. These results support further development of GLY-200 for the treatment of T2D and obesity.

Disclosure

A.Nimgaonkar: Employee; Glyscend Inc. C.Bryant: Employee; Glyscend Inc. K.M.Habegger: Consultant; Glyscend Inc., Research Support; Eli Lilly and Company, Novo Nordisk, Glyscend Inc., Stock/Shareholder; Glyscend Inc. K.Colbert: Consultant; LifeSprout, Employee; Glyscend Inc. T.Carlson: Employee; Glyscend Inc. S.Polomoscanik: None. J.S.Petersen: None. T.H.Jozefiak: Employee; Glyscend Inc., Stock/Shareholder; Glycologix, LLC. M.Fineman: Employee; Glyscend Inc., Stock/Shareholder; Glyscend Inc.
827-P: Effects of Elexacaftor/Tezacaftor/Ivacaftor Triple Combination Therapy on Glycaemic Control and Body Composition in Patients with Cystic Fibrosis–Related Diabetes
Authors: GRANCINI VALERIA , GRAMEGNA ANDREA , ZAZZERON LAURA , ALICANDRO GIANFRANCO , PORCARO LAURA L. , PIEDEPALUMBO FEDERICA V. , LANFRANCHI CHIARA , DACCÒ VALERIA , ORSI EMANUELA
Published: June 2023

Introduction: Cystic fibrosis related diabetes (CFRD) is the most common extra pulmonary complication of cystic fibrosis (CF). Cystic fibrosis transmembrane conductance regulator (CFTR) modulators are a group of new drugs for the treatment of CF and elexacaftor+tezacaftor+ivacaftor (ETI) triple combination therapy has been approved as first choice therapy in the treatment of patients with at least 1 copy of F508del mutation. Data on the effects of CFTR modulators on glucose metabolism in patients with or without CFRD are limited to small studies with conflicting results.

Aim of the study: to evaluate the effectiveness of ETI on glucose metabolism, glucose variability and body composition in patients with CFRD.

Methods: We conducted a prospective observational study on 24 CF patients with CFRD requiring insulin therapy. We performed an evaluation of glycometabolic control, glucose variability (assessed with 14 days-flash glucose monitoring) and body composition (with bio-impedance analysis) before and six months after the beginning of ETI. Data are expressed as median and interquartile ranges.

Results: We demonstrated an improvement in both HbA1c [from 7.0% (6.5, 7.4) to 6.6 (6.0, 7.1), p<0,05] and coefficient of variation [CV - from 35.0 (29.0, 44.5) to 28.2 (25.2, 33.1), p< 0.01], despite unchanged insulin requirements. Over the treatment period, percent of fat mass (FM) significantly increased [from 12.1% (7.2, 16.2) to 15.4% (11.8, 18.6), p<0.05].

Conclusions: ETI improves glycometabolic regulation in patients with CFRD on insulin therapy. A longer follow-up is needed to better characterize the body composition changes induced by ETI and their metabolic consequences.

Disclosure

V.Grancini: None. A.Gramegna: None. L.Zazzeron: None. G.Alicandro: None. L.L.Porcaro: None. F.V.Piedepalumbo: None. C.Lanfranchi: None. V.Daccò: None. E.Orsi: None.
832-P: Coadministration of Metformin with GLY-200, a Clinical-Stage Nonabsorbed Drug for the Treatment of Type 2 Diabetes (T2D), Has No Significant Impact on the Oral Absorption of Metformin in the Rat
Authors: FINEMAN MARK , BRYANT CHRISTINE , JOZEFIAK THOMAS H. , NIMGAONKAR ASHISH , CARLSON TAYLOR
Published: June 2023

Background: GLY-200 is a non-absorbed polymer drug currently in Phase 2 clinical trials for the treatment of T2D. GLY-200 was designed to reversibly enhance the barrier properties of the intestinal mucus lining to non-invasively mimic gastric bypass and duodenal exclusion devices. In view of this mechanism of action, GLY-200 has the potential to interfere with the absorption of orally available drugs. As such, we investigated the effect of GLY-200 on the oral absorption of metformin, an antidiabetic agent commonly used in combination with other glucose-lowering medications.

Methods: Metformin (100 mpk) was administered by oral gavage in saline to male Sprague Dawley rats (6-8 weeks old). GLY-200 (400 mpk) was dosed either simultaneously in the same gavage solution, or prior (1- or 3-hours) to the metformin dose. Blood samples were drawn at 0, 0.25, 0.5, 1, 2, 4, 7, 10, and 24 hours following the metformin dose, and a pharmacokinetic (PK) analysis was performed using a noncompartmental model (Phoenix WinNonlin v. 8.3).

Results: GLY-200 altered the rate but did not meaningfully alter the extent of metformin absorption. The greatest effect was observed when the two drugs were dosed together (Cmax ↓34%; tmax ↑100%; AUC ↑11%). The observed changes may be a result of slowed GI transit with GLY-200 administration.

Conclusions: The oral absorption and PK profile of metformin was not significantly altered when the drug was coadministered with GLY-200 or given 1- or 3-hours after a GLY-200 dose. These results suggest that GLY-200 could be used in combination with metformin, whose pharmacologic action is not dependent on Cmax.

Disclosure

M.Fineman: Employee; Glyscend Inc., Stock/Shareholder; Glyscend Inc. C.Bryant: Employee; Glyscend Inc. T.H.Jozefiak: Employee; Glyscend Inc., Stock/Shareholder; Glycologix, LLC. A.Nimgaonkar: Employee; Glyscend Inc. T.Carlson: Employee; Glyscend Inc.
833-P: Duodenal Targeting by Oral Pharmacologic Duodenal Exclusion Therapy for Treatment of Type 2 Diabetes (T2D)
Authors: NIMGAONKAR ASHISH , BRYANT CHRISTINE , CARLSON TAYLOR , GUERINA FLORENCE V. , COLBERT KEVIN , POLOMOSCANIK STEVEN , PETERSEN JOHN S. , JOZEFIAK THOMAS H. , FINEMAN MARK
Published: June 2023

GLY-200 is an oral, non-absorbed polymeric drug designed to non-invasively and reversibly enhance the mucus lining of the proximal small intestine to mimic the effects of metabolic surgery and duodenal exclusion devices. In healthy volunteers and rat models of T2D (GK, ZDF, and DIO), GLY-200 produced reductions in postprandial glucose and bodyweight compared to control. This study aimed to visualize the retained duodenal barrier in rats using appropriate imaging modalities.

Methods: Imaging of GLY-200 after gavage administration to fasted Sprague-Dawley rats was performed using Computed Tomography (CT) and an In Vivo Imaging System (IVIS). For CT imaging, GLY-200 was covalently conjugated with diatrizoate; images were obtained after transient isoflurane administration 1, 2, and 4 hours after gavage. For IVIS imaging, GLY-200 was reacted with FITC to produce a fluorescein-GLY-200 conjugate. Rats were euthanized 0.5, 1, 2, 4, and 8 hours after dosing and the GI tracts were immediately removed for imaging.

Results: In CT imaging, GLY-200-diatrizoate was retained in the proximal small intestine 1 and 2 hours after administration, with an intense signal only in the duodenum. In comparison, a diatrizoate control was broadly distributed over the small intestine distal to the duodenum by 1 hour. In IVIS imaging, GLY-200-FITC showed intense fluorescence in the proximal small intestine that was predominantly associated with the gut wall and persisted for >4 hours after administration. In comparison, a FITC-dextran70 control was distributed broadly throughout the distal intestine and cecum by 30 minutes with no retention in the duodenum.

Conclusion: Imaging studies confirm that GLY-200 conjugates are retained in the duodenum after oral administration. These data support the hypothesis that GLY-200 treatment results in a pharmacologic duodenal exclusion that could potentially recapitulate the glycemic and weight effects of metabolic surgery and duodenal exclusion devices.

Disclosure

A.Nimgaonkar: Employee; Glyscend Inc. C.Bryant: Employee; Glyscend Inc. T.Carlson: Employee; Glyscend Inc. F.V.Guerina: Employee; Glyscend Inc. K.Colbert: Consultant; LifeSprout, Employee; Glyscend Inc. S.Polomoscanik: None. J.S.Petersen: None. T.H.Jozefiak: Employee; Glyscend Inc., Stock/Shareholder; Glycologix, LLC. M.Fineman: Employee; Glyscend Inc., Stock/Shareholder; Glyscend Inc.
86-LB: Real-World Impact of Oral Semaglutide on Glycemic Control and Weight Outcomes in Type 2 Diabetes (RELATE–Oral Semaglutide)
Authors: AMAMOO JAMES , DOSHI RIDDHI P. , NOONE JOSHUA , TAN XI , XIE LIN , GAMBLE CORY L. , GUEVARRA MICO , CHEN JUSTIN , KING AARON A.
Published: June 2023

Background: The study objective was to evaluate the impact of oral semaglutide type 2 diabetes (oral sema T2D) on changes in HbA1c and weight outcomes in adults with T2D.

Methods: This retrospective cohort study from October 2019 to September 2021 analyzed a linked US database from IQVIA’s Longitudinal Prescription Claims, Professional Fee Claims, and Ambulatory Electronic Medical Records. Adults with T2D with HbA1c ≥7% were included. Analyses were conducted to compare pre- and post-index (12 months) HbA1c and weight-related outcomes.

Results: The final sample included 398 patients. Over 12 months post-index, mean HbA1c decreased significantly from 8.8% to 7.8% (p<0.001), with 32.4% of patients achieving HbA1c <7.0%. Mean BMI decreased significantly from 35.2 to 34.1 kg/m2 (p<0.001), with the proportion of patients with BMI ≥40.0 kg/m2 decreasing from 25.6% to 20.1%, and the proportion of those with BMI ≥30.0 kg/m2 decreasing from 75.6% to 70.4%. Mean weight decreased significantly from 102.4 to 98.9 kg (p<0.001), with 33.4% and 11.1% of patients experiencing a ≥5% and ≥10% decrease in weight, respectively.

Conclusion: At 12-month follow-up, adults initiating oral sema T2D had statistically significant decreases in HbA1c, weight, and BMI from baseline. Further regression analyses will be conducted to control for covariates.

Disclosure

J. Amamoo: None. R. P. Doshi: Employee; IQVIA Inc. J. Noone: Employee; Novo Nordisk. X. Tan: Employee; Merck & Co., Inc., Novo Nordisk, Stock/Shareholder; Merck & Co., Inc., Novo Nordisk. L. Xie: Employee; Pfizer Inc., Novo Nordisk A/S. C. L. Gamble: Employee; Novo Nordisk. M. Guevarra: Employee; Novo Nordisk. J. Chen: Employee; IQVIA Inc. A. A. King: Advisory Panel; Novo Nordisk, Board Member; JDRF, Speaker's Bureau; Sanofi, Abbott, Dexcom, Inc., Lilly Diabetes.
862-P: Reduced Metformin Clearance Is Associated with Increased Metformin-Related Side Effects in Older Adults with Type 2 Diabetes (T2D)
Authors: YEN KEVIN , SRINIVASAN SHYLAJA , DAPKUS LAURA A. , TAMRAZ BANI , MASHARANI UMESH , MCCABE SHANNON E. , KROON LISA
Published: June 2023

The safe use of metformin in the elderly population and in patients with impaired renal function has not been clearly defined. Metformin has side effects that limit use particularly in vulnerable populations. In this pilot study, we aimed to investigate the interplay between metformin pharmacokinetics, pharmacogenetics of metformin transporters and metformin-related side effects. Participants were recruited based on age ≥ 65 years or eGFR=30-59 mL/min. Two sample PK sampling was performed; lactic acid, vitamin B12 and creatinine levels were measured. Participants completed a survey on GI side effects. Metformin clearance (Cl) and area under the curve (AUC) were calculated using previously described limited sampling strategy by Chen et al. Participants were genotyped for variants in the following transporters affecting metformin clearance: OCT1, OCT2, OCT3, OCTN1, MATE1, MATE2-K and PMAT. Nineteen participants with T2D and mean age 72y (range: 56-86y) completed the study. Mean eGFR was 79±27mL/min and median morning dose of metformin was 1000mg (range: 500-1500mg). Mean metformin Cl was 302 ±227ml/min, consistent with previous reports based on age and renal function. Those with GI side effects had lower Cl (389ml/min vs 191ml/min, P = 0.03). There was a positive correlation between metformin AUC and baseline lactic acid levels (R2 = 0.46, P <0.01). There was no relationship between metformin Cl or AUC and vitamin B12 levels. Individuals homozygous for rs272893 in OCTN1 had lower metformin Cl based on a univariate generalized linear model (β: -181 per allele, SE=62, P = 0.003) We confirm that metformin Cl is lower in older adults with T2D and show that lower Cl is associated with increased GI side effects. Genetic variation in metformin transporter OCTN1 was associated with reduced Cl. Larger studies are needed to examine the impact of metformin dose modification in patients with reduced clearance based on pharmacogenetics to minimize side effects.

Disclosure

K.Yen: None. S.Srinivasan: None. L.A.Dapkus: None. B.Tamraz: Advisory Panel; Codex Genetics. U.Masharani: Research Support; Clementia Pharmaceuticals. S.E.Mccabe: None. L.Kroon: None.
865-P: Hypoglycemia Risk Is Similar with Dipeptidyl Peptidase-4 Inhibitors (DPP-4i) Monotherapy vs. Metformin Monotherapy
Authors: PERIYANAYAGAM USHA , WEI YUQIN
Published: June 2023

Introduction: Prescribing DPP-4i medications versus metformin as a first-line treatment is common, although large-scale safety evidence favoring DPP-4is monotherapy is scarce. The goal of this study is to compare the incidence of hypoglycemia in patients with a DPP-4i monotherapy versus metformin monotherapy

Methods: US patients in Komodo's Healthcare Map with diabetes were studied. 2,016,156 patients (59.3% female) on a single-gradient metformin monotherapy and 45,826 patients (52.6% female) on a DPP-4i monotherapy were found from 2016 - 2020. No antidiabetic treatment was prescribed in the previous year and patients were continuously enrolled 1 year before/6 months after their first medication prescription. Propensity score matching (PSM) was performed using age, gender, US regions, chronic kidney disease (CKD), obesity, emergency room visits, Charlson Comorbidity Index (CCI), and proportion of Days Covered (PDC). The PSM sample comprised 45,400 1:1 matched users of each group. The incidence rate of hypoglycemia was calculated using Poisson regression.

Results: Patients in the DPP-4i group were older, 64.3 (SD14.0) versus 50.5 (15.8) years in the metformin group. CKD was recorded in 28.1% of the DPP-4i users and 4.3% of metformin users. A CCI score ≥5 was seen in 53.7% of DPP-4i users and 15.9% of Metformin users. PDC was ≥ 80% in 37.0% and 42.7% of DPP-4I and metformin users. The estimated pre-matched incidence of hypoglycemia was 19.04 and 16.88 per 1000 person-years in DPP-4i and metformin users. The post-matching incidence rates were 19.17 for DPP-4i and 16.82 for metformin users. The DPP-4i to metformin incidence rate ratio was 1.14 (95% CI 0.99 - 1.31, p = 0.062).

Conclusion: The incidence rate of hypoglycemia in a large cohort of patients treated with DPP-4i was comparable to those treated with metformin. The sizable risk of hypoglycemia after DPP-4is should be considered in prescription decision-making.

Disclosure

U. Periyanayagam: None. Y. Wei: None.
869-P: Effect of Dapagliflozin on Renal Oxygen Delivery and Consumption in T2DM and NGT Subjects
Authors: TRIPATHY DEVJIT , CHEN XI , CHILTON ROBERT , HANSIS-DIARTE ANDREA A. , SALEHI MARZIEH , SOLIS-HERRERA CAROLINA , CERSOSIMO EUGENIO , DEFRONZO RALPH A.
Published: June 2023

Improved renal oxygenation is proposed as a potential reno-protective mechanism of SGLT2 inhibitors in T2DM. Bold-MRI studies in nondiabetic subjects showed no effect with dapagliflozin and improved renal cortical oxygenation with empagliflozin in T1DM. No studies have examined renal oxygenation in T2DM. We examined the effect of dapagliflozin (10 mg) on renal oxygen delivery and oxygen consumption in 7 T2DM (age=58±3 yrs, BMI = 30±1.8 kg/m2) and 7 NGT (age = 47±3.4 yrs, BMI = 28.6±1.6kg/m2) subjects who received a single dose of dapagliflozin or placebo. Renal vein (SvO2) and radial artery (SaO2) hemoglobin saturation were measured with i-STAT point of care analyzer and renal blood flow with PAH infusion before and 4 hours after dapagliflozin/placebo.

At baseline arterial (CaO2, 19 ± 0.8 vs 19 ± 0.7 ml/dl, p=NS) and renal venous (CvO2, 16 ± 0.9 vs 18 ± 0.7 ml/dl, p=NS) oxygen Content were similar in DAPA and PLAC. Thus, there was no difference in renal oxygen delivery (478 ± 29 vs 533 ±27 ml/min/m2) between DAPA and PLAC groups. Following DAPA/PLAC renal plasma flow did not change, and there was no change in arterial (CaO2) (19 ± 0.8 vs 18.2 ± 0.7 ml/dl, p=NS) or renal venous (CvO2) (16 ± 0.9 vs 15.5 ± 0.9 ml/dl) oxygen content in DAPA or PLAC groups. Renal oxygen consumption following DAPA (67 ± 10 vs 78 ±13 ml/min/m2, p=NS) and PLAC (42 ± 8 vs 50 ± 6 ml/min/m2, p=NS) groups were not different versus baseline.

Conclusion: A single acute dose of dapagliflozin does not alter renal oxygen delivery or consumption in T2DM or NGT subjects.

Disclosure

D. Tripathy: None. X. Chen: None. R. Chilton: None. A.A. Hansis-Diarte: None. M. Salehi: None. C. Solis-Herrera: None. E. Cersosimo: None. R.A. DeFronzo: Speaker's Bureau; AstraZeneca. Advisory Panel; AstraZeneca, Bayer Inc., Boehringer-Ingelheim, Novo Nordisk. Research Support; AstraZeneca, Boehringer-Ingelheim, Merck & Co., Inc.

Funding

AstraZeneca
87-LB: Real-World Impact of Once-Weekly Injectable Semaglutide on Glycemic Control and Weight Outcomes in Type 2 Diabetes (RELATE-OW Injectable Semaglutide)
Authors: AMAMOO JAMES , DOSHI RIDDHI P. , NOONE JOSHUA , TAN XI , XIE LIN , GAMBLE CORY L. , GUEVARRA MICO , CHEN JUSTIN , KING AARON A.
Published: June 2023

Background: Given the scarcity of real-world evidence on long-term effectiveness, this study assessed the effect of a once-weekly injectable formulation of semaglutide type 2 diabetes (sema OW T2D) on HbA1c and weight outcomes in individuals with T2D.

Methods: This retrospective database study included adults with T2D and HbA1c ≥7%, initiating sema OW T2D from January 2018 to September 2021, using linked data from IQVIA’s Longitudinal Prescription Claims, Professional Fee Claims, and Ambulatory Electronic Medical Records in the US. Descriptive and bivariate analyses were conducted to evaluate pre- and post-index (12 months) changes in HbA1c and weight-related outcomes.

Results: Among the final sample of 1,926 patients, mean HbA1c decreased significantly from 8.9% to 7.6% (p<0.001), with 40.2% of patients achieving HbA1c <7.0% over 12 months post-index. Mean weight decreased from 106.3 to 102.2 kg (p<0.001), with 37.9% and 13.3% of patients experiencing a ≥5% and ≥10% decrease in weight, respectively. Mean BMI decreased from 36.5 to 35.0 kg/m2 (p<0.001), with the proportion of patients with BMI ≥40.0 kg/m2 and BMI ≥30.0 kg/m2 decreasing from 29.2% to 24.4% and 81.1% to 73.6%, respectively.

Conclusion: At 12-month follow-up, adults with T2D initiating sema OW T2D had statistically significant decreases in HbA1c, weight, and BMI.

Disclosure

J. Amamoo: None. R. P. Doshi: Employee; IQVIA Inc. J. Noone: Employee; Novo Nordisk. X. Tan: Employee; Merck & Co., Inc., Novo Nordisk, Stock/Shareholder; Merck & Co., Inc., Novo Nordisk. L. Xie: Employee; Pfizer Inc., Novo Nordisk A/S. C. L. Gamble: Employee; Novo Nordisk. M. Guevarra: Employee; Novo Nordisk. J. Chen: Employee; IQVIA Inc. A. A. King: Advisory Panel; Novo Nordisk, Board Member; JDRF, Speaker's Bureau; Sanofi, Abbott, Dexcom, Inc., Lilly Diabetes.