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To provide real-world data on the addition of basal insulin (BI) in people with type 2 diabetes mellitus (PWD2) suboptimally controlled with glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy. However, real-world data on the addition of BI to GLP-1RA therapy are limited.We used a US electronic medical record data source (IBM® Explorys®) that includes approximately 4 million PWD2 to assess the real-world impact of adding the second-generation BI analogue insulin glargine 300 U/mL (Gla-300) to GLP-1RA therapy. Insulin-naïve PWD2 receiving GLP-1RAs who also received Gla-300 between March 1, 2015 and September 30, 2019 were identified; participants were required to have data for ≥12 months before, and ≥6 months after, addition of Gla-300.The mean (standard deviation [SD]) age of participants (N = 271) was 57.9 (10.8) years. Baseline glycated haemoglobin (HbA1c) was 9.16% and was significantly reduced (-0.97 [SD 1.60]%; P 0.0001) after addition of Gla-300; a significant increase in the proportion of PWD2 achieving HbA1c control was observed after addition of Gla-300 (HbA1c7.0%: 4.80% vs. 22.14%, P 0.0001; HbA1c8.0%: 19.56% vs. 51.29%, P 0.0001). The incidence of overall (8.49% vs. 9.59%; P = 0.513) and inpatient/emergency department (ED)-associated hypoglycaemia (0.37% vs. 0.74%; P = 1.000), as well as overall (0.33 vs. 0.46 per person per year [PPPY]; P = 0.170) and inpatient/ED-associated hypoglycaemia events (0.01 vs. 0.04 PPPY; P = 0.466) were similar before and after addition of Gla-300.In US real-world clinical practice, adding Gla-300 to GLP-1RA significantly improved glycaemic control without significantly increasing hypoglycaemia in PWD2. Further research into the effect of adding Gla-300 to GLP-1RA therapy is warranted.

Innovations in syringe and pen needle (PN) technology over the last 100 years have led to important advances in insulin delivery for people with diabetes, paralleling the strides made in developing recombinant DNA human insulin and insulin analogs with varying onset and duration of action. In this review, the history of advances in insulin delivery is described, focusing on progress in syringe, needle, and PN technologies. The early glass and metal syringes that required sterilization by boiling have been replaced by disposable, single-use syringes or pens with clear labeling for precise insulin dosing. The early needles ranging in length from 19 to 26 mm that required manual sharpening against a whetstone have been replaced by syringe needles of 6 mm and PNs of 4 mm in length as slender as 34 gauge. Imaging studies using ultrasound and computed tomography measured the thickness of skin and subcutaneous tissue layers to show feasibility of targeted insulin administration with shorter needles. These developments, coupled with innovations in needle/PN wall and tip structure, have led to improved injection experience for people with diabetes. It is also important to acknowledge the role of injection technique education, together with these advances in injection technology, for improving clinical outcomes and patient satisfaction. With continued projected growth of diabetes prevalence, particularly in developing countries where expensive and complex insulin delivery systems may not be practical, insulin syringes and pens will continue to serve as reliable and cost-effective means of insulin delivery for people with diabetes.

Insulin exposure varies over 3 days of insulin infusion set (IIS) wear making day-to-day insulin dosing challenging for people with diabetes (PWD). Here we report pharmacodynamic (PD) and pharmacokinetic (PK) data extending these observations to 7 days of IIS wear. PWD (A1C ≤8.5%, C-peptide0.6 nmol/L, ≥6 months pump use) were enrolled in a crossover euglycemic clamp pilot study comparing conventional Teflon angled IISs to an investigational extended-wear IIS. PK/PD data from 6 participants was obtained for 5 hours post-bolus. While PD data were unstable, PK profiles of insulin lispro (0.15 U/kg bolus) show statistically significant, progressive decreases from Day 0 to 7 for tmax (p0.001), t50%(early) (p0.002), t50%(late) (p0.001), and Mean Residence Time (p0.001). AUC0-300 declined by approximately 22% from Day 0 to 7 (n.s.). These results confirm/extend previous observations showing progressive acceleration of insulin exposure over IIS wear time. This may have implications for PWD and designers of closed-loop algorithms, although larger studies are necessary to confirm this.

Hyperglucagonemia contributes to hyperglycemia in patients with type 1 diabetes (T1D); however, novel therapeutics that block glucagon action could improve glycemic control. This phase 2 study evaluated the safety and efficacy of volagidemab, an antagonistic monoclonal glucagon receptor (GCGR) antibody, as an adjunct to insulin therapy in adults with T1D. The primary endpoint was change in daily insulin use at week 12. Secondary endpoints included changes in hemoglobin A1c (HbA1c) at week 13, in average daily blood glucose concentration and time within target range as assessed by continuous blood glucose monitoring (CGM) and seven-point glucose profile at week 12, incidence of hypoglycemic events, the proportion of subjects who achieve HbA1c reduction of ≥0.4%, volagidemab drug concentrations and incidence of anti-drug antibodies. Eligible participants (n = 79) were randomized to receive weekly subcutaneous injections of placebo, 35 mg volagidemab or 70 mg volagidemab. Volagidemab produced a reduction in total daily insulin use at week 12 (35 mg volagidemab: -7.59 units (U) (95% confidence interval (CI) -11.79, -3.39; P = 0.040 versus placebo); 70 mg volagidemab: -6.64 U (95% CI -10.99, -2.29; P = 0.084 versus placebo); placebo: -1.27 U (95% CI -5.4, 2.9)) without meeting the prespecified significance level (P

AIM To confirm the efficacy and safety of dasiglucagon when administered via an autoinjector device. MATERIALS AND METHODS In this double-blind trial, 45 participants with type 1 diabetes were randomized 3:1 to receive a single subcutaneous dose of dasiglucagon 0.6 mg or placebo following controlled induction of hypoglycaemia. The primary endpoint was time to plasma glucose recovery, defined as a plasma glucose increase of 20 mg/dL or higher from baseline without rescue intravenous glucose. RESULTS Median (95% CI) observed time to recovery was 10.0 (8.0; 12.0) minutes for dasiglucagon and 35.0 (20.0; -) minutes for placebo (P

Background Dasiglucagon, a next‐generation, ready‐to‐use aqueous glucagon analog formulation, has been developed to treat severe hypoglycemia in individuals with diabetes. Objective The aim of this trial was to evaluate the safety and efficacy of dasiglucagon in pediatric individuals with type 1 diabetes (T1DM). Participants were children and adolescents (6–17 years) with T1DM. Methods In this randomized double‐blind trial, 42 participants were randomly allocated (2:1:1) to a single subcutaneous (SC) injection of dasiglucagon (0.6 mg), placebo, or reconstituted glucagon (GlucaGen; dosed per label) during insulin‐induced hypoglycemia. The primary endpoint was time to plasma glucose (PG) recovery (first PG increase ≥20 mg/dL after treatment initiation without rescue intravenous glucose). The primary comparison was dasiglucagon vs. placebo; glucagon acted as a reference. Results The median time (95% confidence interval) to PG recovery following SC injection was 10 min (8–12) for dasiglucagon vs. 30 min (20 to –) for placebo (P

Objective: A CGM sensor that is disposable and requires no calibration may make glucose management easier for people living with diabetes. The present study reports on the interim analysis of a new disposable zero-calibration sensor in adults and youth with type 1 (T1D) or type 2 diabetes (T2D) . Methods: A prospective study enrolled individuals (N=123 adults, aged 18-80 years and N=120 youth, aged 2-17 years) with diabetes at 13 sites in the United States. Raw sensor data were compared with a YSI (Yellow Springs Instruments) or blood glucose (BG) reference and involved N=15388 paired points (pps) from the arm of adults, and N=8627pps from the arm and 7781pps from the buttock of youth. Data were processed using a new zero-calibration algorithm. The primary endpoint was agreement within 20%/20mg/dL (sensor glucose [SG] ≥80mg/dL/ Results: The overall 20%/20mg/dL agreement rate was 90.6% for adults, and 87.8% and 88.5% for youth arm and buttock, respectively. For adults, the 15%/15mg/dL agreement rates were 90.1% and 87.6% (SG 180 mg/dL, respectively) . For youth, the 15%/15mg/dL rates were 93.2% and 86.5% for the arm (SG 180 mg/dL, respectively) and 90.3% and 89.5% for the buttock (SG 180 mg/dL, respectively) . The MARDs were 10.2% for adults, and 10.7% and 10.1% for youth arm and buttock, respectively. Conclusion: These interim findings on the clinical performance of the new disposable and calibration-free sensor are good and may support non-adjunctive insulin dosing in standalone CGM and automated insulin delivery systems. Disclosure B.W.Bode: Advisory Panel; CeQur SA, MannKind Corporation, Medtronic, Novo Nordisk, Zealand Pharma A/S, Consultant; Bigfoot Biomedical, Inc., Research Support; Abbott, Beta Bionics, Inc., Dexcom, Inc., Diasome, Dompé, Eli Lilly and Company, Insulet Corporation, IQVIA Inc., Jaeb Center for Health Research, Medtronic, Novo Nordisk, Provention Bio, Inc., REMD Biotherapeutics, Sanvita Medical, Senseonics, ViaCyte, Inc., Speaker’s Bureau; Abbott, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Insulet Corporation, MannKind Corporation, Novo Nordisk, Sanofi, Xeris Pharmaceuticals, Inc., Stock/Shareholder; AgaMatrix, Glytec, LLC. J.Shin: Employee; Medtronic. F.Peng: None. S.Huang: n/a. A.S.Rhinehart: Employee; Medtronic, Stock/Shareholder; Medtronic. R.A.Vigersky: Employee; Medtronic. T.S.Bailey: Advisory Panel; Abbott Diabetes, CeQur SA, MannKind Corporation, Medtronic, Novo Nordisk, Consultant; LifeScan, Sanofi, Research Support; Abbott Diabetes, Abbott Diagnostics, Biolinq, Capillary Biomedical, Inc., Dexcom, Inc., Eli Lilly and Company, Kowa Research Institute, Inc., Livongo, MannKind Corporation, Medtronic, Novo Nordisk, REMD Biotherapeutics, Sanofi, Sanvita Medical, Senseonics, ViaCyte, Inc., vTv Therapeutics, Zealand Pharma A/S, Speaker’s Bureau; Becton, Dickinson and Company, Medtronic, Sanofi. K.N.Castorino: Consultant; Lilly Diabetes, Research Support; Abbott Diabetes, Dexcom, Inc., Drawbridge Health, Inc., Eyenuk, Inc., Laxmi Therapeutic Devices, Medtronic, National Institute of Diabetes and Digestive and Kidney Diseases, Novo Nordisk, Speaker’s Bureau; Dexcom, Inc. M.P.Christiansen: Research Support; Abbott Diabetes, Ascensia Diabetes Care, AstraZeneca, Biolinq, Dexcom, Inc., Eli Lilly and Company, Helixmith, MannKind Corporation, Medtronic, Merck Sharp & Dohme Corp. S.K.Garg: Advisory Panel; Bayer AG, Medtronic, Zealand Pharma A/S, Consultant; Novo Nordisk, Research Support; Dexcom, Inc., Medtronic. K.B.Kaiserman: Advisory Panel; Medtronic, Consultant; Medtronic, Employee; MannKind Corporation, Research Support; Medtronic, Speaker’s Bureau; Medtronic, Stock/Shareholder; MannKind Corporation. D.R.Liljenquist: None. D.I.Shulman: Advisory Panel; Medtronic. R.H.Slover: None.

Insulin exposure and action are known to differ on each of 3 days of infusion set wear during CSII. We extend these observations to 1 week in a pilot phase study comparing conventional Teflon angled infusion sets to a prototype extended wear set using Capillary Biomedical SteadiFlow™ technology. Participants with T1DM for >12 months, A1C Disclosure T.S.Bailey: Advisory Panel; Abbott Diabetes, CeQur SA, MannKind Corporation, Medtronic, Novo Nordisk, Consultant; LifeScan, Sanofi, Research Support; Abbott Diabetes, Abbott Diagnostics, Biolinq, Capillary Biomedical, Inc., Dexcom, Inc., Eli Lilly and Company, Kowa Research Institute, Inc., Livongo, MannKind Corporation, Medtronic, Novo Nordisk, REMD Biotherapeutics, Sanofi, Sanvita Medical, Senseonics, ViaCyte, Inc., vTv Therapeutics, Zealand Pharma A/S, Speaker's Bureau; Becton, Dickinson and Company, Medtronic, Sanofi. J.R.Kastner: Consultant; Capillary Biomedical, Inc. P.Strange: Other Relationship; Capillary Biomedical, Inc., Stock/Shareholder; Capillary Biomedical, Inc. L.Shi: None. K.A.Oberg: Consultant; Beta Bionics, Inc., Companion Medical, Tandem Diabetes Care, Inc. J.I.Joseph: Advisory Panel; Capillary Biomedical, Inc., Stock/Shareholder; Capillary Biomedical, Inc. P.J.Strasma: Board Member; Capillary Biomedical, Inc., Employee; Capillary Biomedical, Inc., Stock/Shareholder; Capillary Biomedical, Inc. D.B.Muchmore: Consultant; Capillary Biomedical, Inc., Diasome, Zucara Therapeutics, Stock/Shareholder; Capillary Biomedical, Inc., Diasome. Funding National Institutes of Health (2R44DK110969-02)

There is limited data on the performance of point of care HbA1c assays when fingerstick samples are tested by intended users in CLIA waived settings. This study evaluated the precision of the Afinion HbA1c Dx (Afinion) when performed at CLIA waived sites (N=5) by operators with no laboratory training. The operators (N=12) self-trained using the materials provided with test purchase, had no prior Afinion system experience, and did not observe one another during testing. For each subject enrolled in the study (N=115) , 2 operators each obtained 2 fingerstick samples (4 total fingersticks per subject) and tested one sample on each of 2 Afinion instruments. The repeatability, between-operator, and between-instrument components of variance were calculated using the REML method for each of 4 HbA1c concentration intervals. The total imprecision was calculated as a composite of 6 relevant components of variance, including a) the components of variance estimated here (repeatability, between-operator, and between-instrument) , and b) components of variance estimated in prior studies (between-run, between-day, and between-lot) . The repeatability was the dominant component, ranging from 0.83-1.14% CV across the HbA1c concentration intervals. The between-operator component was 0.00% CV for 3 out of the 4 HbA1c intervals, and was only 0.19% CV in the remaining interval, indicating the precision of the test is not operator dependent. The between-instrument component ranged from 0.22-0.39% CV. When combined with the other components of variance estimated in prior studies, the total imprecision does not exceed 1.80% CV, which is below the National Academy of Clinical Biochemistry’s (NACB) recommendation for a single method, interlaboratory CV of These results indicate that the precision of the Afinion is comparable to many laboratory HbA1c assays, and suitable for use in CLIA waived settings. Disclosure M.Clendenin: Employee; Abbott. N.Ahmed: Employee; Abbott. K.Kupfer: Employee; Abbott. C.L.Green: Employee; Abbott Diagnostics, Siemens. K.S.Fortner: Employee; Abbott. T.S.Bailey: Advisory Panel; Abbott Diabetes, CeQur SA, MannKind Corporation, Medtronic, Novo Nordisk, Consultant; LifeScan, Sanofi, Research Support; Abbott Diabetes, Abbott Diagnostics, Biolinq, Capillary Biomedical, Inc., Dexcom, Inc., Eli Lilly and Company, Kowa Research Institute, Inc., Livongo, MannKind Corporation, Medtronic, Novo Nordisk, REMD Biotherapeutics, Sanofi, Sanvita Medical, Senseonics, ViaCyte, Inc., vTv Therapeutics, Zealand Pharma A/S, Speaker's Bureau; Becton, Dickinson and Company, Medtronic, Sanofi. S.Brick: None. S.I.Smiley: None. G.S.Strauss: None. A.A.Thorsell: None.

The introduction of home blood glucose monitoring (BGM) 40 years ago revolutionized diabetes self-management, providing valuable glucose data that have helped many people with diabetes (PWD) improve their glycemic management. In the early 2000s, personal continuous glucose monitoring (CGM) systems also became available, raising questions regarding the future role of BGM. However, for some PWD, particularly many with type 2 diabetes who do not take medications associated with increased hypoglycemia risk, BGM remains more easily accessible and more affordable than CGM and can adequately meet their needs. In addition, PWD who use CGM still need to periodically use BGM. This publication reviews key issues related to the optimal and most cost-effective use of BGM. The authors address the accuracy of modern glucose meters and the recommended frequency of monitoring for people with different types of diabetes and therapeutic regimens. They suggest strategies for using glycemic data to inform therapy adjustments, as well as ways to overcome common barriers to BGM use. They then review the use of BGM in patients who also use CGM and describe the latest related technological innovations, including Cloud-based data management, mobile applications, insulin calculators, and remote and automated counseling systems. The authors conclude that BGM remains an important tool in diabetes management, even as diabetes management technologies continue to evolve.

Aims To compare the safety and efficacy of insulin glargine 300 U/mL (Gla-300) versus first-generation standard-of-care basal insulin analogues (SOC-BI; insulin glargine 100 U/mL or insulin detemir) at 6 months. Methods In the 12-month, open-label, multicentre, randomized, pragmatic ACHIEVE Control trial, insulin-naive adults with type 2 diabetes (T2D) and glycated haemoglobin A1c (HbA1c) 64-97 mmol/mol (8.0%-11.0%) after ≥1 year of treatment with ≥2 diabetes medications were randomized to Gla-300 or SOC-BI. The composite primary endpoint, evaluated at 6 months, was the proportion of participants achieving individualized HbA1c targets per HEDIS criteria without documented symptomatic (blood glucose ≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia at any time of the day at 6 months. Results Of 1651 and 1653 participants randomized to Gla-300 and SOC-BI, respectively, 31.3% and 27.9% achieved the composite primary endpoint at 6 months (odds ratio [OR] 1.19; 95% CI 1.01-1.39; P = 0.03 for superiority); 78.4% and 75.3% had no documented symptomatic or severe hypoglycaemia (OR 1.19; 95% CI 1.01-1.41). Changes from baseline to month 6 in HbA1c, fasting plasma glucose, weight, and BI analogue dose were similar between groups. Conclusions Among insulin-naive adults with poorly controlled T2D, Gla-300 was associated with a statistically significant higher proportion of participants achieving individualized HEDIS HbA1c targets without documented symptomatic or severe hypoglycaemia (versus SOC-BI) in a real-life population managed in a usual-care setting. The ACHIEVE Control study results add value to treatment decisions and options for patients, healthcare providers, payers, and decision makers. ClinicalTrials.gov identifier: NCT02451137 This article is protected by copyright. All rights reserved.

Hyperglucagonemia contributes to hyperglycemia in patients with type 1 diabetes (T1D); however, novel therapeutics that block glucagon action could improve glycemic control. This phase 2 study evaluated the safety and efficacy of volagidemab, an antagonistic monoclonal glucagon receptor (GCGR) antibody, as an adjunct to insulin therapy in adults with T1D. The primary endpoint was change in daily insulin use at week 12. Secondary endpoints included changes in hemoglobin A1c (HbA1c) at week 13, in average daily blood glucose concentration and time within target range as assessed by continuous blood glucose monitoring (CGM) and seven-point glucose profile at week 12, incidence of hypoglycemic events, the proportion of subjects who achieve HbA1c reduction of ≥0.4%, volagidemab drug concentrations and incidence of anti-drug antibodies. Eligible participants (n = 79) were randomized to receive weekly subcutaneous injections of placebo, 35 mg volagidemab or 70 mg volagidemab. Volagidemab produced a reduction in total daily insulin use at week 12 (35 mg volagidemab: -7.59 units (U) (95% confidence interval (CI) -11.79, -3.39; P = 0.040 versus placebo); 70 mg volagidemab: -6.64 U (95% CI -10.99, -2.29; P = 0.084 versus placebo); placebo: -1.27 U (95% CI -5.4, 2.9)) without meeting the prespecified significance level (P lt; 0.025). At week 13, the placebo-corrected reduction in HbA1c percentage was -0.53 (95% CI -0.89 to -0.17, nominal P = 0.004) in the 35 mg volagidemab group and -0.49 (95% CI -0.85 to -0.12, nominal P = 0.010) in the 70 mg volagidemab group. No increase in hypoglycemia was observed with volagidemab therapy; however, increases in serum transaminases, low-density lipoprotein (LDL)-cholesterol and blood pressure were observed. Although the primary endpoint did not meet the prespecified significance level, we believe that the observed reduction in HbA1c and tolerable safety profile provide a rationale for further randomized studies to define the long-term efficacy and safety of volagidemab in patients with T1D.

Aims To compare 12‐month clinical effectiveness of insulin glargine 300 units/mL (Gla‐300) versus first‐generation basal insulin analogues (BIAs) (insulin glargine 100 units/mL [Gla‐100] or insulin detemir [IDet]) in patients with type 2 diabetes (T2D) who were at high risk of hypoglycaemia and switched from one BIA to a different one (Gla‐300 or Gla‐100/IDet) in a real‐world setting. Methods DELIVER High Risk was a retrospective observational cohort study of 2550 patients with T2D who switched BIA to Gla‐300 (Gla‐300 switchers) and were propensity score‐matched (1:1) to patients who switched to Gla‐100 or IDet (Gla‐100/IDet switchers). Outcomes were change in glycated haemoglobin A1c (HbA1c), attainment of HbA1c goals (, In patients with type 2 diabetes at high risk of hypoglycaemia, risk of inpatient/emergency department‐related hypoglycaemia was significantly lower during 12 months after switching to insulin glargine 300 units/mL, compared with switching to insulin glargine 100 units/mL or insulin detemir.

Background ACHIEVE Control, a prospective, open-label, randomized, pragmatic, real-life study in insulin-naive people with type 2 diabetes (A1C 8.0–11.0%), demonstrated superiority of insulin glargine 300 units/mL (Gla-300) versus first-generation standard-of-care basal insulin (SOC-BI; glargine 100 units/mL or insulin detemir) in achieving individualized A1C targets without documented symptomatic (glucose ≤3.9 mmol/L [≤70 mg/dL] or Methods Subgroup analyses were performed per concomitant use/nonuse of sulfonylureas, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase 4 inhibitors, or sodium–glucose cotransporter 2 (SGLT2) inhibitors. End points (6 and 12 months) included A1C target attainment without documented symptomatic or severe hypoglycemia, A1C target attainment, and absence of documented symptomatic or severe hypoglycemia. Results Odds ratios (ORs) at 12 months mostly favored Gla-300 versus SOC-BI across subgroups except in analysis of SGLT2 inhibitors, in which ORs were similar. Among sulfonylurea users, ORs at 12 months strongly favored Gla-300 versus SOC-BI for all end points, particularly A1C target achievement without documented symptomatic hypoglycemia (glucose ≤3.9 mmol/L [≤70 mg/dL]; OR 1.25, 95% CI 1.02–1.53) or severe hypoglycemia and achievement of no documented symptomatic hypoglycemia (glucose Conclusion The results suggest that, in insulin-naive people with type 2 diabetes, Gla-300 is effective with a risk of hypoglycemia that is lower than or similar to that of SOC-BI regardless of background medication. Individuals receiving concomitant sulfonylureas were more likely to remain without symptomatic or severe hypoglycemia with Gla-300.

BACKGROUND Severe hypoglycemic episodes are life-threatening events demanding rapid administration of glucagon by a caregiver or bystander. The glucagon analog dasiglucagon is stable in aqueous formulation and therefore suitable for delivery in a ready-to-use autoinjector, potentially increasing speed and ease of use compared with standard glucagon emergency kits (GEKs). METHODS In an open-label, randomized, crossover, comparative device handling study, trained caregivers and untrained bystanders administered the dasiglucagon autoinjector or Eli Lilly GEK to manikins in a simulated emergency hypoglycemia situation. RESULTS In total, 54 participants were randomized (18 patient-caregiver pairs and 18 bystanders). Overall, 94% of trained caregivers were able to administer the dasiglucagon autoinjector successfully within 15 minutes, compared with 56% for the GEK (P

Continuous glucose monitoring devices have significantly improved in many respects compared with earlier versions. As sensor accuracy improved, U.S. Food and Drug Administration approved a nonadjun...

Background: Use of continuous glucose monitoring (CGM) systems is being rapidly adopted as standard of care for insulin-requiring patients with diabetes. The PROMISE study (NCT03808376) evaluated the accuracy and safety of the next-generation implantable Eversense CGM system for up to 180 days. Methods: This was a prospective multicenter study involving 181 subjects with diabetes at 8 USA sites. All subjects were inserted with a primary sensor. Ninety-six subjects had a second sensor, either an identical sensor or a modified sensor (sacrificial boronic acid [SBA]), inserted in their other arm (53 and 43 subjects, respectively). Accuracy was evaluated by comparing CGM to YSI 2300 glucose analyzer (Yellow Springs Instrument [YSI]) values during 10 clinic visits (day 1–180). Confirmed event detection rates, calibration stability, sensor survival, and serious adverse events (SAEs) were evaluated. Results: For primary sensors, the percent CGM readings within 20%/20% of YSI values was 92.9%; overall mean absolute relative difference (MARD) was 9.1%. The confirmed alert detection rate at 70 mg/dL was 93% and at 180 mg/dL was 99%. The median percentage of time for one calibration per day was 56%. Sixty-five percent of the primary sensors survived to 180 days. For the SBA sensors, the percent CGM readings within 20%/20% of YSI values was 93.9%; overall MARD was 8.5%. The confirmed alert detection rate at 70 mg/dL was 94% and at 180 mg/dL was 99%. The median percentage of time for one calibration per day was 63%. Ninety percent of the SBA sensors survived to 180 days. No device- or insertion/removal procedure-related SAEs were reported. Conclusion: These data show the next-generation Eversense CGM system had sustained accuracy and safety up to 180 days, with an improved calibration scheme and survival, using the primary or SBA sensors.

Objective: Most insulin infusion sets (ISs) are labeled for 2- or 3-days use. The Medtronic EWIS is designed to increase wear time up to 7 days. This study reports on EWIS survival and performance during the pivotal trial (ClinicalTrials.gov: NCT04113694). Method: This multi-center (15), single-arm, non-randomized, non-inferiority trial in 259 participants (18-80yrs) with T1D using the MiniMed™ 670G system (with Humalog™ or Novolog™ insulin) involved wearing a 2- or 3-day IS for 2 weeks (run-in) followed by 12 consecutive EWIS wears (study phase). The latter was worn for ≥174 hours or until set failure. Safety and performance (i.e., a priori target of Result: The EWIS survival rate was 74.8% versus the 67.7% rate of 2- or 3-day ISs (p Conclusion: The 7-day EWIS was safe and its performance was superior at ≥174 hours compared to the performance observed for 2- or 3-day infusion sets. Disclosure B. A. Buckingham: Advisory Panel; Self; Medtronic, Tolerion, Inc., Research Support; Self; Beta Bionics, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care. B. Horowitz: Research Support; Self; Abbott Laboratories, BD, Celgene, Crinetics Pharmaceuticals, Gan & Lee Pharmaceuticals, Medtronic, Speaker’s Bureau; Self; AstraZeneca, Lilly Diabetes, Merck & Co., Inc., Novo Nordisk Inc. K. B. Kaiserman: Advisory Panel; Self; Medtronic, Consultant; Self; Medtronic, Employee; Self; MannKind Corporation, Research Support; Self; Medtronic, Speaker’s Bureau; Self; Medtronic, Stock/Shareholder; Self; MannKind Corporation. S. Huang: None. V. Chen: Employee; Self; Medtronic. G. Zhang: Employee; Self; Medtronic. S. Chattaraj: Employee; Self; Medtronic. J. Shin: Employee; Self; Medtronic. R. Vigersky: Employee; Self; Medtronic. R. L. Brazg: Research Support; Self; Abbott Diabetes, Ascensia Diabetes Care, Lexicon Pharmaceuticals, Inc., Lilly Diabetes, Medtronic, Pfizer Inc., Roche Diagnostic USA, Senseonics. T. S. Bailey: Consultant; Self; Abbott Diabetes, LifeScan, Novo Nordisk, Sanofi, Research Support; Self; Abbott, Abbott Diabetes, Biolinq, Capillary Biomedical, Inc., Dexcom, Inc., Eli Lilly and Company, Kowa Research Institute, Inc., Lexicon Pharmaceuticals, Inc., Livongo, Medtronic, Medtrum Technologies, Novo Nordisk, REMD Biotherapeutics, Sanofi, Sanvita, Viacyte, Inc., vTv Therapeutics, Zealand Pharma A/S, Speaker’s Bureau; Self; BD, Medtronic, Sanofi. Y. C. Kudva: Research Support; Self; Dexcom, Inc. S. K. Garg: Advisory Panel; Self; Eli Lilly and Company, Medtronic, Novo Nordisk Inc., Zealand Pharma A/S, Research Support; Self; Dexcom, Inc., Eli Lilly and Company, Medtronic. G. Grunberger: Research Support; Self; Medtronic, Speaker’s Bureau; Self; Abbott Diabetes, Eli Lilly and Company, Novo Nordisk. J. Thrasher: Advisory Panel; Self; Medtronic, Board Member; Self; Medtronic, Consultant; Self; Medtronic, Research Support; Self; Eli Lilly and Company, Lexicon Pharmaceuticals, Inc., Medtronic, Mylan N. V., Novo Nordisk, Sanofi, Speaker’s Bureau; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Medtronic, Sanofi. A. Cavale: Research Support; Self; Eli Lilly and Company, Medtronic. A. Bhargava: Research Support; Self; Abbott, AbbVie Inc., Amgen Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Boston Therapeutics, Inc., Covance Inc., Dexcom, Inc., Eli Lilly and Company, Gan & Lee Pharmaceuticals, Insulet Corporation, Janssen Research & Development, LLC, Kowa Pharmaceuticals America, Inc., Madrigal Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Mylan N. V., Novo Nordisk, Poxel SA, Quintiles, Sanofi, Senseonics, Tolerion, Inc., Viking Therapeutics.

Abnormal regulation of glucagon secretion contributes to impaired glycemic control in patients with T1D. We conducted two 12-week, double-blind, randomized, placebo-controlled trials to evaluate the efficacy of blocking glucagon action with the glucagon receptor antagonist antibody, volagidemab (VOLA), on glycemic control in patients with T1D. In both trials, participants were randomized in a 1:1:1 fashion to weekly subcutaneous injection with placebo (PBO), VOLA 35 mg, or VOLA 70 mg. Participants in Trial 1 (n=75) were unblinded and participants in Trial 2 (n=78) were blinded to the data from the study-provided continuous glucose monitoring (CGM). All participants could monitor glucose values by fingerstick or their own CGM, if these modalities were part of their usual care before the study. In Trial 1, baseline A1C was 7.5% and decreased by 0.39% (PBO), 0.64% (35 mg, p=0.029), and 0.69% (70 mg, p=0.008) at week 12. An A1C target of ≤ 7.0% was achieved in 43% (PBO), 70% (VOLA 35 mg), and 71% (VOLA 70 mg) of participants. Insulin total daily dose (TDD) decreased by 6.3% (PBO), 12.9% (VOLA 35 mg, NS) and 12.2% (VOLA 70 mg, NS) at week 12. In Trial 2, baseline A1C was 7.9% and decreased by 0.03% (PBO), 0.63% (VOLA 35 mg, p=0.001) and 0.66% (VOLA 70 mg, p=0.001). An A1C target of ≤7.0% was achieved in 17% (PBO), 50% (VOLA 35 mg), and 38% (VOLA 70 mg) of participants. Insulin TDD decreased by 3.5% (PBO), 15.1% (VOLA 35 mg, NS), and 10.2% (VOLA 70 mg, NS). A majority of adverse events were Grade 2 or lower in severity. Intermittent Increases in BP and ALT were observed in VOLA vs. placebo participants during the dosing period and returned to BL after treatment discontinuation. These data demonstrate that treatment with VOLA 35 mg or 70 mg once weekly as an adjunct to insulin is safe, well-tolerated, and decreases A1C with a trend toward decreased insulin dosing in people with T1D. Disclosure J. Pettus: Advisory Panel; Self; Novo Nordisk, Sanofi, Consultant; Self; Diasome Pharmaceuticals, Inc., Insulet Corporation, Lilly Diabetes, MannKind Corporation, Tandem Diabetes Care. B. W. Bode: Advisory Panel; Self; Eli Lilly and Company, Consultant; Self; Bigfoot Biomedical, Inc., Companion Medical, Lexicon Pharmaceuticals, Inc., Medtronic, Novo Nordisk Inc., Zealand Pharma A/S, Research Support; Self; Abvance Therapeutics, Dexcom, Inc., Diasome Pharmaceuticals, Inc., Dompe, Eli Lilly and Company, Eyenuk, Inc., Insulet Corporation, Jaeb Center for Health Research, Medtronic, Nova Biomedical, Novo Nordisk, Provention Bio, Inc., REMD Biotherapeutics, Sanofi, Senseonics, Viacyte, Inc., vTv Therapeutics, Xeris Pharmaceuticals, Inc., Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, MannKind Corporation, Medtronic, Novo Nordisk, Sanofi, Stock/Shareholder; Self; AgaMatrix, Aseko, Inc., Glytec, LLC. E. D. Bautista: Consultant; Self; REMD Biotherapeutics. H. Yan: Board Member; Self; REMD Biotherapeutics, Other Relationship; Spouse/Partner; REMD Biotherapeutics. D. Thai: Employee; Self; REMD Biotherapeutics. S. K. Garg: Advisory Panel; Self; Eli Lilly and Company, Medtronic, Novo Nordisk Inc., Zealand Pharma A/S, Research Support; Self; Dexcom, Inc., Eli Lilly and Company, Medtronic. S. Klein: Advisory Panel; Self; Altimmune, Merck & Co., Inc., Novo Nordisk Inc., ProSciento, Research Support; Self; Janssen Research & Development, LLC. S. C. Boeder: Consultant; Self; Cecelia Health, Research Support; Self; Dexcom, Inc. M. P. Christiansen: Research Support; Self; Abbott Diabetes, Biolinq, Dexcom, Inc., Eli Lilly and Company, Medtronic, Merck & Co., Inc., Novo Nordisk A/S, Pfizer Inc., Viacyte, Inc. D. S. Denham: None. T. S. Bailey: Consultant; Self; Abbott Diabetes, LifeScan, Novo Nordisk, Sanofi, Research Support; Self; Abbott, Abbott Diabetes, Biolinq, Capillary Biomedical, Inc., Dexcom, Inc., Eli Lilly and Company, Kowa Research Institute, Inc., Lexicon Pharmaceuticals, Inc., Livongo, Medtronic, Medtrum Technologies, Novo Nordisk, REMD Biotherapeutics, Sanofi, Sanvita, Viacyte, Inc., vTv Therapeutics, Zealand Pharma A/S, Speaker’s Bureau; Self; BD, Medtronic, Sanofi. H. K. Akturk: Consultant; Self; American Diabetes Association, Research Support; Self; Dexcom, Inc., Eli Lilly and Company, IM Therapeutics, MannKind Corporation, REMD Biotherapeutics, Senseonics, Speaker’s Bureau; Self; American Diabetes Association. L. J. Klaff: Research Support; Self; Abbott Diabetes, Dong-A ST Co. Ltd., Gan & Lee Pharmaceuticals, Lexicon Pharmaceuticals, Inc., Lilly Diabetes, Medtronic, Novo Nordisk, Oramed Pharmaceuticals, Inc., Pfizer Inc., REMD Biotherapeutics. J. Rosenstock: Board Member; Self; Applied Therapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Novo Nordisk, Oramed Pharmaceuticals, Inc., Sanofi, Consultant; Self; Applied Therapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Novo No

The efficacy of dasiglucagon 0.6 mg, a glucagon analog stable in aqueous formulation, has been established versus placebo in previously reported trials in adults with type 1 diabetes mellitus. An integrated analysis was conducted to investigate efficacy in demographic and other subgroups. To allow as many individuals as possible in the evaluation, the analysis comprised data from 4 trials in adults, including 2 pivotal trials, an additional phase 3 trial, and a phase 2 trial. The trials were conducted under similar conditions with respect to design characteristics, such as target population, background therapy and treatment duration. All trials included efficacy assessments following insulin-induced hypoglycemia and showed consistent efficacy results across trials. The primary endpoint was time to plasma glucose (PG) recovery, defined as first PG increase ≥ 20 mg/dL after treatment initiation without need for rescue intravenous glucose. A total of 220 participants were exposed to dasiglucagon 0.6 mg across trials. Results of the integrated analysis are shown as a Forest plot of median time to PG recovery for dasiglucagon, including 95% confidence intervals by subgroup. In conclusion, the results showed that the efficacy of dasiglucagon was highly consistent across subgroups, with a median time to recovery from insulin-induced hypoglycemia of 10 minutes in most groups. Disclosure T. Battelino: Advisory Panel; Self; Eli Lilly and Company, Medtronic, Sanofi, Research Support; Self; European Union, National Institute of Diabetes and Digestive and Kidney Diseases, Novartis Pharmaceuticals Corporation, Novo Nordisk, Sanofi, Slovenian Research Agency, Zealand Pharma A/S, Speaker’s Bureau; Self; Abbott Diabetes, AstraZeneca, Dexcom, Inc., Eli Lilly and Company, Medtronic, Novo Nordisk, Pfizer Inc., Roche Diabetes Care, Sanofi, Stock/Shareholder; Self; DreaMed Diabetes, Ltd. L. Dimeglio: Advisory Panel; Self; MannKind Corporation. T. Danne: Research Support; Self; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Medtronic, Novo Nordisk, Sanofi, Tandem Diabetes Care, Zealand Pharma A/S, Stock/Shareholder; Self; DreaMed Diabetes, Ltd. T. S. Bailey: Consultant; Self; Abbott Diabetes, LifeScan, Novo Nordisk, Sanofi, Research Support; Self; Abbott, Abbott Diabetes, Biolinq, Capillary Biomedical, Inc., Dexcom, Inc., Eli Lilly and Company, Kowa Research Institute, Inc., Lexicon Pharmaceuticals, Inc., Livongo, Medtronic, Medtrum Technologies, Novo Nordisk, REMD Biotherapeutics, Sanofi, Sanvita, Viacyte, Inc., vTv Therapeutics, Zealand Pharma A/S, Speaker’s Bureau; Self; BD, Medtronic, Sanofi. R. Tehranchi: Employee; Self; Zealand Pharma A/S. L. J. Klaff: Research Support; Self; Abbott Diabetes, Dong-A ST Co. Ltd., Gan & Lee Pharmaceuticals, Lexicon Pharmaceuticals, Inc., Lilly Diabetes, Medtronic, Novo Nordisk, Oramed Pharmaceuticals, Inc., Pfizer Inc., REMD Biotherapeutics. T. Pieber: Advisory Panel; Self; ADOCIA, Arecor, AstraZeneca, Eli Lilly and Company, Novo Nordisk A/S, Sanofi, Research Support; Self; AstraZeneca, Novo Nordisk A/S. U. Hovelmann: None. L. Plum-moerschel: None. A. E. Melgaard: Employee; Self; Zealand Pharma A/S. R. Aronson: None.

The efficacy of dasiglucagon 0.6 mg has been investigated in multiple trials in individuals with T1DM. The primary endpoint was time to plasma glucose (PG) recovery from insulin-induced hypoglycemia, defined as first PG increase ≥20 mg/dL after treatment initiation without the need for IV glucose. Different PG sampling schemes were used in phase 2 (5-min intervals) versus phase 3 trials (more frequent sampling). Estimating the true but unmeasured time to recovery for each individual enables for a better comparison between trials when compared to use of observed time only. The true time was calculated using linear interpolation between the 2 time points before and after recovery occurred, assuming a linear PG increase in this limited time interval. The difference between the observed and the estimated true recovery for an individual is illustrated in the figure. The PG sample taken at 10 min is the first sample showing an increase of at least 20 mg/dL from the predose level, leading to an observed time to recovery of 10 min. Linear interpolation estimates the increase of 20 mg/dL to occur at 9 min for this individual. Using interpolated PG values, the median estimated true time to recovery for dasiglucagon was 8.7 min in the phase 2 trial and 9.0 to 9.3 min in phase 3 trials. These data provide further insight into the probable “true time to recovery” and confirm the consistent efficacy of dasiglucagon in the treatment of hypoglycemia. Disclosure T. Battelino: Advisory Panel; Self; Eli Lilly and Company, Medtronic, Sanofi, Research Support; Self; European Union, National Institute of Diabetes and Digestive and Kidney Diseases, Novartis Pharmaceuticals Corporation, Novo Nordisk, Sanofi, Slovenian Research Agency, Zealand Pharma A/S, Speaker’s Bureau; Self; Abbott Diabetes, AstraZeneca, Dexcom, Inc., Eli Lilly and Company, Medtronic, Novo Nordisk, Pfizer Inc., Roche Diabetes Care, Sanofi, Stock/Shareholder; Self; DreaMed Diabetes, Ltd. L. Dimeglio: Advisory Panel; Self; MannKind Corporation. T. Danne: Research Support; Self; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Medtronic, Novo Nordisk, Sanofi, Tandem Diabetes Care, Zealand Pharma A/S, Stock/Shareholder; Self; DreaMed Diabetes, Ltd. A. L. Peters: Advisory Panel; Self; Abbott Diabetes, Eli Lilly and Company, MannKind Corporation, Medscape, Merck & Co., Inc., Novo Nordisk Inc., Zealand Pharma A/S, Other Relationship; Self; Livongo, Research Support; Self; Abbott Diabetes, Dexcom, Inc. T. S. Bailey: Consultant; Self; Abbott Diabetes, LifeScan, Novo Nordisk, Sanofi, Research Support; Self; Abbott, Abbott Diabetes, Biolinq, Capillary Biomedical, Inc., Dexcom, Inc., Eli Lilly and Company, Kowa Research Institute, Inc., Lexicon Pharmaceuticals, Inc., Livongo, Medtronic, Medtrum Technologies, Novo Nordisk, REMD Biotherapeutics, Sanofi, Sanvita, Viacyte, Inc., vTv Therapeutics, Zealand Pharma A/S, Speaker’s Bureau; Self; BD, Medtronic, Sanofi. R. Tehranchi: Employee; Self; Zealand Pharma A/S. L. J. Klaff: Research Support; Self; Abbott Diabetes, Dong-A ST Co. Ltd., Gan & Lee Pharmaceuticals, Lexicon Pharmaceuticals, Inc., Lilly Diabetes, Medtronic, Novo Nordisk, Oramed Pharmaceuticals, Inc., Pfizer Inc., REMD Biotherapeutics. T. Pieber: Advisory Panel; Self; ADOCIA, Arecor, AstraZeneca, Eli Lilly and Company, Novo Nordisk A/S, Sanofi, Research Support; Self; AstraZeneca, Novo Nordisk A/S. U. Hovelmann: None. L. Plum-moerschel: None. A. E. Melgaard: Employee; Self; Zealand Pharma A/S. R. Aronson: None.

Background: The prospective, multi-center PROMISE study evaluated the safety and accuracy of the next generation Eversense CGM System for up to 180 days in 181 adults with diabetes at 8 US clinical sites. Methods: Accuracy was evaluated by comparing CGM and reference values from Yellow Springs Instruments (YSI) during 10 clinic visits from day 1-180, which included hyperglycemia and hypoglycemia challenges. Eighty-five and 96 subjects had 1 and 2 sensors inserted in the arm, respectively, with 2 replaced sensors for 279 sensors (558 insertions/removals). The CGM prompts 2 calibrations/day to day 21, after which it primarily prompts 1 calibration/day. Results: The Table shows accuracy analyses based on 49,613 matched pairs over 180 days. Percent CGM readings within 15/15% and 20/20% of YSI values was 85.6% and 92.9%, respectively, and the MARD was 9.1%. MARDs across different glucose ranges from 40-400 mg/dL were ≤9.4% (Table). The confirmed hypoglycemia detection rates at 70mg/dL and 60 mg/dL were 93% and 87%, respectively. Hyperglycemia at 180mg/dL was detected in 99%. There were no device or insertion/removal procedure-related serious adverse events. Two mild skin infections occurred for a rate of 0.36% per procedure. Conclusion: These results indicate the next generation Eversense long-term implantable CGM System has sustained accuracy and safety up to 180 days with primarily one calibration/day. Disclosure S. K. Garg: Advisory Panel; Self; Eli Lilly and Company, Medtronic, Novo Nordisk Inc., Zealand Pharma A/S, Research Support; Self; Dexcom, Inc., Eli Lilly and Company, Medtronic. A. D. Dehennis: Employee; Self; Senseonics. K. Tweden: Employee; Self; Senseonics. F. R. Kaufman: Advisory Panel; Self; Virta Health Corp., Employee; Self; Senseonics, Stock/Shareholder; Self; Medtronic. D. R. Liljenquist: Research Support; Self; Abbott Diabetes, AbbVie Inc., Ascensia Diabetes Care, Dexcom, Inc., Drawbridge Health, Inc., Eyenuk, Inc., Jaeb Center for Health Research, Medtronic, Provention Bio, Inc., Senseonics. B. W. Bode: Advisory Panel; Self; Eli Lilly and Company, Consultant; Self; Bigfoot Biomedical, Inc., Companion Medical, Lexicon Pharmaceuticals, Inc., Medtronic, Novo Nordisk Inc., Zealand Pharma A/S, Research Support; Self; Abvance Therapeutics, Dexcom, Inc., Diasome Pharmaceuticals, Inc., Dompe, Eli Lilly and Company, Eyenuk, Inc., Insulet Corporation, Jaeb Center for Health Research, Medtronic, Nova Biomedical, Novo Nordisk, Provention Bio, Inc., REMD Biotherapeutics, Sanofi, Senseonics, Viacyte, Inc., vTv Therapeutics, Xeris Pharmaceuticals, Inc., Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, MannKind Corporation, Medtronic, Novo Nordisk, Sanofi, Stock/Shareholder; Self; AgaMatrix, Aseko, Inc., Glytec, LLC. M. P. Christiansen: Research Support; Self; Abbott Diabetes, Biolinq, Dexcom, Inc., Eli Lilly and Company, Medtronic, Merck & Co., Inc., Novo Nordisk A/S, Pfizer Inc., Viacyte, Inc. T. S. Bailey: Consultant; Self; Abbott Diabetes, LifeScan, Novo Nordisk, Sanofi, Research Support; Self; Abbott, Abbott Diabetes, Biolinq, Capillary Biomedical, Inc., Dexcom, Inc., Eli Lilly and Company, Kowa Research Institute, Inc., Lexicon Pharmaceuticals, Inc., Livongo, Medtronic, Medtrum Technologies, Novo Nordisk, REMD Biotherapeutics, Sanofi, Sanvita, Viacyte, Inc., vTv Therapeutics, Zealand Pharma A/S, Speaker’s Bureau; Self; BD, Medtronic, Sanofi. R. L. Brazg: Research Support; Self; Abbott Diabetes, Ascensia Diabetes Care, Lexicon Pharmaceuticals, Inc., Lilly Diabetes, Medtronic, Pfizer Inc., Roche Diagnostic USA, Senseonics. D. S. Denham: None. A. Chang: None. H. K. Akturk: Consultant; Self; American Diabetes Association, Research Support; Self; Dexcom, Inc., Eli Lilly and Company, IM Therapeutics, MannKind Corporation, REMD Biotherapeutics, Senseonics, Speaker’s Bureau; Self; American Diabetes Association. Funding Senseonics, Inc.

In PWD2 inadequately controlled with GLP-1 RA therapy, addition of basal insulin is recommended. We used a US electronic medical record data source (IBM Explorys) of ~4 million PWD2 to assess the real-world impact of adding the basal insulin analog Gla-300 to GLP-1RA therapy in PWD2. Insulin-naive PWD2 receiving GLP1-RAs who subsequently received Gla-300 between Mar 1, 2015-Sep 30, 2019 were identified; patients were required to have data for ≥12 months prior, and ≥6-month after, addition of Gla-300. Mean age of participants (N=271) was 57.9 (SD: 10.8) years. Baseline HbA1c was 9.16%, and was significantly reduced (0.97 [SD:1.60], p Disclosure T. S. Bailey: Consultant; Self; Abbott Diabetes, LifeScan, Novo Nordisk, Sanofi, Research Support; Self; Abbott, Abbott Diabetes, Biolinq, Capillary Biomedical, Inc., Dexcom, Inc., Eli Lilly and Company, Kowa Research Institute, Inc., Lexicon Pharmaceuticals, Inc., Livongo, Medtronic, Medtrum Technologies, Novo Nordisk, REMD Biotherapeutics, Sanofi, Sanvita, Viacyte, Inc., vTv Therapeutics, Zealand Pharma A/S, Speaker’s Bureau; Self; BD, Medtronic, Sanofi. J. Westerbacka: Employee; Self; Sanofi, Stock/Shareholder; Self; Sanofi. C. Nicholls: Employee; Self; Sanofi. J. Gill: Employee; Self; Sanofi US, Other Relationship; Self; American Diabetes Association, Stock/Shareholder; Self; Sanofi US. M. Jones s: None. L. Shenoy: None. Funding Sanofi

Dasiglucagon was developed to provide a fast and effective treatment for severe hypoglycemia (SH) in people with diabetes. An integrated cross-program analysis was performed to assess the safety of dasiglucagon in a representative population of T1DM. Three randomized, placebo-controlled phase 3 trials (2 in adults and 1 in pediatric subjects) were included in the analysis (212 adults and 41 children/adolescents with T1DM). No severe or adverse events (AEs) leading to withdrawal were reported. Most AEs were mild or moderate in severity. Nausea and vomiting were the most-frequent AEs reported with active treatment both in adults and children. No differences in the frequency of nausea and vomiting were observed between adults receiving dasiglucagon versus glucagon. A higher percentage of adolescents experienced these events with dasiglucagon than with glucagon, while no treatment-related imbalance was observed in the 6- to 11-year-old age group. In the pediatric trial, no relationship between exposure (AUC0-5 hr or Cmax) to dasiglucagon, and nausea and vomiting was found. The majority of nausea and vomiting occurred within 1-3 hr and 2-3 hr of dosing, respectively. In conclusion, dasiglucagon 0.6 mg for treatment of SH was found to be generally safe, and the safety profile of dasiglucagon was consistent with that observed across the class of glucagon products. Disclosure S. R. Heller: Advisory Panel; Self; Eli Lilly and Company, Novo Nordisk, Zealand Pharma A/S, Consultant; Self; Zealand Pharma A/S, Other Relationship; Self; Dexcom, Inc., Eli Lilly and Company, MannKind Corporation, Novo Nordisk, Speaker’s Bureau; Self; AstraZeneca, Novo Nordisk. R. Aronson: None. L. Dimeglio: Advisory Panel; Self; MannKind Corporation. T. Danne: Research Support; Self; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Medtronic, Novo Nordisk, Sanofi, Tandem Diabetes Care, Zealand Pharma A/S, Stock/Shareholder; Self; DreaMed Diabetes, Ltd. T. Battelino: Advisory Panel; Self; Eli Lilly and Company, Medtronic, Sanofi, Research Support; Self; European Union, National Institute of Diabetes and Digestive and Kidney Diseases, Novartis Pharmaceuticals Corporation, Novo Nordisk, Sanofi, Slovenian Research Agency, Zealand Pharma A/S, Speaker’s Bureau; Self; Abbott Diabetes, AstraZeneca, Dexcom, Inc., Eli Lilly and Company, Medtronic, Novo Nordisk, Pfizer Inc., Roche Diabetes Care, Sanofi, Stock/Shareholder; Self; DreaMed Diabetes, Ltd. T. S. Bailey: Consultant; Self; Abbott Diabetes, LifeScan, Novo Nordisk, Sanofi, Research Support; Self; Abbott, Abbott Diabetes, Biolinq, Capillary Biomedical, Inc., Dexcom, Inc., Eli Lilly and Company, Kowa Research Institute, Inc., Lexicon Pharmaceuticals, Inc., Livongo, Medtronic, Medtrum Technologies, Novo Nordisk, REMD Biotherapeutics, Sanofi, Sanvita, Viacyte, Inc., vTv Therapeutics, Zealand Pharma A/S, Speaker’s Bureau; Self; BD, Medtronic, Sanofi. R. Tehranchi: Employee; Self; Zealand Pharma A/S. L. J. Klaff: Research Support; Self; Abbott Diabetes, Dong-A ST Co. Ltd., Gan & Lee Pharmaceuticals, Lexicon Pharmaceuticals, Inc., Lilly Diabetes, Medtronic, Novo Nordisk, Oramed Pharmaceuticals, Inc., Pfizer Inc., REMD Biotherapeutics. T. Pieber: Advisory Panel; Self; ADOCIA, Arecor, AstraZeneca, Eli Lilly and Company, Novo Nordisk A/S, Sanofi, Research Support; Self; AstraZeneca, Novo Nordisk A/S. U. Hovelmann: None. L. Plum-moerschel: None. A. E. Melgaard: Employee; Self; Zealand Pharma A/S.

Dasiglucagon is a novel glucagon analog, stable in aqueous solution and suitable for delivery in a ready-to-use autoinjector (HypoPal®) for the treatment of severe hypoglycemia. This study was performed to assess HypoPal device handling vs. GEK during simulated episodes of severe hypoglycemia. Participants included persons with diabetes (PWD) and their caregivers and untrained bystanders (UB) with no experience with diabetes. Participants had no experience with either device. PWD were trained by staff and subsequently trained caregivers (TC) on the use of devices; UB received no instruction on use prior to simulations. Primary outcome was success of TC to correctly use HypoPal vs. GEK. Secondary outcomes included success of UB, time to successful administration, and assessment of confidence in, ease of use of and preference for each device. The success rate was significantly greater for HypoPal vs. GEK in TC (p These data support that dasiglucagon HypoPal use is easier, more reliable, and faster than the use of GEK and offers the potential to improve the time to recovery from a severe hypoglycemic event. Disclosure N. Bailey: Research Support; Spouse/Partner; Zealand Pharma A/S. J. Dimsits: Employee; Self; Zealand Pharma A/S. R. Tehranchi: Employee; Self; Zealand Pharma A/S. D. M. Kendall: Employee; Self; Zealand Pharma A/S, Employee; Spouse/Partner; Amgen Inc., Stock/Shareholder; Self; Eli Lilly and Company, MannKind Corporation. T. S. Bailey: Consultant; Self; Abbott Diabetes, LifeScan, Novo Nordisk, Sanofi, Research Support; Self; Abbott, Abbott Diabetes, Biolinq, Capillary Biomedical, Inc., Dexcom, Inc., Eli Lilly and Company, Kowa Research Institute, Inc., Lexicon Pharmaceuticals, Inc., Livongo, Medtronic, Medtrum Technologies, Novo Nordisk, REMD Biotherapeutics, Sanofi, Sanvita, Viacyte, Inc., vTv Therapeutics, Zealand Pharma A/S, Speaker’s Bureau; Self; BD, Medtronic, Sanofi. Funding Zealand Pharma A/S

No point of care HbA1c (A1c) assays are CLIA waived for use in diagnosing diabetes. The accuracy of the Abbott Afinion HbA1c Dx (Afinion) was evaluated for this purpose. Operators with no laboratory training (N=21) tested fingerstick (FS) and venous (V) whole blood samples from subjects at 7 CLIA waived sites with 2 Afinion analyzer models (AS100 and Afinion 2). Operators self-trained on use of the Afinion using only materials that are provided when the test is purchased. A portion of each subject’s V sample was tested with a recognized comparative method (CM) at an NGSP Secondary Reference Laboratory (SRL). Consistent with FDA requirements for total error of A1c test systems, the percentage of Afinion results within an Allowable Total Error (ATE) zone of ±6% of the CM result was calculated, as well as the bias at 6.5% A1c. A total of 1,229 subjects with A1c values spanning the Afinion assay measuring range were enrolled. For the Afinion 2, 95.04% (95% lower confidence limit, LCL: 93.33%) of FS and 94.86% (95% LCL: 93.12%) of V results were within the ATE zone. For the AS100, 94.22% (95% LCL: 92.38%) and 93.36% (95% LCL: 91.41%) of Afinion results were within the ATE zone for FS and V samples, respectively. The bias at 6.5% A1c for the Afinion 2 was -0.13% (-0.008% A1c units) for FS and 0.01% (0.000% A1c units) for V samples. For the AS100, the bias was 0.62% (0.040% A1c units) and 1.13% (0.073% A1c units) for FS and V samples, respectively. No operator effects and no differences between the Afinion and CM results that could potentially impact clinical decision making were observed in this study. In subjects with unreported hemoglobin variants (detected by CM), 16/16 FS and 15/16 V Afinion results were within the ATE zone when compared to a second NGSP certified method at the same SRL. These data support the use of Afinion in CLIA waived settings to diagnose diabetes. Disclosure M. Clendenin: Employee; Self; Abbott. A. J. Nation: None. R. C. San george: Other Relationship; Self; Abbott. K. Kupfer: Employee; Self; Abbott. K. S. Fortner: Employee; Self; Abbott. R. R. Little: None. T. S. Bailey: Consultant; Self; Abbott Diabetes, LifeScan, Novo Nordisk, Sanofi, Research Support; Self; Abbott, Abbott Diabetes, Biolinq, Capillary Biomedical, Inc., Dexcom, Inc., Eli Lilly and Company, Kowa Research Institute, Inc., Lexicon Pharmaceuticals, Inc., Livongo, Medtronic, Medtrum Technologies, Novo Nordisk, REMD Biotherapeutics, Sanofi, Sanvita, Viacyte, Inc., vTv Therapeutics, Zealand Pharma A/S, Speaker’s Bureau; Self; BD, Medtronic, Sanofi. K. N. Castorino: Consultant; Self; Dexcom, Inc., Research Support; Self; Abbott Diabetes, Abbott Laboratories, Dexcom, Inc., Drawbridge Health, Inc., Lilly Diabetes, Medtronic, Novo Nordisk Inc. D. S. Denham: None. E. Kerwin: Consultant; Self; Amphastar, AstraZeneca, Connect Biopharma, GlaxoSmithKline plc., Mylan N. V., Novartis Pharmaceuticals Corporation, Sunovion Pharmaceuticals Inc., Theravance Biopharma, Speaker’s Bureau; Self; Chiesi USA, Inc. M. Mickiewicz: None.

Objective: Most insulin infusion sets (ISs) are labeled for 2- or 3-days use. The Medtronic EWIS is designed to increase wear time up to 7 days, and demonstrated a 74.8% survival rate (77.8%, excluding inadvertent early removal) in the pivotal trial (ClinicalTrials.gov: NCT04113694). This study reports on study participant satisfaction during the EWIS pivotal trial. Method: This multi-center (15), single-arm, non-randomized, non-inferiority trial in 259 participants (18-80yrs) with T1D using the MiniMed™ 670G system (with Humalog™ or Novolog™ insulin) involved wearing a 2- or 3-day IS for 2 weeks (run-in) followed by 12 consecutive EWIS wears (study phase). The latter was worn for ≥174 hours or until set failure. Participants completed a Medtronic Likert-based questionnaire at baseline and study exit. The averaged paired change in score at study-baseline was determined (Wilcoxon signed-rank test). Result: Reported satisfaction data during 2- or 3-day IS versus EWIS wear (Figure) show that ease and convenience of use, comfort, wear duration and time required to change a set were significantly improved with EWIS (p Conclusion: These findings point to significantly greater satisfaction with the EWIS when compared with a 2- or 3-day IS, which may result in reduced care burden and improved adherence. Disclosure R. L. Brazg: Research Support; Self; Abbott Diabetes, Ascensia Diabetes Care, Lexicon Pharmaceuticals, Inc., Lilly Diabetes, Medtronic, Pfizer Inc., Roche Diagnostic USA, Senseonics. B. Horowitz: Research Support; Self; Abbott Laboratories, BD, Celgene, Crinetics Pharmaceuticals, Gan & Lee Pharmaceuticals, Medtronic, Speaker’s Bureau; Self; AstraZeneca, Lilly Diabetes, Merck & Co., Inc., Novo Nordisk Inc. K. B. Kaiserman: Advisory Panel; Self; Medtronic, Consultant; Self; Medtronic, Employee; Self; MannKind Corporation, Research Support; Self; Medtronic, Speaker’s Bureau; Self; Medtronic, Stock/Shareholder; Self; MannKind Corporation. S. Huang: None. V. Chen: Employee; Self; Medtronic. G. Zhang: Employee; Self; Medtronic. S. Chattaraj: Employee; Self; Medtronic. J. Shin: Employee; Self; Medtronic. R. Vigersky: Employee; Self; Medtronic. T. S. Bailey: Consultant; Self; Abbott Diabetes, LifeScan, Novo Nordisk, Sanofi, Research Support; Self; Abbott, Abbott Diabetes, Biolinq, Capillary Biomedical, Inc., Dexcom, Inc., Eli Lilly and Company, Kowa Research Institute, Inc., Lexicon Pharmaceuticals, Inc., Livongo, Medtronic, Medtrum Technologies, Novo Nordisk, REMD Biotherapeutics, Sanofi, Sanvita, Viacyte, Inc., vTv Therapeutics, Zealand Pharma A/S, Speaker’s Bureau; Self; BD, Medtronic, Sanofi. Y. C. Kudva: Research Support; Self; Dexcom, Inc. S. K. Garg: Advisory Panel; Self; Eli Lilly and Company, Medtronic, Novo Nordisk Inc., Zealand Pharma A/S, Research Support; Self; Dexcom, Inc., Eli Lilly and Company, Medtronic. G. Grunberger: Research Support; Self; Medtronic, Speaker’s Bureau; Self; Abbott Diabetes, Eli Lilly and Company, Novo Nordisk. A. Cavale: Research Support; Self; Eli Lilly and Company, Medtronic. J. Thrasher: Advisory Panel; Self; Medtronic, Board Member; Self; Medtronic, Consultant; Self; Medtronic, Research Support; Self; Eli Lilly and Company, Lexicon Pharmaceuticals, Inc., Medtronic, Mylan N. V., Novo Nordisk, Sanofi, Speaker’s Bureau; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Medtronic, Sanofi. A. Bhargava: Research Support; Self; Abbott, AbbVie Inc., Amgen Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Boston Therapeutics, Inc., Covance Inc., Dexcom, Inc., Eli Lilly and Company, Gan & Lee Pharmaceuticals, Insulet Corporation, Janssen Research & Development, LLC, Kowa Pharmaceuticals America, Inc., Madrigal Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Mylan N. V., Novo Nordisk, Poxel SA, Quintiles, Sanofi, Senseonics, Tolerion, Inc., Viking Therapeutics. B. A. Buckingham: Advisory Panel; Self; Medtronic, Tolerion, Inc., Research Support; Self; Beta Bionics, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care.

Aim To compare the second‐generation basal insulin glargine 300 units/mL (Gla‐300) and first‐generation basal insulins on glycaemic control and hypoglycaemia risk in older adults with type 2 diabetes (T2D). Materials and methods DELIVER 3 was a retrospective observational cohort study of electronic medical records. A total of 1176 older adults (aged ≥ 65 years) with T2D and ≥1 HbA1c value during 6 month baseline and 3 to 6 month follow‐up who switched from basal insulin to Gla‐300 were propensity score‐matched to 1176 older adults who switched to a first‐generation basal insulin [insulin detemir (IDet) or insulin glargine 100 units/mL (Gla‐100)]. Outcomes were follow‐up HbA1c, achievement of HbA1c

Background: Barriers to mealtime insulin include complexity, fear of injections, and lifestyle interference. This multicenter, randomized controlled trial evaluated efficacy, safety, and self-reported outcomes in adults with type 2 diabetes, inadequately controlled on basal insulin, initiating and managing mealtime insulin with a wearable patch versus an insulin pen. Methods: Adults with type 2 diabetes (n = 278, age: 59.2 ± 8.9 years), were randomized to patch (n = 139) versus pen (n = 139) for 48 weeks, with crossover at week 44. Baseline insulin was divided 1:1 basal: bolus. Using a pattern-control logbook, subjects adjusted basal and bolus insulin weekly using fasting and premeal glucose targets. Results: Glycated hemoglobin (HbA1c) change (least squares mean ± standard error) from baseline to week 24 (primary endpoint) improved (P

Background: A prior study (PRECISE II) demonstrated that an implantable continuous glucose monitoring (CGM) system (Eversense® CGM System) provided accurate glucose readings through the 90-day sensor life with a favorable safety profile in participants with type 1 or type 2 diabetes (T1D, T2D). This study was performed to further characterize the accuracy of the system. Methods: PRECISION was a prospective multicenter study that evaluated the accuracy and safety of Eversense among adults with T1D or T2D through 90 days (NCT02647905). Accuracy measures included percentage system agreement and mean absolute relative difference (MARD) between Eversense and Yellow Springs Instrument reference measurements from 40 to 400 mg/dL. The primary safety endpoint was incidence of device-related or sensor insertion/removal procedure-related serious adverse events (SAEs) through 90 days. An updated glucose calculation algorithm was also applied to the sensor data from the PRECISE II study to evaluate consistency of accuracy results. Results: Thirty-five participants received the CGM system. Eighty-five percent of CGM values were within 15/15% of reference and the MARD value against reference was 9.6% (95% confidence interval [CI]: 8.9–10.4). All sensors were functional through day 90. No device- or procedure-related SAEs occurred. Application of the updated algorithm to PRECISE II sensor data resulted in 87% of readings within 15/15% of reference and an MARD value against reference of 8.5% (95% CI: 8.0%–9.1%). Conclusions: PRECISION corroborated prior accuracy and safety findings of the Eversense CGM System through the 90-day sensor life. The updated algorithm improved accuracy of measurements in PRECISE II.

AIMS To compare HbA1c and hypoglycaemia in insulin-naive patients with type 2 diabetes (T2D) who initiated insulin glargine 300 units/mL (Gla-300) or 100 units/mL (Gla-100). MATERIALS AND METHODS This retrospective cohort study examined electronic medical records of insulin-naive adults with T2D who initiated Gla-300 or Gla-100 during March 2015 through to December 2016 with active records for ≥12 months before and ≥6 months after initiation, and ≥1 valid HbA1c value during 6-month baseline and 90-180-day follow-up. Outcomes included HbA1c and hypoglycaemia. Cohorts were propensity score-matched (1:2) on baseline demographic and clinical characteristics. Sensitivity analyses were conducted using broader inclusion criteria. RESULTS The matched cohorts included 1004 Gla-300 and 2008 Gla-100 initiators (mean age 60.4 years; 53.2% male). During 6-month follow-up, Gla-300 versus Gla-100 initiators had a greater mean HbA1c decrease (-1.52 ± 2.08% vs. -1.30 ± 2.12%; P = 0.003) and more patients achieved HbA1c

Introduction The LIGHTNING study applied conventional and advanced analytic approaches to model, predict, and compare hypoglycemia rates of people with type 2 diabetes (T2DM) on insulin glargine 300 U/ml (Gla-300) with those on first-generation (insulin glargine 100 U/ml [Gla-100]; insulin detemir [IDet]) or second-generation (insulin degludec [IDeg]) basal-insulin (BI) analogs, utilizing a large real-world database. Methods Data were collected between 1 January 2007 and 31 March 2017 from the Optum Humedica US electronic health records [EHR] database. Patient-treatments, the period during which a patient used a specific BI, were analyzed for patients who switched from a prior BI or those who newly initiated BI therapy. Data were analyzed using two approaches: propensity score matching (PSM) and a predictive modeling approach using machine learning. Results A total of 831,456 patients with T2DM receiving BI were included from the EHR data set. Following selection, 198,198 patient-treatments were available for predictive modeling. The analysis showed that rates of severe hypoglycemia (using a modified definition) were approximately 50% lower with Gla-300 than with Gla-100 or IDet in insulin-naïve individuals, and 30% lower versus IDet in BI switchers (all p

Background: Technosphere Insulin (TI) is an ultra-rapid-acting inhaled insulin. This study assessed the mean peak two-hour postprandial glucose concentration with the initial TI dose (dose 1) calculated per the current label (United State Prescribing Information) compared with a ~2× higher dose (dose 2). Secondary objectives were to evaluate hypoglycemia within the two-hour postprandial period, evaluate change in forced expiratory volume in one second (FEV1) before and after the two-hour postprandial period, and monitor for other adverse events. Methods: Twenty patients with diabetes, on basal-bolus insulin therapy, received an initial dose 1 of TI followed by the higher dose 2, one to three days later. Subjects received an identical meal for both visits, and TI doses were administered immediately prior to the meal. Results: The higher dose 2 provided significant reductions in mean postprandial glucose excursion (PPGE) in the two-hour postprandial period starting from 45 minutes ( P = .008) to 120 minutes ( P < .0001). Mean peak glucose was reduced from 228.6 to 179.3 mg/dL ( P < .001) at two hours. Two hypoglycemic events (one level 1, one level 2) were observed in a single subject during the two-hour postprandial period with dose 2. There were no significant changes in FEV1 after either dose of TI. Conclusions: The higher dose 2 reduced PPGE versus the current label recommended dose 1 within the two-hour postprandial timeframe without any new safety concerns. When confirmed with a larger study, this higher TI dosing recommendation may help patients and clinicians minimize immediate postprandial hyperglycemia when titrating TI for prandial glucose control.

Basal insulin therapy often involves a compromise between achievement of glycaemic targets and avoidance of hypoglycaemia, dependent on how intensively insulin is titrated. In the Phase 3a EDITION 1, 2 and 3 studies, insulin glargine 300 U/mL (Gla‐300) provided glycaemic control equivalent to that of insulin glargine 100 U/mL (Gla‐100), with less hypoglycaemia in individuals with type 2 diabetes mellitus (T2DM). The current study evaluated the rates of confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia over six months of treatment with Gla‐300 or Gla‐100 in the EDITION studies, as a function of HbA1c. Analysis was performed on patient‐level data pooled from the three EDITION studies, and annualized hypoglycaemia rate as a function of HbA1c at Month 6 was fitted using a negative binomial regression model. Participants treated with Gla‐300 experienced a consistently lower rate of confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia as compared with those treated with Gla‐100, regardless of HbA1c at Month 6. Results suggest that treatment with Gla‐300 vs Gla‐100 could allow individuals with T2DM to achieve equivalent glycaemic control with less hypoglycaemia.

IMPORTANCE: Weight loss improves cardiometabolic risk factors in people with overweight or obesity. Intensive lifestyle intervention and pharmacotherapy are the most effective noninvasive weight loss approaches. OBJECTIVE: To compare the effects of once-weekly subcutaneous semaglutide, 2.4 mg vs placebo for weight management as an adjunct to intensive behavioral therapy with initial low-calorie diet in adults with overweight or obesity. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, parallel-group, 68-week, phase 3a study (STEP 3) conducted at 41 sites in the US from August 2018 to April 2020 in adults without diabetes (N = 611) and with either overweight (body mass index ≥27) plus at least 1 comorbidity or obesity (body mass index ≥30). INTERVENTIONS: Participants were randomized (2:1) to semaglutide, 2.4 mg (n = 407) or placebo (n = 204), both combined with a low-calorie diet for the first 8 weeks and intensive behavioral therapy (ie, 30 counseling visits) during 68 weeks. MAIN OUTCOMES AND MEASURES: The co–primary end points were percentage change in body weight and the loss of 5% or more of baseline weight by week 68. Confirmatory secondary end points included losses of at least 10% or 15% of baseline weight. RESULTS: Of 611 randomized participants (495 women [81.0%], mean age 46 years [SD, 13], body weight 105.8 kg [SD, 22.9], and body mass index 38.0 [SD, 6.7]), 567 (92.8%) completed the trial, and 505 (82.7%) were receiving treatment at trial end. At week 68, the estimated mean body weight change from baseline was –16.0% for semaglutide vs –5.7% for placebo (difference, −10.3 percentage points [95% CI, −12.0 to −8.6]; P

Background: Accuracy of a seventh-generation “G7” continuous glucose monitoring (CGM) system was evaluated in children and adolescents with type 1 diabetes (T1D). Methods: Sensors were worn on the upper arm and abdomen. The CGM data were available from 127 of 132 participants, ages 7 to 17 years, across 10.5 days of use, various glucose concentration ranges, and various rates of glucose change for comparisons with temporally matched venous blood glucose measurements (YSI). Data were also available from 28 of 32 participants, ages 2 to 6 years, for whom capillary (fingerstick) blood provided comparator glucose values. Accuracy metrics included the mean absolute relative difference (MARD) between CGM and comparator glucose pairs, the proportion of CGM values within 15 mg/dL or 15% of comparator values Results: For participants aged 7 to 17, a total of 15 437 matched pairs were obtained from 122 arm-placed and 118 abdomen-placed sensors. For arm-placed sensors, the overall MARD was 8.1% and overall %15/15, %20/20, and %30/30 agreement rates were 88.8%, 95.3%, and 98.7%, respectively. For abdomen-placed sensors, the overall MARD was 9.0% and overall %15/15, %20/20, and %30/30 agreement rates were 86.0%, 92.9%, and 97.7%, respectively. Good accuracy was maintained across wear days, glucose ranges, and rates of glucose change. Among those aged 2 to 6, a total of 343 matched pairs provided an overall MARD of 9.3% and an overall %20/20 agreement rate of 91.5%. Conclusions: The G7 CGM placed on the arm or abdomen was accurate in children and adolescents with T1D. NCT#: NCT04794478

Purpose: A proposal that an Insulin Advisory Committee develop insulin titration guidelines 100 years after its discovery. Findings: Glucose control metrics remain poor despite significant advances in diabetes technology. Summary: A century after the introduction of insulin, health care providers and patients with type 1 diabetes have worldwide access to a variety of insulin delivery devices (IDDs), glucose monitors, bolus calculators (BCs), continuous glucose monitors (CGMs), and automated insulin delivery (AID) systems. However, these advances have not enabled most patients to achieve today’s clear A1c and time-in-range goals. Much of this failure arises from the lack of clear insulin titration guidelines for determining appropriate insulin doses. The lack of dosing clarity results in local physicians, clinics, and individual patients managing insulin titrations as they see fit, creating significant inefficiencies for reaching recommended glycemic goals. This review (1) details the widespread problems generated by nonphysiological dose settings in today’s BCs, insulin pumps, and AID systems; (2) presents a method to develop and implement optimized total daily doses of insulin to correct the most common problem of hyperglycemia; (3) discusses using large device databases to provide clear insulin titration guidelines that optimize BC settings from an optimized total daily dose (TDD) of insulin for patients with T1D; and (4) recommends the formation of an Insulin Advisory Committee to clarify the steps to take toward universal insulin titration guidelines, optimized BC settings, and a systematic logic for their use in insulin delivery devices.

Background: A composite metric for the quality of glycemia from continuous glucose monitor (CGM) tracings could be useful for assisting with basic clinical interpretation of CGM data. Methods: We assembled a data set of 14-day CGM tracings from 225 insulin-treated adults with diabetes. Using a balanced incomplete block design, 330 clinicians who were highly experienced with CGM analysis and interpretation ranked the CGM tracings from best to worst quality of glycemia. We used principal component analysis and multiple regressions to develop a model to predict the clinician ranking based on seven standard metrics in an Ambulatory Glucose Profile: very low–glucose and low-glucose hypoglycemia; very high–glucose and high-glucose hyperglycemia; time in range; mean glucose; and coefficient of variation. Results: The analysis showed that clinician rankings depend on two components, one related to hypoglycemia that gives more weight to very low-glucose than to low-glucose and the other related to hyperglycemia that likewise gives greater weight to very high-glucose than to high-glucose. These two components should be calculated and displayed separately, but they can also be combined into a single Glycemia Risk Index (GRI) that corresponds closely to the clinician rankings of the overall quality of glycemia (r = 0.95). The GRI can be displayed graphically on a GRI Grid with the hypoglycemia component on the horizontal axis and the hyperglycemia component on the vertical axis. Diagonal lines divide the graph into five zones (quintiles) corresponding to the best (0th to 20th percentile) to worst (81st to 100th percentile) overall quality of glycemia. The GRI Grid enables users to track sequential changes within an individual over time and compare groups of individuals. Conclusion: The GRI is a single-number summary of the quality of glycemia. Its hypoglycemia and hyperglycemia components provide actionable scores and a graphical display (the GRI Grid) that can be used by clinicians and researchers to determine the glycemic effects of prescribed and investigational treatments.

Background: Diabetes-related distress is common among persons affected by diabetes and is associated with suboptimal glycemic control and complications, thus constituting a relevant patient-report outcome (PRO). Improving glycemic control may reduce diabetes distress and improve treatment satisfaction. This post hoc analysis evaluated PRO data for a pooled cohort of adults with type 1 diabetes (T1D) receiving sotagliflozin as adjunct to optimized insulin in the inTandem1 and inTandem2 studies. Methods: Clinically meaningful changes in the Diabetes Treatment Satisfaction Questionnaire status version (DTSQs) and the two-item Diabetes Distress Scale (DDS2) total and individual scores were examined in the pooled data from the first 24 weeks of the studies. Results: In the cohort of patients with a baseline DTSQs total score ?32 (?76% of entire cohort), nearly twice as many patients treated with sotagliflozin 200 (45.9%) or 400 mg (42.3%) experienced a >3-point improvement from baseline versus those treated with placebo (24%). Treatment with sotagliflozin led to statistically significant (P < 0.05) improvements across all DTSQs items. Approximately 42% of all patients were considered to have a high risk of diabetes distress (total DDS2 score ?6) at baseline following insulin optimization. More patients shifted from high to low risk with sotagliflozin compared with placebo (?40% vs. 23%; P ? 0.0002). The baseline-Adjusted difference in DDS2 from placebo was significantly (P < 0.001) reduced by-0.5 and-0.6 for sotagliflozin 200 and 400 mg, respectively. Conclusions: Patients with T1D treated with sotagliflozin in addition to optimized insulin therapy reported meaningful improvements in treatment satisfaction and diabetes distress. NCT02384941 and NCT02421510