Background:Ultra rapid lispro (URLi) is a new insulin lispro formulation that has accelerated absorption and improved postprandial glucose control compared with insulin lispro (Humalog(R)). The compatibility and safety of URLi versus lispro were evaluated in patients with type 1 diabetes using continuous subcutaneous insulin infusion (insulin pump). Methods:In this phase 3, double-blind, crossover study, 49 patients were randomized to two 6-week treatment periods, after a 2-week lead-in period on lispro. The primary endpoint was the rate of infusion set failures due to a pump occlusion alarm, or unexplained hyperglycemia with blood glucose >13.9 mmol/L (250 mg/dL) that did not decrease within 1 h after a correction bolus. Results:There was no significant difference in the rate of infusion set failures between URLi and lispro (0.03 vs. 0.05 events/30 days,P = 0.375). A higher rate of premature infusion set changes was observed with URLi (1.13 vs. 0.78 events/30 days;P = 0.028), translating to one additional infusion set change approximately every 3 months. A trend toward improved glycemic control was observed with URLi treatment: Time in range 3.9-10.0 mmol/L (71-180 mg/dL) was 65.7% +/- 1.3% versus 63.0% +/- 1.3%. Treatment-emergent adverse events (TEAEs) were reported by 46.9% of patients on URLi treatment and 18.8% on lispro. This difference was driven by an increase in infusion site reactions-more than 90% were mild. Incidence of all other TEAEs and severe hypoglycemia was similar between treatments. Conclusions:URLi was compatible with insulin pump use with a safety profile similar to lispro.

Background: This study evaluated glucose control by continuous glucose monitoring (CGM) during treatment with ultra-rapid lispro (URLi) or lispro used in combination with insulin glargine or degludec in adults with type 1 diabetes in a substudy of the PRONTO-T1D study. Methods: Ambulatory glucose profiles were evaluated in 269 patients from PRONTO-T1D assigned to double-blind URLi (n = 97) or lispro (n = 99) given 0–2 min before the start of the meal (mealtime), or open-label URLi (n = 73) given 20 min after the meal (postmeal URLi). Blinded CGM was used for up to 14 days before baseline and the 26-week primary endpoint. The primary objective was to compare mealtime URLi and lispro with respect to incremental area under the serum glucose concentration versus time curve from 0 to 2 h (iAUC0–2h) after breakfast. Results: Mealtime URLi was superior in reducing the iAUC0–2h when compared to lispro for breakfast (least squares mean [LSM] difference −28.1 mg·h/L, P = 0.048) and for all meals combined. iAUC0–3h and iAUC0–4h were also reduced. Postmeal URLi resulted in similar postprandial glucose (PPG) control to mealtime lispro, but less optimal PPG control compared to mealtime URLi. Mealtime URLi increased daytime time in range (71–180 mg/dL [3.9–10.0 mmo/L]) (LSM difference = +43.6 min, P = 0.020) and decreased nighttime time in hypoglycemia (LSM difference ≤70 mg/dL [3.9 mmol/L] = −11.5 min, P = 0.009) compared to mealtime lispro. Conclusions: Results of this CGM substudy support the improved PPG control seen with mealtime URLi in the PRONTO-T1D study and show that mealtime URLi resulted in improved daytime time in target range.

The Omnipod Horizon™ System is a hybrid closed-loop system (HCL) consisting of a tubeless insulin pump and Dexcom G6 sensor which provides automated insulin delivery with glucose targets from 110-150mg/dL, adjustable by time of day to allow therapy personalization. This study is the first outpatient safety and effectiveness evaluation of the system. Participants aged 6-13.9y with T1D>6mo and A1C<10.0% used the HCL system at home for 14 days (first 2 days hotel, n=8) over winter holidays with unrestricted eating and exercise. Participants set protocol-determined higher targets of 130-150mg/dL for 9 days, then could freely choose their targets from 110-150mg/dL for the last 5 days. Primary outcomes were safety measures and percent time 70-180mg/dL for the 5 days of HCL use with free choice of target. Children thus far (n=15) had a mean±SD age of 11±2y, T1D duration 5±3y, and A1C 7.7±0.9%. Participants primarily chose the 110 (69% of study time), 120 (10%), and 130mg/dL (21%) targets. For 72 patient-days of HCL use, percent time from 70-180mg/dL was 64.1±10.0% (Table). Percent time <70mg/dL was low: 0.9±1.2% overall and 0.5±0.5% overnight. There were no serious adverse events. The HCL system was safe and performed well in children with T1D when used at home for 5 days with free choice of target glucose. Participants were invited to continue in a 3mo outpatient study of the system which is currently underway. Disclosure B.A. Buckingham: Advisory Panel; Self; ConvaTec Inc., Medtronic. Research Support; Self; Beta Bionics, Inc., Dexcom, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care. G.P. Forlenza: Advisory Panel; Self; Medtronic. Consultant; Self; Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care. Research Support; Self; Abbott, Dexcom, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care. A.B. Criego: Other Relationship; Self; Dexcom, Inc., Lilly Diabetes, Medtronic, Omnipod. S.A. Brown: Research Support; Self; Dexcom, Inc., Insulet Corporation, Roche Diabetes Care, Tandem Diabetes Care, Tolerion, Inc. B.W. Bode: Advisory Panel; Self; InPen, Medtronic. Consultant; Self; ADOCIA, Eli Lilly and Company, Lexicon Pharmaceuticals, Inc., Novo Nordisk A/S, Pfizer Inc. Research Support; Self; Dexcom, Inc., Diasome Pharmaceuticals, Inc., Eli Lilly and Company, Gan & Lee Pharmaceuticals, Medtronic, Novo Nordisk A/S, Provention Bio, Inc., Senseonics, Xeris Pharmaceuticals, Inc. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., InPen, Janssen Pharmaceuticals, Inc., MannKind Corporation, Medtronic, Novo Nordisk A/S, Sanofi, Sanofi, Senseonics, Xeris Pharmaceuticals, Inc. Stock/Shareholder; Self; Glytec. C.J. Levy: Consultant; Self; Dexcom, Inc. Employee; Spouse/Partner; Allergan plc. Research Support; Self; Abbott, Dexcom, Inc., Insulet Corporation. T.T. Ly: Employee; Self; Insulet Corporation. Funding Insulet Corporation

This post hoc analysis explored whether mealtime fast‐acting insulin aspart treatment provided an advantage in postprandial plasma glucose (PPG) control vs. insulin aspart in people with Type 2 diabetes receiving high doses of bolus insulin.

Objectifs L’ajustement des doses d’insulines sur le comptage des glucides (CG) est un « gold standard » pour l’amélioration du contrôle glycémique dans le diabète de type 1. Cette analyse post-hoc de l’étude randomisée de phase III ONSET 1 a évalué l’intérêt du CG dans l’ajustement des doses de l’insuline Faster Aspart (FIA) et l’insuline asparte (IASP) au moment du repas associés à de l’insuline detemir. Méthodologie Les patients ayant l’habitude du CG le poursuivaient (HbA1c, FIA et IASP 7,6 %) et les patients restants utilisaient un algorithme de titration du bolus (HbA1c, FIA : 7,5 %, IASP : 7,6 %). Patients et méthodes La diminution du taux d’HbA1c est significativement plus importante avec FIA en comparaison à IASP et la non-infériorité est confirmée (différence estimée entre les traitements DET=−0,15 % [IC 95 % : −0,23 ; −0,07]). Avec le CG, la diminution de l’HbA1c est significativement plus importante avec FIA versus IASP (DET : −0,19 % [IC 95 % : −0,30 ; −0,09]) et comparable pour les deux traitements avec l’algorithme. L’incidence de survenue des épisodes hypoglycémiques et les doses de bolus sont comparables pour les deux traitements indépendamment de la méthode d’ajustement, de même que la dose totale d’insuline ou la prise de poids. Discussion FIA est efficace sur le contrôle glycémique quelle que soit la méthode de titration. Pour les diabétiques de type 1 capables d’ajuster leur dose d’insuline sur le CG, FIA permet une amélioration du contrôle glycémique vs. IASP avec un effet comparable sur le poids, la dose d’insuline et sans augmentation des hypoglycémies.

Limiting excursions of postprandial glucose (PPG) is desirable in people with diabetes. This multicentre, treat-to-target, phase 3 trial evaluated the efficacy of faster-acting insulin aspart (faster aspart) in type 1 diabetes (T1D). Primary endpoint was change from baseline in HbA1c after 26 weeks treatment. Post run-in, adult subjects were randomized to double-blind mealtime faster aspart (n=381), insulin aspart (IAsp) (n=380) or open-label postmeal faster aspart (n=382); each with insulin detemir. HbA1c was reduced for faster aspart and IAsp (Figure), confirming noninferiority to IAsp for both mealtime and postmeal dosing (estimated treatment difference [ETD] [95% confidence interval]: mealtime, −0.15% [−0.23; −0.07]); postmeal, 0.04% [−0.04; 0.12]); HbA1c reduction was significantly greater for mealtime faster aspart vs. IAsp. Superiority to IAsp for 2-h PPG increment during a standardized meal test was confirmed for faster aspart (ETD: −0.67 mmol/L [−1.29; −0.04]; −12.01 mg/dL [−23.33; −0.70]). One-hour PPG increment was also reduced (ETD: −1.18 mmol/L [−1.65; −0.71]; −21.21 mg/dL [−29.65; −12.77]). No significant differences in overall rate of severe or confirmed hypoglycemic episodes (plasma glucose <3.1 mmol/L [56 mg/dL]). In summary, faster aspart effectively improved glycemic control with superior PPG control for mealtime faster aspart vs. IAsp, representing a clinical advance in treating T1D.

Die postprandiale Blutzuckereinstellung (PPG) bei Menschen mit Diabetes ist immer noch unzureichend. Schnell wirksames Insulin aspart (Faster aspart) ist Insulin aspart (IAsp) in einer neuen Formulierung, mit dem Ziel einer rascheren Insulinresorption. Diese multizentrische Treat-to-Target-Studie untersuchte Wirksamkeit und Sicherheit von Faster aspart bei Erwachsenen mit Typ 1 Diabetes.

Schnell wirksames Insulin aspart (Faster aspart) ist Insulin aspart (IAsp) in einer neuen Formulierung mit rascherem Wirkbeginn. In dieser multizentrischen doppelblinden Treat-to-Target-Studie wurde Wirksamkeit und Sicherheit von Faster aspart vs. IAsp im Rahmen einer Basal-Bolus-Behandlung bei Erwachsenen mit unzureichend eingestelltem Typ 2 Diabetes unter Basalinsulin und oralen Antidiabetika geprüft.

Objectifs ONSET 1 est une etude randomisee de phase IIIa evaluant l’insuline Faster Aspart (FIA) vs l’insuline Aspart (IASP) chez des patients DT1 pendant 52 semaines. Methodologie Les patients randomises en double aveugle ont recu pendant 26 semaines FIA ou IASP au moment du repas ou FIA en ouvert apres le repas associes a l’insuline detemir. Prolongation de 26 semaines pour les patients sous FIA ( n = 381) ou IASP ( n = 381) au moment du repas. Resultats A S52, la variation de l’HbA1c depuis l’inclusion (−0,08 % [FIA] vs. +0,01 % [IASP]) est en faveur de FIA avec une difference estimee entre les traitements (DET) de −0,10 % [IC95 % −0,19 ; −0,00]. La variation depuis l’inclusion de la GPP incrementale a 1 h apres un repas-test est de −1,05 mmol/L (FIA) vs. −0,14 mmol/L (IASP) (DET : −0,91 mmol/L [−1,40 ; −0,43] ; −16,48 mg/dL [−25,17 ; −7,80]). Une tendance comparable en faveur de FIA est observee pour la GPP incrementale a 2 h (DET [IC95 %] : −0,42 mmol/L [−1,11 ; 0,27] ; −7,60 mg/dL [−19,98 ; 4,78]). La moyenne du profil glycemique en automesure (7-9-7 points) est significativement en faveur de FIA (DET : −0,23 mmol/L [−0,46 ; −0,00] ; −4,14 mg/dL [−8,23 ; −0,06]). La dose mediane totale d’insuline est de 0,77 (FIA) vs. 0,83 (IASP) U/kg. Aucune difference n’a ete observee sur la variation du poids (+ 1,18 kg [FIA] vs. + 1,05 kg [IASP] ; DET : 0,13 kg [−0,38 ; 0,65]) ni pour les hypoglycemies confirmees ou severes : FIA (53,29 evenements/patient-annee) vs. IASP (53,19 evenements/patient-annee) (ratio estime : 1,01 [IC95 % : 0,88 ; 1,15]). Discussion Ces resultats confirment l’efficacite et la tolerance a long terme de FIA chez les DT1.

Objectifs L’efficacité et la tolérance d’insuline degludec/liraglutide (IDegLira) ont été démontrées chez les DT2 insuffisamment contrôlés sous insuline basale, avec des diminutions plus importantes de l’HbA1c en comparaison à l’insuline basale. Le bénéfice cardiovasculaire du liraglutide versus placebo a également été démontré dans les critères d’efficacité cardiovasculaire de l’étude LEADER. Patients et méthodes Cette analyse s’est intéressée à l’effet d’IDegLira versus insuline degludec (IDeg ; DUAL II) et versus insuline glargine U100 (DUALV), les deux en association avec la metformine pendant 26 semaines, sur les marqueurs de risque cardiovasculaire. Résultats Dans les deux études, une diminution plus importante de la pression artérielle systolique (PAS) a été observée avec IDegLira et une légère–mais significative–augmentation de la fréquence cardiaque avec IDegLira versus insulines de comparaison (tous p<0,001). Une perte de poids a été observée avec IDegLira versus une prise de poids avec les insulines de comparaison. Le profil lipidique s’est amélioré sous IDegLira dans les deux études : les valeurs de cholestérol total et de LDL-cholestérol étaient significativement plus basses versus insulines de comparaison. Dans DUAL II, les taux d’apolipoprotéine B et de BNP étaient significativement plus faibles avec IDegLira versus IDeg alors que les valeurs de CRP-ultrasensible (CRP-us) étaient comparables après 26 semaines de traitement. Discussion IDegLira, en comparaison à un traitement par insuline basale, est associé à une amélioration globale des marqueurs de risque cardiovasculaire après 26 semaines de traitement, ce qui est à mettre en relation avec le composant liraglutide de cette combinaison.