Objective: Develop a test methodology for evaluating the reason for infusion set (IS) failure in persons with diabetes using insulin pump therapy (Continuous Sub-cutaneous Insulin Infusion, CSII). Insulin stability (physical, chemical, and microbiological) and/or the loss of preservatives in the infusate are thought to play significant roles in shortening IS wear time. In-vitro and in-vivo methods were used to assess the cause(s) site inflammation and the loss of preservatives. Method: Fast-acting insulin (insulin aspart and lispro) were pumped through different infusion sets (>4) under simulated-use conditions. The pumped insulin and non-pumped insulin controls were characterized for physical, chemical, and microbiological properties. The pumped insulin, combined with fibrinogen (an initiator for material foreign body responses), were tested in murine macrophage cell culture for inflammatory responses. The corresponding infusion sets were tested in vivo in a diabetic porcine model to determine IS wear-time. Result: Pumped insulins in ≥8 insulin/IS combinations met corresponding criteria in USP insulin monographs, indicating no significant chemical changes. Lower preservative content was found to increase insulin aggregates in-vitro/in-vivo. Pro-inflammatory cytokines (MIP-1α, and MCP-1) increased significantly in the inflammatory in-vitro model. The IS wear-time was shortened from 4.9±0.3 days (control) to 1.7±0.3 days (p<0.0001) with lower preservative content (<50% per label claim). Conclusion: Preliminary findings from in-vitro and in-vivo test model development indicate that macrophage number, the inflammatory response, and device wear time were significantly impacted by loss of preservative and trace aggregates/particles. The new test methodology can further our understanding as to how to improve IS wear time. Disclosure S. Chattaraj: Employee; Self; Medtronic. G. Zhang: None. E. Anselmo: Employee; Self; Medtronic. J.C. Fusselman: None.

Objective: The durability of wearable devices, e.g., insulin infusion sets (IIS), is challenged by external factors such as friction, movement, stretch, moisture, and skin viscoelasticity. Such factors are difficult to investigate in non-clinical settings. We assessed 3 new adhesive patches and compared them to those used with current Medtronic infusion sets to determine which would be suitable for an extended wear infusion set with intended wear time of up to 7 days. Method: Seventy-five adults were recruited in 3 studies to wear 2 patch variants each on conventional IIS sites, for up to 8 days. Non-functional Medtronic pumps were used to simulate use conditions. The primary outcome was wear time. Secondary outcomes included edge lift and descriptive user feedback (e.g., appearance, comfort, irritation score, residue upon removal, and removal discomfort). Results: The results (Figure 1) demonstrated that the 7-day survival rate for existing IIS patches varied from ∼70% to ∼90%. These data indicated that the hub form factor played an insignificant role in the adhesive patch wear time. Two of three new adhesive patches had a 7-day survival rate ≥95% without significantly impacting user experience (i.e., wear comfort or skin reactions). Conclusion: In the simulated-use studies, two new adhesive patches met the primary and secondary outcomes for use with an extended wear infusion set. Disclosure G. Zhang: None. S. Chattaraj: Employee; Self; Medtronic. E. Anselmo: Employee; Self; Medtronic. L. Hoffman: None. M. Tran: None. S. Bondy: Employee; Self; Medtronic. Stock/Shareholder; Self; Medtronic.

Objective: Medtronic Mio™ 30 infusion set (M30IS) is a single use IS for pump users with pre-loaded inserter, a 30° insertion angle, and labeled for 3-day use. The M30IS wear duration is impacted by initial local trauma caused by insertion and sustained inflammation by cannula & insulin infusion (insulin aggregates & other impurities in the infusate), with the latter being predominant. An extended Mio™ 30 infusion set (EM30IS) was developed by improving insulin formulation stability in the fluid path. This study reports on the performance of the EM30IS in persons with T1D during an early feasibility trial (ClinicalTrials.gov: NCT05544643). Method: This is a X over study of EM30IS and M30IS on 21 subjects with type 1 diabetes. Each subject wore both sets 4-5 times each on a preferred site that was continuously infused with insulin lispro or aspart subcutaneously via a Medtronic 780G pump for 3 days (M30IS), 7 days (EM30IS) or until failure. Endpoints of safety and effectiveness (failure rate due to unexplained hyperglycemia <16%) were evaluated. Exploratory analyses related to performance and glycemic control were also evaluated. Results: The EM30IS survival rate at 6 days (70%) was comparable to M30IS survival rate at 3 days (63%). Glycemic control outcomes were equivalent (see Table 1) and there were no episodes of EM30IS-related severe hypoglycemia or DKA. Conclusion: The EM30IS was safe and its performance at 6 days was equivalent to the performance of M30IS at 3 days. Disclosure O. Cohen: Employee; Medtronic. Y. Cohen: None. S. Chattaraj: Employee; Medtronic. G. Zhang: Employee; Medtronic. E. Anselmo: Employee; Medtronic. A. Tirosh: Advisory Panel; Medtronic. Research Support; Medtronic. Speaker's Bureau; Medtronic. Advisory Panel; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Advisory Panel; Sanofi. Speaker's Bureau; Sanofi. Research Support; Sanofi. Advisory Panel; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Funding Medtronic

Objective: The Medtronic Extended infusion set (EIS) is the first and only infusion set approved for up to 7-day use. Prior studies established clinical safety and efficacy of the EIS. The purpose of this retrospective analysis was to assess real-world data on the EIS performance and user behaviors associated with the EIS including wear duration and asynchronous reservoir changes. Methods: A limited launch of the EIS outside the US (OUS) included MiniMed™ 640G/670G/780G users. Due to regional legal requirements, aggregated pump data from EIS users were not separated from other user data. To identify EIS users, an algorithm was developed based on the expected behavior patterns associated with an infusion set change, e.g., tubing fills. From the same cohort, individuals using the EIS (n=108) versus regular 3-day sets (n=414) were identified by a mean or median time between substantial tubing fills. To assess synchronous and asynchronous set/reservoir changes, reservoir changes were determined based on pump rewind commands in the CareLink™ system. Results: Mean EIS use lifetime was 6.74 days, with >70% of sets used for more than 6 days. No user complaint was received during limited launch. The EIS set change rate at 7 days (168 hrs) was 48.2%, and was comparable to the 48.9% rate of 3-day sets at 3 days (72 hrs). In addition, CareLink™ data indicated that while users with a total daily dose (TDD) of insulin less than 40 U may not require an asynchronous reservoir fill, some users with higher TDD did asynchronously and successfully change their reservoirs while retaining the infusion set. Conclusion: In the OUS limited EIS launch, the EIS performed similarly to the pivotal trial results, with no user complaints. As expected, pump users with TDD less than 40 U changed the infusion set and reservoir at the same time on the seventh day. The product has launched in the US and may potentially reduce user burden by effectively halving the number of required infusion set changes compared to standard 3-day sets. Disclosure T.Kwa: Employee; Medtronic. G.Zhang: Employee; Medtronic. A.Roy: Employee; Medtronic. M.Liu: Employee; Medtronic. E.Anselmo: Employee; Medtronic. J.Shin: Employee; Medtronic. O.Cohen: Employee; Medtronic. S.Chattaraj: Employee; Medtronic.

Objective: Insulin pump users worldwide depend on insulin infusion sets (IISs) for predictable delivery of insulin to the subcutaneous tissue. Yet emerging data indicates that IISs are associated with many pump-related adverse events and may contribute to potentially life-threatening problem of unexplained hyperglycemia. The relative scarcity of published research on IISs to date contributed to the difficulty of IIS section and recommendation. In this cross-over clinical study, a commercial Mio30 infusion set (M30IS) with 30° Teflon cannula was put into head-to-head comparison with a commercial Quick-set infusion set (QIS) with Teflon cannula. Method: This is a cross over study of M30IS and QIS on 20 subjects with Type 1 diabetes. Each subject wore both sets for a month each on a preferred site that was continuously infused with insulin lispro or insulin aspart subcutaneously via a Medtronic 780G pump system for 3 days or until failure. The overall IIS survival rates, glycemic control outcomes (i.e., mean sensor glucose and time spent in established glucose ranges), total daily insulin delivered (TDD), and satisfaction with both IISs were determined. Result: The 20 study subjects comprised of 50% men/women, at 41.3 ± 13.7 years, with BMI 25.7 ± 4.3 and HbA1c 7.0 ± 0.8. Based on the data collected, mean wear duration for the M30IS and QIS was 3.03 and 3.20 days, respectively. The M30IS had slightly more set failures (9.9%) than the QIS (4.4%). TDD and %Time in Range were statistically identical for both M30IS and QIS. Between the two IISs, more people preferred QIS over M30IS Teflon cannula. Conclusion: Choosing between IISs with angled and 90° Teflon cannulas may be a personal preference. In terms of glycemic control, there was no statistical difference between the two IISs. Disclosure O.Cohen: Employee; Medtronic. Y.Cohen: None. S.Chattaraj: Employee; Medtronic. G.Zhang: Employee; Medtronic. E.Anselmo: Employee; Medtronic. A.Tirosh: Advisory Panel; Medtronic, Novo Nordisk, Sanofi, Eli Lilly and Company, Research Support; Medtronic, Sanofi, Speaker's Bureau; Medtronic, Novo Nordisk, Sanofi, Eli Lilly and Company. Funding Medtronic