Introduction and Objective: We present interim data from a double-blind, placebo-controlled study investigating tolerability and efficacy of GL0034, a novel glucagon-like peptide-1 receptor agonist, in T2DM on metformin and/or an SGLT2-inhibitor. A symptom score was used to evaluate gastrointestinal adverse events (GI AEs). Methods: Participants were randomized to receive GL0034 once weekly in two different dose escalation regimens (table) or placebo over 16 weeks. Results: GL0034 was well tolerated with similar numbers of GI AEs with both dose escalation regimens, but a numerically higher symptom score in cohort 1 (Table). The incidence of all treatment-emergent AEs (TEAEs) was comparable between the cohorts. During the relatively short treatment period of 16 weeks, GL0034 significantly reduced body weight and improved glycemic control versus placebo as indicated by reductions in HbA1c, mean daily self-monitored plasma glucose (SMPG), peak glucose concentration after a liquid meal test and waist circumference. Efficacy results were not significantly different between the two GL0034 cohorts. Conclusion: GL0034 was well tolerated with two different dose-escalation regimens with maximum doses of 2.4 and 3.0 mg/week and led to pronounced improvements in body weight and glucose control in people with type 2 diabetes. Disclosure R. Thennati: Employee; Current; Sun Pharmaceutical Industries Ltd. G. Andersen: Consultant; Current; LaVita GmbH. V. Burade: Employee; Current; Sun Pharmaceutical Industries Ltd. T. Heise: Research Support; Ended; Afon Technology. Research Support; Current; Betagenon AB, Civica, Corteria Pharmaceuticals. Research Support; Ended; Cytoki Pharma. Research Support; Current; DioGenX, ENYO Pharma, Gan & Lee Pharmaceuticals. Consultant; Current; Gan & Lee Pharmaceuticals. Research Support; Current; Nanexa, Neodyne Biosciences, Sam Chun Dang. Research Support; Ended; Liom. Research Support; Current; Sun Pharmaceutical Industries Ltd., Zealand Pharma A/S. Other - Travel Grants; Current; Zealand Pharma A/S. Research Support; Current; AstraZeneca, Biocon, Eli Lilly and Company. Speaker's Bureau; Current; Eli Lilly and Company. Research Support; Current; Novo Nordisk, Roche Diagnostics. Consultant; Current; i2o Therapeutics. Speaker's Bureau; Current; Novo Nordisk. R. Nagaraja: None. M. Natarajan: None. P. Shahi: None. B. Thorens: Advisory Panel; Current; Sun Pharmaceutical Industries Ltd. R. Pratley: Consultant; Current; Lilly USA LLC. Research Support; Current; National Institutes of Health, Novo Nordisk. Speaker's Bureau; Current; Novo Nordisk. Other - Consulting: Thru 12/31/2023 payment directed to Dr. Pratley's employer; as of 1/1/2024 payment directed to Dr. Pratley personally.; Current; Novo Nordisk. Consultant; Current; Pfizer Inc., Recordati Rare Diseases Inc., Regeneron Pharmaceuticals Inc., Response Pharmaceuticals, Rona Therapeutics Ltd. Research Support; Current; Sanofi. Consultant; Current; Scholar Rock Inc. Other - Consulting: Thru 12/31/2023 payment directed to Dr. Pratley's employer; as of 1/1/2024 payment directed to Dr. Pratley personally.; Current; Sun Pharmaceutical Industries Ltd. Consultant; Current; Third Rock Ventures, Verdiva Bio Dev Limited. Research Support; Current; AstraZeneca AB, Boehringer Ingelheim International GmbH, Abbott Laboratories. Consultant; Current; Abbott Laboratories, AbbVie Inc. Other - Consulting; stock options; Current; Altanine, Inc. Consultant; Current; Amgen Inc., AstraZeneca Pharmaceuticals LP. Other - Consulting: Thru 12/31/2023 payment directed to Dr. Pratley's employer; as of 1/1/2024 payment directed to Dr. Pratley personally.; Current; Bayer AG, Bayer HealthCare Pharmaceuticals Inc. Research Support; Current; Biomea Fusion. Consultant; Current; Boehringer Ingelheim Pharmaceuticals Inc., Carmot Therapeutics, Inc., Corcept Therapeutics. Research Support; Current; Dompé, Eli Lilly and Company. Other - Consulting: Thru 12/31/2023 payment directed to Dr. Pratley's employer; as of 1/1/2024 payment directed to Dr. Pratley personally.; Current; Eli Lilly and Company. Research Support; Current; Endogenex Inc. Other - Consulting: Thru 12/31/2023 payment directed to Dr. Pratley's employer; as of 1/1/2024 payment directed to Dr. Pratley personally.; Current; Endogenex Inc. Consultant; Current; F. Hoffmann-La Roche Ltd. Research Support; Current; Fractyl Health, Inc. Other - Consulting: Thru 12/31/2023 payment directed to Dr. Pratley's employer; as of 1/1/2024 payment directed to Dr. Pratley personally.; Ended; Gasherbrum Bio Inc., Genprex. Consultant; Current; Hanmi Pharm. Co., Ltd. Other - Consulting: Thru 12/31/2023 payment directed to Dr. Pratley's employer; as of 1/1/2024 payment directed to Dr. Pratley personally.; Ended; Intas Pharmaceuticals Ltd. Research Support; Current; Lexicon Pharmaceuticals, Inc. Consultant; Current; Lexicon Pharmaceuticals, Inc. Speaker's Bureau; Current; Lilly USA LLC. M.A. Nauck: Advisory Panel; Current; Boehringer Ingelheim International GmbH, Eli Lilly and Company. Speaker's Bureau; Current; Novo Nordisk. Advisory Panel; Current; Pfizer Inc., Regor. Consultant; Current; Structure Therapy. Speaker's Bureau; Current; Eli Lilly and Company, Novo Nordisk, Medscape, Medical Learning Institute. Advisory Panel; Current; Sun Pharmaceutical Industries Ltd.

Introduction and Objective: Currently available glucagon-like peptide-1 receptor agonists are dosed once-daily or once-weekly. Extending the dosing interval aims to increase convenience and adherence. We developed NEX-22A, a prolonged-release formulation of liraglutide based on atomic layer deposition (ALD) technology, for once-monthly subcutaneous (s.c.) injection. This open, single ascending dose, phase 1 study assessed the pharmacokinetics (PK), safety and tolerability of a single s.c. injection of NEX-22A. Methods: Three cohorts (N=9) received doses of NEX-22A at 1.5 mg, 4.5 mg and 10 mg, respectively. The PK and safety profiles were followed for 36 days. Results: At baseline, participants (3 female and 6 male) had a mean ± SD age of 59.7 ± 4.1 years, BMI 28.3 ± 3.8 kg/m2 and HbA1c 7.2 ± 0.4%. A dose-linear increase in peak concentrations and duration of PK exposure was observed (Fig. 1). Following administration of NEX-22A 10 mg, liraglutide plasma concentrations were detected for up to 30 days with a maximum concentration (Cmax ) of ~4.9 nmol/L, between 24-48 hours post-injection. Seven participants experienced mild injection site reactions (most common: erythema), which usually resolved within 1 week. No gastrointestinal adverse events were reported. Conclusion: NEX-22A, a novel once-monthly formulation of liraglutide using ALD technology, was well tolerated and showed exposure for up to 30 days after a single s.c. injection. J. DeVries: Research Support; Neodyne, Gan & Lee Pharmaceuticals. Consultant; Gan & Lee Pharmaceuticals. Research Support; Liom. Advisory Panel; Liom. Speaker's Bureau; Novo Nordisk A/S. T. Heise: Research Support; ADOCIA, Afon Technology, AstraZeneca, Altimmune Inc, Biocon, BIOTON, Civica Foundation, Eli Lilly and Company, Zealand Pharma A/S, Betagenon, Cass Pharmaceuticals, Novo Nordisk A/S, Corteria, Zealand Pharma A/S, Cytoki, Enyo Pharma, Gan & Lee Pharmaceuticals, Genova, Nanexa, Neodyne, SamChunDang Pharma. Co., Spiden, Sun Pharmaceutical Industries Ltd. Speaker's Bureau; Eli Lilly and Company, Novo Nordisk A/S. Consultant; Gan & Lee Pharmaceuticals. G. Andersen: None. E. Westrin: Other Relationship; Nanexa AB. M. Nehlin: Consultant; Nanexa AB. M. Gårdmark: None. K.A. Bäck: Employee; Nanexa AB. O.R. Luhr: Consultant; Nanexa AB. Study funded by Nanexa

Introduction & Objective: Efsitora is an insulin receptor agonist designed to have a flat pharmacokinetic profile and long half-life enabling weekly dosing. While these features may provide stable glucose levels, their impact on hypo risk is less clear. A phase 1 study was conducted to assess hypo risk using controlled, experimental conditions that mimic hypo risk situations that may be encountered in daily life. Methods: This single-site, open-label, 2-period, fixed-sequence (glargine-efsitora) study was conducted in 54 participants with T2D previously on basal insulin (BMI 21.8-39.7 kg/m2, HbA1c 6.5-9.4%). After titration to stable fasting glucose (FG) with glargine or efsitora, the incidence of hypo was assessed during 3 test conditions: prolonged fasting 24-hrs (PF), PF with exercise (EX), and after receiving a double dose (DD) of study insulin. Results: Mean FG at start of tests was 6 mg/dL lower with PF and EX and 10 mg/dL lower with DD in the efsitora group compared to glargine. Incidence of Level 1 hypo (≥54 to <70 mg/dL) was not significantly different under any test condition: incidence efsitora vs glargine, difference in proportion (95%CI) for PF: 44.7 vs 42.6%, 2.1 (-17.2, 21.4); EX: 65.9 vs 50.0%, 15.9 (-3.0, 34.8); DD: 68.1 vs 61.7%, 6.4 (-12.8, 25.6). Level 1 hypo resolved spontaneously or after 15g oral glucose. Level 2 (<54 mg/dL) was infrequent in both treatments and all test conditions. No severe hypo occurred in this study. Mean nadir glucose for hypo was similar between treatments and test conditions ranging from 62.8-66.3 mg/dL. Duration of hypo events was also similar between treatments ranging from 76.6 to 115.2 mins depending on the test condition. Conclusion: Once weekly efsitora did not increase the incidence, duration, or severity of hypo compared to once daily glargine during periods of provocation in patients with T2D. Disclosure T. Heise: Research Support; ADOCIA, AstraZeneca, Biocon, Crinetics Pharmaceuticals, Inc., Eli Lilly and Company, Genova, Novo Nordisk A/S. Consultant; Gan&Lee Pharmaceuticals. Speaker's Bureau; Eli Lilly and Company. Research Support; Altimmune Inc., Sanofi, Zealand Pharma A/S, BIOTON, Civica Foundation, Enyo Pharma, Gan&Lee Pharmaceuticals, Nanexa AB, SamChunDang Pharm. Co. G. Andersen: Employee; Profil Institut für Stoffwechselforschung GmbH. E.J. Pratt: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. J. Leohr: None. T. Fukuda: Employee; Eli Lilly and Company. Q. Wang: Employee; Eli Lilly and Company. C.M. Kazda: Employee; Eli Lilly and Company. J.M. Bue-Valleskey: Employee; Eli Lilly and Company. R.M. Bergenstal: Other Relationship; Abbott. Research Support; Arkray Marketing. Consultant; Ascensia Diabetes Care, Bigfoot Biomedical, Inc., CeQur. Other Relationship; Dexcom, Inc., Eli Lilly and Company. Consultant; embecta, Hygieia. Research Support; Insulet Corporation. Consultant; MannKind Corporation. Other Relationship; Medtronic, Novo Nordisk. Consultant; Onduo LLC, Roche Diabetes Care. Other Relationship; Sanofi. Research Support; Tandem Diabetes Care, Inc. Other Relationship; UnitedHealth Group. Consultant; Vertex Pharmaceuticals Incorporated, Zealand Pharma A/S. Funding This research was funded by Eli Lilly and Company.

Insulin efsitora alfa (efsitora) is a basal insulin with a flat pharmacokinetic profile and long half-life, enabling weekly dosing. These attributes may provide stable glucose levels. This exploratory phase 1 study aimed to assess the hypoglycemic risk during experimental conditions that mimic situations encountered in daily life. This was a single-site, open-label, two-period, fixed-sequence study in participants with type 2 diabetes (T2D) previously treated with basal insulin. The incidence, duration, and nadir glucose of hypoglycemia were assessed after treatment with efsitora versus insulin glargine (glargine) during three provocation conditions: 24-h prolonged fasting, prolonged fasting with exercise, and double dosing of study insulin. The 54 enrolled adults (BMI 21.8–39.7 kg/m2, HbA1c 6.5–9.4

Objectif Efsitora est un agoniste du récepteur à l’insuline hebdomadaire. Son impact sur le risque hypoglycémique a été évalué dans une étude de phase 1 dans des conditions expérimentales imitant des situations du quotidien augmentant ce risque. Patients et méthodes Cette étude monocentrique, menée en ouvert, sur 2 périodes et à séquence fixe (glargine-efsitora) incluait 54 participants DT2 précédemment traités par insuline basale. Après la titration pour atteindre une glycémie à jeun (GJ) stable avec glargine ou efsitora, l’hypoglycémie a été testée dans 3 situations expérimentales : jeûne prolongé de 24h (JP), JP avec exercice (EX) et après double dose (DD) de l’insuline de l’étude. Résultats La GJ moyenne initiale était inférieure de 6mg/dL avec JP et EX, et inférieure de 10mg/dL avec DD avec efsitora vs glargine. L’incidence de l’hypoglycémie de niveau 1 (≥54 à<70mg/dL) n’était pas significativement différente entre efsitora et glargine quelle que soit la situation testée : les différences en proportion (IC à 95 %) étaient pour JP : 44,7 vs 42,6 % ; 2,1(–17,2 ; 21,4) ; EX : 65,9 vs 50,0 % ; 15,9(–3,0 ; 34,8) ; DD : 68,1 vs 61,7 % ; 6,4(–12,8 ; 25,6). Aucune hypoglycémie sévère n’est survenue. Le nadir moyen et la durée des hypoglycémies étaient similaires entre les traitements. Discussion Chez les patients DT2, efsitora 1×/semaine n’a pas augmenté l’incidence, la durée ou la sévérité de l’hypoglycémie vs glargine 1×/jour dans des conditions expérimentales.

AIM:To study safety, efficacy and weight loss with ADO09, a co-formulation of insulin A21G and pramlintide, in type 1 diabetes. MATERIALS AND METHODS:A randomized, two-arm ambulatory 16-week study compared ADO09 with insulin lispro in 80 participants with type 1 diabetes. We compared changes of weight, glycated haemoglobin, glycaemic patterns during continuous glucose monitoring, and insulin doses at baseline and at the end of treatment. RESULTS:A significant and continuing weight loss, the primary endpoint, was observed with ADO09 compared with lispro as prandial insulin. In the whole group, the weight loss with ADO09 relative to lispro was 2.1 kg. Glycaemic control was relatively good (7.7% mean glycated haemoglobin) in both groups and did not change during treatment. Prandial insulin doses were reduced by 21% in the ADO09 group, whereas basal insulin dosage was not modified. Gastrointestinal symptoms were more frequent with ADO09, but no clear difference in hypoglycaemia was observed. CONCLUSIONS:These results extend previous observations on the efficacy and safety of this insulin/pramlintide co-formulation. They show a beneficial effect on weight, using less mealtime insulin and without increased hypoglycaemia.

This randomized, double-blind, cross-over study compared PK/PD-properties of Humalog and GN1101DP, a proposed insulin lispro (INS) biosimilar with an identical primary structure and high physicochemical and bio-functional similarity to Humalog. Thirty-five Caucasian and 13 Chinese healthy subjects completed the study and received a single dose of 0.3 U/kg of GN1101DP and Humalog under euglycemic automated glucose clamp conditions (ClampArt®, plasma glucose (PG) target 81 mg/dL, clamp duration 12 hours post-dose, wash-out period 2-14 days between the two dosings). Plasma INS concentrations were determined by tandem ultra performance liquid chromatography-mass spectrometry. GN1101DP demonstrated both PK- and PD-bioequivalence to Humalog with superimposable INS concentration and glucose infusion rate (GIR) profiles, point estimates close to 100%, and 90% confidence intervals were within the pre-defined similarity range of 80-125%. Bioequivalence was observed in all and also separately in Caucasian and Chinese subjects (Figure). Clamp quality was high (mean PG-variations of ~5% and deviations from target <0.6 mg/dL). Both lispro formulations were well tolerated. No injection site reactions occurred. In conclusion, GN1101DP demonstrated PK- and PD-bioequivalence to Humalog in Caucasian and Chinese subjects. Disclosure T.Heise: Advisory Panel; Novo Nordisk, Consultant; Gan & Lee Pharmaceuticals, Research Support; Adocia, AstraZeneca, Biocon, Crinetics Pharmaceuticals, Inc., Eli Lilly and Company, Genova, Novo Nordisk, Sanofi, Zealand Pharma A/S, Speaker's Bureau; Eli Lilly and Company, Novo Nordisk. E.Zijlstra: Other Relationship; Eli Lilly and Company, Speaker's Bureau; Gan & Lee Pharmaceuticals, Novo Nordisk A/S. G.Andersen: None. S.B.Selker: None. C.Shen: None. Y.Wang: None. Funding Genova Biotech Pvt. Ltd.

Aim: For the successful approval and clinical prescription of insulin biosimilars, it is essential to show pharmacokinetic (PK) and pharmacodynamic (PD) bioequivalence to the respective reference products sourced from the European Union and the United States.Methods: Three phase 1, randomized, double-blind, three-period crossover trials compared single doses of the proposed biosimilar insulin analogues aspart (GL-Asp, n = 36), lispro (GL-Lis, n = 38) and glargine (GL-Gla, n = 113), all manufactured by Gan & Lee pharmaceuticals, to the respective EU- and US-reference products in healthy male participants (GL-Asp and GL-Lis) or people with type 1 diabetes (GL-Gla). Study participants received 0.2 U/kg (aspart and lispro) or 0.5 U/kg (glargine) of each treatment under automated euglycaemic clamp conditions. The clamp duration was 12 h (aspart and lispro) or 30 h (glargine). Primary PK endpoints were the total area under the PK curves (AUC(ins.total)) and maximum insulin concentrations (C-ins.max). Primary PD endpoints were the total area under the glucose infusion rate curve (AUC(GIR.total)) and maximum glucose infusion rate (GIR(max)).Results: Bioequivalence to both EU- and US-reference products were shown for all three GL insulins. Least squares mean ratios for the primary PK/PD endpoints were close to 100%, and both 90% and 95% confidence intervals were within 80%-125% in all three studies. There were no noticeable differences in the safety profiles between test and reference insulins, and no serious adverse events were reported for the GL insulins.Conclusion: GL-Asp, GL-Lis and GL-Gla are bioequivalent to their EU- and US-reference products.

AIM:To establish the pharmacokinetic (PK) and pharmacodynamic (PD) equivalence of proposed biosimilar Insulin N (Biocon's Insulin-N; Biocon Biologics Ltd., Bangalore, India) and US-licensed Humulin® N (Humulin-N; Eli Lilly and Company, Indianapolis, IN, USA) in healthy subjects. MATERIALS AND METHODS:This was a phase-1, single-centre, double-blind, randomized, three-period, six-sequence, partially replicated, crossover, 24-h euglycaemic clamp study. Overall, 90 healthy subjects were randomized, of whom 85 completed the study. The subjects received either two single doses of Biocon's Insulin-N and a single dose of Humulin-N or two single doses of Humulin-N and a single dose of Biocon's Insulin-N subcutaneously at a dose of 0.4 IU/kg. The primary PK endpoints were the area under the insulin concentration-time curve from 0 to 24 h (AUCins.0-24h ) and the maximum insulin concentration (Cins.max ). The primary PD endpoints were the area under the glucose infusion rate (GIR) curve from 0 to 24 h (AUCGIR.0-24h ) and the maximum GIR (GIRmax ). RESULTS:Biocon's Insulin-N was found to be equivalent to Humulin-N for the primary PK (geometric 90% confidence interval for the least squares mean ratio: AUCins.0-24h , 100.98%-115.66% and Cins.max , 95.91%-110.16%) and PD endpoints (intra-subject variability ≥0.294; 95% upper confidence interval [(μT - μR)2  - θσ2 WR] <0; point estimates of geometric least squares mean ratio: AUCGIR.0-24h , 104.61% and GIRmax , 100.81%). The safety profile of Biocon's Insulin-N was similar to that of Humulin-N, and no serious adverse events were reported. CONCLUSION:PK and PD equivalence was shown between Biocon's Insulin-N and Humulin-N in healthy subjects, and both treatments were well tolerated and considered safe.

Aim: Pramlintide improves postprandial glucose but requires additional injections. We investigated the pharmacokinetics/pharmacodynamics, efficacy and safety of ADO09, pramlintide/insulin A21G co-formulation, in type 1 diabetes (T1D). Materials and Methods: This double-blinded, randomized, two-period cross-over study compared prandial administration of ADO09 or insulin aspart over 24 days in T1D using either & LE;40 U bolus insulin per day [low-dose group (LD), n = 28] or 40-75 U [high-dose group (HD), n = 16]. Glycaemic responses through continuous glucose monitoring, and pharmacokinetics/pharmacodynamics profiles following mixed-meal-tolerance tests were evaluated at baseline and at the end of treatment. Results: Glucose increments from 0 to 4 h after mixed-meal-tolerance test (primary endpoint) were 39% (not statistically significantly) lower with ADO09 in the low-dose group and 69% lower in the high-dose group. Mean continuous glucose monitoring glucose during ambulatory treatment was lower with ADO09 than with aspart (LD: -8.2 & PLUSMN; 7.9 mg/dl, p = .0001; HD: -7.0 & PLUSMN; 10 mg/ml, p = .0127), and time-in-range (70-180 mg/dl) improved (LD: +4%, p = .0134; HD: +4%, p = .0432). Body weight declined significantly with ADO09 (LD: -0.8 kg; HD: -1.6 kg). Hypoglycaemic events were slightly more frequent with ADO09 versus aspart (LD: 142 vs. 115; HD: 96 vs. 79). Gastrointestinal events occurred more frequently with ADO09 but were generally transient, and no other safety signals were identified. Conclusions: In comparison with aspart, ADO09 was well tolerated and effective in T1D across a wide range of dosage, significantly improving the average blood glucose level and body weight during 24 days of ambulatory treatment. Meal test profiles confirmed improvement of glycaemic patterns and other responses with ADO09.

ADO09 is a co-formulation of Pram and insulin A21G developed to deliver the positive effects of Pram without additional injections. This double-blind randomized cross-over trial investigated the effects of pre-meal ADO09 vs. insulin aspart (ASP) on mixed meal tolerance tests (MMTT) and CGM over 24 days in 16 T1D subjects (BMI 30.5 ± 3.1 kg/m²) using daily prandial insulin doses of 45-75 U. ADO09 reduced incremental AUC glucose 0-4h during MMTT by 69% (p=0.006) and deltaPG 1h by 82 mg/dL (p<0.001) vs. ASP (figure). Post-meal glucagon levels were lowered by up to 85% and speed of gastric emptying (acetaminophen absorption) reduced by >50% with ADO09. CGM over the final 3 weeks showed higher time in range (+58 min), lower time >180 mg/dL (-71 min) and slightly higher time <70 mg/dL (+13mins) with ADO09. Body weight decreased by 1.6 kg with ADO09 (p=0.007) as did daily prandial insulin doses (-12 U vs. ASP, median 35.0 U vs. 47.3; p=0.0004). Slightly more hypoglycemic episodes were noted with ADO09 (n=96 vs. 79) with no difference in nocturnal hypoglycemia. While more adverse events (AEs) occurred with ADO09 (22 vs. 10), most AEs were mild and of gastro-intestinal nature (nausea, decreased appetite).In conclusion, ADO09 improved blood glucose control and reduced both body weight and prandial insulin doses vs. insulin aspart in T1D subjects with high prandial insulin needs.View largeDownload slideView largeDownload slide DisclosureG. Meiffren: Employee; Self; ADOCIA, Stock/Shareholder; Self; ADOCIA. J. Devries: Advisory Panel; Self; ADOCIA, Novo Nordisk Inc., Zealand Pharma A/S, Speaker's Bureau; Self; Novo Nordisk Inc. T. Heise: Advisory Panel; Self; Novo Nordisk A/S, Valbiotis, Research Support; Self; ADOCIA, Afon Technology Ltd., AstraZeneca, Biocon, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Gan & Lee Pharmaceuticals, Johnson & Johnson, Julphar, Mylan N. V., Nestlé, Neuraly, Nordic Bioscience, Novo Nordisk, Sanofi, Zealand Pharma A/S, Speaker's Bureau; Self; Novo Nordisk A/S. G. Andersen: None. R. Eloy: Employee; Self; ADOCIA, Stock/Shareholder; Self; ADOCIA. C. Mégret: Employee; Self; ADOCIA, Stock/Shareholder; Self; ADOCIA. S. Famulla: None. C. Seroussi: Employee; Self; ADOCIA, Stock/Shareholder; Self; ADOCIA. Y. Chan: Employee; Self; ADOCIA. M. Gaudier: Employee; Self; ADOCIA, Stock/Shareholder; Self; ADOCIA. O. Soula: Employee; Self; ADOCIA, Employee; Spouse/Partner; ADOCIA, Stock/Shareholder; Self; ADOCIA, Stock/Shareholder; Spouse/Partner; ADOCIA.

The cover image is based on the Original Article ADO09, a co-formulation of the amylin-analog pramlintide and the insulin analog A21G, lowers postprandial blood glucose versus insulin lispro in type 1 diabetes (T1D) by Grit Andersen et al., https://doi.org/10.1111/dom.14302.

BACKGROUNDADO09 is a co-formulation of Pram and insulin A21G developed to deliver the positive effects of Pram without additional injections.METHODS j a a rg a n g 1 9 | n r. 3 | a u g u s t u s 2 0 2 1 type 1-diabetes is op dit punt nog werk aan de winkel.Een mooi bijkomend effect van ADO09 is de afname van gewicht en (daarmee?)een daling van de insulinedagdosis.Er volgt een fase-2-studie.

This randomized, double-blind, three-way crossover trial (NCT04236895) compared the PK and PD properties of GL-GLA, a proposed biosimilar IG by Gan & Lee, US- and EU-licensed Lantus® (US-IG and EU-IG) in 114 male subjects with type 1 diabetes (mean±SD age 42±8 years, BMI 25.8±2.0 kg/m²). Each subject received a single 0.5 U/kg dose of either GL-GLA, EU-IG, or US-IG in each of the 3 euglycemic glucose clamp periods (ClampArt, clamp level 100 mg/dl, clamp duration 30h post-dose). PK is presented as concentrations of the mainly absorbed IG metabolite M1. GL-GLA and comparator insulins showed superimposable profiles for PK and glucose infusion rates (GIR, Figure). PK BE was demonstrated between GL-GLA and the comparator insulins as the point estimates for measured metabolite M1 were close to 100% and 90% CIs were well contained within the pre-defined similarity margins of 80-125% (Figure). Likewise, the primary PD endpoints met BE-criteria as did secondary PK/PD-endpoints including AUCM1.0-12h, AUCM1.12-24h, AUCGIR.0-12h, and AUCGIR.12‑24h. All insulins were well tolerated with similar adverse event rates (19% [GL-GLA]; 26% [US-IG]; 21% [EU-IG]) and only few events of injection site reactions per insulin.In conclusion, GL-GLA demonstrated both PK- and PD-bioequivalence to US- and EU-licensed insulin glargine formulations.View largeDownload slideView largeDownload slide DisclosureT. Heise: Advisory Panel; Self; Novo Nordisk A/S, Valbiotis, Research Support; Self; ADOCIA, Afon Technology Ltd., AstraZeneca, Biocon, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Gan & Lee Pharmaceuticals, Johnson & Johnson, Julphar, Mylan N. V., Nestlé, Neuraly, Nordic Bioscience, Novo Nordisk, Sanofi, Zealand Pharma A/S, Speaker’s Bureau; Self; Novo Nordisk A/S. L. Plum-moerschel: None. G. Andersen: None. J. Lu: Employee; Self; Gan & Lee Pharmaceuticals. M. G. Wilson: Consultant; Self; Gan & Lee Pharmaceuticals, Employee; Spouse/Partner; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company, Stock/Shareholder; Spouse/Partner; Eli Lilly and Company. E. Zijlstra: Speaker’s Bureau; Self; Novo Nordisk A/S.FundingGan & Lee Pharmaceuticals