bluuebunny/crossref_metadata_2025 huggingface dataset:
1004-P: Oral Insulin (ORMD-0801) Effects on Glucose Parameters in Uncontrolled T2DM on OADs
Authors: ELDOR ROY , FLEMING G. ALEXANDER , NEUTEL JOEL , HOMER KENNETH E. , KIDRON MIRIAM , ROSENSTOCK JULIO
Published: June 2020

ORMD-0801 is a novel oral human insulin formulation which can potentially improve acceptance and adherence, as well as glycemic control by increasing hepatic insulin exposure, without increasing hypoglycemia risk. This randomized, placebo-controlled, multi-center, phase 2b 12-week study, in 273 T2DM subjects, on metformin ±1-2 oral antidiabetic drugs (OADs), including sulfonylurea, compared placebo vs. 32 mg ORMD-0801 capsules administered once daily (QD) at bedtime, or two (BID) or three (TID) times daily at bedtime, and 30-40 min before breakfast/lunch. Blinded continuous glucose monitoring (CGM) was performed during a two-week run-in period and over the last two weeks of treatment. HbA1c levels improved from baseline for all active treatment regimens (Table). Glucose AUC improved from baseline following QD and BID treatment. Hypoglycemia rates were low and relatively similar to the placebo arm, and body weight was unchanged in all treatment arms. Frequency of drug-related adverse events was similar across treatment groups.

In conclusion, ORMD-0801 elicited clinically significant HbA1c reductions among T2DM patients inadequately controlled on standard therapies, without increasing hypoglycemia rates, or inducing severe or serious adverse effects or significant weight gain.

Disclosure

R. Eldor: Advisory Panel; Self; Oramed. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Medtronic, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi. Stock/Shareholder; Self; Oramed. G. Fleming: Consultant; Self; ADOCIA, Biocon, Caladrius Biosciences, Inc., Dance Biopharm Holdings, Inc., Diasome Pharmaceuticals, Inc., Intarcia Therapeutics, MannKind Corporation, NuSirt Biopharma, Inc., Oramed Pharmaceuticals, Sanofi, Tolerion, Inc. J. Neutel: None. K.E. Homer: None. M. Kidron: Employee; Self; Oramed Pharmaceuticals. Stock/Shareholder; Self; Oramed Pharmaceuticals. J. Rosenstock: Research Support; Self; AstraZeneca, Bristol-Myers Squibb, Genentech, Inc., GlaxoSmithKline plc., Lexicon Pharmaceuticals, Inc., Oramed Pharmaceuticals, PegBio Co., Ltd., Pfizer Inc., REMD Biotherapeutics. Other Relationship; Self; Applied Therapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi.
1005-P: Comparison of Hypoglycemia Safety between U-100 Human Regular Insulin and Rapid-Acting Insulin Delivered By V-Go Wearable Insulin Delivery in Type 2 Diabetes
Authors: MORA PABLO F. , SUTTON DAVID R. , GORE ASHWINI , BALIGA BANTWAL , GOLDFADEN REBECCA F. , NIKKEL CARLA C. , SINK JOHN H. , ADAMS-HUET BEVERLEY A.
Published: June 2020

Hypoglycemia was evaluated in a 14-week multi-center randomized, parallel, non-inferiority study comparing the efficacy and safety of Rapid Acting Insulin (RAI) versus Human Regular Insulin (HRI) when delivered by V-Go. Glucose lowering agents were to remain stable unless hypoglycemia warranted removal and down-titration of insulin was recommended if glucose levels were consistently lower than target range. Patients were instructed to self-monitor blood glucose (SMBG) daily and perform 7-point SMBG profiles within 3 days of each study visit. Hypoglycemia was defined as: Level 1: ≤70 mg/dl; Level 2: ≤54 mg/dl; and Level 3: severe cognitive impairment requiring external assistance for recovery. The intent to treat population (ITT) consisted of 136 patients randomized to continue treatment with RAI (n=67) or switch to HRI (n=69). Percentages of hypoglycaemia events were similar between groups when comparing pre to post-randomization and the between group difference was not significant. Post-randomization hypoglycemic event rate/person week decreased in both groups compared to pre-randomization. No level 3 events were reported in either group. The incident rate ratio (IRR) was not significant at any level. This study demonstrates the risk of hypoglycemia is not increased when using HRI compared to RAI in V-Go in a T2D population.

Disclosure

P.F. Mora: Speaker’s Bureau; Self; Dexcom, Inc., Insulet Corporation, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc., Sanofi US, Valeritas, Inc. D.R. Sutton: Employee; Spouse/Partner; Valeritas, Inc. Speaker’s Bureau; Self; Amarin Corporation, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk A/S, Valeritas, Inc. A. Gore: Advisory Panel; Spouse/Partner; Janssen Pharmaceuticals, Inc. Consultant; Spouse/Partner; Janssen Pharmaceuticals, Inc. Consultant; Self; Novo Nordisk Inc. Speaker’s Bureau; Spouse/Partner; Janssen Pharmaceuticals, Inc. Speaker’s Bureau; Self; Janssen Pharmaceuticals, Inc., Merck & Co., Inc. B. Baliga: Speaker’s Bureau; Self; Amarin Corporation, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk Inc., Senseonics, Valeritas, Inc. R.F. Goldfaden: None. C.C. Nikkel: Employee; Self; Valeritas, Inc. Stock/Shareholder; Self; Valeritas, Inc. J.H. Sink: Employee; Self; Valeritas, Inc. B.A. Adams-Huet: Consultant; Self; Valeritas, Inc.

Funding

Valeritas, Inc.
1009-P: Glucose Outcomes in Adult Patients with Type 1 Diabetes on a Hybrid Closed-Loop System: A Single Center Study
Authors: KIM STEPHANIE , BEDRICH MARLENE , KOBASIC KRYSTAL , CROSS HAZEL , FISHER LAWRENCE , MASHARANI UMESH
Published: June 2020

Objectives: Medtronic’s 670G insulin pump was the first to incorporate automatic basal insulin delivery based on input from CGM data, a setting called Smart Guard Automode. We assessed glycemic control (A1c) in 52 patients with T1DM who used the Medtronic 670G hybrid closed loop system and started Automode from 2017 to 2019. Our goal was to determine the effects of Automode use on A1c over time. The average age was 46.4 ± 12.3 years, 53.4% male and 78.8% Caucasian. The average age at diagnosis was 19.1 ± 13.5 years and duration was 27.3 ± 14.6 years. Diabetic complications were present in 55.8% patients.

Methods: Patients were divided into two groups depending on whether their A1c was above or below the mean baseline A1c for the cohort; 26 patients had A1c ≤7.6% (mean 6.9 ± 0.4, range 6.2 to 7.6, Group 1) and 26 had A1c >7.6 (mean 8.3 ± 0.5, range 7.7-9.3, Group 2). Follow-up A1c was assessed a mean of 17.1 ± 7.3 months after beginning Automode.

Results: 1. The average A1c of the 52 patients prior to initiating Automode was 7.6 ± 0.8 (range 6.2-9.3). Follow-up A1c for the cohort was 7.5 ± 0.67 (range 6.3-9). 2. At follow-up, Group 1’s mean A1c remained about the same at 7.1 ± 0.5 (range 6.3-8.4) whereas Group 2’s mean A1c was reduced to 7.8 ± 0.6 (range 6.9-9). Females displayed greater A1c improvement (-0.2 ± 0.6, range -1.2-9) than males (-0.1 ± 0.6, range -1.4-0.7) and those with complications showed greater A1c improvement (-0.2 ± 0.5, range -1.2-0.7) than those without (-0.1 ± 0.6, range -1.4-0.9). Additionally, the 27 patients with duration of diabetes ≥25 years showed greater improvement in A1c (-0.2 ± 0.5, range -1.2-0.7) than those with duration <25 years (-0.06 ± 0.6, range -1.4-0.9).

Conclusion: Patients with worse baseline glucose control (mean 8.3 ± 0.5) had improved A1c using the hybrid closed loop system compared to patients with higher A1c (mean 6.9 ± 0.4). We also observed a nonsignificant trend towards improvements in females, patients with complications and longer duration of diabetes.

Disclosure

S. Kim: None. M. Bedrich: None. K. Kobasic: Stock/Shareholder; Self; Abbott Laboratories, AbbVie Inc., General Electric, Medtronic. H. Cross: None. L. Fisher: None. U. Masharani: None.
1010-P: Personalized Automated Determination of Insulin Pump Settings for People with Type 1 Diabetes Switching from MDI to Pump Therapy and Vice Versa
Authors: NIMRI REVITAL , MULLER IDO , ATLAS ERAN , PHILLIP MOSHE
Published: June 2020

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 < 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 < 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 < 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)
1014-P: Unannounced Meals at Home with the Medtronic Advanced Hybrid Closed-Loop
Authors: TIROSH AMIR , SHALIT ROY , HIRSH MAYA LARON , COHEN OHAD , KURTZ NATALIE , ROY ANIRBAN , GROSMAN BENYAMIN
Published: June 2020

Background and Aims: Advanced Hybrid closed loop (AHCL) algorithm combines automated basal rate with additional enhancement when a rise in glucose level is detected. This study assessed the effectiveness and safety of AHCL with unannounced meals.

Methods: Fourteen participants were using Medtronic AHCL system at home for a mean of 72.6 days. Each participant spent 4 days in a protected free-living environment while consuming pre-defined meals consisting of up to 80 grams of carbohydrates each day. On day 5, participants initiated a 3-months unannounced meal phase at their homes with the instruction to announce only meals containing over 80 grams.

Results: Fourteen subjects with T1DM (10 males, mean age 44.3±3.9 years) and baseline HgbA1C% of 6.75± 1.2 were enrolled. Patients spent 97±3% of time in Auto-Mode, with mean SG of 157.8±19.2. Mean %time in range70-180was 67.6±12.8, %time <70 mg/dL of 2±1.7%, and % time <54 mg/dL of 0.4±0.5%. Table 1 summarizes the glycemic indices.

Conclusion: Medtronic AHCL system is designed for best performance with meal announcement. Nevertheless, when meals containing ≤ 80 gram of carbohydrates are consumed without meal announcement, the system can provide safe glycemic control with about 67.6% of TIR.

Disclosure

A. Tirosh: Advisory Panel; Self; Novo Nordisk Inc., Sanofi. R. Shalit: Research Support; Self; Medtronic. M. Laron Hirsh: None. O. Cohen: Employee; Self; Medtronic. N. Kurtz: Employee; Self; Medtronic. A. Roy: Employee; Self; Medtronic. B. Grosman: Employee; Self; Medtronic.

Funding

Medtronic
1016-P: Treatment Preferences and Quality of Life in Brazilian T1DM
Authors: COELHO RAQUEL C.L. , PAGANO ADRIANA S. , SOARES ALEIDA N. , REIS JANICE S.
Published: June 2020

We carried out an observational study to analyze if the quality of life of T1DM patients is affected by different insulin treatment systems. The study involved 113 T1DM patients from a public diabetes center, mean age 32.61(±12.59) years, 46% male treated with MDI or CSII. The Insulin System Rating Questionnaire (IDSRQ) was validated in Brazilian Portuguese (Table 1) and was self-completed by the subjects during a routine visit. Multiple comparison analysis (Table 2) showed that CSII had a significant effect versus syringe and versus pen for treatment satisfaction and clinical efficacy domains. CSII was associated with a higher treatment satisfaction and patient’s perception of better clinical efficacy than MDI.

Disclosure

R.C.L. Coelho: None. A.S. Pagano: None. A.N. Soares: None. J.S. Reis: None.
1018-P: Ultra-Rapid Lispro (URLi) Showed Greater Reduction in Postprandial Glucose (PPG) vs. Humalog in Children, Adolescents, and Adult Patients with Type 1 Diabetes (T1D)
Authors: ARONSON RONNIE , LINNEBJERG HELLE , LEOHR JENNIFER , LABELL ELIZABETH S. , COUTANT DAVID E. , ZHANG QIANYI , DANNE THOMAS , POLLOM ROBYN K.
Published: June 2020

URLi is a novel insulin lispro formulation that was developed to more closely match physiological insulin secretion. This 2-site, randomized, 2-period crossover, double-blind study evaluated the pharmacokinetics and glucodynamics during a liquid test meal, after a single 0.2 U/kg SC dose of URLi or Humalog in 13 children, 14 adolescents, 15 adults with T1D. Onset of insulin appearance was faster with URLi vs. Humalog in children (1.1 vs. 6.5 min; p=0.0002), adolescents (1.9 vs. 6.4 min; p=0.001), and adults (0.9 vs. 4.8 min; p=0.004). Early exposure (AUC0-15min) was greater with URLi vs. Humalog: 7-fold (p<0.0001) in children, 4 fold (p=0.0003) in adolescents, 5-fold (p<0.0001) in adults; late exposure (AUC3-7h) was reduced by 58% (p<0.0001) in children, 40% (p=0.013) in adolescents, 37% (p=0.021) in adults. Total exposure was similar in URLi and Humalog. At 1h, URLi reduced PPG by 42 mg/dL (p=0.008) in children, 19 mg/dL (p=0.195) in adolescents, 34 mg/dL (p=0.018) in adults, vs. Humalog. At 2h, URLi reduced the PPG by 32 mg/dL (p=0.11) in children, 39 mg/dL (p=0.051) in adolescents and was not statistically different in adults, vs. Humalog. URLi was well tolerated in all age groups.

In summary, URLi accelerated insulin lispro absorption, reduced late exposure and early PPG following a test meal vs. Humalog in children, adolescents, and adults with T1D.

Disclosure

R. Aronson: None. H. Linnebjerg: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. J. Leohr: None. E.S. LaBell: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company, Johnson & Johnson, Novartis AG. D.E. Coutant: Employee; Self; Eli Lilly and Company. Employee; Spouse/Partner; Eli Lilly and Company. Q. Zhang: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. T. Danne: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Novo Nordisk A/S, Sanofi. R.K. Pollom: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company.

Funding

Eli Lilly and Company
1019-P: Variability of 501 Inhaled Insulin Absorption and Action
Authors: ZIJLSTRA ERIC , ANDERSEN GRIT , PLUM-MOERSCHEL LEONA , RHODES MELISSA , PATTON RYAN , BUECHE BLAINE , KUO MEI-CHANG , LE TRUC H. , STEDMAN BENJAMIN J. , PATTON JOHN S.
Published: June 2020

501 inhaled insulin (INH) is a novel liquid formulation of human insulin for inhalation with faster onset of action than s.c. insulin lispro (LIS). This randomized, replicated cross-over trial investigated the variability of INH vs. LIS during 10-hour glucose clamps in non-smoking subjects with T1D. Fourteen subjects (age [mean±SD] 32.5±7.9 years, BMI 26.5±2.1 kg/m2, HbA1c 7.5±0.8 %) received 2 single doses of 92.2 IU INH via the Afina inhaler (n=13 completing subjects) and 2 injections of an equivalent 12 U LIS dose (n=12). The inhalations were performed by the subjects after a brief training on the correct inhalation technique; injections were given by trained staff. Repeated dosing of INH by the same subject resulted in reproducible insulin absorption and insulin action, with lower or similar variability vs. LIS (Table 1). The response to INH between subjects was more variable than for LIS. The 13.8±8.1% mean relative biopotency of INH was consistent with previous findings. INH was well tolerated, adverse events (8 with INH, 13 with LIS) were mild to moderate in severity. No cough and no acute changes in spirometry were observed with any inhalation.

In conclusion, the intra-individual response to self-administration of 501 inhaled insulin is as reproducible as that of s.c. insulin lispro injected by experienced staff. This is a clinically meaningful outcome and enables individual dose titration of 501 insulin in future treatment.

Disclosure

E. Zijlstra: Employee; Self; Profil. Speaker’s Bureau; Self; Aerami Therapeutics, Eli Lilly and Company, Novo Nordisk A/S. G. Andersen: Employee; Self; Profil Institute for Clinical Research. L. Plum-Moerschel: Other Relationship; Self; Eli Lilly and Company, Novo Nordisk A/S. M. Rhodes: None. R. Patton: None. B. Bueche: None. M. Kuo: None. T.H. Le: None. B.J. Stedman: None. J.S. Patton: Board Member; Self; Dance Biopharm Holdings, Inc.
1024-P: Technosphere Insulin Added to Basal Insulin Is Associated with Less Weight Gain than Basal Insulin plus Insulin Aspart or Insulin Analog (Aspart) 70/30 Mixture in Type 2 DM
Authors: MANOUKIAN JONATHAN , KENDALL DAVID M. , MOREY PATRICK M. , HOOGWERF BYRON J.
Published: June 2020

Technosphere Insulin (TI) is a dry-powder formulation of recombinant human insulin adsorbed onto Technosphere microparticles for oral inhalation. Data from two 52-wk randomized phase 3 trials in type 2 DM were combined to analyze the effects of TI on body weight. In one trial, patients on basal insulin were randomized to prandial TI or insulin aspart. In the other trial, basal insulin plus prandial TI was compared to 70/30 insulin analog mixture. Primary efficacy end point in each trial was change in A1C. Weight data were captured in each study. Weight and A1C data were analyzed based on modified Intention to Treat Analyses and LS mean changes from baseline. In these analyses, the TI arms were combined and comparisons were made between TI and each of the comparator arms. Aspart and 70/30 arms were not compared to each other. Data for 26 and 52 wk time points are reported. Results At both 26 and 52 weeks, TI was associated with less weight gain than either aspart or premixed insulin. Differences were significant for TI vs. each comparator. A1C differences among treatment arms were small and only statistically significant for TI vs. aspart at 52 weeks.

Conclusion: In insulin treated T2DM persons, TI is associated with less weight gain than Insulin aspart or premixed 70/30 analog insulin. These weight differences appear to be independent of changes in A1C.

Disclosure

J. Manoukian: Employee; Self; MannKind Corporation. D.M. Kendall: Employee; Self; MannKind Corporation. Stock/Shareholder; Self; Eli Lilly and Company. P.M. Morey: Employee; Self; MannKind Corporation. B.J. Hoogwerf: Consultant; Self; MannKind Corporation. Employee; Spouse/Partner; MannKind Corporation. Stock/Shareholder; Spouse/Partner; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company.
1029-P: Effectiveness of Premix Insulin (Premix) in Type 2 Diabetes (T2D): A Retrospective UK Cohort Study
Authors: JUDE EDWARD B. , ALI AMAR , EMRAL RIFAT , NANDA NITHYA , LUBWAMA ROBERT , PALMER KAREN D. , SHAUNIK ALKA , RASKIN PHILIP , GOMEZ-PERALTA FERNANDO , TRESCOLI CARLOS
Published: June 2020

NICE guidelines suggest premix as a treatment option for people with T2D with HbA1c ≥9 % uncontrolled by ≥2 oral antidiabetic drugs (OADs). This retrospective cohort study explored real-world evidence for glycemic control with premix. UK electronic medical record data from THIN database were captured for adults with T2D uncontrolled (HbA1c ≥9 %) on ≥2 OADs initiating premix (index date) from 1/1/2010 to 12/31/2016. Baseline data were collected 12 months pre-index and outcomes followed for 24 months. Glycemic control was assessed by time to first achievement of HbA1c target <7.5 % and change in HbA1c over time, and evaluated by baseline characteristics. The final cohort had 974 participants (mean age 62 years; 56% male; mean BMI 31 kg/m2; 27% overweight; 44% obese; 8% Class III obese; mean HbA1c 11.3 %). Common comorbidities were hypertension (64%), dyslipidemia (23%) and nephropathy (21%). Background medication included metformin (99%), DPP-4i (51%), TZD (42%), SU (19%) and SGLT2i (0.5%). Probability of first achievement of HbA1c target <7.5 % was highest at 3-6 months (18%), 14% at 6-9 months, 15% at 9-12 months, and lower from 12 to 24 months (Figure). Target achievement differed by baseline HbA1c, but not OAD use. Probability of achieving glycemic targets on premix at 6 months was low, with little additional clinical benefit beyond 12 months, suggesting a high unmet need for early and timely therapy intensification.

Disclosure

E.B. Jude: Speaker’s Bureau; Self; AstraZeneca, Novo Nordisk Inc., Sanofi. Other Relationship; Self; Lilly Diabetes, Menarini Group. A. Ali: Advisory Panel; Self; Eli Lilly and Company, Napp Pharmaceuticals, Novo Nordisk A/S, Sanofi. Research Support; Self; Eli Lilly and Company, Gelesis. Speaker’s Bureau; Self; Eli Lilly and Company, Novo Nordisk A/S, Sanofi. Stock/Shareholder; Self; Amarin Corporation. R. Emral: Advisory Panel; Self; Lilly Diabetes, Merck Sharp & Dohme Corp. Speaker’s Bureau; Self; AstraZeneca, Novo Nordisk Inc., Sanofi-Aventis. N. Nanda: Advisory Panel; Self; Novartis AG. Speaker’s Bureau; Self; AstraZeneca, Novo Nordisk Inc., Pfizer Inc., Sanofi. R. Lubwama: Employee; Self; Sanofi US. K.D. Palmer: Employee; Self; Sanofi. A. Shaunik: None. P. Raskin: None. F. Gomez-Peralta: Advisory Panel; Self; Abbott, Menarini Group, Novartis AG, Sanofi. Speaker’s Bureau; Self; Abbott, Boehringer Ingelheim International GmbH, Lilly Diabetes, Novartis AG, Novo Nordisk A/S, Sanofi. C. Trescoli: None.

Funding

Sanofi
103-LB: Individual Glycemic Response to Faster Aspart Delivered by the Ilet Bionic Pancreas with Non-default vs. Default Tmax Settings
Authors: CASTELLANOS LUZ E. , ZHENG HUI , BALLIRO COURTNEY A. , SHERWOOD JORDAN , EKELUND MAGNUS , EL-KHATIB FIRAS , DAMIANO EDWARD , RUSSELL STEVEN J.
Published: June 2020

We examined automated glycemic control with the insulin-only configuration of the iLet® bionic pancreas using faster aspart (Fiasp), comparing non-default tmax settings of the iLet® to a default tmax setting in a two-period, random-order cross-over design within each of three cohorts with eight different participants. Each participant was randomized to use the default tmax setting (t65 minutes) followed by the non-default tmax setting (t50, t40, or t30 minutes in cohorts 1, 2, and 3, respectively), or vice versa, for one week each. The group mean CGM glucose (CGMG) was significantly lower (two-sided p-value <0.05) in the t50 versus t65 arm (-7.4 [-12.3; -2.4] mg/dl, p=0.011; 150.3 versus 157.7 mg/dl) and in the t40 versus t65 arm (-7.5 [-12.9; -2.1] mg/dl, p=0.015; 150.1 versus 157.6 mg/dl), but was not significantly different in the t30 versus t65 arm (-7.7 [-16.8; 1.4] mg/dl, 144.2 versus 151.9 mg/dl). Group mean time <54 mg/dl was not significantly different between non-default and default tmax settings in all three cohorts, (+0.09%, +0.18%, and +0.17% in cohorts 1, 2, and 3, respectively, all p>0.05). Using an autoregressive time series model, we determined the intra-individual statistical significance of differences in mean CGMG and time <54 mg/dl between non-default and default tmax settings. The mean CGMG was significantly different for four of eight subjects in the t50 versus t65 cohort (mean -13±7 mg/dl), seven of eight subjects in the t40 versus t65 cohort (mean -8±8 mg/dl), and five of eight subjects in the t30 versus t65 cohort (mean -12±6 mg/dl). One subject had a significant change in time <54 mg/dl (+1.2% of time; 1.2% versus 0%) in the t40 versus t65 arm. The majority of subjects had a significant reduction in mean CGMG with a non-default tmax setting while using Fiasp in the iLet. Use of different tmax settings could translate to clinically significant reductions in mean CGMG for many patients, with low risk of a significant increase in hypoglycemia.

Disclosure

L.E. Castellanos: None. H. Zheng: None. C.A. Balliro: None. J. Sherwood: None. M. Ekelund: Employee; Self; Novo Nordisk. Stock/Shareholder; Self; Novo Nordisk. Stock/Shareholder; Spouse/Partner; Novo Nordisk. F. El-Khatib: Other Relationship; Self; Beta Bionics, Inc. E. Damiano: Board Member; Self; Beta Bionics, Inc. Employee; Self; Beta Bionics, Inc. Stock/Shareholder; Self; Beta Bionics, Inc. Stock/Shareholder; Spouse/Partner; Beta Bionics, Inc. S.J. Russell: Consultant; Self; Beta Bionics, Inc., ConvaTec Inc., Novo Nordisk A/S, Senseonics. Research Support; Self; Beta Bionics, Inc., Novo Nordisk A/S, Zealand Pharma A/S. Stock/Shareholder; Self; Companion Medical. Other Relationship; Self; Ascensia Diabetes Care, Roche Diabetes Care.
1030-P: Self-Adjusting Subcutaneous Insulin Algorithm (SQIA) for Patients NPO or on TPN or Enteral Feedings
Authors: RUSHAKOFF ROBERT J. , ROV-IKPAH ESTHER , LUIS CRAIG SAN , JOHNSON CRAIG , PATZEK SOPHIE , JUTTUKONDA VENKATESWARLU , MACMASTER HEIDEMARIE W.
Published: June 2020

We programmed a SQIA in the EMR. It requires the nurse to enter current glucose in the MAR, and then the calculated dose is shown. New dose is based on previous dose, and current and previous glucoses. The SQIA titrates the glucose to 120 -180 mg/dl for patients who are NPO, on TPN or Enteral Feedings (TF). No new orders are required even if insulin is added to TPN, or changes made in TF rates. Glucose and insulin data are shown in the table. The higher glucoses were at titration initiation. Two examples of how the titration worked are shown. Individual data demonstrate ability of the SQIA to titrate insulin and maintain glucoses in range despite significant changes to the rate of TF or addition of basal insulin as shown in Patient B. An automated SQIA allows insulin doses to be adjusted to the individual patient’s needs and maintain glucoses in range.

Disclosure

R.J. Rushakoff: None. E. Rov-Ikpah: None. C. San Luis: None. C. Johnson: None. S. Patzek: None. V. Juttukonda: None. H.W. Macmaster: None.
1033-P: Trends in U.S. Insulin Use for People with Diabetes: 2009-2017
Authors: PEREZ-NIEVES MAGALY , JUNEJA RATTAN , FAN LUDI , MEADOWS ERIC , LAGE MAUREEN J. , EBY ELIZABETH L.
Published: June 2020

Objective: Examine trends of insulin regimens, delivery devices and glucose monitoring among people with type 1 diabetes (T1D) or type 2 diabetes (T2D) in the U.S. from 2009-2017.

Methods: The IBM® MarketScan® Commercial and Medicare databases were used to identify trends for insulin use over 9 years among people with T1D or T2D who filled a prescription for insulin in a calendar year. Total annual sample size ranged from 373,975 to 660,512. The analyses examined insulin regimen, method of delivery, and use of glucose monitoring systems separately for people with T1D or T2D. Generalized estimating equations were used to test whether trends were statistically significant.

Results: For people with either T1D or T2D, use of short/rapid insulin only and use of analog insulins increased while premix insulin use decreased (all P<0.0001) from 2009 to 2017. Basal insulin only use increased for people with T2D over the study period (P<0.0001). Among people with T1D, vial with pump use increased significantly; the use of disposable pens increased in both cohorts (all P<0.0001). The observed use of continuous glucose monitoring (CGM) was numerically higher for patients with T1D compared to patients with T2D, although use significantly increased (both P<0.0001) over the study period for both cohorts.

Conclusion: Results suggest that insulin prescribing continues to change with advances in insulin delivery technology and glucose monitoring systems.

Disclosure

M. Perez-Nieves: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. R. Juneja: Employee; Self; Eli Lilly and Company. L. Fan: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. E. Meadows: Employee; Self; Eli Lilly and Company. Employee; Spouse/Partner; Eli Lilly and Company. Stock/Shareholder; Spouse/Partner; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. M.J. Lage: Consultant; Self; Eli Lilly and Company. Consultant; Spouse/Partner; Eli Lilly and Company. E.L. Eby: Employee; Self; Eli Lilly and Company.
1036-P: Bioequivalence of Ultra-Rapid Lispro (URLi) U100 and U200 Formulations in Healthy Subjects
Authors: LINNEBJERG HELLE , LABELL ELIZABETH S. , DELLVA MARY A. , LIM SHUFEN , COUTANT DAVID E. , LEOHR JENNIFER
Published: June 2020

URLi is a novel insulin lispro formulation developed to more closely match physiological insulin secretion. URLi U200 is a concentrated formulation. This randomized, double-blind, 4-period, replicated crossover, euglycemic clamp study (NCT03616977) assessed pharmacokinetics (PK) and glucodynamics (GD) after 15 U subcutaneous doses of U100 and U200 URLi in 68 healthy subjects (mean ± SD age 39.6 ± 9.6 y).

Similar mean PK and GD profiles were observed after dosing U100 and U200 URLi. The formulations were bioequivalent (BE): the 90% CI of ratios of geometric least-square means for the maximum insulin concentration (Cmax) and total exposure (AUC0-∞) were within BE limits of 0.80-1.25. Additionally, the 90% CI for the ratios of geometric means for maximum (Gtot) and total glucose infused (Rmax) were within the BE limits.

The time to early half Cmax (early 50% tmax) occurred at approximately the same time for both formulations. Additionally, insulin exposure within the first 15 and 30 minutes was similar for U100 and U200 URLi.

The tolerability of the U200 and U100 URLi formulations were comparable. This study demonstrated that U100 and U200 URLi formulations were BE and the faster insulin absorption was maintained in the U200 formulation. The GD were similar and support the ability of patients to transfer from U100 to U200 URLi in a 1:1 unit conversion.

Disclosure

H. Linnebjerg: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. E.S. LaBell: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company, Johnson & Johnson, Novartis AG. M.A. Dellva: Employee; Self; Eli Lilly and Company. S. Lim: Employee; Self; Eli Lilly and Company. D.E. Coutant: Employee; Self; Eli Lilly and Company. Employee; Spouse/Partner; Eli Lilly and Company. J. Leohr: None.

Funding

Eli Lilly and Company
1043-P: GoBolus Study: Impact of Faster Aspart on Glycemic Control in a Real-World Population with Type 1 Diabetes on Basal-Bolus Therapy as Multiple Daily Injections Using Flash Glucose Monitoring
Authors: DANNE THOMAS , SCHWEITZER MATTHIAS AXEL , KEUTHAGE WINFRIED , KIPPER STEFAN , KRETZSCHMAR YASMIN , SIMON JÖRG , ZIEGLER RALPH
Published: June 2020

Background and Methods: Randomized trials have shown that faster aspart (FA) improves glycemic control in patients with T1D. The German observational study GoBolus (NCT03450863) collected real-world clinical and patient-reported data of patients with T1D treated with basal/bolus therapy as multiple daily injections (MDIs), who were switched from other bolus insulins to FA by their physician.

Results: Overall, 243 patients were enrolled, with a mean age of 49.9 years, mean baseline A1C of 8.1%, mean BMI of 28.1 kg/m2 and mean diabetes duration of 18.8 years: 55.6% were male. Over 24 weeks’ FA treatment, primary endpoint (A1C) decreased by 0.19% (p<0.01) without changes in insulin doses or basal/bolus insulin ratios. Flash glucose monitoring data (Figure) showed increased “time in range” (TIR, 3.9-10 mmol/L) from 46.9% to 50.1% (p=0.01) and decreased time in hyperglycemia (>10 and >13.9 mmol/L) from 49.1% to 46.1% (p=0.03) and 20.4% to 17.9% (p=0.01), respectively, without change for time in hypoglycemia (<3.9 and <3.0 mmol/L). Mean interstitial and 3-h postprandial glucose improved from 10.4 to 10.1 mmol/L (p=0.04) and 11.9 to 11.0 mmol/L (p<0.01), respectively.

Conclusions: Switching bolus insulin to FA in patients with T1D on MDIs improved glycemic control, increased TIR and decreased time in hyperglycemia.

Disclosure

T. Danne: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Novo Nordisk A/S, Sanofi. M. Schweitzer: Employee; Self; Novo Nordisk A/S. W. Keuthage: Advisory Panel; Self; Deutschland GmbH, Novo Nordisk A/S, Roche Diabetes Care. Board Member; Self; Abbott, Berlin-Chemie AG. S. Kipper: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. Y. Kretzschmar: Employee; Self; Novo Nordisk A/S. J. Simon: None. R. Ziegler: Advisory Panel; Self; Abbott, Lilly Diabetes, Novo Nordisk A/S, Roche Diabetes Care. Consultant; Self; Novo Nordisk A/S, Roche Diabetes Care. Speaker’s Bureau; Self; Abbott, Dexcom, Inc., Novo Nordisk A/S, Roche Diabetes Care.

Funding

Novo Nordisk
1054-P: Patiromer to Enable Spironolactone in Patients with Resistant Hypertension and Chronic Kidney Disease (AMBER): Results in the Prespecified Subgroup with Diabetes
Authors: AGARWAL RAJIV , ROSSIGNOL PATRICK , ARTHUR SUSAN , CONRAD ANSGAR , WHITE WILLIAM B. , WILLIAMS BRYAN
Published: June 2020

Background: Spironolactone (SPIRO) reduces BP in patients (pts) with resistant hypertension (RHTN); however, its use in pts with advanced chronic kidney disease (CKD) is often limited by hyperkalemia (HK). In AMBER, patiromer (PAT) enabled more persistent use of SPIRO in pts with RHTN and CKD. As SPIRO is recommended in RHTN and DM increases HK risk, we report results in prespecified subgroups with type 1 or 2 DM (DM+) and without (DM-).

Methods: Randomized, double-blind, placebo (PBO)-controlled trial in adults with RHTN and eGFR 25 to ≤45 mL/min/1.73 m2. Pts were assigned (1:1) to PBO or PAT, and SPIRO 25 mg QD, with dose titrations permitted after 1 wk for PAT and 3 wks for SPIRO. Primary endpoint: between-group difference at Wk 12 in % of pts on SPIRO.

Results: 295 pts were randomized, 145 (49%) DM+ and 150 (51%) DM-. Baseline mean (SD) serum K+ (mEq/L) was 4.76 (0.34) in DM+ and 4.67 (0.39) in DM-. Significantly more pts treated with PAT than with PBO remained on SPIRO at Wk 12 in both subgroups (Figure). LS Mean (SE) cumulative SPIRO dose was higher with PAT than PBO, by 438.7 (177.7) mg in DM+ and 317.8 (175.0) mg in DM-. Adverse events of hyperkalemia or blood K+ increased occurred in 7 (PBO) and 8 (PAT) DM+ patients and 7 (PBO) and 1 (PAT) DM- patients.

Conclusions: PAT enabled more pts with advanced CKD and RHTN to continue treatment with SPIRO, regardless of DM status.

Disclosure

R. Agarwal: Other Relationship; Self; AbbVie Inc., Akebia Therapeutics, Amgen, AstraZeneca, Bayer Inc., Bird Rock Bio, Boehringer Ingelheim Pharmaceuticals, Inc., Celgene, Daiichi Sankyo, Eli Lilly and Company, GlaxoSmithKline plc., Ironwood Pharmaceuticals, Johnson & Johnson, Merck & Co., Inc., Novartis Pharmaceuticals Corporation, OPKO Health, Inc., Reata, Relypsa, Inc.,Sandoz, Sanofi, Takeda Pharmaceutical Company Limited, ZS Pharma. P. Rossignol: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Idorsia, Novartis France, Novo Nordisk Inc., Relypsa, Inc., Servier, Vifor Pharma Group. Stock/Shareholder; Self; CardioRenal: cofounder. S. Arthur: Employee; Self; Relypsa, Inc. A. Conrad: Employee; Self; Relypsa, Inc. Stock/Shareholder; Self; Vifor Pharma Group. W.B. White: Consultant; Self; Relypsa, Inc. B. Williams: Consultant; Self; Novartis AG, Relypsa, Inc., Vascular Dynamics Inc. Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Novartis AG, Pfizer Inc., Servier.

Funding

Relypsa, Inc.
1058-P: Effects of Treatment with Testosterone Undecanoate Injections (TU) on Estimated Glomerular Filtration Rate (eGFR) in Men with Hypogonadism and Type 2 Diabetes Mellitus (T2DM) Compared with an Untreated Control Group: Real-World Data
Authors: HAIDER KARIM S. , HAIDER AHMAD , SAAD FARID
Published: June 2020

Background: Reduced eGFR is associated with increased risk of cardiovascular disease and mortality.

Methods: In a urological practice registry of 858 men with hypogonadism, 356 men (41.5%) had T2DM. 178 received TU 1000 mg every 12 weeks (T-group). 178 opted against treatment (CTRL). Changes over time between groups were compared and adjusted for age, weight, waist circumference, fasting glucose, blood pressure, lipids and quality of life to account for baseline differences between the groups. eGFR was calculated using the Modification of Diet in Renal Disease (MDRD) formula.

Results: Mean follow-up 8.2±2.9, baseline age: 61.5±5.4 (T-group) and 63.7±4.9 years (CTRL). Creatinine decreased by 0.16±0.03 mg/dL at 11 years in the T-group and increased by 0.32±0.03 mg/dL in CTRL. Estimated adjusted difference between groups: -0.48 mg/dL (p<0.0001 for all). T-group: eGFR increased by 9.8±1.4 mL/min/1.73 m². The peak mean value was recorded in year 8 after which a small but steady decline occurred. CTRL: eGFR decreased progressively by 22.3±1.3 mL/min/1.73 m². Difference between groups: 32.2 mL/min/1.73 m² (p<0.0001 for all). Systolic blood pressure decreased in the T-group by 32.3±1.2 mmHg and increased in CTRL by 14.5±1.1 mmHg. Difference between groups: -46.8 mmHg (p<0.0001 for all). Diastolic blood pressure decreased in the T-group by 19.2±0.9 mmHg and increased in CTRL by 9.5±0.8 mmHg. Difference between groups: -28.7 mmHg (p<0.0001 for all). During the entire observation period, 13 deaths (7.3%) and no cardiovascular events occurred in the T-group. In CTRL, 48 deaths (27.0%), 55 cases of myocardial infarction (30.9%) and 45 cases of stroke (25.3%) were recorded. Nephropathy occurred in 0.6% in the T-group and in 4% in CTRL (p<0.05).

Conclusions: Long-term testosterone therapy in men with hypogonadism and T2DM prevents age-related deterioration in GFR.

Disclosure

K.S. Haider: None. A. Haider: None. F. Saad: Consultant; Self; Bayer AG. Stock/Shareholder; Self; AbbVie Inc., Bayer AG.

Funding

Bayer AG
1066-P: Comparison of Efficacy of Lixisenatide Combined with Basal Insulin with or without Metformin in Asian and Caucasian Patients with Type 2 Diabetes: A Pooled Analysis of Phase-III Studies
Authors: YUEZHONG REN , LIU MINZHI , WU GUANGYU , ZHANG XIA , CUI NAN
Published: June 2020

Lixisenatide (LIXI), a short acting glucagon-like peptide-1 receptor agonist, was reported to reduce post-prandial glucose and provide a complementary effect when combined with basal insulin (BI). Analysis comparing the efficacy of LIXI combined with BI in Asians and Caucasians is lacking. A pooled analysis of 2 multi-national phase III studies, GetGoal-L and GetGoal-L-C, was performed to assess the efficacy of LIXI vs. placebo as add-on treatment to BI ± metformin in Asian and Caucasian patients with T2DM. After pooling the data, baseline characteristics were similar between Asians and Caucasians except body weight, BMI and BI dose which were higher in Caucasians. After 24 weeks, LIXI significantly reduced HbA1c in both ethnic groups compared to placebo, with no statistically significant difference between the 2 groups: Asian [LS mean (s.e.) (95%CI): -0.49 (-0.68 to -0.30)] and Caucasian [LS mean (s.e.) (95% CI): -0.45 (-0.63 to -0.26)]; P=0.24. There was also no significant interaction between ethnicity and treatment (P=0.63). ANCOVA analysis showed that treatment with LIXI contributed to an HbA1c reduction of -0.56% after adjustment of baseline HbA1c level in Asian patients and -0.41% in Caucasian patients. Addition of LIXI to BI ± metformin reduced HbA1c to a similar extent in both Caucasian and Asian T2DM patients.

Disclosure

R. Yuezhong: None. M. Liu: None. G. Wu: Employee; Self; Sanofi. X. Zhang: None. N. Cui: None.

Funding

Sanofi
1068-P: Adherence to Metformin Treatment in T2DM Subjects Is Higher Than Anticipated and Is Associated with the Use of Fixed-Dose Combinations but Not with XR Form
Authors: LANKOVA IVANA , MISKOVA IVA , FRANKOVA STEPANKA , KOBROVA DANA , CAJKA TOMAS , HRICKO JIRI , PAUCOVA MICHAELA , HRÁDKOVÁ VIKTORIE , VLASAKOVA ZUZANA , PELIKANOVA TEREZIE , MRAZ MILOS , HALUZIK MARTIN
Published: June 2020

Metformin is considered the first-line treatment in all subjects with type 2 diabetes mellitus (T2DM) not having a contraindication for its use. Patient compliance with metformin is not optimal; however, objective compliance data are scarce. The aim of our study was to analyse the adherence to metformin treatment by determining its plasma levels and to identify its determinants in a broad spectrum of T2DM patients.

In total, 309 patients with T2DM from a single tertiary diabetes centre (mean age 66.5 ± 9.0 years, HbA1C 57.2 ± 13.1 mmol/mol, BMI 30.8 ± 4.9 kg/m2) using standard or XR (sustained release) form of metformin were included in the study. Blood sampling for metformin together with a short questionnaire were performed during a regular outpatient visit. Hydrophilic interaction chromatography and high-resolution mass spectrometry (Q Exactive Plus instrumentation) were used to quantify metformin levels. Values ​​below 100 ng/ml were deemed sub-therapeutic.

Out of 309 patients, sub-therapeutic values were measured in 4.2% and zero levels in 1.9% of subjects. The use of XR form did not increase compliance (16.7 vs. 15.4 vs. 13.8% of subjects for zero vs. sub-therapeutic vs. therapeutic range, n.s.), while all subjects using combination preparation with another antidiabetic agent (11.0%) were in therapeutic range. Zero levels of metformin were associated with a trend to increased HbA1C, higher number of other antidiabetic drugs and more frequent insulin use, whereas age, BMI and diabetes duration had no effect on metformin compliance. Adherence to metformin also increased with education status while not being affected by smoking or alcohol use.

In conclusion, in a tertiary diabetes centre the compliance with metformin treatment was greater than 93% and increased with the use of combination preparations, lower number of antidiabetic drugs and higher education status. The XR form was not associated with increased adherence rate.

Disclosure

I. Lankova: None. I. Miskova: None. S. Frankova: None. D. Kobrova: None. T. Cajka: None. J. Hricko: None. M. Paucova: None. V. Hrádková: None. Z. Vlasakova: None. T. Pelikanova: None. M. Mraz: None. M. Haluzik: Advisory Panel; Self; Lilly Diabetes, Sanofi. Consultant; Self; Ethicon US, LLC. Speaker’s Bureau; Self; AstraZeneca, Mundipharma International, Novartis AG, Novo Nordisk A/S.

Funding

Institute for Clinical and Experimental Medicine (00023001); RVOVFN64165
107-LB: Single Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of MK-1092 in Healthy Subjects (HS)
Authors: MORROW LINDA , GRIMM MICHAEL , BEYSEN CARINE , WALFORD GEOFFREY , DUNCAN KELLY , MITRA PRANAB K. , VADDADY PAVAN , HOMPESCH MARCUS
Published: June 2020

Background: MK-1092, a first-in-class insulin receptor partial agonist, is being developed as a novel basal insulin for patients with T1DM and T2DM. The primary objective of this first-in-human study was to assess safety and tolerability of single subcutaneous (SC) doses of MK-1092 in HS. Secondary objectives were to estimate PK profiles, to determine the maximal glucose infusion rate (GIRmax) required to maintain target glucose levels during euglycemic clamp conditions and to explore the glycemic effect of insulin lispro when added to a single dose of MK-1092 in HS.

Methods: In part 1 of this single-site study, 5 cohorts of HS (n=8/cohort) were blinded and randomized (3:1) to receive MK-1092 (4, 8, 16, 32 or 64 nmol/kg) or glargine (3 nmol/kg [0.5 units/kg]). Subjects received single SC doses of MK-1092 or glargine and placebo matched to the alternative active treatment under euglycemic clamp conditions. Part 2 of the study was started once a safe and tolerated MK-1092 dose that achieved GIRmax ~1-2 mg/kg/min was identified in Part 1. In the open-label part 2 of the study, 4 HS received lispro (1.2 nmol/kg [0.2 units/kg], IV) approximately 12 hr after a single SC dose of MK-1092 (8 nmol/kg) to confirm high dose lispro could reduce hyperglycemia (defined as GIRmax > 4mg/kg/min) after MK-1092 dosing.

Results: All doses tested were safe and well tolerated. There were no SAEs and no discontinuations due to AEs. AEs were mild or moderate and resolved spontaneously. The geometric mean of apparent terminal t1/2 ranged from 5.4 to 9.3 hr, Tmax ranged from 12 to 18 hr, AUC0-∞ ranged from 10.6 to 161 nM*hr and Cmax ranged from 0.38 to 6.82 nM at 4 to 64 nmol/kg MK-1092. Mean GIRmax for glargine was 2.72 mg/kg/min and 0.92, 1.69, 3.10, 3.32 and 4.39 mg/kg/min for 4, 8, 16, 32 and 64 nmol/l MK-1092, respectively. Adding lispro to 8.0 nmol/kg MK-1092 resulted in a mean GIRmax of 11.34 mg/kg/min.

Conclusion: Single doses of MK-1092 are well-tolerated and lower glucose in healthy subjects.

Disclosure

L. Morrow: Employee; Spouse/Partner; Lilly Diabetes. Employee; Self; ProSciento. M. Grimm: None. C. Beysen: Employee; Self; ProSciento. G. Walford: Employee; Self; Merck & Co., Inc. K. Duncan: Employee; Self; Merck & Co., Inc. Stock/Shareholder; Self; Merck & Co., Inc. P.K. Mitra: Employee; Self; Merck Sharp & Dohme Corp. Stock/Shareholder; Self; Bristol-Myers Squibb. P. Vaddady: Employee; Self; Merck & Co., Inc. Stock/Shareholder; Self; Merck & Co., Inc. M. Hompesch: Board Member; Self; ProSciento. Employee; Self; ProSciento. Stock/Shareholder; Self; ProSciento.