DreaMed Diabetes Research Articles

275-OR: Association between Treatment Adherence and CGM Outcomes in People with T1D Using Smart Insulin Pens in a Real-World Setting

Adherence to insulin therapy can be challenging for individuals with T1D. This analysis explored how adherence to basal and bolus insulin injections influences glycemic outcomes. Data were collected from adults (≥18 years) administering basal insulin (degludec) and bolus insulin (aspart or faster aspart) using smart insulin pens with CGM; data were aggregated in 14-day periods. Treatment adherence was defined as the number of missed basal insulin doses (>40 hrs between doses), flex basal insulin doses (dosing time deviated >±6 hrs from previous day) and missed bolus insulin doses (meals with no bolus dose within -15 to +60 mins from meal onset). Glycemic outcomes included time in range (TIR), time below range, glucose management index (GMI), and coefficient of variation. Multinational data from 403 adults who had 3588 14-day periods with ≥70% CGM coverage were analyzed. Individuals with one missed basal dose per 14-days had a lower TIR (-4.04% [95% CI: -6.83; -1.26]) and higher GMI (0.20% [95% CI: 0.02; 0.38]) than individuals without missed basal doses; flex basal doses were not associated with TIR changes. Missed bolus insulin doses were also associated with lower TIR (Table). These real-world data confirm associations between missed basal and bolus insulin doses and impaired TIR, highlighting a need for digital tools such as smart insulin pens to help individuals manage their diabetes. Disclosure T.Danne: Research Support; Abbott Diabetes, AstraZeneca, Bayer Inc., Boehringer-Ingelheim, Dexcom, Inc., Eli Lilly and Company, Novo Nordisk A/S, Sanofi, Medtronic, Stock/Shareholder; DreaMed Diabetes, Ltd. N.V.Hartvig: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. A.Kaas: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. N.N.Knudsen: Employee; Novo Nordisk. J.K.Mader: Advisory Panel; Novo Nordisk A/S, Abbott Diabetes, Roche Diabetes Care, Eli Lilly and Company, Sanofi, Medtronic, Becton, Dickinson and Company, Pharmasense, embecta, Research Support; A. Menarini Diagnostics, Abbott Diabetes, Roche Diabetes Care, Dexcom, Inc., Profusa, Inc., Speaker's Bureau; Novo Nordisk A/S, A. Menarini Diagnostics, Abbott Diabetes, Roche Diabetes Care, Eli Lilly and Company, Sanofi, Boehringer Ingelheim Inc., Becton, Dickinson and Company, Ypsomed AG, Viatris Inc., Servier Laboratories, Medtrust, Stock/Shareholder; Decide Clinical Software GmbH. Funding Novo Nordisk A/S

164-LB: Durable Improvement in HbA1c in Youth-Onset T2D—A Post Hoc Analysis of the DINAMO Trial of Empagliflozin and Linagliptin vs. Placebo

The increasing prevalence of childhood overweight and obesity has led to a substantial increase in T2D in youth. The clinical course of youth-onset T2D is more aggressive than in adults, with a faster decline in beta‑cell function leading to worse glycemic control and an early onset of complications. The DINAMO trial compared the efficacy and safety of empagliflozin and linagliptin with placebo in 157 participants aged 10-17 years. Participants were randomized (1:1:1) to linagliptin 5 mg, empagliflozin 10 mg, or placebo. At Week 12, those in the empagliflozin group who did not attain HbA1c <7.0% were re‑randomized (1:1) to empagliflozin 10 or 25 mg. Responders were defined as having no rescue medication and a HbA1c change from baseline ≤-0.5% or attained HbA1c <7.0% at Week 26. Empagliflozin results were pooled. Significantly more participants responded to empagliflozin vs placebo (rate difference 23.6, 95% CI 4.3-41.4; p=0.01); this response was maintained to Week 52 by 40% of the group. Results for linagliptin vs placebo were not significant. Empagliflozin provided a clinically meaningful response even at higher HbA1c and FPG levels (Table). These results show that empagliflozin provides a clinically relevant, statistically significant, and durable improvement in glycemic control, suggesting SGLT2 inhibitors could be a new therapy for T2D in youth. Disclosure L. M. Laffel: Advisory Panel; Medtronic, Lilly Diabetes, Novo Nordisk, Vertex Pharmaceuticals Incorporated, Roche Diagnostics, Provention Bio, Inc., Consultant; Dexcom, Inc., Janssen Pharmaceuticals, Inc., Medscape. T. Danne: Research Support; Abbott Diabetes, AstraZeneca, Bayer Inc., Boehringer-Ingelheim, Dexcom, Inc., Eli Lilly and Company, Novo Nordisk A/S, Sanofi, Medtronic, Stock/Shareholder; DreaMed Diabetes, Ltd. W. V. Tamborlane: None. G. J. Klingensmith: Advisory Panel; Boehringer Ingelheim Inc., Consultant; AstraZeneca, Boehringer Ingelheim Inc., Novo Nordisk, Takeda Pharmaceutical Co., Ltd. D. Neubacher: Employee; Boehringer Ingelheim Pharma GmbH&Co. KG. I. Tartakovsky: Employee; Boehringer Ingelheim International GmbH. J. Marquard: Employee; Boehringer Ingelheim Inc. P. Zeitler: Consultant; Eli Lilly and Company, Boehringer Ingelheim Inc., Johnson & Johnson. S. M. Willi: Advisory Panel; Boehringer Ingelheim International GmbH, Medtronic. Funding Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance

89-OR: Effective Real-World Usage of Artificial Intelligence–Based Decision Support System for Diabetes Management

Background: Artificial intelligence-based decision support system (AI-DSS) for frequent insulin dose adjustment was demonstrated to be effective in improving glycemic control in our previous clinical trials. We aimed to assess the effectiveness of AI-DSS in real world diabetes clinics. Methods: Data was collected and evaluated from routine AI-DSS usage for individuals with type 1 diabetes treated at 21 diabetes clinics (in the USA and 2 in Israel) . Two analyses were made: (1) Insulin dose recommendations were compared for rate of agreement/disagreement between those suggested by the AI-DSS and the approved recommendations by health care providers (HCP) . (2) Glycemic outcomes were compared between baseline and after 3 months of AI-DSS use. Included in this analysis were individuals who had mean baseline glucose level ≥ 182 mg/dL and at least one AI-DSS recommendation within the 3-months. Results: A total of 8 recommendations, provided to 370 individuals, were evaluated. Full agreement on the direction of insulin dose adjustments was observed in 87%, 87%, and 83% of the basal rate, carbs ratio (CR) , and correction factor (CF) pump settings parameters, respectively. Full disagreement on the direction of dose change was observed in only 0.9%, 0.5%, and 1.2% for the basal rate, CR and CF, respectively. Glycemic outcome analysis included 1 eligible individuals (mean of 1.6 recommendations within a 3-month interval) . Average sensor percentage of time in range [70-180 mg/dL] increased by 4% (p=0.003) : 43% increased time in range by more than 5% and 33% increased by 10% or more. Time in hyperglycemia [> 180 mg/dL] was reduced by 5% (p<0.01) while time in severe hypoglycemia [< 54 mg/dL] remained below 0.5%. Conclusion: A high rate of agreement with automated insulin adjustments was observed among HCPs at academic centers who used the AI-DSS in their workflow. Glycemic control was significantly improved for sub-optimally controlled individuals already after 3-months of follow up. Disclosure R.Nimri: Employee; DreaMed Diabetes, Ltd., Research Support; Abbott Diabetes, Dexcom, Inc., Insulet Corporation, Medtronic, Speaker's Bureau; Eli Lilly and Company, Novo Nordisk, Stock/Shareholder; DreaMed Diabetes, Ltd. A.Tirosh: Advisory Panel; Abbott Diagnostics, AstraZeneca, Boehringer Ingelheim International GmbH, Merck & Co., Inc., Novo Nordisk, Sanofi, Consultant; Bayer AG, DreaMed Diabetes, Ltd., Research Support; Medtronic, Speaker's Bureau; Eli Lilly and Company. I.Muller: Board Member; DreaMed Diabetes, Ltd. Y.Shtrit: Employee; DreaMed Diabetes, Ltd. M.Phillip: Advisory Panel; Dompé, Insulet Corporation, Medtronic, Pfizer Inc., Board Member; DreaMed Diabetes, Ltd., Consultant; QuLab Medical Ltd., Other Relationship; Dexcom, Inc., Dompé, DreaMed Diabetes, Ltd., Eli Lilly and Company, Medtronic, NG Solutions Ltd, Novo Nordisk, OPKO, Pfizer Inc., Sanofi, Stock/Shareholder; DreaMed Diabetes, Ltd., NG Solutions Ltd.

105-LB: Glucose Variability with Second-Generation Basal Insulin Analogs Glargine 300 U/mL and Degludec 100 U/mL, Evaluated by CGM in People with T1D—The InRange Randomized Controlled Trial

Background: InRange has previously demonstrated that insulin glargine 300 U/mL (Gla-300) is non-inferior to insulin degludec 100 U/mL (IDeg-100) in terms of time in glucose range 70--180 mg/dL (primary endpoint) and total glucose coefficient of variation (CV) as measured by CGM in people with T1D. Methods: InRange (NCT04075513) was a multicenter, randomized, active-controlled, parallel-group, 12-week open-label trial comparing Gla-300 vs. IDeg-100 in adults with T1D using 20-day CGM profiles (≥10 days evaluable) . Here we present data for within- and between-day CV. Results: Overall, 343 participants were randomized (172 Gla-300, 171 IDeg-100) : mean ± SD age was 42.8 ± 13.3 years and T1D duration was 20.5 ± 12.8 years. Both within-day and between-day glucose CV at Week 12 were similar with Gla-300 and IDeg-100 (Table) . Within-day glucose CV at Week 12 was below the threshold for glycemic stability (36%) in both groups and was also similar in both treatment groups irrespective of glycemic stability at baseline (CV ≤36% or >36%) . The LS mean within-day glucose CV of participants with CV >36% at baseline reached 33.67 (Gla-300) and 35.38 (IDeg-100) at Week 12. Conclusion: Using clinically relevant CGM metrics, InRange shows that Gla-300 and IDeg-100 provide similar within- and between-day glucose variability in people with T1D. Disclosure R. M. Bergenstal: Advisory Panel; Hygieia, Medtronic, Roche Diabetes Care, Zealand Pharma A/S, Consultant; Abbott Diabetes, Ascensia Diabetes Care, Bigfoot Biomedical, Inc., CeQur SA, Dexcom, Inc., Eli Lilly and Company, Novo Nordisk, Onduo LLC, Sanofi, United HealthCare Services, Inc., Research Support; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic, Novo Nordisk, Sanofi. T. Battelino: Advisory Panel; Abbott Diabetes, Indigo Diabetes, Lilly Diabetes, Medtronic, Novo Nordisk, Sanofi, Research Support; Medtronic, Novartis Pharmaceuticals Corporation, Novo Nordisk, Zealand Pharma A/S, Speaker’s Bureau; Abbott Diabetes, Dexcom, Inc., Lilly Diabetes, Medtronic, Novo Nordisk, Sanofi, Stock/Shareholder; DreaMed Diabetes, Ltd. S. Edelman: Consultant; Abbott Diabetes, Lilly Diabetes, Sanofi-Aventis U. S., Xeris Pharmaceuticals, Inc. P. Choudhary: Advisory Panel; Abbott Diabetes, Lilly Diabetes, Medtronic, Research Support; Novo Nordisk, Speaker’s Bureau; Dexcom, Inc., Glooko, Inc., Insulet Corporation, Sanofi. T. Danne: Consultant; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, Dexcom, Inc., Lilly, Medtronic, Novo Nordisk, Roche Pharmaceuticals, Sanofi, Ypsomed AG, Research Support; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, Dexcom, Inc., Lilly, Medtronic, Novo Nordisk, Roche Pharmaceuticals, Sanofi, Ypsomed AG, Stock/Shareholder; DreaMed Diabetes, Ltd. E. Renard: Consultant; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, Dexcom, Inc., Insulet Corporation, LifeScan, Lilly, Novo Nordisk, Roche Diabetes Care, Sanofi, Tandem Diabetes Care, Inc. J. Westerbacka: Employee; Sanofi, Stock/Shareholder; Sanofi. B. Mukherjee: Employee; Sanofi, Stock/Shareholder; Sanofi. P. Picard: n/a. V. Pilorget: None. Funding Sanofi

1395-P: The Role of Adipocyte Connexin-43 in Mediating Adipose Tissue Inflammation and Dysfunction in Obesity

Obesity is a leading global health concern and a major risk factor for type-2 diabetes. Thus, identifying mechanisms linking obesity to insulin resistance is of great importance. Chronic low-grade inflammation of the adipose tissue (AT) observed in obesity has been shown as an important pathophysiological link between obesity and the development of systemic insulin resistance, by various mechanisms. Gap junction (GJ) intercellular-communication, primarily composed of connexin- (Cx) 43, has been recently reported to have immunomodulatory roles in various tissues, and increased Cx43 expression and GJ activity have been implicated in the response of various tissues to chronic stress conditions. We have therefore aimed to study the role of Cx43 in shaping the AT adaptive or maladaptive response to these cellular insults of obesity. In a diet-induced obesity mouse model we demonstrated an increase in Cx43 expression in the intact AT, which could be primarily attributed to increased Cx43 expression in adipocytes. In high fat diet-fed adipocyte-specific Cx43 knock-out mice (AdCx43KO) , we observed increased infiltration of macrophages to the AT as compared to wild-type (WT) mice. This was accompanied by morphologic changes in the AT, with increased variability in adipocyte size. While AdCx43KO mice did not significantly differ from WT mice in body weight, adiposity or food intake, the AdCx43KO mice demonstrated reduced whole-body insulin sensitivity assessed by insulin tolerance test. Mechanistically, we observed that adipocytes can interact directly with neighboring adipocytes as well as with macrophages via Cx43-composed gap junctions, an interaction that is likely to be key in attenuation of the tissue inflammatory response. Our results suggest an immunomodulatory and metabolic role for adipocyte-Cx43 in obesity. Disclosure S.Ron: None. I.Ron: None. M.Rathaus: None. R.Livne: None. A.Tirosh: Advisory Panel; Abbott Diagnostics, AstraZeneca, Boehringer Ingelheim International GmbH, Merck & Co., Inc., Novo Nordisk, Sanofi, Consultant; Bayer AG, DreaMed Diabetes, Ltd., Research Support; Medtronic, Speaker's Bureau; Eli Lilly and Company. Funding Israel Science Foundation (922/17)

554-P: Complex Meal Handling with Advanced Hybrid Closed-Loop (AHCL) System

Background and Aims: Meal management is a major challenge for people with type 1 diabetes (PWD) . We aimed to explore 3 approaches to complex meal planning, from a most comprehensive scheme in open loop (OL) to a simplified, carbohydrate (CHO) counting-free scheme when using the MiniMed™ 780G system AHCL. Methods: Participants (N=13, mean age 46.8±12.8 years and baseline A1C of 6.1±1.2%) consumed a high fat, high protein, meal using 3 types of insulin boluses;1) OL utilizing the dual-wave bolus and elaborate CHO counting;2) AHCL with accurate CHO amount;3) AHCL with a predefined bolus and no CHO counting, Results: No significant differences in TIR and 5-hour iAUC were observed between the 3 bolus groups (P=0.401, P=0.526, respectively) There were no significant differences in other glucose metrics. (Table 1) Conclusion: Our results indicate that glycemic control following a complex meal challenge is similar when using AHCL with or without accurate CHO counting and with less tendency for hypoglycemia when compared with the most elaborate meal management in OL. Thus, the current burden of meal management for PWD during OL system use is alleviated with AHCL. Disclosure M.Laron hirsh: None. R.Shalit: Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Novo Nordisk. S.Shalem: None. O.Cohen: Employee; Medtronic. N.Kurtz: Employee; Medtronic. A.Roy: Employee; Medtronic. B.Grosman: Employee; Medtronic. T.Cukierman-yaffe: Research Support; European Association for the Study of Diabetes, Medtronic, Merck Sharp & Dohme Corp., Novo Nordisk, Speaker's Bureau; AstraZeneca, Eli Lilly and Company, Medtronic, Merck Sharp & Dohme Corp., Novo Nordisk, Sanofi. A.Tirosh: Advisory Panel; Abbott Diagnostics, AstraZeneca, Boehringer Ingelheim International GmbH, Merck & Co., Inc., Novo Nordisk, Sanofi, Consultant; Bayer AG, DreaMed Diabetes, Ltd., Research Support; Medtronic, Speaker's Bureau; Eli Lilly and Company.

287-OR: Eliminating Manual Meal Bolusing: A Feasibility Trial Using MiniMed 780G and Hand Gesture Algorithms

Background: Carb-counting is a significant burden for persons with diabetes who require insulin to mitigate postprandial hyperglycemia. A closed-loop (CL) system with auto meal-bolus that eliminates manual mealtime bolusing was studied in adults with T1D. Methods: The system included the MiniMed™ 780G pump and a smartphone-paired smartwatch with the KLUE application that detects eating hand-gestures using motion sensors. A smartphone algorithm converted eating hand-gestures to carb amounts that were relayed to the pump for automatic bolusing. For 6 days, participants (N=17, aged 18-75 years) with T1D used the system with the KLUE app disabled and completed traditional carb-counting and -entry (Baseline) . Thereafter, the KLUE app was enabled for 5 days and carb-counting/carb-entry was prohibited (Study) . Participants were given the same 5 test-meals (one/day) of varying caloric and carb sizes during both periods. Otherwise, they had no other meal restrictions. Results: No significant difference in TIR was observed between periods and time spent at <70 mg/dL was significantly less during the Study period (Table) . Conclusion: Data suggest that the novel CL system maintains glycemic control similar to that with manual meal bolusing. By eliminating the burden of carb-counting, the new CL system may improve the quality of life in persons with T1D. Disclosure A.Roy: Employee; Medtronic. A.Tirosh: Advisory Panel; Abbott Diagnostics, AstraZeneca, Boehringer Ingelheim International GmbH, Merck & Co., Inc., Novo Nordisk, Sanofi, Consultant; Bayer AG, DreaMed Diabetes, Ltd., Research Support; Medtronic, Speaker's Bureau; Eli Lilly and Company. B.Grosman: Employee; Medtronic. D.Miller: Employee; Medtronic. T.Engel: None. O.Cohen: Employee; Medtronic. R.Shalit: Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Novo Nordisk. S.Shalem: None. M.Laron hirsh: None. Y.Cohen: None.

1401-P: Long-Term Metabolic Effects of Noncaloric Sweeteners

Accumulating evidence link sugar-containing foods and beverages to adverse health outcomes. Non-Caloric Sweeteners (NCSs) are an alternative sugar source that lead to reduction in calories, and may mitigate body weight gain and hyperglycemia, especially in patients with diabetes. Yet, contradicting studies suggest that NCSs may mediate metabolic derangements. Here, we aim to assess long-term metabolic effects of chronic consumption of NCSs. To this aim, mice consuming either regular diet or high fat diet (HFD) were supplemented with NCSs in their drinking water at concentrations consumed by humans. Under HFD, mice consuming reb M or sucralose had significant lower body weight compared to fructose. In comparison to fructose consumption, a significantly lower blood glucose levels were observed in mice under chow diet drinking either sucralose or reb M. Under HFD, a significant decrease in blood glucose levels was found only in mice consuming ace-k. On HFD, all NCSs other than saccharin, resulted in significantly improved insulin sensitivity compared to fructose. A significant decrease in fasting glucose was found only in sucralose and reb M groups under these conditions. A trend towards higher levels of plasma insulin was observed in mice under HFD drinking either fructose or saccharin. None of the interventions caused a decrease in fluid consumption as compared to water, nor were significant differences in daily food intake, daily caloric intake or energy expenditure. RER displayed a normal nocturnal pattern in all groups and no significant change in voluntary physical activity was observed. As compared to fructose, NCS consumption decreased markers of NAFLD in obesity. In summary, our results suggest that chronic consumption of NCS do not result in any observed metabolic alternations, and may attenuate some of the metabolic derangements associated with fructose and high fat-based diet. Disclosure M.Rathaus: None. L.Azem: None. R.Livne: None. S.Ron: None. I.Ron: None. A.Tirosh: Advisory Panel; Abbott Diagnostics, AstraZeneca, Boehringer Ingelheim International GmbH, Merck & Co., Inc., Novo Nordisk, Sanofi, Consultant; Bayer AG, DreaMed Diabetes, Ltd., Research Support; Medtronic, Speaker's Bureau; Eli Lilly and Company.

994-P: DINAMO—Diabetes Study of Linagliptin and Empagliflozin in Children and Adolescents with Type 2 Diabetes (T2D) : Innovative Study Design and Baseline Characteristics

T2D in youth remains challenging to manage and there is need for an expanded treatment armamentarium. The DINAMO study was designed to overcome recruitment difficulties that plagued previous T2D studies in youth. Within 3 years, DINAMO enrolled 158 patients aged to <18 years at 64 sites in 12 countries with HbA1c 6.5-10.5% on metformin and/or insulin. Unique to this study, participants with a modifiable exclusion initially could be re-screened up to 5 times. Patients were randomized to linagliptin (5 mg) , empagliflozin (mg) , or placebo (1:1:1) . At week 12, 50% of empagliflozin patients who could not attain HbA1c <7.0% were re-randomized to either remain on mg or increase to 25 mg. HbA1c change from baseline to week 26 was the primary efficacy endpoint and safety was evaluated over 52 weeks. The main reason for screen failure was HbA1c out of range (57%) . Baseline characteristics of participants are shown below. The study will be completed in fall 2022. Innovative approaches (e.g., testing multiple agents against a single placebo, re-screening patients with modifiable exclusion criteria, using a consortium model to consolidate efforts of several centers, and creating a Steering Committee to adjust study design) can successfully overcome the challenges of conducting clinical trials in youth with T2D. Disclosure L.M. Laffel: Advisory Panel; Medtronic, Roche Diabetes Care. Consultant; Boehringer Ingelheim International GmbH, Dexcom, Inc., Dompé, Insulet Corporation, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk, Provention Bio, Inc. T. Danne: Consultant; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, Dexcom, Inc., Lilly, Medtronic, Novo Nordisk, Roche Pharmaceuticals, Sanofi, Ypsomed AG. Research Support; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, Dexcom, Inc., Lilly, Medtronic, Novo Nordisk, Roche Pharmaceuticals, Sanofi, Ypsomed AG. Stock/Shareholder; DreaMed Diabetes, Ltd. W.V. Tamborlane: Consultant; AstraZeneca, Boehringer Ingelheim International GmbH, Medtronic, Novo Nordisk, Sanofi, Takeda Pharmaceutical Company Limited. G.J. Klingensmith: Research Support; AstraZeneca, Novo Nordisk, Takeda Pharmaceutical Company Limited. Stock/Shareholder; Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care, Inc. C. Schroeder: Employee; Boehringer Ingelheim Inc. D. Neubacher: Employee; Boehringer Ingelheim International GmbH. N. Soleymanlou: Employee; Boehringer Ingelheim Pharmaceuticals Inc., Boehringer Ingelheim Pharmaceuticals Inc. J. Marquard: Employee; Boehringer Ingelheim Inc. P. Zeitler: Consultant; Boehringer Ingelheim International GmbH, Daiichi Sankyo, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk, Takeda Pharmaceutical Company Limited. S.M. Willi: Advisory Panel; Boehringer Ingelheim International GmbH, Medtronic. Research Support; Jaeb Center for Health Research, Provention Bio, Inc. Other Relationship; National Institute of Diabetes and Digestive and Kidney Diseases. Funding Boehringer Ingelheim

779-P: Announced Meals at Will with the MINIMED Advanced Hybrid Closed-Loop

Background: We compared glycemic outcomes and participant experience during MiniMed™ 780G Advanced Hybrid Closed Loop (AHCL) system use while announcing all meals vs. announcing meals at will. Methods: Participants with T1DM used the AHCL system at home during two 90 days phases in which they were given instructions first to announce all meals (AM) , and next, for meals containing up to 80 grams of carbohydrates, to announce meals at will (AMW) . Results: Fourteen subjects (males, mean age 44.3±11) with T1DM were enrolled, with a baseline A1C of 6.9±1%. Table 1 summarizes glycemic indices and AHCL data, demonstrating that patients chose to bolus only slightly less during AMW compared to AM (5.5 vs. 5.2 boluses) , without resultant deterioration in glycemic indices (A1c 6.4 vs. 6.5%, TIR 78.1 vs. 78.8%, p=ns) . Subjects surveyed regarding the option not to have to bolus for all meals experienced a significant reduction in reported effort to manage diabetes (p=0.045) and 86% endorsed worrying less about their diabetes. Most (93%) preferred the AMW phase of the study. Conclusion: The MinMed™ AHCL system is designed for optimal performance with meal announcement. Nonetheless, when meals containing < 80 grams of carbohydrates are consumed with announcement of meals at will, there is a slight reduction in the number of daily boluses with no decline in glycemic control, yet markedly less diabetes related distress and improved treatment satisfaction. Disclosure N. Minsky: None. R. Shalit: Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Novo Nordisk. O. Cohen: Employee; Medtronic. N. Kurtz: Employee; Medtronic. A. Roy: Employee; Medtronic. B. Grosman: Employee; Medtronic. A. Tirosh: Advisory Panel; Abbott Diagnostics, AstraZeneca, Boehringer Ingelheim International GmbH, Merck & Co., Inc., Novo Nordisk, Sanofi. Consultant; Bayer AG, DreaMed Diabetes, Ltd. Research Support; Medtronic. Speaker's Bureau; Eli Lilly and Company.

1335-P: Deciphering Liver Glycome Regulation by the PGC-1/FN3K Axis

Diabetes in general, and specifically in the context of obesity, is characterized by hyperglycemia resulting in non-enzymatic glycation of proteins, a key event in the pathophysiology of diabetes and its chronic complications. Yet, the full scope of molecular targets for glycation, particularly in liver, is incompletely understood. De-glycation, which removes the attached sugars, is controlled intracellularly by fructosamine-3-kinase (FN3K) , a kinase that phosphorylates the attached sugar and has been proposed to have a protective role against the deleterious effects of glycation related to diabetes. However, FN3K has been suggested to be ubiquitously expressed and to act as a constitutive housekeeping gene. Furthermore, whether intracellular de-glycation is regulated in physiological contexts and what factors are involved in its regulation remain unknown. Our data identify that regulation of protein glycation in liver is controlled by the key metabolic regulators PGC-1s (PGC-1alpha and PGC-1beta) in response to metabolic cues, particularly in the fed state. Liver-specific deletion of PGC-1s results in reduction of Fn3k expression and concomitant increase in specific protein glycation. In accordance, overexpression of PGC-1alpha in liver-derived cells induces Fn3k and a reduction in protein glycation. Purification of glycated proteins followed by mass spectrometric analysis reveals significant alterations in intracellular protein glycation in response to PGC1-alpha expression. Mechanistically, PGC-1alpha effect on Fn3k involves the activity of the transcription factor Foxo1. Thus, in liver, fasting and re-feeding govern intracellular protein glycation via PGC-1 dependent induction of FN3K. Our work reveals the scope and dynamic nature of the liver glycome, establishing the PGC1/FN3K axis as a key regulator of protein glycation. Disclosure E.Glick saar: None. Y.G.Daime: None. A.Tirosh: Advisory Panel; Abbott Diagnostics, AstraZeneca, Boehringer Ingelheim International GmbH, Merck & Co., Inc., Novo Nordisk, Sanofi, Consultant; Bayer AG, DreaMed Diabetes, Ltd., Research Support; Medtronic, Speaker’s Bureau; Eli Lilly and Company. N.Minsky: None.

813-P: Treatment Satisfaction and Health Status in People with T2D Treated with Insulin Glargine 300 U/mL (Gla-300) : Patient-Reported Outcomes (PRO) from ATOS Study

Patients' satisfaction is a key determinant of treatment adherence and persistence, for optimal management of T2D. ATOS, a 12-month prospective observational study conducted in Asia, Middle East, North Africa, Latin America, and Eastern Europe, showed that initiation of Gla-300 in insulin-naïve people with T2D resulted in improved glycemic control with low rates of hypoglycemia. This analysis evaluated changes in treatment satisfaction and health status among participants. Data was collected using PRO questionnaires - Diabetes Treatment Satisfaction Questionnaire status (DTSQs) and change versions (DTSQc) , EuroQoL 5-dimension scale version 3L (EQ-5D-3L) at baseline, Month 3, 6 and 12. Overall, 3931 participants completed the questionnaires. Mean ±SD age was 57.5 ±10.6 years, duration of diabetes was 10.1 ±6.2 years and baseline HbA1c was 9.3 ±1.0 %. Treatment satisfaction improved over time (DTSQs score of 21.7 at baseline to 29.8 and 31.3 at Month 6 and 12, respectively) and perceived frequency of hyperglycemia decreased over 12 months. DTSQc results were aligned with DTSQs. EQ-5D-3L results showed that proportion of people with better health status increased over time (Table) . Results showed that initiating Gla-300 in insulin-naïve people with T2D across multiple geographic regions improved treatment satisfaction and health status. Disclosure N.Khan: None. G.R.Galstyan: n/a. A.Tirosh: Advisory Panel; Abbott Diagnostics, AstraZeneca, Boehringer Ingelheim International GmbH, Merck & Co., Inc., Novo Nordisk, Sanofi, Consultant; Bayer AG, DreaMed Diabetes, Ltd., Research Support; Medtronic, Speaker's Bureau; Eli Lilly and Company. A.Bhansali: None. H.Vargas-uricoechea: Advisory Panel; Sanofi, Speaker's Bureau; Abbott. S.B.Harris: Consultant; Abbott, AstraZeneca, Eli Lilly and Company, Novo Nordisk, Sanofi, Other Relationship; Abbott, AstraZeneca, Bayer Inc., Dexcom, Eli Lilly and Company, HLS Therapeutics, Janssen Pharmaceuticals, Inc., Novo Nordisk, Sanofi, Research Support; Applied Therapeutics Inc., AstraZeneca, Canadian Institutes of Health Research, Juvenile Diabetes Research Foundation (JDRF) , Novo Nordisk, Sanofi, The Lawson Foundation. A.Roborel de climens: Employee; IQVIA Inc., Sanofi. M.N.Mabunay: Employee; Sanofi. M.Coudert: Employee; Sanofi. V.Pilorget: None. Funding Sanofi

1263-P: Adolescent Obesity and Incident Type 1 Diabetes in Young Adulthood

Background: Studies in children reported an association between increased body mass index (BMI) and risk for developing type 1 diabetes (T1D) . We studied the association between adolescent BMI and incident T1D in young adulthood in a nationwide cohort of 1,462,362 adolescents which was recently used to assess the association between adolescent BMI and early-onset type 2 diabetes (Diabetes Care 2020 Jul;43 (7) :1487-1495) . Methods: All Israeli adolescents, ages 16-19, undergoing medical evaluation in preparation for mandatory military conscription between January 1996 and December 2016 were included for analysis unless they had a history of dysglycemia. Data were linked to information about adult onset of T1D in the Israeli National Diabetes Registry. Weight and height were measured at the study entry. Cox proportional models were applied, with BMI analyzed both as a categorical and as a continuous variable. Islet autoantibody data were available for a subpopulation of the cohort. Results: There were 777 incident cases of T1D during 15,810,751 person-years (mean age at diagnosis 25.2±3.9 years) . BMI was associated with incident T1D. In a multivariable model adjusted for age, sex and socio-demographic variables, the hazard ratios (HRs) for T1D were 1. (95% CI 0.87-1.27) for the 50th-74th BMI percentiles, 1.41 (1.11-1.78) for the 75th-84th BMI percentiles, 1.54 (1.23-1.94) for adolescents with overweight (85th-94th percentiles) , and 2. (1.58-2.66) for adolescents with obesity (BMI≥95th percentile) . One increment in BMI standard deviation was associated with 25% greater risk for incidence of T1D (HR=1.25, 95%CI 1.17-1.32) . Association persisted when the definition of T1D included the presence of islet autoantibodies; when the study population was restricted to those with unimpaired health. Conclusions: Excessively high BMI in apparently healthy adolescents is associated with increased risk for incident T1D in early adulthood. Disclosure I.Zucker: None. D.Tzur: None. C.Melzer cohen: None. O.Pinhas-hamiel: Advisory Panel; Novo Nordisk, Speaker's Bureau; Pfizer Inc. G.Chodick: None. I.Raz: None. A.Afek: None. H.C.Gerstein: Advisory Panel; Abbott, Eli Lilly and Company, Hanmi Pharm. Co., Ltd., Novo Nordisk, Pfizer Inc., Sanofi, Viatris Inc., Consultant; Kowa Company, Ltd., Other Relationship; DKSH, Eli Lilly and Company, Sanofi, Zuellig Pharma Holdings Pte. Ltd., Research Support; AstraZeneca, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk, Sanofi. A.Tirosh: Advisory Panel; Abbott Diagnostics, AstraZeneca, Boehringer Ingelheim International GmbH, Merck & Co., Inc., Novo Nordisk, Sanofi, Consultant; Bayer AG, DreaMed Diabetes, Ltd., Research Support; Medtronic, Speaker's Bureau; Eli Lilly and Company. G.Twig: None. Y.Zloof: None. A.Bardugo: None. A.M.Tsur: None. M.Lutski: None. Y.Cohen: None. T.Cukierman-yaffe: Research Support; European Association for the Study of Diabetes, Medtronic, Merck Sharp & Dohme Corp., Novo Nordisk, Speaker's Bureau; AstraZeneca, Eli Lilly and Company, Medtronic, Merck Sharp & Dohme Corp., Novo Nordisk, Sanofi. N.Minsky: None. E.Derazne: None. Funding This work was partially supported by an internal grant from the Israel Defense Forces Medical Corps.

346-P: Predicting True Time to Recovery from Insulin-Induced Hypoglycemia with Dasiglucagon

The efficacy of dasiglucagon 0.6 mg has been investigated in multiple trials in individuals with T1DM. The primary endpoint was time to plasma glucose (PG) recovery from insulin-induced hypoglycemia, defined as first PG increase ≥20 mg/dL after treatment initiation without the need for IV glucose. Different PG sampling schemes were used in phase 2 (5-min intervals) versus phase 3 trials (more frequent sampling). Estimating the true but unmeasured time to recovery for each individual enables for a better comparison between trials when compared to use of observed time only. The true time was calculated using linear interpolation between the 2 time points before and after recovery occurred, assuming a linear PG increase in this limited time interval. The difference between the observed and the estimated true recovery for an individual is illustrated in the figure. The PG sample taken at 10 min is the first sample showing an increase of at least 20 mg/dL from the predose level, leading to an observed time to recovery of 10 min. Linear interpolation estimates the increase of 20 mg/dL to occur at 9 min for this individual. Using interpolated PG values, the median estimated true time to recovery for dasiglucagon was 8.7 min in the phase 2 trial and 9.0 to 9.3 min in phase 3 trials. These data provide further insight into the probable “true time to recovery” and confirm the consistent efficacy of dasiglucagon in the treatment of hypoglycemia. Disclosure T. Battelino: Advisory Panel; Self; Eli Lilly and Company, Medtronic, Sanofi, Research Support; Self; European Union, National Institute of Diabetes and Digestive and Kidney Diseases, Novartis Pharmaceuticals Corporation, Novo Nordisk, Sanofi, Slovenian Research Agency, Zealand Pharma A/S, Speaker’s Bureau; Self; Abbott Diabetes, AstraZeneca, Dexcom, Inc., Eli Lilly and Company, Medtronic, Novo Nordisk, Pfizer Inc., Roche Diabetes Care, Sanofi, Stock/Shareholder; Self; DreaMed Diabetes, Ltd. L. Dimeglio: Advisory Panel; Self; MannKind Corporation. T. Danne: Research Support; Self; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Medtronic, Novo Nordisk, Sanofi, Tandem Diabetes Care, Zealand Pharma A/S, Stock/Shareholder; Self; DreaMed Diabetes, Ltd. A. L. Peters: Advisory Panel; Self; Abbott Diabetes, Eli Lilly and Company, MannKind Corporation, Medscape, Merck & Co., Inc., Novo Nordisk Inc., Zealand Pharma A/S, Other Relationship; Self; Livongo, Research Support; Self; Abbott Diabetes, Dexcom, Inc. T. S. Bailey: Consultant; Self; Abbott Diabetes, LifeScan, Novo Nordisk, Sanofi, Research Support; Self; Abbott, Abbott Diabetes, Biolinq, Capillary Biomedical, Inc., Dexcom, Inc., Eli Lilly and Company, Kowa Research Institute, Inc., Lexicon Pharmaceuticals, Inc., Livongo, Medtronic, Medtrum Technologies, Novo Nordisk, REMD Biotherapeutics, Sanofi, Sanvita, Viacyte, Inc., vTv Therapeutics, Zealand Pharma A/S, Speaker’s Bureau; Self; BD, Medtronic, Sanofi. R. Tehranchi: Employee; Self; Zealand Pharma A/S. L. J. Klaff: Research Support; Self; Abbott Diabetes, Dong-A ST Co. Ltd., Gan & Lee Pharmaceuticals, Lexicon Pharmaceuticals, Inc., Lilly Diabetes, Medtronic, Novo Nordisk, Oramed Pharmaceuticals, Inc., Pfizer Inc., REMD Biotherapeutics. T. Pieber: Advisory Panel; Self; ADOCIA, Arecor, AstraZeneca, Eli Lilly and Company, Novo Nordisk A/S, Sanofi, Research Support; Self; AstraZeneca, Novo Nordisk A/S. U. Hovelmann: None. L. Plum-moerschel: None. A. E. Melgaard: Employee; Self; Zealand Pharma A/S. R. Aronson: None.

345-P: The Next Generation Glucagon Analog Dasiglucagon Consistently Achieves Rapid Recovery from Hypoglycemia across Subgroups

The efficacy of dasiglucagon 0.6 mg, a glucagon analog stable in aqueous formulation, has been established versus placebo in previously reported trials in adults with type 1 diabetes mellitus. An integrated analysis was conducted to investigate efficacy in demographic and other subgroups. To allow as many individuals as possible in the evaluation, the analysis comprised data from 4 trials in adults, including 2 pivotal trials, an additional phase 3 trial, and a phase 2 trial. The trials were conducted under similar conditions with respect to design characteristics, such as target population, background therapy and treatment duration. All trials included efficacy assessments following insulin-induced hypoglycemia and showed consistent efficacy results across trials. The primary endpoint was time to plasma glucose (PG) recovery, defined as first PG increase ≥ 20 mg/dL after treatment initiation without need for rescue intravenous glucose. A total of 220 participants were exposed to dasiglucagon 0.6 mg across trials. Results of the integrated analysis are shown as a Forest plot of median time to PG recovery for dasiglucagon, including 95% confidence intervals by subgroup.In conclusion, the results showed that the efficacy of dasiglucagon was highly consistent across subgroups, with a median time to recovery from insulin-induced hypoglycemia of 10 minutes in most groups.View largeDownload slideView largeDownload slide DisclosureT. Battelino: Advisory Panel; Self; Eli Lilly and Company, Medtronic, Sanofi, Research Support; Self; European Union, National Institute of Diabetes and Digestive and Kidney Diseases, Novartis Pharmaceuticals Corporation, Novo Nordisk, Sanofi, Slovenian Research Agency, Zealand Pharma A/S, Speaker’s Bureau; Self; Abbott Diabetes, AstraZeneca, Dexcom, Inc., Eli Lilly and Company, Medtronic, Novo Nordisk, Pfizer Inc., Roche Diabetes Care, Sanofi, Stock/Shareholder; Self; DreaMed Diabetes, Ltd. L. Dimeglio: Advisory Panel; Self; MannKind Corporation. T. Danne: Research Support; Self; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Medtronic, Novo Nordisk, Sanofi, Tandem Diabetes Care, Zealand Pharma A/S, Stock/Shareholder; Self; DreaMed Diabetes, Ltd. T. S. Bailey: Consultant; Self; Abbott Diabetes, LifeScan, Novo Nordisk, Sanofi, Research Support; Self; Abbott, Abbott Diabetes, Biolinq, Capillary Biomedical, Inc., Dexcom, Inc., Eli Lilly and Company, Kowa Research Institute, Inc., Lexicon Pharmaceuticals, Inc., Livongo, Medtronic, Medtrum Technologies, Novo Nordisk, REMD Biotherapeutics, Sanofi, Sanvita, Viacyte, Inc., vTv Therapeutics, Zealand Pharma A/S, Speaker’s Bureau; Self; BD, Medtronic, Sanofi. R. Tehranchi: Employee; Self; Zealand Pharma A/S. L. J. Klaff: Research Support; Self; Abbott Diabetes, Dong-A ST Co. Ltd., Gan & Lee Pharmaceuticals, Lexicon Pharmaceuticals, Inc., Lilly Diabetes, Medtronic, Novo Nordisk, Oramed Pharmaceuticals, Inc., Pfizer Inc., REMD Biotherapeutics. T. Pieber: Advisory Panel; Self; ADOCIA, Arecor, AstraZeneca, Eli Lilly and Company, Novo Nordisk A/S, Sanofi, Research Support; Self; AstraZeneca, Novo Nordisk A/S. U. Hövelmann: None. L. Plum-moerschel: None. A. E. Melgaard: Employee; Self; Zealand Pharma A/S. R. Aronson: None.

344-P: Integrated Safety Analysis of Dasiglucagon for Treatment of Severe Hypoglycemia

Dasiglucagon was developed to provide a fast and effective treatment for severe hypoglycemia (SH) in people with diabetes. An integrated cross-program analysis was performed to assess the safety of dasiglucagon in a representative population of T1DM. Three randomized, placebo-controlled phase 3 trials (2 in adults and 1 in pediatric subjects) were included in the analysis (212 adults and 41 children/adolescents with T1DM). No severe or adverse events (AEs) leading to withdrawal were reported. Most AEs were mild or moderate in severity. Nausea and vomiting were the most-frequent AEs reported with active treatment both in adults and children. No differences in the frequency of nausea and vomiting were observed between adults receiving dasiglucagon versus glucagon. A higher percentage of adolescents experienced these events with dasiglucagon than with glucagon, while no treatment-related imbalance was observed in the 6- to 11-year-old age group. In the pediatric trial, no relationship between exposure (AUC0-5 hr or Cmax) to dasiglucagon, and nausea and vomiting was found. The majority of nausea and vomiting occurred within 1-3 hr and 2-3 hr of dosing, respectively. In conclusion, dasiglucagon 0.6 mg for treatment of SH was found to be generally safe, and the safety profile of dasiglucagon was consistent with that observed across the class of glucagon products. Disclosure S. R. Heller: Advisory Panel; Self; Eli Lilly and Company, Novo Nordisk, Zealand Pharma A/S, Consultant; Self; Zealand Pharma A/S, Other Relationship; Self; Dexcom, Inc., Eli Lilly and Company, MannKind Corporation, Novo Nordisk, Speaker’s Bureau; Self; AstraZeneca, Novo Nordisk. R. Aronson: None. L. Dimeglio: Advisory Panel; Self; MannKind Corporation. T. Danne: Research Support; Self; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Medtronic, Novo Nordisk, Sanofi, Tandem Diabetes Care, Zealand Pharma A/S, Stock/Shareholder; Self; DreaMed Diabetes, Ltd. T. Battelino: Advisory Panel; Self; Eli Lilly and Company, Medtronic, Sanofi, Research Support; Self; European Union, National Institute of Diabetes and Digestive and Kidney Diseases, Novartis Pharmaceuticals Corporation, Novo Nordisk, Sanofi, Slovenian Research Agency, Zealand Pharma A/S, Speaker’s Bureau; Self; Abbott Diabetes, AstraZeneca, Dexcom, Inc., Eli Lilly and Company, Medtronic, Novo Nordisk, Pfizer Inc., Roche Diabetes Care, Sanofi, Stock/Shareholder; Self; DreaMed Diabetes, Ltd. T. S. Bailey: Consultant; Self; Abbott Diabetes, LifeScan, Novo Nordisk, Sanofi, Research Support; Self; Abbott, Abbott Diabetes, Biolinq, Capillary Biomedical, Inc., Dexcom, Inc., Eli Lilly and Company, Kowa Research Institute, Inc., Lexicon Pharmaceuticals, Inc., Livongo, Medtronic, Medtrum Technologies, Novo Nordisk, REMD Biotherapeutics, Sanofi, Sanvita, Viacyte, Inc., vTv Therapeutics, Zealand Pharma A/S, Speaker’s Bureau; Self; BD, Medtronic, Sanofi. R. Tehranchi: Employee; Self; Zealand Pharma A/S. L. J. Klaff: Research Support; Self; Abbott Diabetes, Dong-A ST Co. Ltd., Gan & Lee Pharmaceuticals, Lexicon Pharmaceuticals, Inc., Lilly Diabetes, Medtronic, Novo Nordisk, Oramed Pharmaceuticals, Inc., Pfizer Inc., REMD Biotherapeutics. T. Pieber: Advisory Panel; Self; ADOCIA, Arecor, AstraZeneca, Eli Lilly and Company, Novo Nordisk A/S, Sanofi, Research Support; Self; AstraZeneca, Novo Nordisk A/S. U. Hovelmann: None. L. Plum-moerschel: None. A. E. Melgaard: Employee; Self; Zealand Pharma A/S.

745-P: Effectiveness and Safety of Insulin Glargine 300 U/mL (Gla-300) in Insulin-Naïve People with Type 2 Diabetes (T2DM): ATOS Study Subgroup Analysis by Baseline (BL) HbA1c

ATOS was a 12-month prospective observational study in 18 countries outside US and Western Europe in insulin-naive adults with T2DM, uncontrolled (HbA1c >7-≤11%) on ≥1 oral antihyperglycemic drug. In this subgroup analysis participants were stratified by BL HbA1c: 50% of participants with BL HbA1c Disclosure N. Khan: None. A. Tirosh: Advisory Panel; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Sanofi, Consultant; Self; DreaMed Diabetes, Ltd. H. Vargas-uricoechea: Advisory Panel; Spouse/Partner; Sanofi. M. N. Mabunay: Employee; Self; Sanofi, Stock/Shareholder; Self; Sanofi. M. Coudert: Employee; Self; Sanofi. V. Pilorget: Employee; Self; Sanofi. G. R. Galstyan: None. Funding Sanofi

194-OR: Real-World Effectiveness and Safety of Insulin Glargine 300 U/mL (Gla-300) in Older Adults (≥70 Years) with Type 2 Diabetes (T2DM): A Subgroup Analysis of the ATOS Study

ATOS was a 12-month prospective observational study in 18 countries outside US and Western Europe in insulin-naïve adults with T2DM, uncontrolled (HbA1c >7-≤11%) on ≥1 oral anti-hyperglycemic drug. This subgroup analysis of ATOS compared the effectiveness and safety of Gla-300 in older (≥70 years [Y]; N=514) and younger (<70 Y; N=3908) adults. People aged ≥70 Y had a longer duration of T2DM and more comorbidities than those aged <70 Y. Physician-set individualized HbA1c (%) goals at baseline in the <70 vs. ≥70 Y groups were <7: 14.6 vs. 6.2%; 7-<7.5: 72.9 vs. 52.1%; 7.5-<8: 9.3 vs. 30.9%; ≥8: 3.2 vs. 10.7%. HbA1c target achievement was higher in the older population than in the <70 Y age group: Month 6 (32.3%, vs. 24.2%) and Month 12 (53.2% vs. 43.4%). HbA1c reductions from baseline to Month 6 (-1.48 vs. -1.51%) and Month 12 (-1.76 vs. -1.89%) were similar in both groups. A very low rate of hypoglycemia was reported, although numerically higher in ≥70 Y group. Increases in the Gla-300 dose was similar across the groups. Incidence of any and serious treatment-emergent adverse events was low. Consistent results were observed in subgroup of <65 vs. ≥65 Y. Initiation of Gla-300 in the older adults is effective in achieving their pre-defined HbA1c goals with low risk of hypoglycemia in both older and younger adults with T2DM.View largeDownload slideView largeDownload slide DisclosureG. R. Galstyan: None. A. Tirosh: Advisory Panel; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Sanofi, Consultant; Self; DreaMed Diabetes, Ltd. H. Vargas-uricoechea: Advisory Panel; Spouse/Partner; Sanofi. M. N. Mabunay: Employee; Self; Sanofi, Stock/Shareholder; Self; Sanofi. M. Coudert: Employee; Self; Sanofi. V. Pilorget: Employee; Self; Sanofi. N. Khan: None. FundingSanofi

743-P: Real-World Effectiveness and Safety of Insulin Glargine 300 U/mL (Gla-300) in Insulin-Naïve People with Type 2 Diabetes (T2DM) and Renal Impairment (RI): A Subgroup Analysis of the ATOS Study

ATOS, a prospective, 12-month observational study in 18 countries outside US and Western Europe, showed that initiation of Gla-300 in people with T2DM resulted in improved glycemic control with low rates of hypoglycemia and minimal weight change. Here we present the results from a subgroup analysis in participants with (N=581) or without (N=3841) a history of RI (~70% microalbuminuria, Table). Patients with RI were older (62.2±10.3 vs. 56.4±10.7 years), had a longer duration of T2DM (mean: 12.7±6.9 vs. 9.8±6.0 years) and more comorbidities than patients without RI. Baseline HbA1c was comparable between groups (9.3%). Physician-set individualized HbA1c (%) goals at baseline in the RI vs. non-RI groups were Disclosure A. Tirosh: Advisory Panel; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Sanofi, Consultant; Self; DreaMed Diabetes, Ltd. N. Khan: None. H. Vargas-uricoechea: Advisory Panel; Spouse/Partner; Sanofi. M. N. Mabunay: Employee; Self; Sanofi, Stock/Shareholder; Self; Sanofi. M. Coudert: Employee; Self; Sanofi. V. Pilorget: Employee; Self; Sanofi. G. R. Galstyan: None. Funding Sanofi

1010-P: Personalized Automated Determination of Insulin Pump Settings for People with Type 1 Diabetes Switching from MDI to Pump Therapy and Vice Versa

Transition from MDI to pump therapy may be beneficial to a wide range of people with diabetes such as young children, newly diagnosed, switching to closed-loop therapy and more. At times the reverse transition is needed, such as during pump malfunction, or when a "pump holiday" is required. The Switch Advisor is a decision support system developed to ease, personalize and optimize the transition between MDI to pump therapy or vice versa. Methods: The Switch Advisor was evaluated for safety in two feasibility, one arm studies. Each study included 4 weeks of data collection while participants used their regular treatment modality, then participants switched to the second mode of therapy based on algorithm recommendations. CGM related matrices were compared between the data collection period and 2 weeks after switching to the second mode of therapy. Primary outcomes were time in hypoglycemia &amp;lt; 54 mg/dl and time in range of 70-180 mg/dl. Results: 11 participants [aged 22.8y (3.7), A1c 7.3% (0.8), and 56.5 (7.7) mmol/mol, mean (SD)] completed the first study of, transition from pump to MDI therapy. 12 participants [aged 12.7 (4.3), A1c 8.4 (0.9) and 68 (9.8) mmol/mol] completed the second study of, transition from MDI to pump therapy. Mean percent (SD) TIR 70-180 mg/dl was 62% (13) and time &amp;lt; 54 mg/dl was 3% (2) during pump therapy and 58% (9) and 4% (5) after switching to MDI, respectively (P=N.S). TIR 70-180 mg/dl was 50% (15) and time &amp;lt; 54 mg/dl was 3% (3) during MDI therapy and 63% (15) and 2% (3) after switching to pump therapy (P=0.01, P=N.S, respectively). TDD of insulin was 59 (24) U during pump therapy and 54 (26) U after switch to MDI (N=9) and 30 (18) U during MDI therapy and 33(14) U after switching to pump therapy (N=10). No serious adverse events occurred during both studies. Conclusions: An automated algorithm to determine initial pump therapy settings and MDI was found to be feasible and safe. RCT studies are needed to confirm the results of these feasibility studies. Disclosure R. Nimri: Employee; Self; DreaMed Diabetes. Stock/Shareholder; Self; DreaMed Diabetes. I. Muller: Board Member; Self; DreaMed Diabetes. E. Atlas: Board Member; Self; DreaMed Diabetes. Employee; Self; DreaMed Diabetes. Stock/Shareholder; Self; DreaMed Diabetes. M. Phillip: Consultant; Self; Qulab Medical, RSP Systems A/S. Research Support; Self; JDRF. Stock/Shareholder; Self; NG Solutions Ltd, Nutriteen Professionals Ltd. Other Relationship; Self; AstraZeneca, Dexcom, Inc., DreaMed Diabetes, Eli Lilly and Company, Insulet Corporation, Medtronic, Novo Nordisk A/S, OPKO Health, Inc., Pfizer Inc., Sanofi-Aventis. Funding JDRF (1-SRA-2017-422-M-B)