bluuebunny/crossref_metadata_2025 huggingface dataset:
612-P: Impact of Digital Intervention Tools on Engagement and Glycemic Outcomes
Authors: HERSHCOVITZ YIFAT , DAR SHARON , MANEJWALA OMAR , BACHER DROR
Published: June 2021

Introduction: Digital therapeutic platforms in diabetes aim to improve condition self-management and clinical outcomes. Engagement actions are well evaluated by digital monitoring or by logging iterations, and clinical outcomes by target range measurements. A new product modification in the Dario application included development of in-App educational interactions about healthy eating habits. In addition, user experience feature that help users understand the context of their blood glucose measurement was developed. This study evaluated the effect of the digital product modification.

Method: A retrospective data evaluation study was performed on DarioTM members during the time before and after product modification. Digital engagement and clinical outcomes were measured on first to six months per each period to examine if habit formation was achieved.

Results: A group of total 9794 users who had enrolled in a membership for 6 months or longer was evaluated. The ratio of measurements logged with context (fasting, pre-meal, post-meal, bedtime) was increased significantly by 56% in the first month following product modification on average (51.3%. vs. 32.8%) (P<0.001). Differences in the level of digital engagement remained stable over a 6 months period. The average number of days between measurements, i.e., “recency” decreased by 21% on average (2.71 vs. 3.45). Average ratios of high readings (180-400 mg/dL) were reduced by 12% on average over six months.

Conclusion: The present study demonstrates that product updates to digital platforms that guide on healthy eating and help users understand their glucose readings in context may assist users in improving the management of their diabetes.

Disclosure

Y. Hershcovitz: Employee; Self; DarioHealth. S. Dar: Employee; Self; DarioHealth. O. Manejwala: Employee; Self; DarioHealth, Stock/Shareholder; Self; DarioHealth. D. Bacher: Employee; Self; DarioHealth.
63-LB: Achieving Both Target Time-in-Range and Coefficient of Variation
Authors: TAKEISHI SOICHI , INOUE TATSUO
Published: June 2021

We studied how to achieve both the target time in range (70-180 mg/dL) [TIR] and target coefficient of variation (CV). In a cross-sectional study, we analyzed 24-h glucose levels measured using CGM (iPro2) for 150 patients with type 2 diabetes. We calculated the “mean of all absolute differences between glucose levels and the ‘reference glucose levels (R)’” (M1, in mg/dL), corresponding to 21 R (110, 111⋯130 mg/dL), as a metric to achieve the target TIR. We also calculated the “percentage of the mean absolute deviation to mean glucose levels” (M2, in %) as a metric to achieve the target CV. The R values for which M1 most correlated to TIR were 117 and 118 mg/dL (r = -0.95, p < 0.001). M2 correlated to CV (r = 0.99, p < 0.001; M2 = 0.85 × CV - 0.43). The optimal cutoff value (OC) for TIR > 70% in “M1 for R of 117.5 mg/dL” (M1, 117.5) was 44.6 mg/dL (sensitivity, 96%; specificity, 96%; AUC, 0.99; p < 0.001). The OC for CV < 36% in M2 was 31.5% (sensitivity, 100%; specificity, 100%; AUC, 1). The OC for “both TIR > 70% and CV < 36%” in “M1, 117.5 × M2,” was 842.0 (sensitivity, 90%; specificity, 89%; AUC, 0.96; p < 0.001). Putting all glucose levels close to 117.5 mg/dL may be the most efficient method to increase the TIR as much as possible. Based on our results, the simple target values are as follows: “M1, 117.5 of 42.5 mg/dL” (75-160) [if all glucose levels are within 75-160 mg/dL, M1, 117.5 is sure to be < 42.5 mg/dL] × M2 of 20% = 850 (≈ 842)” (T1); “M1, 117.5 of 27.5 mg/dL (90-145) × M2 of 30% = 825 (≈ 842)” (T2). For T1, if the range that satisfies both 75-160 mg/dL and “‘24 h mean glucose levels on the day before’ ± ‘20 % of the mean glucose levels’” (mean ± 20%) is used as an alarm threshold in a personal CGM, keeping all glucose levels within the range as much as possible may achieve both TIR > 70% and CV < 36%. For T2, if the range that satisfies both 90-145 mg/dL and mean ± 30% is used as an alarm threshold, keeping all glucose levels within the range as much as possible may achieve both TIR > 70% and CV < 36%.

Disclosure

S. Takeishi: None. T. Inoue: None.
63-OR: Focused Educational Screening Improves Knowledge of Diabetes as a Leading Risk Factor for Chronic Kidney Disease
Authors: VO LISA , PARIS MELANIE , ALAWODE MOLLY , SPIGLER MICHAEL
Published: June 2021

Background: Diabetes is the leading cause of chronic kidney disease (CKD) and a major risk factor in the progression of kidney failure or end-stage kidney disease. An estimated 34.2 million Americans have diabetes, and 1 in 3 adults with diabetes may have CKD, many of whom do not know they have it. Interventions to increase CKD awareness and its complications may help promote early testing and identification among adults with diabetes. The American Kidney Fund (AKF) developed a 5-minute CKD education session and focused this intervention in the District of Columbia-Maryland-Virginia (DMV) metropolitan area.

Methods­: In 2020, AKF administered a 5-item questionnaire at two AKF kidney disease screening events to assess CKD knowledge before and after 5-minute CKD education sessions. Individuals demonstrating CKD risk factors, including self-reported history of diabetes or elevated blood sugar level results, attended the education sessions. We compared responses from 129 participants and performed a paired samples t-test to determine the education sessions’ effectiveness in improving CKD knowledge.

Results: The average pre-post scores increased from 57% to 89% (t(128)=10.65, p<0.001), with the largest gains in understanding the definition of CKD (11% to 86%, t(128)=17.62, p<0.001). There was a significant difference in pre-post scores for identifying diabetes and high blood pressure as the top risk factors for CKD (49% to 86%, t(128)=6.62, p<0.001). For the best ways to prevent CKD, keeping a healthy blood sugar level and healthy blood pressure level was also significant (65% to 89%, t(128)=4.91, p<0.001).

Conclusion: Our study demonstrated low awareness of CKD risk factors. Educational sessions are effective for improving CKD knowledge and increasing awareness about diabetes as a major risk factor. Our study supports the expansion of CKD-related educational programs for populations at high risk for CKD.

Disclosure

L. Vo: None. M. Paris: None. M. Alawode: None. M. Spigler: None.
637-P: Effectiveness of Fixed Ratio Combination of IGlarLixi in People with Type 2 Diabetes Mellitus: Experience from Routine Clinical Practice
Authors: KIS JANOS T. , NAGY GABOR , STELLA PETER
Published: June 2021

Background: Currently no data are available on the real-world effectiveness of the fixed ratio combination of insulin glargine 100 U/ml and lixisenatide (iGlarLixi). This non-interventional study (it was conducted in Hungary) aimed to evaluate its effects on glycaemic control and hypoglycaemia in real-world practice.

Methods: The single-arm, 6-month (with follow-up visits at 3 and 6 months) study included uncontrolled adults with type 2 diabetes (HbA1c>7,5%) treated by oral antidiabetics (OAD) +/- basal insulin. iGlarLixi treatment was started at the time of inclusion.

Results: Of the included 442 participants, 353 were involved in the efficacy analyses. 282 (79.9%) subjects were treated with OADs, while the remaining 71 (20.1%) with basal insulin and OAD(s) before inclusion. The proportion of participants achieving at least 1.0% HbA1c reduction during the observation period was 60.9% (primary endpoint). All glycaemic variables (mean±SD) improved significantly (p<0,001) during follow-up (HbA1c from 8.9±1.3% to 7.4 ±1.0%, fasting blood glucose from 9.0±2.2 mmol/L to 6.9±1.2 mmol/L, and postprandial blood glucose from 11.3±2.3 mmol/L to 8.5±1.5 mmol/L). All changes were clinically and statistically significant. Body weight was also decreased from 90.5±18.0 kg to 88.2±17.8 kg. Only 37 subjects (10.5%) self-reported at least one symptomatic hypoglycaemic episode during the study. There was no severe hypoglycaemic episode being reported. Frequency of gastrointestinal adverse events was low (5 patients, 1.4%).

Conclusion: The first prospective, non-interventional study confirmed several results from the LIXILAN programme in a real-life setting. iGlarLixi significantly improved glycaemic control with low frequency of hypoglycaemia and gastrointestinal adverse events in a heterogenous population of people with type 2 diabetes. Results confirm similar efficacy and safety in routine clinical care than in randomized controlled trials.

Disclosure

J. T. Kis: None. G. Nagy: Employee; Self; Sanofi-Aventis. P. Stella: Employee; Self; Sanofi-Aventis.

Funding

Sanofi
641-P: Novel Microsphere Formulation Developments of Long-Acting GLP-1 RA Including Exenatide, Liraglutide, and Semaglutide
Authors: JUNG JIN G.
Published: June 2021

Objective: Clinical applications of Glucagon-like peptide-1 receptor agonists (GLP1-RA) were greatly limited due to its short half-life. The current study aims at the formulation and characterization of sustained-release (SR)-GLP1-RAs to prolong the release profile with lag phase-free formulation technology.

Methods: The long-acting drugs of those GLP1-RAs were prepared by an ultrasonic spray drying process with biodegradable PLGA polymer. Once the PLGA polymer and each API were dissolved in acetic acid, those were applied to the ultrasonic spray dryer to produce the microspheres which encapsulate the API in PLGA polymer. The pharmacokinetic profiles of long-acting SR-Exenatide, SR-Liraglutide, and SR-Semaglutide were determined by using Sprague-Dawley rats after a single injection subcutaneously. APIs were used as controls.

Results: The optimized SR-Exenatide has demonstrated favorable physicochemical properties, such as mean particle size (20 ± 3 μm), percent of entrapment efficiency (90 ± 5 %), and the final drug loading (5 ± 0.5 %), with uniformly sized microspheres. Furthermore, the pharmacokinetic parameters appeared that its release profile extends up to 4 weeks without lag phase which showed 11.4 days of Tmax and 68% of relative bioavailability (BA) when 2mg/kg dose applied. Not only SR-Exenatide but also SR-Liraglutide and SR-Semaglutide showed the extended-release profile up to 1 week and 4 weeks in the rats, respectively.

Conclusion: Those results showed the potentials of lag phase-free, long-acting, high productivity, and mass production. Taken together with the lag phase-free formulation and long-acting ultrasonic spray drying technologies, it will provide the rationales for the clinical development of SR-GLP1-RAs for once-weekly or -monthly formulations. As we have a GMP facility to produce long-acting drugs, we will actively and clinically investigate those SR-GLP1-RAs for antidiabetic therapy.

Disclosure

J. G. Jung: None.
642-P: A Model-Based Evaluation of Nausea and Vomiting Events for Additional Doses of Dulaglutide in Existing and Dulaglutide-Naïve Patients with Type 2 Diabetes
Authors: THAM LAI-SAN , LIM JEAN S.K. , TANG CHENG CAI , JUNG HEIKE , KONIG MANIGE , LOO LI SHEN
Published: June 2021

Dulaglutide (DU) 3 mg and 4.5 mg once weekly (QW) doses were recently approved for additional glycemic control in adult patients with type 2 diabetes. If needed, a dose-escalation scheme from 1.5 mg to 3 mg and then 4.5 mg can be applied after at least 4-weeks on each dose. For GLP-1 receptor agonists, such as DU, common gastrointestinal (GI) side effects include nausea (N) and vomiting (V). These GI effects are dose-dependent but attenuate over time with chronic dosing. To enhance prescriber understanding of GI effects following dose escalation in existing and DU-naïve patients, a Markov chain Monte Carlo pharmacokinetic/pharmacodynamic joint model was developed with Phase 3 AWARD-11 data (n=1842) which compared 3 mg and 4.5 mg DU to 1.5 mg, to evaluate probabilities of daily N and V events. The model was initiated with priors from a similar Phase 2 model (n=317). In this model, dose increment raised the probability of developing a GI event, and preceding N events enhanced the probability of V events. Development of GI tolerance to N and V was both time and DU concentration dependent. Model-predictions of the percentage of patients presenting with ≥1 N or V event per day for a given dosing scenario were generated via simulations of 100 trials with 300 patients per scenario from the AWARD-11 dataset and compared with the AWARD-11 dose-escalation scheme over a 52-week duration. Patients already on DU 1.5 mg QW for at least 4 weeks can escalate to 3 mg QW any time, and if needed increase to 4.5 mg QW after 4 weeks on 3 mg. Simulations showed ≤3% and ≤1% increase in N and V events, respectively compared to AWARD-11 dose escalation scheme. For DU-naïve patients starting at 0.75 mg QW, N and V events were reduced by ≤2% and ≤1%, respectively, after escalating to 1.5 mg QW and 3 mg after ≥4 weeks at each dose. Whether in DU-naïve patients or those already on 1.5mg, simulations showed no meaningful increase in N and V when dose escalation occurred at intervals of at least 4 weeks.

Disclosure

L. Tham: Employee; Self; Eli Lilly and Company. J. S. K. Lim: Employee; Self; Eli Lilly and Company. C. Tang: Employee; Self; Eli Lilly and Company, Employee; Spouse/Partner; Novartis AG. H. Jung: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. M. Konig: Employee; Self; Eli Lilly and Company. L. Loo: Employee; Self; Eli Lilly and Company, Employee; Spouse/Partner; Eli Lilly and Company.
644-P: Discovery of Nonpeptide, Orally Available Small Molecule GLP-1 Receptor Agonists
Authors: IM A-RANG , PARK JUNG-EUN , HONG DAHAE , JE IN-GYU , KIM JUNG HO , CHANG MIN WHAN , HONG CHANG-HEE , SHIN JAE EUI , SOHN TE-IK , JUN YEARIN , JANG EUNHYE , YOO YEONGRAN , JEON WOOJIN , AN KYUNGMI
Published: June 2021

GLP-1R agonists comprise a growing class of agents that deliver unprecedented efficacy in the treatment of diabetes. We discovered promising compounds for the development of a novel small molecule GLP-1R agonist and examined their efficacy in cynomolgus monkey. The in vitro activities of the compounds were evaluated by measuring cAMP accumulation in cells expressing human GLP-1R. All compounds demonstrated potent cAMP accumulation of EC50 value below 20 nM, with one compound showing 1.5 nM. In addition, the compounds showed excellent selectivity against related class B GPCR, with no stimulatory activity on human GIP, GCG, and GLP-2 receptors. In the intravenous glucose tolerance test, according to the present disclosure, the compounds increased insulin secretion in cynomolgus monkey (dosed 50 mg/kg, p.o.), demonstrating their efficacy as orally available GLP-1 receptor agonists. Moreover, inhibitory effect on the hERG current was investigated and the compounds were shown to have favorable safety profile with IC50 values ranging from 34.6 to more than 100 μM.

In conclusion, we discovered promising compounds which have potential to be developed as an orally active, non-peptide GLP-1R agonist for the treatment of type 2 diabetes with favorable safety profile regarding the hERG current.

Disclosure

A. Im: None. Y. Jun: None. E. Jang: None. Y. Yoo: None. W. Jeon: None. K. An: None. J. Park: None. D. Hong: None. I. Je: None. J. Kim: None. M. Chang: None. C. Hong: None. J. Shin: None. T. Sohn: None.
655-P: Multitarget Engagement Effect of a Novel Long-Acting Glucagon/GIP/GLP-1 Triple Agonist (HM15211) in Animal Model of NASH
Authors: KIM JUNG KUK , LEE JONG SUK , KWON HYUNJOO , PARK EUNJIN , LEE JONGSOO , BAE SUNGMIN , LEE SANG HYUN , CHOI IN YOUNG
Published: June 2021

NASH is a complex disease progressed by multiple mechanism. To date, no approved drug is available due to unsatisfied efficacy. Of note, recent studies demonstrate advantages of targeting multiple aspects of this disease. To aid multi-targeting and provide a novel treatment option with improved efficacy, HM15211, a long-acting Glucagon/GIP/GLP-1 triple agonist, has been developed. Previously, enhanced anti-steatosis effect of HM15211 and underlying mechanism were evidenced in DIO mice. Here, potential benefits of HM15211 was investigated by comparing its therapeutic effects with NASH drug candidates in high-fat diet induced mouse model of NASH. AMLN-diet induced NASH mice were administered either with HM15211 or obeticholic acid (OCA) for 12 weeks, followed by histological analysis. HM15211 treatment more efficiently normalized hepatic lipid contents (-48.9%, -93.0% vs. vehicle for OCA, HM15211) and steatosis score (2.9, 2.1, 0.1 for vehicle, OCA, HM15211) compared to OCA treatment. Consistently, HM15211 treatment significantly reduced histological score for lobular inflammation (1.6, 1.1, 0.9 for vehicle, OCA, HM15211) and ballooning (1.4, 0.7, 0.0 for vehicle, OCA, HM15211) along with blood ALT (546, 349, 138 U/L for vehicle, OCA, HM15211) even greater than OCA treatment. Notably, while all individuals (7/7) treated with HM15211 achieved NASH resolution criteria, only 14.3% (1/7) achieved it after OCA treatment. Additional study was performed to compare therapeutic effect of HM15211 with incretin analogs, and greater reduction in all sub-components of NAS was consistently observed when compared to acylated GLP-1 or GLP-1/GIP in AMLN mice, highlighting potential benefits of multi-target engagement of HM15211 over other incretin analog and FXR agonist for NASH treatment. Therefore, HM15211 may be a novel therapeutic option for NASH. Efficacy study in biopsy proven NASH patients is ongoing to assess the clinical relevance of these finding.

Disclosure

J. Kim: Employee; Self; Hanmi Pharmaceutical. J. Lee: Employee; Self; Hanmi Pharmaceutical. H. Kwon: Employee; Self; Hanmi Pharmaceutical. E. Park: Employee; Self; Hanmi Pharmaceutical. J. Lee: Employee; Self; Hanmi Pharmaceutical. S. Bae: Employee; Self; Hanmi Pharmaceutical. S. Lee: Employee; Self; Hanmi Pharmaceutical. I. Choi: Employee; Self; Hanmi Pharmaceutical.
656-P: Antifibrotic Potential of a Novel Long-Acting Glucagon/GIP/GLP-1 Triple Agonist (HM15211) in Preclinical Models of Fibrosis
Authors: KIM JUNG KUK , LEE JONG SUK , LEE SEON MYEONG , KWON HYUNJOO , CHOI JAEHYUK , PARK EUNJIN , BAE SUNGMIN , KIM DAEJIN , KIM YOUNG HOON , CHOI IN YOUNG
Published: June 2021

Fibrosis due to nonalcoholic steatohepatitis (NASH) remains a major cause of liver-related mortality. Since complex biological pathways are involved in fibrosis progression, multi-disciplinary therapeutic approaches should be required to effectively deliver treatment effects on fibrosis. For this purpose, we developed a novel long-acting Glucagon/GIP/GLP-1 triple agonist, HM15211. Here, we evaluated the anti-fibrotic effect of HM15211 in various animal models of fibrosis, and investigated underlying mechanism in vitro. Mice fed with AMLN diet were concomitantly treated with thioacetamide (AMLN/TAA mice) for 16 weeks, and HM15211 was administered during last 8 weeks. HM15211 treatment significantly reduced hepatic (-53.9, -41.4 and -51.9 % vs. vehicle for α-SMA, TIMP-1 and collagen1a1 expression) and blood (-49.3, -48.0 and -49.1% vs. vehicle for TIMP-1, PIIINP and hyaluronic acid level) surrogate markers for fibrosis. HM15211 treatment was also associated with significant reduction in hepatic hydroxyproline (-53.1% vs. Veh) and sirius red positive area (-70.6% vs. Veh) in AMLN/TAA mice. Next, anti-fibrotic effect of HM15211 was further evaluated in choline-deficient and high fat diet (CD-HFD) mice. Strikingly, greater reduction in hepatic hydroxyproline and collagen contents (-4.2, -10.0, -31.2% vs. vehicle for acylated GLP-1, acylated GLP-1/GIP, HM15211) was observed compared to acylated GLP-1 or acylated GLP-1/GIP in CD-HFD mice. Additional in vitro studies in LX2 cell and rat primary hepatic stellate cell (HSC) unveiled that HM15211 could negatively affect multiple steps of TGF-β signaling in HSC. Based on these results, HM15211 may be a novel therapeutic option for liver fibrosis in addition to NASH itself. Hence, related mechanistic studies further highlight direct inhibitory effect of HM15211 on HSC activation. On-going human efficacy study will assess the clinical relevance of these findings.

Disclosure

J. Kim: Employee; Self; Hanmi Pharmaceutical. I. Choi: Employee; Self; Hanmi Pharmaceutical. J. Lee: Employee; Self; Hanmi Pharmaceutical. S. Lee: Employee; Self; Hanmi Pharmaceutical. H. Kwon: Employee; Self; Hanmi Pharmaceutical. J. Choi: Employee; Self; Hanmi Pharmaceutical. E. Park: Employee; Self; Hanmi Pharmaceutical. S. Bae: Employee; Self; Hanmi Pharmaceutical. D. Kim: Employee; Self; Hanmi Pharmaceutical. Y. Kim: None.
66-LB: Real-Time Continuous Glucose Monitor (RTCGM) Use Associated with Decreased Diabetes Medical Costs for Patients with Type 2 Diabetes (T2D)
Authors: NORMAN GREGORY J. , PAUDEL MISTI L. , BANCROFT TIM , LYNCH PETER M.
Published: June 2021

Background: RtCGM allows patients with type 2 diabetes to improve blood glucose control and reduce risk of serious acute and chronic complications of diabetes through continuous monitoring of real-time glucose levels, however little is known about the impact of rtCGM on diabetes-related medical costs in this population.

Methods: A retrospective analysis of administrative claims data from the Optum Research Database was conducted. The T2D cohort included those on intensive insulin therapy (IIT), and non-intensive therapies, including basal insulin only, and non-insulin medications. Patients initiated treatment with rtCGM between October 1, 2017 and February 28, 2019 (index date= earliest observed pharmacy claim). Continuous health plan enrollment of 12 months prior to, and 6 months after index date was required. Individuals with evidence of pregnancy, or type 1 diabetes were excluded. Total diabetes-related medical costs were assessed during the pre-and post-index periods and expressed as change in per-person-per-month (PPPM) costs.

Results: A total of 571 T2D patients met study inclusion criteria (average age = 51.2 (sd = 11.9) years, 46% female, 80% IIT). Average PPPM diabetes-related medical costs decreased by -$424, 95% CI -$816, -$31, p<0.035 after initiating rtCGM treatment (pre-index mean (SD) PPPM costs: $1,680 ($4,519); post-index: $1,256 ($3,679)). These reductions were driven, in part, by reductions in diabetes-related inpatient medical costs (-$358, 95% CI -$706, -10. p<.-044). Inpatient hospital stays were reduced on average -.006 PPPM and hospital days were reduced an average of -.042 PPPM.

Conclusions: These findings provide real-world evidence that rtCGM use was associated with diabetes-related medical cost reductions in patients with T2D. Increased access to rtCGM for patients with T2D may help to reduce diabetes-related cost of care.

Disclosure

G. J. Norman: Employee; Self; Dexcom, Inc. M. L. Paudel: None. T. Bancroft: None. P. M. Lynch: Employee; Self; Dexcom, Inc.
676-P: Semaglutide Achieves Better Metabolic and Weight Control than Other GLP-1 RA in Real Life after 12 Months of Follow-up
Authors: DE LUCAS MARIA DOLORES GARCIA , PÉREZ-BELMONTE LUIS MIGUEL , AVILES BEATRIZ , JIMENEZ ANA ISABEL , FERNANDEZ JOSE MARIA , RUIZ FRANCISCO RIVAS
Published: June 2021

Background and Aims: Weekly sc Semaglutide (WS) has demonstrated safety and efficacy in type 2 diabetes mellitus (T2D) in an extensive clinical development program. The main objective of the study was to assess the change in HbA1c and weight loss greater than 5% after 12 months of follow-up in real life.

Materials and Methods: Retrospective observational study. Inclusion criteria:patients ≥ 18 years of age with T2D, eGFR ≥ 15 ml/min/1.73 m2 treated with WS. Main outcome variable: change in HbA1c (%) and weight ≥ 5% (kg). Secondary outcome variables: adverse events, withdrawal. Statistics: descriptive, student’s t, McNemar, multivariate logistic regression; SPSS vs. 19.0.

Results: 247 patients, 55.4% men, age 62.8 ± 11.20 years, T2D evolution 10.4 ± 7.9 years; 14% smokers, 42.5% ex-smokers; 58% macroangiopathy, 54% microangiopathy; BMI 36.47 ± 6 Kg/m2; HbA1c 7.53 ± 1.4%; eGFR < 60 ml/min/1,73m2 46.5% and MAU > 30 mg/g 29.6%. In their baseline therapy, 55.9% used a GLP1 aR, (Liraglutide 66.7%, Dulaglutide 29.7%, ExenatideLAR 3.6%) and 44.8% insulin therapy. WS was suspended in 6.9% (44% digestive intolerance). 6.1% of patients on insulin had mild hypoglycemia. Overall, change in HbA1c -0.84 ± 1.1% (p <0.0001), change in weight -8 ± 16.6 kg (p <0.0001), weight change ≥ 5% 64.5%. The best compliance on weight change in people over 65 years of age with an OR 1.8 (95% CI: 1.02-3.17). Subpopulations analysis showed a change in HbA1c of -1.1 ± 1.2% (GLP1 aR naive) vs. -0.6 ± 1.9% (GLP1 aR prior-switch) (p 0.0001); weight change ≥ 5% -9.3 ± 6.4 Kg (GLP1aR naive) vs. -6.5 ± 6.7 Kg (GLP1 aR prior - switch) (p 0.0001). Significantly improved TAS (-7.5 ± 12.7 mmHg, p <0.0005), TAD (5.5 ± 9.4 p <0.0005), LDL -13.7 ± 30.11 mg/dl, p <0.0005, MALB 83.2 ± 432.4 mg/g, p <0.001.

Conclusions: In real clinical practice, WS leads to an improvement in metabolic control and weight, both in patients T2D naïve to GLP1 aR (greater benefit), and in T2D patients previously treated with a different GLP1 aR, after one year.

Disclosure

M. Garcia de lucas: Advisory Panel; Spouse/Partner; Boehringer Ingelheim International GmbH, Novo Nordisk Inc., Speaker’s Bureau; Spouse/Partner; AstraZeneca, Lilly Diabetes, Sanofi. L. Pérez-belmonte: None. B. Aviles: None. A. Jimenez: None. J. Fernandez: None. F. Rivas ruiz: None.
684-P: Trends in Type 2 Diabetes Pharmacotherapy and Evolving Use of the Newer Agents
Authors: BAE JAY P. , LIU DONGJU , CHINTHAMMIT CHANADDA , KADZIOLA ZBIGNIEW A. , BOYE KRISTINA , MATHER KIEREN J.
Published: June 2021

Background: Newer treatment options for type 2 diabetes (T2D) and emerging evidence of treatment-specific benefits for ASCVD, CKD, heart failure (HF), hypoglycemia, and obesity provide opportunities for individualizing treatment choices. We used claims data to examine how T2D treatment patterns have changed in recent years as clinical trial data and updated guidelines have emerged.

Method: A retrospective observational study of T2D patients in a health insurance claims database (IBM® MarketScan® 2007 to 2019 Commercial and Medicare Databases). Medication use by class was examined from Jan 2015 through Dec 2019. Data since 2007 were used to establish disease history and categorize individuals according to the ADA/EASD Consensus Statement (2019): ASCVD, CKD, HF, hypoglycemia, and obesity defined risk groups. Alignment of risk group with treatment recommendation was evaluated by comparing use rates in the groups with and without risk. A GEE model was fit with guideline alignment as the dependent variable. The slope parameter and the area under the curve were calculated on the probability scale.

Results: Use of guideline-recommended therapies in the risk groups increased in both cohorts from 2015 to 2019. The Commercial cohort showed better alignment vs. the Medicare cohort over all years. Guideline-recommended therapy use in 2019 was highest in the Commercial CKD and obesity groups (39.2%; 37.6 %) with 5 year growth rates of 74.5% and 54.9%; and lowest in Medicare HF and CKD groups (16.6%; 18.5% ), but showing rapid 5 year growth (145.5% and 132.2% respectively). Use of SU in the hypoglycemia risk group decreased over time, but at comparable rates to those without the risk. The HF risk group was less likely to receive guideline recommended therapies vs. no HF risk.

Conclusion: The data suggest there is considerable room for improvement in individualizing therapies according to ADA risk grouping. Improving alignment through more targeted prescribing could further enhance outcomes without increasing overall use.

Disclosure

J. P. Bae: Employee; Self; Eli Lilly and Company. D. Liu: Employee; Self; Eli Lilly and Company. C. Chinthammit: Employee; Self; Eli Lilly and Company. Z. A. Kadziola: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. K. Boye: Employee; Self; Eli Lilly and Company, Employee; Spouse/Partner; Eli Lilly and Company. K. J. Mather: Employee; Self; Eli Lilly and Company.
692-P: Preclinical Study of a Combined Insulin Infusion and Glucose Sensing Device (Duo)
Authors: ZHANG GINA , ANSELMO EVAN , TO LYNETTE , CHATTARAJ SARNATH
Published: June 2021

Objective: A combination insulin infusion and glucose-sensing device will dramatically improve the ease of use for automated insulin delivery systems. The objective of this preclinical study was to collect safety and efficacy data during 7-day wear of a combined insulin-delivery and glucose-sensing device called the “Duo” set.

Method: In a type 1 diabetes (T1D) porcine model, each animal (N=6) wore the Duo set multiple times (on the abdomen) while receiving Novolog® insulin subcutaneously via a pump for one week or until set failure, determined by (1). blood glucose (BG) value not decreasing by at least 50 mg/dL an hour after a correction bolus for a BG level >350 mg/dL, or (2). evidence of infection at the infusion site. Blood glucose was measured five times/day with a BG meter, and pigs also wore a Guardian™ Sensor (3) glucose sensor (GS3) distant from the Duo-set site. Additionally, physical examination and serum panel tests were conducted for safety evaluation.

Result: There were 15 wears, with 10 wears lasting more than 7 days. Survival rate (67%) was similar to that of the Medtronic 7-day Extended Wear Infusion Set (EWIS) previously tested in the same porcine model (64%). There was no significant difference in total daily insulin dose (TDD) between the Duo set and the EWIS during the entire 7-day wear. There was no significant difference in glucose values between the Duo-set sensor and the GS3 (p>0.10), which agreed with the measured BG values in the range of 70-300 mg/dL (p>0.10). There was no significant device safety concern identified.

Conclusion: The results indicated that no interference of sensor signals was observed from insulin infused though the cannula of the same Duo set in the near proximity or from mechanical inference from the infusion-set movements. These data confirm the feasibility of a combined 7-day set which simultaneously infuses insulin and senses glucose subcutaneously in a T1D porcine model.

Disclosure

G. Zhang: Employee; Self; Medtronic. E. Anselmo: Employee; Self; Medtronic. L. To: None. S. Chattaraj: Employee; Self; Medtronic.
696-P: Insulin Pump Infusion Set Failure (IPISF) Management: T1D Exchange Survey
Authors: WILCOX JOHN H. , GRAY JOHN C. , COOPER NICHOLAS R. , BLANCO LUIS E. , KELLEHER RYAN , VANENGELEN LISANNE M. , LAL RAYHAN
Published: June 2021

Aim: To identify IPISF occurrence and troubleshooting methods, determine habits and perceptions of diabetes technology use, and assess the history and satisfaction of education in those who utilize CSII.

Methods: A 57-item online survey was constructed and included demographic questions, assessment with Likert scales, and open-ended questions regarding infusion sets. Participants were recruited via the T1D Exchange online community database. Statistical analysis was performed using R and JMP.

Results: A total of 715 individuals were surveyed including 639 people with diabetes (PwD) and 76 caretakers among 49 states and territories from 09/2020 - 11/2020. Demographics: PwD age 51.6±15.1 years, caretaker age 46.1±7.6 years (dependent PwD age 15.2±11.2 year), 99.6% type 1 diabetes, 69% female, 92% white, CSII use for 14.1±8.5 years, 44% use AID, HbA1c 6.8±0.97%, TIR 72.3±16.1%, TIR<70% 32%. Infusion set wear time was 3.3±0.95 days and 27% wore infusion sets for >3 days. 97% of participants experience IPISF with 41% reporting ≥1 IPISF/month. Following IPISF, participants administered correction boluses using their pump with (41%) and without (44%) changing their failed infusion set. 61% of subjects had not received IPISF education in over a year and 19% had never received IPISF education. For users who experience ≥1 IPISF/month, hyperglycemia and related symptoms were more likely to alert users of IPISF than pump alarms (n=259, p=0.0355). Respondents with ≥1 IPISF/month were also more likely to both feel burned out by their diabetes technology (p<0.001) and want to end CSII for another diabetes therapy option (p<0.001). Not experiencing ≥1 IPISF/month was a significant indicator of reporting good diabetes control (p=0.0134).

Conclusion: Developing technologies that reduce and mitigate IPISF should be a critical focus, especially as extended wear infusion sets become available.

Disclosure

J. H. Wilcox: Employee; Self; Diatech Diabetes, Inc. J. C. Gray: Employee; Self; Diatech Diabetes, Inc. N. R. Cooper: Employee; Self; Diatech Diabetes, Inc. L. E. Blanco: Employee; Self; Diatech Diabetes, Inc. R. Kelleher: Employee; Self; Diatech Diabetes, Inc. L. M. Vanengelen: Employee; Self; Diatech Diabetes, Inc. R. Lal: Consultant; Self; Abbott Diabetes, Biolinq, Capillary Biomedical, Inc., Morgan Stanley, Tidepool.
7-OR: Racial/Ethnic Differences in Barriers to Type 1 Diabetes (T1D) Self-Management between Non-Hispanic Black and Hispanic Young Adults (YA)
Authors: FINNAN MOLLY , CRESPO-RAMOS GLADYS , AGARWAL SHIVANI
Published: June 2021

Background: YA with T1D of non-Hispanic Black and Hispanic race-ethnicity face unique challenges to diabetes self-management, yet little research acknowledges potentially distinct lived experiences and needs between these racial/ethnic groups.

Methods: We recruited Black and Hispanic YA with T1D from adult and pediatric diabetes centers at Montefiore Medical Center in the Bronx, NY to conduct individual semi-structured interviews focusing on barriers and facilitators to diabetes self-management. Interviews were performed telephonically or in person, and recorded and transcribed. A modified inductive coding approach was used to analyze the data for common themes until thematic saturation was achieved.

Results: We interviewed 39 YA with T1D (18-25 yrs, 26% Black, 74% Hispanic, mean HbA1c 10.3%). Common T1D self-management barriers between Black and Hispanic YA centered on normative development, including competing priorities and peer acceptance of T1D. Differences in self-management barriers were related to culture and lived experience. Black YA reported major challenges related to social determinants of health, such as food insecurity, insurance lapses, and racial bias in the healthcare system. Meanwhile, Hispanic YA reported challenges related to culture and family, such as difficulty incorporating ethnic food into diabetes dietary guidelines and navigating household intergenerational conflict on management of T1D.

Conclusions: Black and Hispanic YA with T1D share common challenges to T1D self-management related to stage of development, but key differences exist between these racial/ethnic groups that should inform future interventions. For Black YA with T1D, addressing social determinants of health is an urgent initial need to help support diabetes self-management while for Hispanic YA, family and food-related conflict management is a priority.

Disclosure

M. Finnan: None. G. Crespo-ramos: None. S. Agarwal: None.

Funding

National Institutes of Health (K23DK115896)
720-P: Using IV Insulin (IVI) Data to Accurately Calculate Prandial Insulin (PI) Requirement
Authors: CHAO JING H. , HIRSCH IRL B.
Published: June 2021

The formula for calculating basal insulin (BI) dose using IVI data is well established. Patients eating on IVI is becoming increasingly common. Guidelines supporting the addition of 2-4U of SQ PI to IVI to curb postprandial hyperglycemia (PPH) are based on minimal evidence. We present a novel formula (NF) to calculate the PI requirement on IVI, supported by data from 30 patients.

We conducted a prospective observational study of 30 patients admitted to the ICU and floors of a tertiary care center, eating on IVI with hourly BG checks, and requiring transition to SQ insulin (SQI) between 1/23/19-1/6/21. PI dose = [difference in 1st hour (hr)] + (1/2 the difference for hrs 2-3) between the increased IVI and BI rates. For example, if BI rate is 2U/hr and drip rate increases to 4, 6, 4 U/hr in 1-3 hrs after intake, the PI dose is 2 + 4/2 + 2/2 = 5U. Glycemic outcomes analyzed: change in BG 0-3 hrs post-meal off IVI, median ± SD BG off IVI, and mean PI dose added to IVI. We compared 0-3 hr post-meal median BG and IVI rates before (control) and after (study group) the addition of PI to IVI.

Four, 21, and 5 patients have no DM, T2D, and T1D, respectively. Steroid was used in 28 patients. Renal transplant (37%), hematologic malignancies (23%), CABG/heart/lung transplant (13%), liver transplant (10%), and others were included. Median ± SD BG after transition to SQI was 177.5 ± 25.4 mg/dL. Defined as having a CV of BG off IVI <31%, 29 patients had a well-matched PI dose. Mean change in BG 0-3 hrs post-meal following the transition was 36.8 mg/dL. Adding PI to IVI resulted in a median ± SD change in BG and IVI rate of -46 ± -17.2 mg/dL and -5.5 ± -1.7 U/hr, respectively. Mean PI dose added to IVI was 12.4U (range 2-42U) for all patients and 10.5U (3-42U) for those with T2D. No hypoglycemia occurred.

We demonstrate that the NF is safe and effective in predicting the PI dose to result in 100% success in IVI to SQI transition in the most complex patients, and the mean PI dose is 3 folds higher than traditionally proposed. Adding PI to IVI effectively curbs the PPH and IVI rates.

Disclosure

J. H. Chao: None. I. B. Hirsch: Consultant; Self; Abbott Diabetes, Bigfoot Biomedical, Inc., Research Support; Self; Insulet Corporation, Leona M. and Harry B. Helmsley Charitable Trust, Medtronic.
735-P: Effects of Insulin Degludec in Patients with Diabetes Using Continuous Glucose Monitoring: A Scoping Review
Authors: WANG CHAOFAN , XU WEN , YANG XUBIN , YAN JINHUA , YANG DAIZHI , YAO BIN , WENG JIANPING
Published: June 2021

Background: The ultra-long-acting insulin degludec (Deg) was reported to have more stable glucose lowering effect with lower risk of hypoglycemia. This review aimed to summarize data on efficacy and safety of Deg in patients with T1DM or T2DM using continuous glucose monitoring (CGM).

Methods: A systematic literature search of studies on Deg in PubMed, EMBASE and Web of Science was performed for articles published before January 2021. Studies reporting data on the efficacy and safety of Deg in patients with diabetes using CGM were included.

Results: Thirteen studies with CGM data in 262 patients with T1DM or T2DM were included. The studies were conducted in Japan (11 studies) and Italy (2 studies). Eleven studies focused on patients with T1D (n=208) and two studies on T2D (n=54). The studies compared Deg with insulin glargine 100U/mL (n=130), insulin glargine 300U/mL (n=100), or insulin detemir (n=32). Regarding the study design, six studies were cross-over and seven studies were switching from other basal insulin to Deg. The sample sizes ranged from 7 to 46. The duration of Deg treatment varied between 3 days to 24 weeks. Three studies reported significant improvement of within-day or between-day glycemic variability by Deg, while the other ten studies revealed no difference in glycemic variability. The glucose lowering effect of Deg was comparable to other basal insulin in eleven studies, while two studies found that Deg could further improve glycemic control. Total daily insulin dose reduced in seven studies switching to Deg, while the insulin dose remained unchanged in six studies. In two studies, Deg reduced hypoglycemia when compared with glargine 100U/mL or detemir, which was not observed in other eight studies. However, three studies showed higher percentage time of hypoglycemia with Deg than glargine 300U/mL.

Conclusion: Deg leads to similarly effective, stable and safe glycemic control with comparable insulin dose requirement to other basal insulin on the current evidence.

Disclosure

C. Wang: None. W. Xu: None. X. Yang: None. J. Yan: None. D. Yang: None. B. Yao: None. J. Weng: None.

Funding

Johnson & Johnson Medical Devices Companies; Novo Nordisk (to J.W.)
754-P: SerpinB1 Delays T1D Progression and Improves Glucose Homeostasis in NOD Mice
Authors: BASILE GIORGIO , KIM HYUNKI , XIAO LING , HU JIANG , WANG HUAFANG , PEMBERTON PHILIP , KULKARNI ROHIT
Published: June 2021

T1D occurs when the functional β-cell mass is reduced by an autoimmune cell-mediated attack. As recently reported, inducing β-cell proliferation during early life results in an almost complete resolution of T1D in rodents. SerpinB1 (sB1), a protease inhibitor, has been shown to promote β-cell proliferation by inhibiting pancreatic elastase, and to regulate specific pro-inflammatory cells, e.g., Th17 cells via blockade of cathepsin proteases. Previous studies have demonstrated beneficial effects of alpha-1-antitrypsin (AAT), another elastase inhibitor similar to sB1, in the progression of T1D in rodents and humans. Here, we tested the effects of sB1 in 1) delaying T1D onset, and 2) improving glucose homeostasis in female NOD mice, by inducing β-cell growth and suppressing autoimmunity. To examine the role of sB1 in T1D development (Study 1) we injected 4-week-old NOD mice daily with vehicle or recombinant mouse serpinb1a (rmsb1a) at different doses, intradermally for 28 weeks. Strikingly, the percentage of diabetes-free animals was higher in the rmsb1a groups compared to the non-injected group. Interestingly, islet infiltration scores were lower in rmsb1a mice compared to the vehicle-injected animals. In addition, β-cell proliferation levels were significantly higher in rmsb1a-treated mice compared to the vehicle group (~3-fold, P<0.05). Finally, rmsb1a treated mice displayed a higher proportion of CD4+FoxP3+ cells and a lower count of Th17 cells compared to the vehicle group. In Study 2, diabetic NOD female mice were injected daily with either vehicle, rmsb1a or rmsb1a+AAT, intradermally for 10 weeks. We observed that glycemic levels were lower in rmsb1a and rmsb1a+AAT treated animals compared to vehicle and CTRL mice. Taken together, the beneficial effects of rmsb1a in delaying the onset and preventing progression of T1D by expanding β-cell numbers and increasing immune cell tolerance, point to the protease inhibitor as a potential therapeutic to limit hyperglycemia in T1D patients.

Disclosure

G. Basile: None. H. Kim: None. L. Xiao: None. J. Hu: None. H. Wang: None. P. Pemberton: Employee; Self; Serplus Technology LLC, Stock/Shareholder; Self; Redd Pharmaceuticals. R. Kulkarni: None.

Funding

National Institutes of Health (R41DK115326, R01DK103215)
755-P: A 26-Week Carcinogenicity Study with the Novel Glucagon Analog Dasiglucagon in CByB6F1-Tg(HRAS)2Jic Mice
Authors: ELANDER MIKAEL , FROUD ADAM
Published: June 2021

Carcinogenicity testing is a regulatory requirement for new pharmaceuticals indicated for chronic diseases. Historically, carcinogenicity testing has been done in 2-year “lifelong” studies in rats and mice. The challenges with these studies in terms of a high false-positive rate and a high background tumor incidence in control animals have led to the development of an alternative transgenic mouse model. The rasH2 mouse is a hemizygous transgenic mouse carrying the human c-Ha-ras gene with its own promoter/enhancer elements, which induces high enhancer activity. The advantages offered by rasH2 mice are the low rate of spontaneous background findings and a lower false-positive rate with a comparable ability to predict known human carcinogens as the 2-year bioassays. We undertook the current carcinogenicity study to assess the novel glucagon analog, dasiglucagon, in the rasH2 mouse model. Four groups of 25 male and female CByB6F1-g(HRAS)2Jic mice received once-daily subcutaneous administration of the vehicle (25 mM sodium phosphate buffer, 17 mg/mL propylene glycol, pH 6.5) or dasiglucagon at 1, 5, and 20 mg/kg. The high dose was selected to result in exposure at least 25 times higher than the relevant clinical exposure. A positive control group received a single intraperitoneal injection of N-methyl-N-nitrosourea. Dasiglucagon at doses up to 20 mg/kg/day to transgenic CByB6F1-Tg(HRAS)2Jic mice for 26 weeks did not result in any neoplastic changes to demonstrate that dasiglucagon was not carcinogenic in the transgenic CByB6F1-Tg(HRAS)2Jic mouse model. Neoplastic findings in stomach of positive control animals demonstrated the functionality of the transgene and the suitability of the batch of transgenic animals. The data provide additional confidence that dasiglucagon has an acceptable profile for use in the treatment of humans.

Disclosure

M. Elander: None. A. Froud: None.
760-P: Allogeneic "Neo-Islets," Organoids Composed of Cultured Pancreatic Islet and Mesenchymal Stromal Cells from Diverse Donors, Afford a Marked Increase in the Global Availability of a Curative, Novel, Anti-Rejection-Drug-Independent Biotherapy of T1DM
Authors: WESTENFELDER CHRISTOF , CHOWDHURY SABIHA S. , GOOCH ANNA
Published: June 2021

The scarcity of suitable pancreas/islet donors, the life-long need for potentially toxic anti-rejection drugs for transplants and certain biotherapies, and failure of some immune-isolating encapsulation devices collectively warrant the urgent development of novel therapies for T1DM that significantly expand the donor pool without reliance on anti-rejection drugs. Allogeneic, i.p.-administered “Neo-Islets” (NIs) are potentially such a therapy. We previously reported that the use of NIs reestablished permanent normoglycemia in autoimmune diabetic NOD mice without immunosuppression. Our FDA-guided pilot study (INAD 012-0776) in insulin dependent, spontaneously diabetic pet dogs showed similar, durable responses, also without immunosuppression. Scoring systems have improved allotransplantation outcomes while their use may actually waste potentially valuable cells for novel diabetes therapies such as NIs.

In preparation for a Phase 1 clinical trial with NIs, we examined whether human “non-clinical grade” islets from diverse, nondiabetic human and canine donors (n=6-8 each) could be processed to generate fully functioning NIs. Islet gene expression profiles (insulin, others) in both species closely correlate with population doublings and GSIS responses. Human-NIs establish normoglycemia in STZ diabetic NOD/SCID mice. Based on these results, an estimated 600 therapeutic doses can be generated from a single islet donor.

Conclusion: human-NIs created from diverse, “non-clinical grade” donors have the potential to greatly expand patient access to this curative therapy, facilitated by biotherapy-specific adjustments in the current scoring systems.

Disclosure

C. Westenfelder: Consultant; Self; SymbioCellTech. S. S. Chowdhury: Employee; Self; SymbioCellTech. A. Gooch: Employee; Self; SymbioCellTech.