We did a randomized crossover non-inferiority trial to compare 3 weeks of automated insulin delivery with (i) carbohydrate counting and (ii) qualitative meal-size estimation (low, medium, high, or very high carbohydrate (CHO)) in 30 adults with T1D (20/30 females, age 44±17 yrs, A1c 7.4±0.7%) . Low, medium, high, and very high CHO meals were defined as <30 g CHO, 30-60 g CHO, 60-90 g CHO, and >90 g CHO, respectively, and their prandial insulin boluses were calculated as the individualized insulin-to-CHO ratios x 15, 35, 65, and 95, respectively. Closed-loop algorithms were otherwise identical in the two arms. The time in range 3.9-10.0 mmol/L (primary outcome) was 74% (SD 10%) with carbohydrate counting and 71% (11%) with qualitative meal-size estimation; difference -3.6% (95% CI, -0.6% to -6.5%) which crossed the pre-specified non-inferiority margin of 4%. Times <3.9 mmol/L and <3.0 mmol/L were low in both two arms. Automated basal insulin delivery was higher in the qualitative meal-size estimation arm (34.6 vs. 32.6 u/day, p=0.003) . We conclude that non-inferiority of the qualitative meal-size estimation was not confirmed, though this method achieved a high time in range and low time in hypoglycemia. The qualitative meal-size estimation method may benefit from larger prandial boluses and more responsive post-meal automatic basal delivery. Disclosure A.Haidar: Consultant; Eli Lilly and Company, Research Support; ADOCIA, Dexcom, Inc., Eli Lilly and Company, Tandem Diabetes Care, Inc. L.Legault: Advisory Panel; Abbott Diabetes, Insulet Corporation, Novo Nordisk A/S, Other Relationship; Eli Lilly and Company, Research Support; AstraZeneca, Merck & Co., Inc. M.Raffray: None. N.Gouchie-provencher: None. A.Jafar: None. M.Devaux: None. M.Ghanbari: None. R.Rabasa-lhoret: Consultant; HLS Therapeutics Inc., Pfizer Inc., Other Relationship; Abbott Diabetes, AstraZeneca, Boehringer Ingelheim International GmbH, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Janssen Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Novo Nordisk Canada Inc., Sanofi, Vertex Pharmaceuticals Incorporated, Research Support; Canadian Institutes of Health Research, Cystic Fibrosis Canada, Diabetes Canada, Fondation Francophone pour la Recherche en Diabète (FFRD) , JDRF, National Institutes of Health, Société Francophone du Diabète (SFD) , Speaker's Bureau; Canadian Medical & Surgical Knowledge Translation Research Group (CMS) , CPD Network, Tandem Diabetes Care, Inc. Funding National Institutes of Health (1DP3DK106930-01)
Background: For some with type 1 diabetes (T1D) , hybrid closed-loop insulin therapy is insufficient to achieve glycemic targets. Low doses of SGLT2i may improve glycemia in those not able to achieve their targets. Methods: A double-blinded, cross-over, randomized controlled trial was performed in sub-optimally controlled (HbA1c 7.0-10.5%) adults with T1D who were not able to achieve a time-in-range (3.9-10.0 mmol/L) of > 70% after 14 days on closed-loop therapy. Three 14-day interventions were performed with placebo, empagliflozin 2.5 mg, or empagliflozin 5 mg, as adjunct to closed-loop therapy, with daily ketone testing. Results: 24 participants completed the study (50% male, age 33 ± 14 yrs, HbA1c 8.1 ± 0.5%) . The time in range was 59 ± 9% for placebo, 72 ± 10% for empagliflozin 2.5 mg, and 70 ± 8 for empagliflozin 5 mg (p < 0.between placebo and empagliflozin 2.5 mg, and placebo and empagliflozin 5 mg) . Empagliflozin 2.5 mg did not increase time spent below 3.9 mmol/L though empagliflozin 5 mg did (p = 0.01) . Average ketone levels were not different between arms (p=ns) . There were no serious adverse events in any intervention. Conclusion: Both empagliflozin 2.5 mg and 5 mg increased the time spent in target on hybrid closed-loop therapy by 11-13 % compared to placebo, in those who otherwise were unable to attain glycemic targets. Disclosure M.Pasqua: None. A.Jafar: None. A.Kobayati: None. M.Tsoukas: Speaker's Bureau; AstraZeneca, Bausch Health, Canada, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Johnson & Johnson, Novo Nordisk Canada Inc. A.Haidar: Consultant; Eli Lilly and Company, Research Support; ADOCIA, Dexcom, Inc., Eli Lilly and Company, Tandem Diabetes Care, Inc. Funding National Institutes of Health (1DP3DK106930)
Tuning a multi-model predictive control AHCL algorithm to the PK/PD properties of URLi may result in improved performance vs Lispro with no increased safety concerns. This was a randomized, double-blind, inpatient, 2-period crossover study in 22 adults with T1D on insulin pumps. Each URLi and Lispro treatment period had a 4-day inpatient visit with insulin doses calculated using the tuned AHCL algorithm. To challenge the algorithm, tests included unannounced exercise, 1 hr delayed bolus, underbolus, and overbolus. Participants (59% male) had mean ±SD age 43.4±13.77 years, T1D duration 25.9±9.61 yrs, and HbA1c 7.6±0.47%. Mean time in range (TIR; 70-180 mg/dL) during the overall inpatient period: URLi 79.4%; Lispro 78.7 % (p=0.80) with a trend towards decreased time <70 mg/dl (1.5 vs 2.4, p=0.08) for URLi. URLi had a significant difference in Level 1 hypoglycemia (30 vs 55 events, p = 0.01) but not Level 2 (4 vs 9 events, p=0.3). TIRs were similar including during meal/challenge periods (Table) with a trend towards greater TIR during the postprandial period and reduced time <70 mg/dl during exercise for URLi. There was greater TIR during overbolus with Lispro. No severe hypoglycemia events occurred. Results suggest reduced hypoglycemia with URLi vs Lispro with comparable glycemic control. The AHCL algorithm showed promising glycemic performance in a supervised setting when used with URLi or Lispro. Disclosure R. Pollom: None. E. Dassau: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. M. Katz: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. L. Nosek: None. H. Coester: None. E. Zijlstra: Other Relationship; Eli Lilly and Company, Speaker's Bureau; Gan & Lee Pharmaceuticals, Novo Nordisk A/S. A. Ghosh: None. A. Haidar: Consultant; Eli Lilly and Company, Other Relationship; Bigfoot Biomedical, Inc., Research Support; Adocia, Dexcom, Inc., Tandem Diabetes Care, Inc. R. Jones: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. J. Leohr: None. S. E. Gleissner: None.
We conducted a randomized, controlled, pilot study to eliminate carbohydrate counting (CC) in adults with type 1 diabetes using an automated insulin (insulin aspart and faster aspart) and pramlintide dual-pump fully closed-loop delivery system. The interventions included 5 arms (n = 11, 8 F, A1C 7.4%) and participants underwent 14 hours of outpatient, free-living, supervised interventions of (i) faster aspart with CC, (ii) faster aspart and pramlintide at a 1u:8µg ratio without CC, and (iii) faster aspart and pramlintide (1:10) without CC (iv) insulin aspart and pramlintide (1:8) without CC, and (v) insulin aspart and pramlintide (1:10) without CC. One participant opted out of the two insulin aspart and pramlintide arms. Prior to each dual-hormone intervention, participants had a 2-4-day drug dose-escalation period. P-values are not reported as this is an underpowered pilot study. During the faster aspart and pramlintide interventions, the mean time in target range (70-180 mg/dL) was 69% (24%) and 77% (13%) with the 1:8 and 1:10 ratios, respectively. During the aspart and pramlintide interventions, the time in range was 71% (15%) and 77% (11%) with the 1:8 and 1:10 ratios, respectively. Compared to the control arm where time in range was 72% (26%), both the insulin aspart and faster aspart arms with the 1:10 ratio provided numerical improvements to time in range. The median time spent below 54mg/dL with each respective ratio was 1.3% (0, 4.5), 0.6% (0, 2.4) on the aspart arms and 0.0% in the faster aspart and control arms. The mean total insulin used throughout the interventions was 38.2 (23.5) units on the control arm, 31.8 (18.4) and 32.5 (17.5) on the faster aspart 1:8 and 1:10 respectively, and 36.6 (26.9) and 32.2 (23.5) on the insulin aspart 1:8 and 1:10 arms respectively. This pilot study suggests that our fully automated dual-hormone delivery system has the potential to alleviate carbohydrate counting without degrading time in the target range; and it will be investigated in a larger subsequent study. Disclosure M.Odabassian: None. M.Tsoukas: Speaker's Bureau; Novo Nordisk Canada Inc., Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Janssen Scientific Affairs, LLC, AstraZeneca, Sanofi. E.Cohen: None. M.Pasqua: None. J.Rutkowski: None. A.Haidar: Consultant; Eli Lilly and Company, Other Relationship; Bigfoot Biomedical, Inc., Research Support; Adocia, Dexcom, Inc., Tandem Diabetes Care, Inc.
We conducted a non-inferiority randomized crossover trial to alleviate carbohydrate counting (CC) in people with diabetes using automated dual-pump delivery of faster aspart (Fiasp) and pramlintide. Adults (N=15, 9 F, 39 ± 14 years, A1c 7.2 ± 0.9%) and adolescents (N=15, 8 F, 16 ± 1 years, A1c 8.4 ± 0.9%) used (i) Fiasp and placebo with CC, (ii) Fiasp and pramlintide with meal announcement (MA) , and (iii) Fiasp and placebo with MA for 2 weeks. Fiasp and pramlintide were delivered at a fixed 1 U:µg ratio to mimic a co-formulation. MA arms delivered fixed, user-specific priming meal boluses, independent of carbohydrate content. Prior to the first arm, participants had a 1-week run-in with automated Fiasp (single pump) delivery and CC, with mean time in range (70-180 mg/dL) of 71% in adults and 64% in adolescents. In adults, mean time in range was 65% on Fiasp and placebo with CC, 71% on Fiasp and pramlintide with MA, and 64% on Fiasp and placebo with MA; non-inferiority with a pre-defined 6.25% margin was achieved in both MA arms with pramlintide and placebo (difference -6 [95% CI -12.6, 0.5]; 1 [-3.0, 4.6]) . In adolescents, mean time in range was 51%, 55%, and 46% in the three respective arms; non-inferiority was only achieved on Fiasp and pramlintide with MA (-4 [-9.0, 1.7]) . We conclude that automated Fiasp and pramlintide delivery may alleviate CC without degrading glucose control. Disclosure E.Cohen: None. E.Palisaitis: Other Relationship; Eli Lilly and Company. J.Rutkowski: None. L.Legault: Advisory Panel; Abbott Diabetes, Insulet Corporation, Novo Nordisk A/S, Other Relationship; Eli Lilly and Company, Research Support; AstraZeneca, Merck & Co., Inc. A.Haidar: Consultant; Eli Lilly and Company, Research Support; ADOCIA, Dexcom, Inc., Eli Lilly and Company, Tandem Diabetes Care, Inc. M.Tsoukas: Speaker's Bureau; AstraZeneca, Bausch Health, Canada, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Johnson & Johnson, Novo Nordisk Canada Inc. J.E.Von oettingen: None. J.Yale: Advisory Panel; Bayer AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk Canada Inc., Sanofi, Research Support; Bayer AG, Speaker's Bureau; Abbott Diabetes, AstraZeneca, Bayer AG, Dexcom, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Canada Inc., Sanofi. N.Garfield: None. M.Vallis: Advisory Panel; Bausch Health, Canada, Novo Nordisk Canada Inc., Consultant; Abbott Diabetes, LifeScan, Speaker's Bureau; AbbVie Inc., Bausch Health, Canada, LifeScan, Novo Nordisk, Novo Nordisk A/S. N.Gouchie-provencher: None. A.Jafar: None. M.Ghanbari: None. Funding Juvenile Diabetes Research Foundation International (2-SRA-2018-654-M-B) , Canada Research Chairs
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