UnitedHealth Group Research Articles

1031-P: Virtual Clinic Support—Patient-Reported Outcome Benefits

Behavioral health support can benefit those living with diabetes, but there is limited information on patient reported outcomes (PROs) associated with a virtual clinic. Adults with diabetes (n=234) received virtual care including support for CGM initiation and management over a 6-month study period. Care was led by a CDCES with support from a behavioral team. Participants completed PROs surveys 1) at baseline and 6 months to evaluate change and 2) each month on diabetes distress (DD), fear of hypoglycemia (FOH), and depression (DEP). Full list of PROs surveys included in table. A positive screen led to recommendation for a brief behavioral intervention. Participants with T1D (n=160) were 44(±14) years and mean baseline A1c of 7.8%. Participants with T2D (n=74) were 55(±12) years and mean baseline A1c of 8.1%. Participants screened positive for DD, FOH, or DEP 67% of the time with FOH as the most common concern. Of those with a positive screen, 70% of T1D and 59% of T2D participants had at least one behavioral team contact. Virtual clinic care was associated with a benefit on 7 of 9 PROs for T1D and 7 of 9 PROs for T2D (p values < 0.05; see table). For these virtual clinic adults with diabetes, PROs improved 78% of the time with noteworthy benefits of less FOH, less DD, and more glucose monitoring satisfaction. Paired with the glycemic improvements observed in this virtual clinic study, there were robust benefits on the quality of life of adults with diabetes. Disclosure K.K.Hood: Consultant; Cecelia Health. S.Oser: Advisory Panel; Cecelia Health, Dexcom, Inc., Consultant; Medscape, Research Support; Abbott Diabetes. T.Oser: Advisory Panel; Cecelia Health, Consultant; Dexcom, Inc., Medscape, Research Support; Abbott. D.Raghinaru: None. Z.Thompson: None. R.S.Weinstock: Consultant; Jaeb Center for Health Research, Other Relationship; Wolters Kluwer Health, Research Support; Insulet Corporation, Medtronic, Eli Lilly and Company, Novo Nordisk, Boehringer Ingelheim Inc., Hemsley Charitable Trust, National Institute of Diabetes and Digestive and Kidney Diseases, Tandem Diabetes Care, Inc., Kowa Pharmaceuticals America, Inc. R.Beck: Consultant; Eli Lilly and Company, Novo Nordisk, Diasome, Insulet Corporation, Research Support; Tandem Diabetes Care, Inc., Beta Bionics, Inc., Dexcom, Inc., Bigfoot Biomedical, Inc., Medtronic, Ascensia Diabetes Care, Roche Diabetes Care, Eli Lilly and Company, Novo Nordisk. G.Aleppo: Advisory Panel; Medscape, Consultant; Bayer Inc., Insulet Corporation, Research Support; Dexcom, Inc., Eli Lilly and Company, Emmes, Insulet Corporation, Fractyl Health, Inc., WellDoc, Speaker's Bureau; Dexcom, Inc. R.M.Bergenstal: Advisory Panel; Abbott Diabetes, Eli Lilly and Company, Medtronic, Novo Nordisk, Roche Diabetes Care, Zealand Pharma A/S, Consultant; Ascensia Diabetes Care, Bigfoot Biomedical, Inc., CeQur SA, Dexcom, Inc., Hygieia, Onduo LLC, Sanofi, Vertex Pharmaceuticals Incorporated, Research Support; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic, Novo Nordisk, Sanofi, UnitedHealth Group. T.L.Cushman: None. R.L.Gal: None. C.Kollman: Research Support; Insulet Corporation, Dexcom, Inc., Tandem Diabetes Care, Inc. D.F.Kruger: Advisory Panel; Abbott Diabetes, Lilly, Medtronic, Novo Nordisk, Research Support; Dexcom, Inc., Beta Bionics, Inc., Speaker's Bureau; Dexcom, Inc., Lilly, Xeris Pharmaceuticals, Inc., Novo Nordisk. M.L.Johnson: Research Support; Abbott, Lilly, Insulet Corporation, NIH - National Institutes of Health, Patient-Centered Outcomes Research Institute, Novo Nordisk, Tandem Diabetes Care, Inc., Medtronic, Hemsley Charitable Trust, Jaeb Center for Health Research. T.S.Mcarthur: None. B.A.Olson: Stock/Shareholder; Abbott. Funding The Leona M. and Harry B. Helmsley Charitable Trust; Dexcom, Inc.

944-P: Continuous Glucose Monitoring (CGM) Sampling Duration to Estimate Long-Term Glycemic Control in Adults with T2D Not Using Insulin

Objective: Current consensus is that 10-14 days of continuous glucose monitoring (CGM) sampling time is adequate to assess long-term glycemic control in T1D and insulin-using T2D populations. Optimal CGM sampling duration has not been widely studied in people with T2D not using insulin. We studied the relationship between true and estimated long-term (90-day) glycemic control in people with T2D not using insulin. Methods: The study population (N = 829) was composed of adults with T2D enrolled in Level2, a virtual specialty clinic, with CGM data on 75% (68) of the 90 days preceding an A1c lab result and no insulin fills during this period. The mean age and A1c were 56 years and 6.7% respectively. We computed the median absolute percentage error (MAPE) and Pearson correlations (R) between glycemic metrics from sampling periods of increasing duration and the full 90-day period. Because this population was at low risk for hypoglycemia glucose management indicator (GMI) and time above range (>180 mg/dL, TAR) were the primary outcomes of interest. We also assessed the correlations between GMI and A1c. Results: GMI and TAR from 14-day measurements were highly correlated (R = 0.92) with 90-day values, increasing to R = 0.94 with 30-day measurements. Correlations of GMI and A1c were high with 14 and 30 days (R = 0.79, R = 0.82) but did not exceed R = 0.85 with longer sampling periods. MAPE was 2.2 (SD = 2.6) and 1.5 (SD = 2.1) for GMI with 14- and 30-day measurements, respectively, and 29.2 (SD = 47.4) and 21.2 (SD = 27.1) for TAR. Conclusion: In the T2D population not using insulin, 14 days of CGM data is sufficient to estimate long-term mean glucose and the discordance with A1c is consistent with previous studies of people with T1D and insulin-using T2D. TAR is subject to greater error than in previous studies of people with T1D and insulin-using T2D and more work is needed to understand this discrepancy. Disclosure S.Bacon: Employee; Optum Labs, Research Support; Level2. N.Thompson: Employee; Level2, Stock/Shareholder; UnitedHealth Group. D.Ferrell: Stock/Shareholder; Level2, Medexpress Urgent Care. J.Fung: Employee; Level2.

227-OR: Increasing Quarterly Use of Intermittent CGM among Individuals with T2D Is Associated with Improved Glycemic Control over a One-Year Time Frame

Introduction: Continuous glucose monitoring (CGM) is an important tool for biofeedback in diabetes self-management. Intermittent use CGM for T2D users is one approach to address cost and access limitations, but to date only limited evidence supports intermittent use. The objective of this study was to understand the impact of intermittent use CGM in T2D non-intensive insulin users in a real-world setting. Methods: As part of an ongoing implementation study within the Livongo whole person digital health program, a select population of individuals living with T2D who had not previously used CGM and either used no insulin or basal insulin only were mailed and asked to wear Dexcom G6 CGM sensors for 7-10 days per quarter for 4 consecutive quarters. In this analysis, we examined data from 227 individuals who adhered to wearing CGM for at least 7 days in 2 or more quarters. A multiple linear regression design quantified the impact of the primary variable of interest - the number of quarters with CGM wear (2, 3, or 4) - on changes in glycemic control between the first and latest available sensors, while including additional variables (potential confounds) associated with demographic traits, medication use, and temporal aspects of CGM wear. Results: Glycemic control at baseline varied widely; 54% of individuals had a Time In Range (TIR) less than the target of 70%. Among the full sample (N = 227), each additional quarter of CGM use (beyond 2) resulted in clinically meaningful average improvements (and significant partial correlations, all p < .05) in mean sensor glucose (11.8 mg/dL decrease), TIR (7.7 point increase), Time Above Range (7.9 point decrease), and the Glycemia Risk Index (9.3 point decrease). Conclusion: Type 2 non-intensive insulin users who were adherent to quarterly use of intermittent CGM over one year saw meaningful improvements in glycemic control. Providing access to CGM technology may facilitate improvement in outcomes and disease management. Disclosure R.J.Ellis: Employee; Teladoc Health. T.Kompala: Employee; Teladoc Health, Stock/Shareholder; Teladoc Health. R.J.Brooks: Employee; Teladoc Health, Stock/Shareholder; Dexcom, Inc. J.Hone: Employee; Teladoc Health, UnitedHealth Group. A.Salehi: Employee; Teladoc Health. R.James: Employee; Teladoc Health.

943-P: Improved Glycemic Outcomes after One Year among Level 2 Members

Background: Level2’s virtual specialty clinic, offered across the United States to people with type 2 diabetes on participating insurance plans, combines providers, coaches, continuous glucose monitors (CGM), and fitness trackers to help members gain insight, and focus on long-term behavior change. We retrospectively assessed differences in glycemic outcomes following one year of participation in Level2. Methods: People joining Level2 between 01/01/21 and 07/31/21 with 15 months of Level2 participation and 3 prior months of continuous enrollment in a participating commercial health plan were included in the analysis. We used CGM-derived GMI and A1c values available from a database of de-identified administrative claims to determine baseline and 12-month follow-up glycemic outcomes. Wilcoxon signed-rank tests were used to test for pair-wise improvements in glycemic measures between baseline and follow-up overall and stratified by baseline A1c. Results: Of the 3,440 people identified for the analysis, a subset (N = 200) had both baseline A1c and valid GMIs during follow-up. This subset was 53% (N = 106) male with mean age of 55.4 (SD = 8.5) years and had mean baseline A1c of 7.97% (SD = 1.02). The median difference between baseline A1c and follow-up GMI was -0.83% (p < 0.001) overall, with significant differences of -0.82% (p < 0.001) and -2.41% (p < 0.001) in those with baseline 7% < A1c < 9% and A1c > 9%, respectively. Over 50% of people had a decrease in glycemic outcome of more than 0.5%, with 67% and 95% of people improving by more than 0.5% in the 7-9% and > 9% groups respectively. There were 87 people that also had an A1c at 12-month follow-up; the median difference in A1c was -0.65% (p < 0.001), 50% had a decrease of more than 0.5%, and median difference between GMI/A1c follow up values was 0.13 (p = 0.11). Conclusion: Level2 members with baseline A1c and follow-up GMI saw significant improvements in glycemic control over one year of engagement. These improvements were observed for measures of both follow-up A1c and GMI. Disclosure S.Bacon: Employee; Optum Labs, Research Support; Level2. N.Thompson: Employee; Level2, Stock/Shareholder; UnitedHealth Group. D.Ferrell: Stock/Shareholder; Level2, Medexpress Urgent Care. J.Fung: Employee; Level2.

85-LB: CGM Outcomes and Hypoglycemia Duration with Once-Weekly Insulin Icodec vs. Once-Daily Insulin Glargine U100 in Insulin-Naïve T2D—ONWARDS 1 Exploratory Analysis

In ONWARDS 1, a phase 3a, treat-to-target trial (NCT04460885) in insulin-naïve T2D randomized 1:1 to once-weekly icodec or once-daily glargine U100, time in, above and below range (TIR, TAR, TBR) and hypoglycemia duration were assessed with double-blinded CGM at pre-specified periods throughout the trial. TIR (70-180 mg/dL), TAR (>180 mg/dL), TBR (<70 and <54 mg/dL), median duration of hypoglycemia <70 mg/dL and the proportion of an episode spent <54 mg/dL were assessed at weeks (wks) 0-4, 22-26, 48-52, and 74-78. At wks 22-26, 48-52, and 74-78, mean TIR with icodec met the recommended target of >70%, and TIR and TAR were significantly improved with icodec vs glargine, with no significant difference between arms in TBR <54 mg/dL (table). There was a difference in favor of glargine in TBR <70 mg/dL at wks 48-52 and 74-78, but mean TBR <70 mg/dL and TBR <54 mg/dL were below recommended targets (4% and 1%, respectively) at all time periods for both arms. TIR, TBR and TAR did not differ significantly between arms at wks 0-4. Median duration of hypoglycemia <70 mg/dL and proportion of time <54 mg/dL were similar between arms at all time periods. In summary, TIR and TAR at wks 22-26, 48-52, and 74-78 were significantly improved with icodec vs glargine U100, with no significant difference in TBR <54 mg/dL and a similar duration of hypoglycemia <70 mg/dL between arms. Disclosure R. M. Bergenstal: Advisory Panel; Abbott Diabetes. Research Support; Abbott Diabetes. Consultant; Ascensia Diabetes Care, Bigfoot Biomedical, Inc., CeQur SA, Dexcom, Inc. Research Support; Dexcom, Inc. Advisory Panel; Eli Lilly and Company. Research Support; Eli Lilly and Company. Consultant; Hygieia. Research Support; Insulet Corporation, Medtronic. Advisory Panel; Medtronic, Novo Nordisk. Research Support; Novo Nordisk. Consultant; Onduo LLC. Advisory Panel; Roche Diabetes Care. Research Support; Sanofi. Consultant; Sanofi. Research Support; UnitedHealth Group. Consultant; Vertex Pharmaceuticals Incorporated. Advisory Panel; Zealand Pharma A/S. S. K. Watt: Employee; Novo Nordisk. A. S. A. Matos: Employee; Novo Nordisk A/S. I. Lingvay: Advisory Panel; Novo Nordisk A/S. Research Support; Novo Nordisk A/S. Advisory Panel; Lilly Diabetes, Boehringer-Ingelheim. Research Support; Boehringer-Ingelheim. Consultant; Carmot Therapeutics, Inc., Merck Sharp & Dohme Corp., Janssen Scientific Affairs, LLC, Pfizer Inc. Advisory Panel; Sanofi. Consultant; Intercept, Intarcia, Valeritas, TargetRWE, Shionogi, Zealand Pharma, Structure, Bayer. J. K. Mader: Advisory Panel; Novo Nordisk A/S. Speaker's Bureau; Novo Nordisk A/S, A. Menarini Diagnostics. Research Support; A. Menarini Diagnostics, Abbott Diabetes. Advisory Panel; Abbott Diabetes. Speaker's Bureau; Abbott Diabetes. Advisory Panel; Roche Diabetes Care. Speaker's Bureau; Roche Diabetes Care. Research Support; Roche Diabetes Care. Advisory Panel; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Advisory Panel; Sanofi. Speaker's Bureau; Sanofi. Advisory Panel; Medtronic. Speaker's Bureau; Boehringer Ingelheim Inc., Becton, Dickinson and Company. Advisory Panel; Becton, Dickinson and Company. Speaker's Bureau; Ypsomed AG, Viatris Inc., Servier Laboratories. Research Support; Dexcom, Inc., Profusa, Inc. Stock/Shareholder; Decide Clinical Software GmbH. Advisory Panel; Pharmasense, embecta. Speaker's Bureau; Medtrust. T. Nishida: Employee; Novo Nordisk Pharma Ltd. Stock/Shareholder; Novo Nordisk A/S. J. Rosenstock: Advisory Panel; Applied Therapeutics Inc. Research Support; Applied Therapeutics Inc. Advisory Panel; Boehringer Ingelheim Inc. Research Support; Boehringer Ingelheim Inc. Advisory Panel; Eli Lilly and Company. Research Support; Eli Lilly and Company, Merck & Co., Inc., Novartis. Advisory Panel; Novo Nordisk. Research Support; Novo Nordisk. Advisory Panel; Oramed Pharmaceuticals. Research Support; Pfizer Inc. Advisory Panel; Sanofi. Research Support; Sanofi. Advisory Panel; Zealand Pharma A/S, Intarcia Therapeutics, Inc. Research Support; Intarcia Therapeutics, Inc. Advisory Panel; Hanmi Pharm. Co., Ltd. Funding Novo Nordisk A/S

1234-P: Derivation of a Claims-Computable Major Adverse Cardiovascular Event Estimator (ACME) in Adults with Type 2 Diabetes

Major adverse cardiovascular events (MACE) are a major cause of morbidity and mortality among adults with type 2 diabetes. Currently available risk prediction models estimate long-term risk (typically 10-year) and require clinical data not routinely available in real-world data sources, which limit their use on population level. Using de-identified claims data from OptumLabs® Data Warehouse for enrollees in private and Medicare Advantage health plans linked to 100% sample of Medicare fee-for-service beneficiaries between 2014 and 2021, we derived ACME to estimate annualized risk of non-fatal myocardial infarction, non-fatal stroke, or all-cause mortality in patients with type 2 diabetes aged ≥21 years (N=6,623,526). The Cox proportional hazards model, combined with an estimate of the baseline hazard using the Nelson-Aalen estimator to allow conditional survival predictions, included 28 covariates available in claims (age, sex, cardiovascular comorbidities, and cardiovascular medications). The study population had mean age 68.1 (SD, 10.6) years, 49.8% were women, and 73.0% were non-Hispanic White. ACME’s concordance index was 0.74 (se = 0.0002) and it performed comparably in all racial and ethnic groups. Strongest predictors of MACE were acute myocardial infarction and stroke within the past 3 months, heart failure hospitalization within the past year, and end-stage kidney disease. Overall, 4.2% of patients were predicted to have low (<1%) annualized MACE risk, 62.8% were predicted to have moderate (≥1 to <5%) annualized risk, and 33.0% were predicted to have high (≥5%) annualized risk. Other thresholds can be chosen for individualized applications. ACME can support population risk stratification and health management efforts at the health system and payer levels, participant identification for decentralized pragmatic clinical trials of cardiovascular disease and its prevention, and risk-stratified observational studies using real-world data. Disclosure R.G.Mccoy: Consultant; Emmi. G.Umpierrez: Research Support; Abbott, Dexcom, Inc., Baxter. R.J.Galindo: Consultant; Novo Nordisk, Eli Lilly and Company, Sanofi, Pfizer Inc., Bayer Inc., WW (Weight Watchers), Research Support; Novo Nordisk, Eli Lilly and Company, Dexcom, Inc. J.Brito: None. M.Mickelson: None. E.Polley: None. K.Swarna: None. Y.Deng: None. J.Herrin: Consultant; Johnson & Johnson Medical Devices Companies. J.Ross: Research Support; Johnson & Johnson. D.M.Kent: Research Support; W.L. Gore. B.Borah: Consultant; Boehringer Ingelheim Inc., Exact Sciences. W.Crown: Consultant; Janssen Scientific Affairs, LLC, UnitedHealth Group, Viatris Inc. V.M.Montori: None. Funding Patient-Centered Outcomes Research Institute (DB-2020C2-20306)

263-OR: Older Adults Benefit from Virtual Support for CGM Use but Require Longer Visits

The Virtual Diabetes Specialty Clinic (VDiSC) provided type 1 (T1D) and type 2 diabetes (T2D) adults taking insulin virtual care with remote CGM training and support. HbA1c improved from baseline to 6 months in T1D (7.8% to 7.0%) and T2D (8.2% to 7.0%) with increased time in range (70-180 mg/dL; TIR). Here we compare glycemic outcomes (Table 1) and duration of remote CGM training visits (Table 2) in adults ages <40 yr, 40-59 yr and ≥ 60 yr. HbA1c and %TIR improved in each group. Limitations include a small sample size that was mostly White. Results suggest that both T1D and T2D adults ≥60 years of age experience glycemic benefit after remote training and support in the use of CGM from CDCESs, but when compared to young adults, older adults require more time for training. Support for approaches that address the individual needs of older adults with diabetes is required. Disclosure R.S.Weinstock: Consultant; Jaeb Center for Health Research, Other Relationship; Wolters Kluwer Health, Research Support; Insulet Corporation, Medtronic, Eli Lilly and Company, Novo Nordisk, Boehringer Ingelheim Inc., Hemsley Charitable Trust, National Institute of Diabetes and Digestive and Kidney Diseases, Tandem Diabetes Care, Inc., Kowa Pharmaceuticals America, Inc. T.S.Mcarthur: None. B.A.Olson: Stock/Shareholder; Abbott. S.Oser: Advisory Panel; Cecelia Health, Dexcom, Inc., Consultant; Medscape, Research Support; Abbott Diabetes. T.Oser: Advisory Panel; Cecelia Health, Consultant; Dexcom, Inc., Medscape, Research Support; Abbott. D.Raghinaru: None. R.Beck: Consultant; Eli Lilly and Company, Novo Nordisk, Diasome, Insulet Corporation, Research Support; Tandem Diabetes Care, Inc., Beta Bionics, Inc., Dexcom, Inc., Bigfoot Biomedical, Inc., Medtronic, Ascensia Diabetes Care, Roche Diabetes Care, Eli Lilly and Company, Novo Nordisk. G.Aleppo: Advisory Panel; Medscape, Consultant; Bayer Inc., Insulet Corporation, Research Support; Dexcom, Inc., Eli Lilly and Company, Emmes, Insulet Corporation, Fractyl Health, Inc., WellDoc, Speaker's Bureau; Dexcom, Inc. Z.Thompson: None. R.M.Bergenstal: Advisory Panel; Abbott Diabetes, Eli Lilly and Company, Medtronic, Novo Nordisk, Roche Diabetes Care, Zealand Pharma A/S, Consultant; Ascensia Diabetes Care, Bigfoot Biomedical, Inc., CeQur SA, Dexcom, Inc., Hygieia, Onduo LLC, Sanofi, Vertex Pharmaceuticals Incorporated, Research Support; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic, Novo Nordisk, Sanofi, UnitedHealth Group. T.L.Cushman: None. R.L.Gal: None. C.Kollman: Research Support; Insulet Corporation, Dexcom, Inc., Tandem Diabetes Care, Inc. D.F.Kruger: Advisory Panel; Abbott Diabetes, Lilly, Medtronic, Novo Nordisk, Research Support; Dexcom, Inc., Beta Bionics, Inc., Speaker's Bureau; Dexcom, Inc., Lilly, Xeris Pharmaceuticals, Inc., Novo Nordisk. K.K.Hood: Consultant; Cecelia Health. M.L.Johnson: Research Support; Abbott, Lilly, Insulet Corporation, NIH - National Institutes of Health, Patient-Centered Outcomes Research Institute, Novo Nordisk, Tandem Diabetes Care, Inc., Medtronic, Hemsley Charitable Trust, Jaeb Center for Health Research. Funding The Leona M. and Harry B. Helmsley Charitable Trust; Dexcom, Inc.

149-LB: Telemedicine Intervention Impact on Diabetes Self-Management—Twelve-Month Virtual Diabetes Specialty Clinic (VDISC) Study Outcomes

The impact of a telemedicine model for a virtual diabetes clinic was assessed 6 months following completion of a 6-month intervention of education and support for diabetes self-management, including initiation and use of CGM. One hundred and sixty-one participants ≥18 years old with T1D (N=109) or T2D (N=52) using MDI/pump participated in the 12-month study. At the end of the 6-month intervention period, mean HbA1c decreased from 7.6% at baseline to 7.0% in T1D and from 8.1% to 7.0% in T2D (P<0.001). At 12 months (6 months after discontinuation of the intervention), mean HbA1c was 7.0% for T1D and 7.2% for T2D (P<0.001 compared with baseline). Mean time in range 70-180 mg/dL was 51% at baseline, increasing to 62% at 6 months (P<0.001) and 64% at 12 months in T1D (P<0.001) and from 49% to 66% (P<0.001) and 68% (P<0.001), respectively, in T2D. Similar improvements were observed for mean glucose and hyperglycemia metrics. A sustained reduction in hypoglycemia also was observed. The virtual diabetes clinic intervention was successful in promoting improved glycemic outcomes, which were sustained 6 months after the intervention was completed. These findings demonstrate the impact that virtual care and education can have on self-management over time and provide opportunity to expand care models that could minimize barriers to specialty care access. Disclosure R. L. Gal: None. S. Oser: Advisory Panel; Cecelia Health, Dexcom, Inc., Consultant; Medscape, Research Support; Abbott Diabetes. T. Oser: Advisory Panel; Cecelia Health, Consultant; Dexcom, Inc., Medscape, Research Support; Abbott. K. K. Hood: Consultant; Cecelia Health. T. L. Cushman: None. M. L. Johnson: Research Support; Abbott, Lilly, Insulet Corporation, NIH - National Institutes of Health, Patient-Centered Outcomes Research Institute, Novo Nordisk, Tandem Diabetes Care, Inc., Medtronic, Hemsley Charitable Trust, Jaeb Center for Health Research. C. Kollman: Research Support; Insulet Corporation, Dexcom, Inc., Tandem Diabetes Care, Inc. R. Beck: Consultant; Eli Lilly and Company, Novo Nordisk, Diasome, Insulet Corporation, Research Support; Tandem Diabetes Care, Inc., Beta Bionics, Inc., Dexcom, Inc., Bigfoot Biomedical, Inc., Medtronic, Ascensia Diabetes Care, Roche Diabetes Care, Eli Lilly and Company, Novo Nordisk. D. Raghinaru: None. G. Aleppo: Advisory Panel; Medscape, Consultant; Bayer Inc., Insulet Corporation, Research Support; Dexcom, Inc., Eli Lilly and Company, Emmes, Insulet Corporation, Fractyl Health, Inc., WellDoc, Speaker's Bureau; Dexcom, Inc. B. A. Olson: Stock/Shareholder; Abbott. D. F. Kruger: Advisory Panel; Abbott Diabetes, Lilly, Medtronic, Novo Nordisk, Research Support; Dexcom, Inc., Beta Bionics, Inc., Speaker's Bureau; Dexcom, Inc., Lilly, Xeris Pharmaceuticals, Inc., Novo Nordisk. R. M. Bergenstal: Advisory Panel; Abbott Diabetes, Eli Lilly and Company, Medtronic, Novo Nordisk, Roche Diabetes Care, Zealand Pharma A/S, Consultant; Ascensia Diabetes Care, Bigfoot Biomedical, Inc., CeQur SA, Dexcom, Inc., Hygieia, Onduo LLC, Sanofi, Vertex Pharmaceuticals Incorporated, Research Support; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic, Novo Nordisk, Sanofi, UnitedHealth Group. R. S. Weinstock: Consultant; Jaeb Center for Health Research, Other Relationship; Wolters Kluwer Health, Research Support; Insulet Corporation, Medtronic, Eli Lilly and Company, Novo Nordisk, Boehringer Ingelheim Inc., Hemsley Charitable Trust, National Institute of Diabetes and Digestive and Kidney Diseases, Tandem Diabetes Care, Inc., Kowa Pharmaceuticals America, Inc. A. Bradshaw: None. T. S. Mcarthur: None.

Outpatient treatment of COVID-19 and incidence of post-COVID-19 condition over 10 months (COVID-OUT): a multicentre, randomised, quadruple-blind, parallel-group, phase 3 trial

Post-COVID-19 condition (also known as long COVID) is an emerging chronic illness potentially affecting millions of people. We aimed to evaluate whether outpatient COVID-19 treatment with metformin, ivermectin, or fluvoxamine soon after SARS-CoV-2 infection could reduce the risk of long COVID. We conducted a decentralised, randomised, quadruple-blind, parallel-group, phase 3 trial (COVID-OUT) at six sites in the USA. We included adults aged 30-85 years with overweight or obesity who had COVID-19 symptoms for fewer than 7 days and a documented SARS-CoV-2 positive PCR or antigen test within 3 days before enrolment. Participants were randomly assigned via 2 × 3 parallel factorial randomisation (1:1:1:1:1:1) to receive metformin plus ivermectin, metformin plus fluvoxamine, metformin plus placebo, ivermectin plus placebo, fluvoxamine plus placebo, or placebo plus placebo. Participants, investigators, care providers, and outcomes assessors were masked to study group assignment. The primary outcome was severe COVID-19 by day 14, and those data have been published previously. Because the trial was delivered remotely nationwide, the a priori primary sample was a modified intention-to-treat sample, meaning that participants who did not receive any dose of study treatment were excluded. Long COVID diagnosis by a medical provider was a prespecified, long-term secondary outcome. This trial is complete and is registered with ClinicalTrials.gov, NCT04510194. Between Dec 30, 2020, and Jan 28, 2022, 6602 people were assessed for eligibility and 1431 were enrolled and randomly assigned. Of 1323 participants who received a dose of study treatment and were included in the modified intention-to-treat population, 1126 consented for long-term follow-up and completed at least one survey after the assessment for long COVID at day 180 (564 received metformin and 562 received matched placebo; a subset of participants in the metformin vs placebo trial were also randomly assigned to receive ivermectin or fluvoxamine). 1074 (95%) of 1126 participants completed at least 9 months of follow-up. 632 (56·1%) of 1126 participants were female and 494 (43·9%) were male; 44 (7·0%) of 632 women were pregnant. The median age was 45 years (IQR 37-54) and median BMI was 29·8 kg/m2 (IQR 27·0-34·2). Overall, 93 (8·3%) of 1126 participants reported receipt of a long COVID diagnosis by day 300. The cumulative incidence of long COVID by day 300 was 6·3% (95% CI 4·2-8·2) in participants who received metformin and 10·4% (7·8-12·9) in those who received identical metformin placebo (hazard ratio [HR] 0·59, 95% CI 0·39-0·89; p=0·012). The metformin beneficial effect was consistent across prespecified subgroups. When metformin was started within 3 days of symptom onset, the HR was 0·37 (95% CI 0·15-0·95). There was no effect on cumulative incidence of long COVID with ivermectin (HR 0·99, 95% CI 0·59-1·64) or fluvoxamine (1·36, 0·78-2·34) compared with placebo. Outpatient treatment with metformin reduced long COVID incidence by about 41%, with an absolute reduction of 4·1%, compared with placebo. Metformin has clinical benefits when used as outpatient treatment for COVID-19 and is globally available, low-cost, and safe. Parsemus Foundation; Rainwater Charitable Foundation; Fast Grants; UnitedHealth Group Foundation; National Institute of Diabetes, Digestive and Kidney Diseases; National Institutes of Health; and National Center for Advancing Translational Sciences.

State restrictions on abortion are associated with fewer abortions in patients with high-risk cardiovascular conditions

ObjectivesPatients with modified World Health Organization (mWHO) class IV cardiovascular conditions are at high risk of severe maternal morbidity and mortality in pregnancy and are advised to avoid pregnancy or consider abortion if they become pregnant. We aimed to determine if state-level abortion policy is associated with receiving an abortion in this high-risk population. Study designWe conducted a descriptive retrospective cross-sectional study of abortion among people 15-44 years of age with mWHO class IV cardiovascular conditionsstate policy on abortion using US claims data from United health Group from 2017 to 2020. ResultsThere was a statistically significant association between restrictive abortion policy at that state level and lower number of pregnancies ending in abortions in this high-risk group. ConclusionsStates with the most restrictive abortion policy have the lowest proportion of pregnancies ending in abortion among patients with mWHO class IV cardiovascular conditions. ImplicationsVariation in receiving abortion by state of residence among patients with mWHO class IV cardiovascular conditions may indicate an impending rise in severe maternal morbidity and mortality related to cardiovascular disease in pregnancy, and the risk factor is where a person lives. This trend may be exacerbated by the Supreme Court Decision Dobbs v Jackson Women’s Health.

Efficacy and Safety of Zavegepant Nasal Spray for the Acute Treatment of Migraine: Results of a Phase 3 Double-Blind, Randomized, Placebo Controlled Trial (PL5.002)

Efficacy and Safety of Zavegepant Nasal Spray for the Acute Treatment of Migraine: Results of a Phase 3 Double-Blind, Randomized, Placebo Controlled Trial (PL5.002)

Long-Term Safety and Tolerability of Zavegepant 10 mg Nasal Spray During Concomitant Use of CGRP Monoclonal Antibodies: Results From a 1-Year Open-label Safety Trial (P10-12.009)

Long-Term Safety and Tolerability of Zavegepant 10 mg Nasal Spray During Concomitant Use of CGRP Monoclonal Antibodies: Results From a 1-Year Open-label Safety Trial (P10-12.009)

Zavegepant 10 mg Nasal Spray is Effective for the Acute Treatment of Migraine Regardless of Attack Frequency: Pooled Results From 2 Randomized, Placebo-Controlled Clinical Trials (S47.003)

Zavegepant 10 mg Nasal Spray is Effective for the Acute Treatment of Migraine Regardless of Attack Frequency: Pooled Results From 2 Randomized, Placebo-Controlled Clinical Trials (S47.003)

Effects of Rimegepant 75 mg on Monthly Migraine Days: a 52-Week, Open-Label Extension Study (P10-12.010)

Effects of Rimegepant 75 mg on Monthly Migraine Days: a 52-Week, Open-Label Extension Study (P10-12.010)

Safety and Tolerability of Rimegepant Every Other Day for Preventive Treatment of Migraine Plus As-Needed for Acute Treatment of Migraine: Results from A 52-Week, Open-Label Extension Phase (P12-12.006)

Safety and Tolerability of Rimegepant Every Other Day for Preventive Treatment of Migraine Plus As-Needed for Acute Treatment of Migraine: Results from A 52-Week, Open-Label Extension Phase (P12-12.006)

Disease Modifying Therapy in Newly Diagnosed People with Multiple Sclerosis – A Real-World Administrative Claims Study (P3-3.017)

<h3>Objective:</h3> To characterize the initial disease modifying therapy (DMT) and time-to-treatment of people who receive a diagnosis of Multiple Sclerosis (MS). <h3>Background:</h3> Initiation of DMT expeditiously after diagnosis is important to reduce disease activity and optimize clinical outcome. MS diagnosis can occur in emergency, inpatient, or outpatient settings so a comprehensive view of subsequent care and treatment can be difficult to ascertain. Administrative claims are a useful tool to observe initiation of care. <h3>Design/Methods:</h3> Longitudinal data of suspected newly diagnosed people with MS (PwMS) from a large payer commercial claims database spanning 2016–2021 were analyzed. Inclusion criteria required any combination of 3 non-overlapping claims with an MS diagnosis (ICD-10-CM: G35) and/or DMT within a year following the first G35. A minimum 5 years of continuous medical and prescription coverage with 2 years prior to and 1 year following the first G35 was required to establish likely initial diagnosis and observe initiation of DMT. Time-to-treatment statistics were calculated for DMTs initiated within a year of the first G35. <h3>Results:</h3> Out of 2,024 cohort members meeting inclusion criteria, 17% started a DMT within 30 days of first MS diagnosis code, and an additional 16% started between 31 and 60 days. 34% of members in this cohort did not have a DMT claim observed in the year following their initial G35. Time-to-treatment varies by DMT. The most frequent therapies initiated within a year were glatiramer acetate, dimethyl fumarate, and ocrelizumab with median (interquartile range) time-to-DMT of 35 (15–70), 47 (22–85), and 79 (51–131) days, respectively. <h3>Conclusions:</h3> Many apparent newly diagnosed PwMS did not start a DMT within a year following the initial MS claim. There is substantial variation in initial DMT and time-to-DMT of those that started within a year. Further study is warranted to understand factors that impact initiation of DMT. <b>Disclosure:</b> Dr. Jordan has received personal compensation for serving as an employee of Octave Bioscience. Dr. Jordan has received personal compensation for serving as an employee of Rally Health/Optum. Dr. Jordan has stock in Octave Bioscience. Dr. Jordan has stock in UnitedHealth Group. Mrs. Hua has received personal compensation for serving as an employee of Octave. Dr. Ghoreyshi has received personal compensation for serving as an employee of Octave Bioscience. Dr. Ghoreyshi has received personal compensation for serving as an employee of Verily Life Sciences. Dr. Ghoreyshi has stock in Octave Bioscience. Dr. Edgeworth has received personal compensation for serving as an employee of Octave Bioscience. Dr. Edgeworth has received personal compensation for serving as an employee of Cigna. Dr. Edgeworth has stock in Octave Bioscience. Dr. Edgeworth has stock in Cigna. Dr. Edgeworth has stock in OnCall Health Corporation, DBA Cayaba Care. Dr. Edgeworth has stock in Winnow AI, Inc. .

Evaluation of the Biodistribution, Efficacy, and Side-Effect Profile of Deflazacort, Prednisolone and Vamorolone in a DMD Mouse Model (S34.010)

Evaluation of the Biodistribution, Efficacy, and Side-Effect Profile of Deflazacort, Prednisolone and Vamorolone in a DMD Mouse Model (S34.010)

Significant reduction in migraine days with Remote Electrical Neuromodulation (REN) for migraine prevention: A double-blind randomized sham-controlled clinical trial (S47.010)

Significant reduction in migraine days with Remote Electrical Neuromodulation (REN) for migraine prevention: A double-blind randomized sham-controlled clinical trial (S47.010)

Myasthenia Gravis Treatments Are Associated with Negative Patient Sentiment in Digital Conversation Data (P7-8.013)

<h3>Objective:</h3> To explore patient experiences with treatments for Myasthenia Gravis (MG) via digital conversations with a focus on corticosteroids and Immunoglobulin (Ig) therapies. <h3>Background:</h3> MG is a rare, chronic autoantibody disease that requires long-term treatment and is associated with high disease and treatment burden and reduced quality of life. <h3>Design/Methods:</h3> One year (8/2021–8/2022) of conversations focused on MG and treatments, specifically corticosteroids and Ig, originating from US internet protocol addresses were tagged based on self-identification in the conversations or on public profiles. Advanced search techniques together with artificial intelligence powered algorithms were used to extract and organize data by topics into a large, unstructured dataset. Sentiment analysis via natural language processing was conducted to categorize conversations as positive, negative or neutral and analyzed to derive the most frequent drivers of each sentiment. <h3>Results:</h3> Among 13,234 conversations extracted from topical sites, message boards, social networks and blogs, 19% were related to MG treatments. Most conversations had negative sentiment (59%), 39% were neutral, and 1% were positive. Among corticosteroid and Ig treated individuals, respectively, posts with negative (69% and 61%) and neutral (31% and 39%) sentiments were the norm, with virtually no “positive” conversations. “Treatment issues” was the dominant driver of negative sentiment among the corticosteroid and Ig related conversations. When posting about “barriers to treatment”, corticosteroid related conversations were most frequently about lack of effectiveness and side effects, while patients discussing Ig treatments most frequently focused on side effects and cost/insurance. <h3>Conclusions:</h3> Digital conversations reveal a high degree of negativity and concern related to MG treatment, specifically, corticosteroids and Immunoglobulin therapies. There is a need for new treatments that provide effectiveness through symptom control with few side effects. By capturing patient voice, this study reinforces limitations of current treatments and highlights the need for improved options for individuals with MG. <b>Disclosure:</b> Dr. Pesa has received personal compensation for serving as an employee of Janssen. Dr. Pesa has stock in J&amp;J. Dr. Chaudhry has received personal compensation for serving as an employee of Johnson &amp; Johnson. Dr. Chaudhry has received personal compensation for serving as an employee of Takeda Pharmaceuticals. Mrs. Brethenoux has received personal compensation for serving as an employee of Cien+ . Mr. Furey has nothing to disclose. The institution of Mrs. Gil Valletta has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Janssen. The institution of Mrs. Gil Valletta has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for A- Speakers. The institution of Mrs. Gil Valletta has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for The Cleveland Clinic. Mrs. Gil Valletta has received personal compensation in the range of $500-$4,999 for serving as an officer or member of the Board of Directors for United Health Group. Mrs. Gil Valletta has received personal compensation in the range of $100,000-$499,999 for serving as an officer or member of the Board of Directors for Zumiez. Miss Gonzalez Quijano has nothing to disclose. Mr. Lorenzo has nothing to disclose.

Aspirin and Statins Reduce the Risk of Stroke in Women with Endometriosis (S3.002)

<h3>Objective:</h3> To determine (1) the risk of stroke in women with endometriosis and (2) the effect of aspirin and statins on that risk. <h3>Background:</h3> Endometriosis is an inflammatory chronic gynecologic condition that affects approximately 10% of reproductive aged women. Previous research suggests that endometriosis increases stroke risk, but the role of medications known to prevent stroke in modifying this risk is uncertain. <h3>Design/Methods:</h3> We retrospectively analyzed data from the California Teachers Study, a large prospective cohort of female teachers followed continuously since 1995, excluding those with prior stroke or heart attack. This analyses’ exposure was self-reported history of endometriosis, and the outcome was hospitalization for any stroke (ischemic stroke, intracerebral and subarachnoid hemorrhage). Study covariates were self-reported use of aspirin and statin, race-ethnicity, hysterectomy, and vascular risk factors: hypertension, diabetes mellitus, obesity, migraine, current or prior tobacco use, malignancy, and oral contraceptive use. We used Cox proportional hazards models to calculate hazard ratios (HR) and 95% confidence intervals (CI) for stroke by age among women with and without history of endometriosis after adjustment for demographics and vascular risk factors. We examined association of aspirin and statin use with stroke among women with endometriosis. <h3>Results:</h3> Of 121,993 women, 13,938 (11.4%) reported a history of endometriosis. Women with endometriosis had slightly higher rates of vascular risk factors than women without endometriosis. Adjusted risk of stroke in the endometriosis group was higher than in the non-endometriosis group (HR 1.20, CI 1.09–1.28). Stroke occurred at a younger age among women with endometriosis (77.9 vs 80.2, p&lt;0.01). Within the endometriosis group, stroke risk in users of aspirin (HR 0.80, CI 0.69–0.92) or statins (HR 0.74, CI 0.62–0.88) was lower than that of non-users. <h3>Conclusions:</h3> In a large cohort study, history of endometriosis was associated with increased stroke risk and, among women with endometriosis, aspirin and statin use decreased this risk. <b>Disclosure:</b> Dr. Seitz has stock in Baxter International Inc. (&lt;0.0003% ownership), Bristol-Myers Squibb Company (&lt;0.0001%), Colgate-Palmolive Company (&lt;0.0002%), CVS Health Corporation (&lt;0.0002%), Johnson &amp; Johnson (&lt;0.00004%), Eli Lilly and Company (&lt;0.00005%), Proctor &amp; Gamble Company (&lt;0.00005%), UnitedHealth Group Incorporated (&lt;0.00002%), Walgreen Boots Alliance, Inc. (&lt;0.0002%), White Mountains Insurance (&lt;0.002%). Ms. Bull has stock in United Bank. Ms. Bull has received research support from Weill Cornell Medical College. Dr. Parikh has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for cases of neurological illness. The institution of Dr. Parikh has received research support from Leon Levy Foundation. The institution of Dr. Parikh has received research support from Florence Gould Foundation. The institution of Dr. Parikh has received research support from NY State Empire Clinical Research Investigator Program. The institution of Dr. Parikh has received research support from NIA. The institution of Dr. Parikh has received research support from Medtronic. Dr. Navi has nothing to disclose. Dr. Merkler has received personal compensation in the range of $0-$499 for serving as a Consultant for GLG. Dr. Merkler has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for The Neurohospitalist. Dr. Merkler has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for n/a. The institution of Dr. Merkler has received research support from AHA. The institution of Dr. Merkler has received research support from Weill Cornell Medical College. Dr. Kamel has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for JAMA Neurology. Dr. Kamel has received personal compensation in the range of $50,000-$99,999 for serving as a Endpoint adjudication committee with Boehringer-Ingelheim. The institution of Dr. Liberman has received research support from NIH.