What Is DeSci: Challenges and Market Perceptions

The governance of biological emergencies has been an important issue during the last decade. Much policy work has been done on the topic, aiming at covering the necessities associated to bio-preparedness – ie, preparedness for biological threats. In this context, there is a lot to be said and understood by looking at emerging biological entities, such as new viruses or bacteria. Some of the most important international organizations worry about this issue: The North Atlantic Treaty Organization (NATO), World Health Organization (WHO), or European Union (EU) have specific sections specialized in dealing with this matter. Such concern has been fed by the expert opinion asserting that a big pandemic is imminent. This is based on several developments that have taken place during the last decades: the 80s saw the expansion of Ebola and HIV, and the 90s and 2000s witnessed the appearance of the Creutzfeld-Jacob’s disease, severe acute respiratory syndrome (SRAS), and different types of influenza viruses coming from other species, such as the avian influenza or the H1N1. These outbreaks, together with the Anthrax attacks that took place in the aftermath of 9/11 and the research on genetic engineering of viruses has led to a general state of fear of biological threats. Such events are characterized by a strong interaction between the social and the biological, between populations and viruses. I suggest that conceptualizing viruses as bio-objects will be helpful in our attempt to understand such interaction. The bio-objects framework, which has been developed by the research network “Bio-objects and their Boundaries: Governing Matters at the Intersection of Society, Science and Politics” (1,2) has provided an interesting way of thinking about emerging biological entities. A number of analyses with different biological entities have already been reported in this same journal. MicroRNA’s (3), dried blood spots (4), genetically modified insects (5), transgenic food (6), or HeLa cells (7) serve as examples. Such variety of work shows the versatility of the concept. In an attempt to understand the dynamic processes that give raise and regulate emerging biological entities, the concept provides a theoretical and methodological tool useful to explore new fields related to biology and life sciences. In this article I will claim that the bio-objects framework is a useful tool to connect some biological dimensions of biosecurity with the political and the social. The framework is beneficial when we aim at tracking and following biological entities that are controversial and subject to change. Controversies are common in the area of biosecurity, an area that embraces institutional entities situated in the intersection of science, economy, security, law, society, and politics. It is within this background that viruses need to be understood nowadays: as objects that transgress existing boundaries and classifications while their identity is continually challenged. They are, in that sense, suitable to be understood as bio-objects. I will try to illustrate these ideas using a recent controversy on the consequences of genetic engineering on Highly Pathogenic Avian Influenza (HPAI) A/H5N1, a virus that appeared in 1997 in Southeast Asia and that has been threatening to overcome the human/animal interface since then. By following research articles, pieces of news and reports, I have carried out an exploratory analysis that intends to understand viruses as immersed in a bio-objectification process.

There is limited comparative evidence for the CV safety and hypoglycemia risk of basal insulins in older patients with T2D. This secondary analysis from DEVOTE investigated the CV safety and severe hypoglycemia risk of insulin degludec (degludec) vs. insulin glargine 100 units/mL (glargine U100) in older patients (65-74 and ?75 years age groups). Data from DEVOTE (a treat-to-target, randomized, double-blind trial evaluating 7637 patients with T2D over a median period of 2 years at high risk of CV events) were stratified by three age groups. At baseline, A1C, fasting plasma glucose and estimated glomerular filtration rates decreased with increasing age. Older patients had a higher risk of major adverse cardiovascular events (MACE), all-cause mortality and severe hypoglycemia, regardless of treatment. Treatment differences for MACE, all-cause mortality and severe hypoglycemia were similar across age groups (Figure), with no significant interactions between treatment and age group. Degludec was associated with a lower risk of severe hypoglycemia vs. glargine U100, regardless of age. This analysis supported the CV safety of degludec and demonstrated a lower risk of severe hypoglycemia vs. glargine U100 in older patients with T2D. Disclosure R.E. Pratley: Other Relationship; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eisai Inc., GlaxoSmithKline plc., Janssen Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Ligand Pharmaceuticals, Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Pfizer Inc., Sanofi-Aventis, Takeda Development Center Americas, Inc. S.S. Emerson: Consultant; Self; Bayer AG, CTI BioPharma, Arena Pharmaceuticals, SFJ Pharmaceuticals Group, Genentech, Inc., GlaxoSmithKline plc., Janssen Research & Development, Novartis AG, Novo Nordisk A/S, Pfizer Inc., Roche Pharma, Allergan, AstraZeneca, Coherus Biosciences Inc, Emmaus Life Sciences Inc., Indivior, Sandoz, Seattle Genetics. Research Support; Self; National Heart, Lung, and Blood Institute. E. Franek: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim GmbH, Merck Sharp & Dohme Corp., Novo Nordisk A/S. Speaker's Bureau; Self; AstraZeneca, Bristol-Myers Squibb Company, Boehringer Ingelheim GmbH, Eli Lilly and Company, Merck & Co., Inc., Merck Sharp & Dohme Corp., Novo Nordisk A/S, Servier. M.P. Gilbert: Consultant; Self; Sanofi US, Novo Nordisk A/S. S.P. Marso: Consultant; Self; Abbott Vascular, Novo Nordisk A/S, University of Oxford, AstraZeneca, Bristol-Myers Squibb Company. Research Support; Self; Novo Nordisk A/S, The Medicines Company, Terumo Medical Corporation. D.K. McGuire: Consultant; Self; AstraZeneca, Sanofi-Aventis, Eli Lilly and Company, Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc., Pfizer Inc., Novo Nordisk A/S. Research Support; Self; AstraZeneca, Sanofi-Aventis, Janssen Pharmaceuticals, Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S, Lexicon Pharmaceuticals, Inc., Eisai Inc., GlaxoSmithKline plc., Esperion Therapeutics. T.R. Pieber: Consultant; Self; Arecor, AstraZeneca, Eli Lilly and Company, Novo Nordisk A/S, Sanofi. Employee; Self; CBmed. Research Support; Self; Novo Nordisk A/S, AstraZeneca. N.R. Poulter: Advisory Panel; Self; AstraZeneca, Novo Nordisk A/S, Amgen Inc.. Research Support; Self; Servier. Speaker's Bureau; Self; AstraZeneca, Novo Nordisk A/S, Amgen Inc., Servier. Other Relationship; Self; International Society of Hypertension. C.T. Hansen: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. M.V. Hansen: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. T. Mark: Employee; Self; Novo Nordisk A/S. Employee; Spouse/Partner; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. A.C. Moses: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. B. Zinman: Consultant; Self; Novo Nordisk A/S, Boehringer Ingelheim Pharmaceuticals, Inc., AstraZeneca, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Sanofi, Merck & Co., Inc., Abbott.

T2D is associated with an increased risk of cardiovascular disease (CVD) and CKD. CKD is a known risk factor for major adverse cardiovascular events (MACE), all-cause mortality and hypoglycemia. This secondary, pooled analysis from DEVOTE examined whether baseline CKD stages were associated with an increased risk of MACE, all-cause mortality or severe hypoglycemia in T2D patients. DEVOTE was a treat-to-target, randomized, double-blind trial in 7637 patients with T2D at high CV risk, treated once daily with insulin degludec or insulin glargine 100 units/mL. According to baseline CKD stages (CKD stage 2: n=3118; stage 3: n=2704; stages 4+5: n=214), more patients had a history of CVD (CKD stages 3–5), were older and had lower A1C vs. those with normal kidney function (normal + CKD stage 1, n=1486). Risk of MACE and all-cause mortality was significantly higher (p<0.05) in those with a higher baseline CKD stage (Figure). There was a significantly higher rate of severe hypoglycemia for stages 3 and 4+5 vs. stage 2 or normal + stage 1. There were no significant interactions between treatment and CKD stages. Comparisons between treatment groups by CKD stage mirrored those from the primary analyses. Increasing severity of baseline CKD stages was associated with a higher risk of MACE, all-cause mortality and severe hypoglycemia in T2D patients at high CV risk. Disclosure A. Amod: Advisory Panel; Self; Novo Nordisk A/S, AstraZeneca, Merck Sharp & Dohme Corp., Merck Serono, Boehringer Ingelheim Pharmaceuticals, Inc., Aspen Pharmacare, Sanofi-Aventis. Consultant; Self; Servier, Medscheme, Discovery Health. Speaker's Bureau; Self; Novo Nordisk A/S, AstraZeneca, Merck Sharp & Dohme Corp., Merck Serono, Boehringer Ingelheim Pharmaceuticals, Inc., Aspen Pharmacare, Sanofi-Aventis, Novartis AG, Ascendis Health, Cipla Medpro. S.S. Emerson: Consultant; Self; Bayer AG, CTI BioPharma, Arena Pharmaceuticals, SFJ Pharmaceuticals Group, Genentech, Inc., GlaxoSmithKline plc., Janssen Research & Development, Novartis AG, Novo Nordisk A/S, Pfizer Inc., Roche Pharma, Allergan, AstraZeneca, Coherus Biosciences Inc, Emmaus Life Sciences Inc., Indivior, Sandoz, Seattle Genetics. Research Support; Self; National Heart, Lung, and Blood Institute. S.P. Marso: Consultant; Self; Abbott Vascular, Novo Nordisk A/S, University of Oxford, AstraZeneca, Bristol-Myers Squibb Company. Research Support; Self; Novo Nordisk A/S, The Medicines Company, Terumo Medical Corporation. D.K. McGuire: Consultant; Self; AstraZeneca, Sanofi-Aventis, Eli Lilly and Company, Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc., Pfizer Inc., Novo Nordisk A/S. Research Support; Self; AstraZeneca, Sanofi-Aventis, Janssen Pharmaceuticals, Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S, Lexicon Pharmaceuticals, Inc., Eisai Inc., GlaxoSmithKline plc., Esperion Therapeutics. T.R. Pieber: Consultant; Self; Arecor, AstraZeneca, Eli Lilly and Company, Novo Nordisk A/S, Sanofi. Employee; Self; CBmed. Research Support; Self; Novo Nordisk A/S, AstraZeneca. R. Pop-Busui: Research Support; Self; AstraZeneca. R.E. Pratley: Other Relationship; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eisai Inc., GlaxoSmithKline plc., Janssen Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Ligand Pharmaceuticals, Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Pfizer Inc., Sanofi-Aventis, Takeda Development Center Americas, Inc. B. Zinman: Consultant; Self; Novo Nordisk A/S, Boehringer Ingelheim Pharmaceuticals, Inc., AstraZeneca, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Sanofi, Merck & Co., Inc., Abbott. M.V. Hansen: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. T. Jia: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. T. Mark: Employee; Self; Novo Nordisk A/S. Employee; Spouse/Partner; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. N.R. Poulter: Advisory Panel; Self; AstraZeneca, Novo Nordisk A/S, Amgen Inc.. Research Support; Self; Servier. Speaker's Bureau; Self; AstraZeneca, Novo Nordisk A/S, Amgen Inc., Servier. Other Relationship; Self; International Society of Hypertension.

CV safety profiles for insulin degludec (degludec) and insulin glargine 100 units/mL (glargine U100) were established by the DEVOTE and ORIGIN trials. In the LEADER trial, the GLP-1 analog liraglutide significantly reduced risks of MACE and mortality vs. placebo in patients with type 2 diabetes (T2D) and high CV risk. This post-hoc analysis compared effects of concomitant liraglutide vs. no liraglutide use on MACE and mortality in 7637 patients with T2D and high CV risk randomized 1:1 to degludec/glargine U100 in DEVOTE (NCT01959529). Hazard ratios (HRs) for MACE/mortality were calculated using a Cox regression model adjusted for treatment and time-varying liraglutide use at any time in the trial, without interaction. Sensitivity analyses adjusted for baseline covariates including age, sex, smoking, T2D duration, CV risk, insulin therapy, A1C, LDL, HDL and liver/kidney function. At baseline, 436 (5.7%) patients were on liraglutide: 187 (2.4%) started and 210 (2.7%) stopped liraglutide thereafter. Mean liraglutide exposure from randomization was 731 days. Liraglutide use was associated with significantly lower HRs for MACE and mortality vs. no liraglutide use (Table). HRs from sensitivity analyses were consistent with these results. Thus, liraglutide was associated with significantly lower MACE and mortality rates in basal insulin users. Disclosure K. Brown-Frandsen: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. S.S. Emerson: Consultant; Self; Bayer AG, CTI BioPharma, Arena Pharmaceuticals, SFJ Pharmaceuticals Group, Genentech, Inc., GlaxoSmithKline plc., Janssen Research & Development, Novartis AG, Novo Nordisk A/S, Pfizer Inc., Roche Pharma, Allergan, AstraZeneca, Coherus Biosciences Inc, Emmaus Life Sciences Inc., Indivior, Sandoz, Seattle Genetics. Research Support; Self; National Heart, Lung, and Blood Institute. S.P. Marso: Consultant; Self; Abbott Vascular, Novo Nordisk A/S, University of Oxford, AstraZeneca, Bristol-Myers Squibb Company. Research Support; Self; Novo Nordisk A/S, The Medicines Company, Terumo Medical Corporation. D.K. McGuire: Consultant; Self; AstraZeneca, Sanofi-Aventis, Eli Lilly and Company, Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc., Pfizer Inc., Novo Nordisk A/S. Research Support; Self; AstraZeneca, Sanofi-Aventis, Janssen Pharmaceuticals, Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S, Lexicon Pharmaceuticals, Inc., Eisai Inc., GlaxoSmithKline plc., Esperion Therapeutics. T.R. Pieber: Consultant; Self; Arecor, AstraZeneca, Eli Lilly and Company, Novo Nordisk A/S, Sanofi. Employee; Self; CBmed. Research Support; Self; Novo Nordisk A/S, AstraZeneca. N.R. Poulter: Advisory Panel; Self; AstraZeneca, Novo Nordisk A/S, Amgen Inc.. Research Support; Self; Servier. Speaker's Bureau; Self; AstraZeneca, Novo Nordisk A/S, Amgen Inc., Servier. Other Relationship; Self; International Society of Hypertension. B. Zinman: Consultant; Self; Novo Nordisk A/S, Boehringer Ingelheim Pharmaceuticals, Inc., AstraZeneca, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Sanofi, Merck & Co., Inc., Abbott. R. Grøn: Employee; Self; Novo Nordisk A/S. M. Lange: Board Member; Self; Beta Bionics. Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. Research Support; Spouse/Partner; Takeda Pharmaceuticals U.S.A., Inc. A.C. Moses: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. P. Örsy: Employee; Self; Novo Nordisk A/S. M.F. Ranthe: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. R.E. Pratley: Other Relationship; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eisai Inc., GlaxoSmithKline plc., Janssen Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Ligand Pharmaceuticals, Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Pfizer Inc., Sanofi-Aventis, Takeda Development Center Americas, Inc..

Introduction: Reviewing rCGM patterns may prompt lifestyle or therapeutic changes to achieve glycaemic targets but evidence for rCGM use in primary care management of T2D is limited. Methods: Two-arm RCT. Participants: Adults with T2D, HbA1c ≥0.5% above target, prescribed ≥2 non-insulin glycemia medications or insulin. Intervention: 1-hour diabetes education and (at 0/3/6/9/12 months): HbA1c assessment + wearing FreeStyle Libre Pro (Abbott) for up to 14 days prior to being discussed at a clinic visit. Physicians were trained in interpreting ambulatory glucose profiles. Control: 3-monthly ‘usual care’ clinic visits + r-CGM device worn (blinded, research data) at 0 and 12 months. Primary outcome: difference in mean HbA1c at 12 months. Secondary outcomes: mean differences in time in range (TIR: 4-10 mmol/L) and diabetes-specific distress (PAID) at 12 months, and HbA1c at 6 months. ITT analysis. Results: In 25 primary care practices, participants were: 299 adults with T2D, aged (mean(SD)) 60(10) years, HbA1c: 8.9(1.2)%, diabetes duration (median(IQR)) of 12(8,20) years. At 12 months, the between-group difference in mean HbA1c was 0.2% (p=0.112). The estimated mean percentage TIR was 8.4% higher in the intervention than the control arm (p=0.004). Diabetes-specific distress did not differ between arms (0.5; p=0.71). At 6 months, HbA1c was significantly lower in the intervention arm (0.5%; p<0.001). We found little evidence of changes in the number of glycemic medications in either arm. Discussion: Use of 3-monthly rCGM in adults with T2D in primary care does not improve HbA1c at 12 months. We showed a statistically and clinically significant reduction in HbA1c at 6 months in the intervention group, as well as significant improvements in TIR at 12 months, with no change in diabetes distress. Our findings suggest the primary impact of r-CGM use on HbA1c in this setting is short term, and not associated with increase in the number of diabetes medications. Disclosure J. Furler: Research Support; Self; Abbott, Sanofi. D.N. O’Neal: None. J. Speight: Research Support; Self; AstraZeneca, Medtronic, Sanofi. Speaker’s Bureau; Self; Novo Nordisk A/S, Roche Diabetes Care. J.E. Manski-Nankervis: Research Support; Self; Australian National Health and Medical Research Council, Boehringer Ingelheim International GmbH, Diabetes Australia, Eli Lilly and Company. Speaker’s Bureau; Self; RACGP. S. Thuraisingam: None. E. Holmes-Truscott: Research Support; Self; Sanofi. Speaker’s Bureau; Self; Novo Nordisk Inc. K.R. De La Rue: None. L.E. Ginnivan: None. R.C. Doyle: None. K. Khunti: Advisory Panel; Self; Amgen Inc., AstraZeneca, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis, Servier, Takeda Pharmaceutical Company Limited. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis. Speaker’s Bureau; Self; AstraZeneca, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Menarini Group, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi, Servier, Takeda Pharmaceutical Company Limited. M. Catchpool: None. K. Dalziel: None. J.I. Chiang: None. I. Blackberry: None. R. Audehm: Advisory Panel; Self; AstraZeneca, Novartis Pharmaceuticals Corporation. M. Kennedy: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi. M.J. Clark: None. A.J. Jenkins: Advisory Panel; Self; Abbott, Australian Diabetes Society, Medtronic. Research Support; Self; Abbott, GlySens Incorporated, Medtronic, Mylan. Speaker’s Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc. A.S. Januszewski: None. D. Liew: Advisory Panel; Self; AstraZeneca, Bayer AG. Research Support; Self; AbbVie Inc., AstraZeneca, Bristol-Myers Squibb Company, CSL Behring, Pfizer Inc. P.M. Clarke: None. J.D. Best: Consultant; Self; Abbott. Funding National Health and Medical Research Council of Australia (APP1104241); Sanofi Australia; Abbott Diabetes Care

Data science is revolutionizing various industries and its impact on healthcare and life sciences is particularly profound. The vast amounts of data generated in these fields present both opportunities and challenges, necessitating professionals to extract insights and create value from these data resources. However, effective data-driven solutions in healthcare require a unique combination of technical data science skills and deep-domain expertise in areas such as medicine, public health, and sports science. This review discusses the growing importance of domain knowledge in data science and the need for interdisciplinary professionals who can bridge the gap between data analysis and practical applications in the healthcare sector. Furthermore, this paper highlights specific applications of data science in healthcare and life sciences, leveraging artificial intelligence (AI) and advanced computational methods. By integrating cutting-edge data science techniques with profound domain understanding, these applications aim to drive innovation, advance medical research, improve patient outcomes, and deepen our understanding of human health and well-being. Overall, this review underscores the synergies between data science and domain expertise in healthcare and life sciences, emphasizing the importance of interdisciplinary collaboration in unlocking the full potential of data-driven solutions in these critical fields.

Methodological Considerations In The Assessment Of Comorbidities Among Patients With Hemophilia Using Retrospective Claims Data

Risk‐based decision making and ethical considerations in donor compensation for plasma‐derived medicinal products

This issue is made up of a special collection of articles that have been submitted to the journal, which tackle issues that have primarily been the subject and object of the life and biological sciences; this includes pregnancy, obesity, antibiotic resistance, and immunity within the context of viruses and super-bugs. All of these issues in different ways have increasingly become the subject of theories and methods within the humanities and social sciences. This includes approaches, which work across disciplines and intellectual traditions, in order to open up the complexity of what might count as an object of knowledge within these different contexts. Each paper in this special collection is engaged in productive approaches that cut across disciplines and that enable dialogues and exchanges to take place between the social sciences, life sciences and philosophy. The articles respond to some of the new developments across the life and biological sciences, which include the field of epigenetics, the genome and microbiome and new theorisations of immunity. They engage in different ways with emergent issues, problematics, ontologies, controversies and debates within these fields. These are explored at the intersection of science and technology studies (Landecker), new materialism (Jamieson; Warins et al; Yoshizawa); and critical theorizations of immunity, which draw primarily from cultural studies of immunity, including the writings of Ed Cohen (2009), Robert Esposito (2013) and Margrit Shildrick (2010, 2015) (see Davies et al; Newman et al).

Introduction and Objective: The gut-derived hormone, glucose-dependent insulinotropic polypeptide (GIP[1-42]), increases glucagon levels during normal-to-low plasma glucose concentrations in persons with type 1 diabetes (T1D); potentially safeguarding against hypoglycemia. Here, we evaluated the effects of exogenous GIP[1-42] and its naturally occurring truncated variant GIP[1-30]NH2, on glucagon secretion during insulin-induced hypoglycemia in persons with T1D. Methods: Men with T1D were included in a randomized, double-blind, placebo-controlled, crossover study involving five study days. Each day was initiated at euglycemia, and involved an iv infusion (time 0-135 min) of GIP[1-42] (4 or 8 pmol/kg/min), GIP[1-30]NH2 (4 or 8 pmol/kg/min), or placebo (saline). On all days, insulin (1.5 mU/kg/min) was infused, and blood glucose kept >2.5 mmol/l (time 30-90 min), after which recovery was monitored (90-135 min). The primary outcome was plasma glucagon baseline-subtracted area under the curve (bsAUC) and secondary outcomes included absolute plasma glucagon concentrations and amount of glucose infused. Results: Ten individuals were included (age [mean±SD]: 31±10 years, BMI: 24±3 kg/m2, HbA1c: 6.6±0.6 %, stimulated C-peptide: 31±22 pmol/l). Both GIP variants increased plasma glucagon compared with placebo before initiating the insulin infusion, but this effect was negated during the insulin infusion, and no significant differences were found in bsAUC for glucagon between interventions. During high-dose GIP[1-42], less glucose was required to recover from hypoglycemia compared to placebo (0.14±0.08 vs. 0.19±0.09 g/kg, P = 0.03) Conclusion: In persons with T1D, exogenous GIP increased plasma glucagon levels during euglycemia, but insulin-induced hypoglycemia eliminated this effect. Nevertheless, high-dose GIP[1-42] reduced the amount of glucose needed to recover from hypoglycemia. Disclosure N.E. Sørum: None. J. Warnøe: None. J.J. Holst: Advisory Panel; Novo Nordisk A/S. Consultant; Novo Nordisk A/S. Other Relationship; Novo Nordisk A/S. Consultant; AstraZeneca, Fractyl Health, Inc., MSD Life Science Foundation, Structure Therapeutics, Inc. B. Hartmann: Employee; Bainan Biotech. L.S. Gasbjerg: Stock/Shareholder; Antag Therapeutics, Bainan Biotech. J. Størling: Stock/Shareholder; Novo Nordisk A/S. T.F. Dejgaard: Advisory Panel; Novo Nordisk A/S. Speaker's Bureau; Novo Nordisk A/S. Research Support; Novo Nordisk A/S. Speaker's Bureau; Boehringer-Ingelheim. Advisory Panel; Eli Lilly and Company, Medtronic. M.B. Christensen: None. F.K. Knop: Consultant; 89bio, Inc, AstraZeneca. Speaker's Bureau; AstraZeneca. Advisory Panel; Boehringer-Ingelheim. Consultant; Cytoki Pharma. Advisory Panel; Eli Lilly and Company. Consultant; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Research Support; Gubra. Advisory Panel; Novo Nordisk A/S. Consultant; Novo Nordisk A/S. Employee; Novo Nordisk A/S. Research Support; Novo Nordisk A/S. Speaker's Bureau; Novo Nordisk A/S. Stock/Shareholder; Novo Nordisk A/S, Eli Lilly and Company. Advisory Panel; Sanofi. Consultant; Structure Therapeutics, Inc. Advisory Panel; Zealand Pharma A/S. Consultant; Zealand Pharma A/S. Research Support; Zealand Pharma A/S. Speaker's Bureau; Zealand Pharma A/S. Stock/Shareholder; Zealand Pharma A/S, Gubra. Advisory Panel; Zucara Therapeutics. Consultant; Zucara Therapeutics. Stock/Shareholder; Antag Therapeutics. A.B. Lund: Consultant; Zealand Pharma A/S. Advisory Panel; Eli Lilly and Company. Research Support; Novo Nordisk. Speaker's Bureau; Novo Nordisk, Boehringer-Ingelheim. Funding The Leona M. and Harry B. Helmsley Charitable Trust

Introduction and Objective: This study investigated the separate and combined effects of a six-week subcutaneous (s.c.) infusion of glucose-dependent insulinotropic polypeptide 1-42 (GIP) and once-weekly s.c. semaglutide on glycemic control in type 2 diabetes (T2D). We hypothesized that the combination would enhance glycemic control. Methods: This randomized, placebo-controlled, double-blind trial engaged 61 participants with T2D (18-75 years, BMI≥25 kg/m², HbA1c≥6.5%, no GLP-1-based medications or insulin). They received either 0.5 mg weekly s.c. semaglutide or placebo injections, and a six-week continuous s.c. infusion of 16 pmol/kg/min GIP or placebo via an infusion pump. The primary endpoint was change in mean glucose levels from baseline to the end of treatment; comparison 1: placebo + placebo vs. placebo + GIP; comparison 2: semaglutide + placebo vs. semaglutide + GIP. Differences were estimated using a constrained linear mixed model with 97.5% confidence intervals (CI). Results: Differences in mean sensor-detected glucose change were 0.80 mmol/l (CI -0.18 to 1.80) (comparison 1) and 0.05 mmol/l (CI -0.85 to 0.95) (comparison 2). The most frequent adverse event (AE) was injection site reaction to GIP infusion. Gastrointestinal AEs were more common and frequent in the semaglutide groups. Conclusion: In individuals with T2D, six weeks of s.c. infusion of GIP, alone or in combination with semaglutide, did not affect mean glucose levels significantly. Disclosure M.M. Helsted: None. C.C. Fonnesbech-Wulff: Stock/Shareholder; Novo Nordisk. N.L. Schaltz: None. I.W. Lund: None. J. Forman: None. C.K. Nielsen: Stock/Shareholder; Novo Nordisk A/S. A. Englund: None. B. Hartmann: Employee; Bainan Biotech. T. Vilsbøll: Advisory Panel; Boehringer-Ingelheim, AstraZeneca, Bristol-Myers Squibb Company, Carmot Therapeutics, Inc. Research Support; Dexcom, Inc. Advisory Panel; Eli Lilly and Company, GlaxoSmithKline plc. Speaker's Bureau; Medscape. Advisory Panel; Novo Nordisk, Sun Pharmaceutical Industries Ltd, Roche Diabetes Care, Amgen Inc, Sanofi, Zealand Pharma A/S. J.J. Holst: Advisory Panel; Novo Nordisk A/S. Consultant; Novo Nordisk A/S. Other Relationship; Novo Nordisk A/S. Consultant; AstraZeneca, Fractyl Health, Inc., MSD Life Science Foundation, Structure Therapeutics, Inc. A.B. Lund: Consultant; Zealand Pharma A/S. Advisory Panel; Eli Lilly and Company. Research Support; Novo Nordisk. Speaker's Bureau; Novo Nordisk, Boehringer-Ingelheim. M.B. Christensen: None. F.K. Knop: Consultant; 89bio, Inc, AstraZeneca. Speaker's Bureau; AstraZeneca. Advisory Panel; Boehringer-Ingelheim. Consultant; Cytoki Pharma. Advisory Panel; Eli Lilly and Company. Consultant; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Research Support; Gubra. Advisory Panel; Novo Nordisk A/S. Consultant; Novo Nordisk A/S. Employee; Novo Nordisk A/S. Research Support; Novo Nordisk A/S. Speaker's Bureau; Novo Nordisk A/S. Stock/Shareholder; Novo Nordisk A/S, Eli Lilly and Company. Advisory Panel; Sanofi. Consultant; Structure Therapeutics, Inc. Advisory Panel; Zealand Pharma A/S. Consultant; Zealand Pharma A/S. Research Support; Zealand Pharma A/S. Speaker's Bureau; Zealand Pharma A/S. Stock/Shareholder; Zealand Pharma A/S, Gubra. Advisory Panel; Zucara Therapeutics. Consultant; Zucara Therapeutics. Stock/Shareholder; Antag Therapeutics. L.S. Gasbjerg: Stock/Shareholder; Antag Therapeutics, Bainan Biotech. Funding This work was supported by the investigator-sponsored studies programme of Novo Nordisk under universal trial number (U1111-1259-1491). The grant was received as pure support without any obligation with Novo Nordisk and covers the expenses of the study.

The DEPICT-2 trial (NCT02460978) evaluated the efficacy and safety of dapagliflozin (DAPA) as add-on to adjustable insulin (INS) in patients (pts) with inadequately controlled T1D (A1c 7.5-10.5%) over 24 weeks. This phase 3 study randomized pts 1:1:1 to DAPA 5 mg (n=271), 10 mg (n=270) or placebo (PBO; n=272) plus INS. INS dose could be adjusted by the investigator according to self-monitored blood glucose readings, local guidance and individual circumstances. At Week 24, DAPA 5 and 10 mg significantly decreased A1c (0.37% and 0.42% reductions in the DAPA 5 mg and 10 mg groups respectively), total daily insulin dose (TDD), and body weight (Table). As measured by masked continuous glucose monitoring (CGM), mean interstitial glucose, mean amplitude of glucose excursion (MAGE) and mean percent of readings within target glycemic range (>70-≤180 mg/dL) vs. PBO were improved. There was an increase in pts who reduced their A1c by ≥0.5% without severe hypoglycemia (odds ratios [95% CI]: 2.71 [1.81, 4.06] and 3.07 [2.05, 4.60] for DAPA 5 and 10 mg respectively). Hypoglycemic events, including severe hypoglycemia were balanced between treatment groups. There were more adjudicated definite diabetic ketoacidosis (DKA) events on DAPA. In conclusion, DAPA vs. PBO as add-on to INS in pts with T1D was well tolerated, improved glycemic control and decreased variability without increasing hypoglycemia but with more DKA events. Disclosure C. Mathieu: Research Support; Self; Novo Nordisk A/S. Advisory Panel; Self; Novo Nordisk A/S. Speaker9s Bureau; Self; Novo Nordisk A/S. Research Support; Self; Sanofi. Speaker9s Bureau; Self; Sanofi. Advisory Panel; Self; Sanofi. Research Support; Self; Merck Sharp & Dohme Corp.. Speaker9s Bureau; Self; Merck Sharp & Dohme Corp.. Advisory Panel; Self; Merck Sharp & Dohme Corp.. Research Support; Self; Eli Lilly and Company. Speaker9s Bureau; Self; Eli Lilly and Company. Advisory Panel; Self; Eli Lilly and Company. Research Support; Self; Novartis AG. Speaker9s Bureau; Self; Novartis AG. Advisory Panel; Self; Novartis AG, Bristol-Myers Squibb Company. Speaker9s Bureau; Self; AstraZeneca. Advisory Panel; Self; AstraZeneca, Pfizer Inc., Janssen Pharmaceuticals, Inc., Boehringer Ingelheim GmbH. Speaker9s Bureau; Self; Boehringer Ingelheim GmbH. Advisory Panel; Self; Hanmi Pharmaceutical. Research Support; Self; Roche Diagnostics Corporation. Advisory Panel; Self; Roche Diagnostics Corporation. Research Support; Self; Medtronic. Advisory Panel; Self; Medtronic, MannKind Corporation. Research Support; Self; Intrexon. Advisory Panel; Self; Intrexon, Dianax, UCB, Inc.. Research Support; Self; Abbott. P. Dandona: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca. Research Support; Self; AstraZeneca. P. Gillard: None. P.A. Senior: Consultant; Self; Abbott, AstraZeneca. Research Support; Self; AstraZeneca, Prometic Life Sciences Inc., Novo Nordisk Inc., Sanofi. Consultant; Self; Eli Lilly and Company. Speaker9s Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc.. Consultant; Self; Novo Nordisk Inc., Janssen Pharmaceuticals, Inc.. Speaker9s Bureau; Self; Janssen Pharmaceuticals, Inc.. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Speaker9s Bureau; Self; AstraZeneca, Merck & Co., Inc., Abbott. Research Support; Self; Viacyte, Inc.. C. Hasslacher: None. E. Araki: Speaker9s Bureau; Self; Astellas Pharma US, Inc., MSD K.K., Kowa Pharmaceuticals America, Inc., Sanofi, Novo Nordisk Inc.. Research Support; Self; Astellas Pharma US, Inc., MSD K.K., Ono Pharmaceutical Co., Ltd., Shionogi & Co., Ltd., Takeda Pharmaceuticals U.S.A., Inc., Daiichi Sankyo Company, Limited, Nippon Boehringer Ingelheim Co. Ltd., Novartis Pharma K.K., Novo Nordisk Inc., Sanofi, Mitsubishi Tanabe Pharma Corporation, Sumitomo Dainippon Pharma Co., Ltd., Taisho Toyama?Pharmaceutical Co. M. Lind: Consultant; Self; AstraZeneca. Research Support; Self; AstraZeneca. Consultant; Self; Novo Nordisk Inc.. Advisory Panel; Self; Novo Nordisk Inc.. Research Support; Self; Novo Nordisk Inc.. Consultant; Self; Eli Lilly and Company. Research Support; Self; Dexcom, Inc.. Consultant; Self; Eli Lilly and Company. Advisory Panel; Self; MSD K.K.. Research Support; Self; Pfizer Inc.. Consultant; Self; Medtronic. S.C. Bain: Research Support; Self; Novo Nordisk Inc., AstraZeneca. S. Jabbour: None. N. Arya: Employee; Self; AstraZeneca. F.A. Thoren: Employee; Self; AstraZeneca. A. Langkilde: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca.

Hyperglycemia, high BP and dyslipidemia are common risk factors for CVD. The aim of this study was to assess the proportion of participants treated with once-weekly (OW) semaglutide, or a comparator, achieving a metabolic composite target endpoint in the SUSTAIN trials. Participants from SUSTAIN 1-5, 7-10 and SUSTAIN China with uncontrolled T2D treated with OW semaglutide vs comparators (incl. placebo) were pooled, and the proportion achieving the endpoint (HbA1c <7%, BP <140/90 mmHg and non-HDL cholesterol <130 mg/dL) was assessed. Endpoints were analyzed using on treatment without rescue medication data for each trial, using a binomial logistic regression model with treatment, region/country, and stratification factor as fixed effects and baseline value (HbA1c/BP/Non-HDL) as covariate. Pooled analysis was conducted using logistic regression with treatment and trial as fixed effects and baseline value as covariate. Treatment with 0.5 and 1 mg OW semaglutide was associated with higher odds (OR range 1.4-24.4) of achieving the endpoint vs comparators (Figure). The proportion of participants reaching the composite endpoint across all trials was 24% and 32% for 0.5 mg and 1.0 mg semaglutide, respectively, vs 11% for comparators (p<0.0001). The results indicate that OW semaglutide may assist with the co-management of T2D and cardiometabolic risk factors, which could reduce the risk of CVD in people with T2D. Disclosure L.Ji: Other Relationship; Eli Lilly and Company, Novo Nordisk, Merck & Co., Inc., Bayer Inc., Sanofi-Aventis U.S., Roche Pharmaceuticals, MSD Life Science Foundation, AstraZeneca, Boehringer Ingelheim Inc., Abbott, Metronics. C.H.Sorli: Employee; Acerus Pharmaceuticals. A.Ahmann: Advisory Panel; Medtronic. B.Ahrén: Speaker's Bureau; Novo Nordisk, Nestlé Health Science, Stock/Shareholder; Novo Nordisk, AstraZeneca, Eli Lilly and Company. M.Capehorn: Advisory Panel; Novo Nordisk, Lilly Diabetes, Boehringer Ingelheim Pharmaceuticals Inc., Research Support; Boehringer Ingelheim Inc., Novo Nordisk, Lilly, Speaker's Bureau; Novo Nordisk, Lilly, Boehringer Ingelheim Inc. P.Hu: Employee; Novo Nordisk (China). I.Lingvay: Advisory Panel; Novo Nordisk A/S, Lilly Diabetes, Boehringer-Ingelheim, Sanofi, Consultant; Carmot Therapeutics, Inc., Merck Sharp & Dohme Corp., Janssen Scientific Affairs, LLC, Pfizer Inc., Intercept, Intarcia, Valeritas, TargetRWE, Shionogi, Zealand Pharma, Structure, Bayer, Research Support; Novo Nordisk A/S, Boehringer-Ingelheim. W.Liu: Employee; Novo Nordisk (China). H.W.Rodbard: Advisory Panel; Merck Sharp & Dohme Corp., Pacira BioSciences, Inc., Research Support; Eli Lilly and Company, Medtronic, Sanofi, Novo Nordisk. Z.Shen: Employee; Novo Nordisk (China).

Introduction and Objective: Single-dose intranasal oxytocin has been shown to reduce food intake and improve glucose tolerance. Further, oxytocin mRNA expression has been reported throughout the small intestine, pointing to a potential role for oxytocin in postprandial metabolism. We investigated the effects of intravenous infusion with oxytocin on ad libitum food intake, appetite sensations, and postprandial metabolism. Methods: In a randomized, placebo-controlled, double-blind, crossover study, overnight fasted individuals with obesity underwent two 4.5-hour intravenous infusions with oxytocin (0.2 IU/min) and placebo (saline), respectively, on separate days interposed by a wash-out period of seven days. After 30 minutes of infusion, a standardized liquid mixed meal was ingested, and after 4 hours, food intake (primary endpoint) was assessed during an ad libitum meal. During the test days, appetite and satiety sensations were assessed by visual analogue scales, and circulating concentrations of glucose and appetite-regulating hormones were measured. Results: Twenty-four individuals (12 female, median age 42 [interquartile range (IQR) 29;55] years, BMI 36.2 [32.1;37.6] kg/m2, glycated hemoglobin (HbA1c) 34 [32;36] mmol/mol (5.2 [5.1;5.4]%)) were included. Ad libitum food intake was similar during infusion of oxytocin and placebo, respectively (660 [405;870] vs. 596 [458;902] kcal). Compared to placebo, the oxytocin infusion did not affect sensations of hunger, fullness, satiety, and appetite nor circulating concentrations of glucose, insulin, C-peptide, glucagon, glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide, and cholecystokinin. Conclusion: In individuals with obesity, 4.5-hour intravenous infusion with oxytocin had no effect on ad libitum food intake, appetite and satiety sensations, or circulating concentrations of appetite and glucose-regulating hormones. Disclosure I. Gether: None. P.T. Olafsson: None. V. Kliim-Hansen: None. C.K. Nielsen: Stock/Shareholder; Novo Nordisk A/S. M.G. Pedersen: None. J.J. Holst: Advisory Panel; Novo Nordisk A/S. Consultant; Novo Nordisk A/S. Other Relationship; Novo Nordisk A/S. Consultant; AstraZeneca, Fractyl Health, Inc., MSD Life Science Foundation, Structure Therapeutics, Inc. B. Hartmann: Employee; Bainan Biotech. J.F. Rehfeld: None. M.B. Christensen: None. F.K. Knop: Consultant; 89bio, Inc, AstraZeneca. Speaker's Bureau; AstraZeneca. Advisory Panel; Boehringer-Ingelheim. Consultant; Cytoki Pharma. Advisory Panel; Eli Lilly and Company. Consultant; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Research Support; Gubra. Advisory Panel; Novo Nordisk A/S. Consultant; Novo Nordisk A/S. Employee; Novo Nordisk A/S. Research Support; Novo Nordisk A/S. Speaker's Bureau; Novo Nordisk A/S. Stock/Shareholder; Novo Nordisk A/S, Eli Lilly and Company. Advisory Panel; Sanofi. Consultant; Structure Therapeutics, Inc. Advisory Panel; Zealand Pharma A/S. Consultant; Zealand Pharma A/S. Research Support; Zealand Pharma A/S. Speaker's Bureau; Zealand Pharma A/S. Stock/Shareholder; Zealand Pharma A/S, Gubra. Advisory Panel; Zucara Therapeutics. Consultant; Zucara Therapeutics. Stock/Shareholder; Antag Therapeutics. L.S. Gasbjerg: Stock/Shareholder; Antag Therapeutics, Bainan Biotech. A.B. Lund: Consultant; Zealand Pharma A/S. Advisory Panel; Eli Lilly and Company. Research Support; Novo Nordisk. Speaker's Bureau; Novo Nordisk, Boehringer-Ingelheim. Funding Novo Nordisk Foundation (NNF23OC0084114), Independent Research Fund Denmark (3101-00442A), Gangstedfonden (A43111)

Late-Breaking Science Abstracts From the American Heart Association's Scientific Sessions 2018 and Late-Breaking Abstracts in Resuscitation Science From the Resuscitation Science Symposium 2018.