bluuebunny/crossref_metadata_2025 huggingface dataset:
820-P: Testosterone Treatment Improves Glycemic Control and Leads to Remission in 56.8% of Patients with Hypogonadism and Type 2 Diabetes (T2DM) : Update of Real-World Data from a Registry Study
Authors: HAIDER AHMAD , HAIDER KARIM S. , SAAD FARID
Published: May 2022

Background: Prevalence of hypogonadism is as high as 50% in men with T2DM. ADA Guidelines recommend measuring testosterone in men with T2DM.

Methods: In a registry of 883 men with hypogonadism, 370 men (41.9%) have T2DM. 190 received TU 1000 mg/12 weeks (T-group) , 180 opted against treatment (CTRL) . All patients received standard diabetes care including lifestyle courses at a diabetes center. Remission was defined as discontinuation of diabetes drugs and HbA1c <6.5% for the remaining observation time. Means and standard deviations of absolute measures over 13 years of treatment are reported.

Results: Mean follow-up 9.3±3.2, baseline age: 61.0±5.3 (T-group) and 63.0±4.9 (CTRL) years.

HbA1c decreased from 9.5±1.4% to 5.5±1.2% (79.8±15.5 to 36.6±1.9 mmol/mol) in the T-group and increased from 7.8±0.7% to 10.5±1.2% (61.8±7.7 to 91.7±13.3 mmol/mol) in CTRL (p<0.00for both) .

Fasting glucose (mmol/L) decreased from 7.9±1.3 to 5.4±0.1 in the T-group and increased from 6.4±0.8 to 8.2±1.3 in CTRL (p<0.00for both) .

HOMA-IR decreased from 10.2±2.1 to 1.5±0.3 in the T-group and increased from 7.3±1.3 to 14.8±2.5 in CTRL (p<0.00for both) .

In the T-group, 89 men (46.8%) received insulin at baseline at a mean dose of 38.0±13.3 U/d. Dose requirement declined from 38.0±13.3 to 4.1±5.7 during the observation period. In CTRL, 71 men (39.4%) received insulin at baseline at a mean dose of 31.2±6.1 U/d. Dose requirement increased from 31.2±6.1 to 44.5±5.6 (p<0.00for both) .

In the T-group, 1patients (56.8%) went into remission. The median time to remission was 87 months.

Conclusions: Long-term testosterone therapy with TU in men with hypogonadism and T2DM progressively improved glycemic control. More than half of men achieved remission. Glycemic control deteriorated in untreated men.

Disclosure

A.Haider: Other Relationship; Bayer AG. K.S.Haider: Other Relationship; Bayer AG. F.Saad: Consultant; Bayer AG, Stock/Shareholder; AbbVie Inc., Bayer AG, GlaxoSmithKline plc.

Funding

Bayer AG
833-P: Impact of Hypoglycemia on Insulin Titration and Fasting Plasma Glucose in Basal Insulin–Treated Type 2 Diabetes: A Subanalysis of the SoliMix Trial
Authors: GIORGINO FRANCESCO , ROSENSTOCK JULIO , RITZEL ROBERT , DEYNELI OGUZHAN , ALVAREZ AGUSTINA , SOUHAMI ELISABETH , MELAS-MELT LYDIE , MCCRIMMON RORY J.
Published: May 2022

Introduction: The SoliMix trial (EudraCT: 2017-003370-13) found better HbA1c with weight benefit and lower hypoglycemia risk for iGlarLixi vs. premix BIAsp 30 in people with type 2 diabetes advancing from basal insulin plus oral antihyperglycemic drugs. This exploratory analysis investigated whether hypoglycemia influenced insulin titration and achievement of fasting plasma glucose (FPG) targets with each therapeutic option.

Methods: Total insulin dose changes from baseline to Week 12 were stratified by hypoglycemia (yes/no) in each treatment arm and ADA Level 2 hypoglycemia (<54 mg/dL [<3.0 mmol/L]) event rates during Weeks 0-12 were modeled according to FPG at Week 12 (when most insulin titration occurred) .

Results: Lesser insulin dose increases occurred in both treatment groups for those who experienced hypoglycemia (mean ± SD iGlarLixi: 3.9 ± 12.5 U; BIAsp 30: 11.0 ± 18.8 U) vs. those who did not (mean ± SD iGlarLixi: 11.2 ± 9.9 U; BIAsp 30: 19.4 ± 19.3 U) . While higher FPG at Week 12 correlated with greater event rates of hypoglycemia in both treatment arms, event rates were higher for BIAsp 30 than for iGlarLixi irrespective of FPG (Figure) .

Conclusions: More frequent hypoglycemia with premix BIAsp 30 than with iGlarLixi may result in lower insulin doses, thus hampering insulin titration and resulting in higher FPG.

Disclosure

F.Giorgino: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk, Consultant; Lilly Diabetes, Sanofi, Research Support; Lilly Diabetes, Roche Diabetes Care, Takeda Pharmaceutical Company Limited. J.Rosenstock: Consultant; AstraZeneca, Other Relationship; Applied Therapeutics, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Hanmi Pharm. Co., Ltd., Intarcia Therapeutics, Inc., Novo Nordisk, Oramed Pharmaceuticals, Sanofi, Zealand Pharma A/S, Research Support; Genentech, Inc., Merck & Co., Inc., Metacrine, Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc., vTv Therapeutics. R.Ritzel: Consultant; Novo Nordisk, Sanofi, Speaker's Bureau; AstraZeneca, Lilly, Novartis Pharmaceuticals Corporation, Novo Nordisk, Pfizer Inc., Sanofi. O.Deyneli: Advisory Panel; Abbott Diabetes, AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Novo Nordisk, Roche Diagnostics, Sanofi, Speaker's Bureau; Abbott, AstraZeneca, Berlin-Chemie AG, Bilim Ilaç, Boehringer Ingelheim International GmbH, Medtronic, Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk, Roche Diabetes Care, Sanofi. A.Alvarez: Employee; Sanofi. E.Souhami: Employee; Sanofi, Stock/Shareholder; Sanofi. L.Melas-melt: None. R.J.Mccrimmon: Advisory Panel; Novo Nordisk, Sanofi, Research Support; Diabetes UK, European Union, MedImmune.

Funding

Sanofi
838-P: Lipotoxicity-Induced Liver Cell Injury Is Prevented by a Novel Positive Allosteric Modulator of the GABAA Receptor
Authors: ROHBECK ELISABETH , ROMERO ALEJANDRA , KNEBEL BIRGIT , BELGARDT BENGT-FREDERIK , RODEN MICHAEL , ROMACHO TANIA , ECKEL JÜRGEN
Published: May 2022

NAFLD is a highly prevalent condition currently lacking an approved pharmacological therapy. GABA, besides being a neurotransmitter, has been proposed to protect from liver toxicity in both in vivo an in vitro models. We aimed to determine if a novel positive allosteric modulator (PAM) of the GABAA receptor, the thioacrylamide-derivative HK4 which is devoid of blood brain barrier penetration, can protect human hepatocytes against lipotoxicity-induced injury.

Patch clamping in HEK-293 cells and calcium influx measurements in INS-1E cells proved HK4 as a selective PAM of the GABAA receptor. The expression of several main GABAA receptor subunits (α1, α3, α5, β2/3 and γ2) was demonstrated by Western blotting of HepG2 cells. Next generation sequencing was performed and an effect of HK4 on the gene expression profile in response to palmitate was observed. A preventive effect of HK4 on palmitate-induced apoptosis was demonstrated by reduced caspase 3/7 activity both in HepG2 (47.32 ± 6.92 % vs. 1065 ± 98.68 %) and human primary hepatocytes (57.13 ± 21.47 % vs. 155.1 ± 3.78 %) . This effect was further confirmed by the TUNEL assay (6.41 ± 1.42 % vs. 11.62 ± 0.99 % TUNEL positive cells) . This anti-apoptotic effect was mediated through reduced protein expression of cleaved PARP-1, reduced phosphorylation of NF-κB, and by upregulation of the ER chaperone PDI, as measured by Western blotting.

In conclusion, GABAergic signaling reduces lipotoxic-induced apoptosis in hepatocytes by preventing inflammation, DNA damage and ER stress. Therefore, we propose that HK4 may arise as an innovative pharmacological tool to treat or prevent NASH as a first-in-class drug.

Disclosure

E.Rohbeck: None. A.Romero: None. B.Knebel: None. B.Belgardt: None. M.Roden: Advisory Panel; Eli Lilly and Company, Research Support; Boehringer Ingelheim International GmbH, Nutricia, Speaker's Bureau; Novo Nordisk. T.Romacho: None. J.Eckel: Stock/Shareholder; CureDiab GmbH.

Funding

EFRE-0400192
84-LB: A Personalized Retrospective Continuous Glucose Monitoring (CGM) Report Improves Engagement and Glycemic Control in a Remote Monitoring Diabetes Program (RDMP)
Authors: ELLIS ROBERT J. , KOMPALA TEJASWI , WENG KEVIN , BROOKS ROBERT J. , SALEHI ATOUSA , JAMES ROBERTA , LIU HAU
Published: May 2022

Introduction: Retrospective review of CGM data is associated with improved glycemic control in people with diabetes, but self-initiated data review is uncommon. The objective of this study was to examine the impact of a novel “CGM-powered Insights Report” on program engagement and glycemic control within Livongo for Diabetes, a RDMP.

Methods: Members enrolled in the RDMP and who authorized data sharing of their existing Dexcom CGM automatically received biweekly Insight Report emails. These Reports provided personalized analysis of CGM trends and suggested next steps within the digital coaching program. The impact of engaging with Insight Reports was assessed via (1) odds ratios and Fisher’s exact tests on the relative recency of key RMDP program feature utilization; and (2) linear regression to quantify its impact on changes in glycemic control.

Results: 1105 members (436 T1D, 464 T2D using insulin, 205 T2D not using insulin) who received their first report by February 1, 2022 were included for analysis. On average, members received 7 Reports and opened 51% of them. Members who opened at least one Report (vs. opened no Reports) were more likely to subsequently utilize the mobile app (OR 1.6) , web portal (OR 1.9) , food logger (OR 1.8) and 1-on-1 coach chat feature (OR 3.2) (all p < .05) . After controlling for demographic and clinical characteristics, baseline glucose metrics, and number of Reports received, members who opened more Reports were more likely to show improvements in mean sensor glucose, Time In Range, and Time Above Range (all p < .05) .

Conclusions: For CGM users within an RDMP, engagement with a personalized Insights Report is associated with increased engagement across other program features, and improvements in glycemic control. Beyond the benefits of CGM itself, surfacing actionable insights within an RDMP adds value by driving members towards increased program engagement, specifically digital coaching.

Disclosure

R. J. Ellis: Employee; Teladoc Health. T. Kompala: Consultant; Eli Lilly and Company, Employee; Teladoc Health. K. Weng: Employee; Teladoc Health. R. J. Brooks: Employee; Teladoc Health, Stock/Shareholder; Dexcom, Inc., Teladoc Health. A. Salehi: Employee; Livongo. R. James: Employee; Livongo, Teladoc Health. H. Liu: Employee; Teladoc Health, Stock/Shareholder; Teladoc Health.
841-P: Scientific Basis for the First-in-Human Trial of “Neo-Islet”–Mediated Functional Cure of T1DM: The Intraperitoneal Administration of “Neo-Islets,” 3-D Organoids of Allogeneic Islet and Mesenchymal Stromal Cells from Rodents, Dogs, and Humans Durably Cures
Authors: WESTENFELDER CHRISTOF , CHOWDHURY SABIHA S. , GOOCH ANNA
Published: May 2022

Initial reports from Clinical Trials with cell-based interventions for the urgently needed therapy of T1DM show: (1) An open, s.c.-placed encapsulation device containing insulin-producing progenitor cells that require anti-rejection drugs has failed to adequately improve glycemic control. (2) The i.v. administration of stem cell-derived insulin-producing cells, requiring anti-rejection drugs, has shown promising results in 1 or 2 subjects. However, their unknown systemic location and inability to retrieve these cells remain a concern. Our approach harnesses the immune-modulating and -isolating, anti-inflammatory, angiogenic, anti-apoptotic and other trophic actions of Mesenchymal Stromal Cells (MSCs) . First, we demonstrated that allogeneic Neo-islets (NIs) , islet-sized organoids composed of equal numbers of MSCs and culture expanded Islet Cells do, when given i.p., omentally engraft, redifferentiate, re-express all islet hormones (Abstract this meeting) and permanently restore euglycemia in auto-immune diabetic NOD mice, i.e., without encapsulation devices or antirejection drugs. The omentum becomes the new endocrine pancreas. Second, i.p. therapy of spontaneously diabetic pet dogs with allogeneic canine NIs significantly improved glycemia and insulin needs (> 3 years) , and this without immune response. Third, human NIs permanently correct streptozotocin-induced diabetes in NOD/SCID mice. Removal of the omentally-engrafted NIs promptly restores the diabetic state. No long-term complications of the NI therapy have been observed. Based on this body of evidence, a successful Pre-IND meeting with the FDA was held and final Proof-of-Concept studies that are expected to lead IND approval are ongoing.

Disclosure

C.Westenfelder: None. S.S.Chowdhury: Employee; SymbioCellTech, LLC. A.Gooch: Board Member; SymbioCellTech, LLC., Employee; SymbioCellTech, LLC., Stock/Shareholder; SymbioCellTech, LLC.
846-P: Advancing Therapy in Basal Insulin–Treated Type 2 Diabetes: Exploratory Analysis of the SoliMix Trial by Baseline Age, Diabetes Duration, and Renal Function
Authors: HOME PHILIP , ROSENSTOCK JULIO , GIORGINO FRANCESCO , BLÜHER MATTHIAS , DJABALLAH KHIER , PEGELOW KATRIN , MELAS-MELT LYDIE , MCCRIMMON RORY J.
Published: May 2022

Introduction: SoliMix (EudraCT: 2017-003370-13) found better HbA1c, weight benefit, and lower hypoglycemia risk with iGlarLixi vs. premix BIAsp 30 in people with type 2 diabetes (T2D) advancing from basal insulin (BI) + oral antihyperglycemic drugs (OADs) .

Methods: Adults with T2D and HbA1c 7.5-10.0 % on BI + 1-2 OADs were randomized to once-daily iGlarLixi or twice-daily BIAsp 30 for 26 weeks. Primary outcomes were non-inferiority in HbA1c change or superiority in body weight change from baseline to Week 26. SoliMix endpoints were assessed here by baseline age (<65, ≥65 years) , T2D duration (<10, ≥years) , and renal function (eGFR ≥90, ≥60-<90, and <60 mL/min/1.73 m2) .

Results: No differences in treatment effect were observed across subgroups for HbA1c or body weight changes (heterogeneity p>0.05; Table) ; both primary objectives were met in the age, T2D duration, and the eGFR ≥60-<90 mL/min/1.73 m2 subgroups. Baseline subgroup had no effect on the lesser insulin dose increments seen in SoliMix with iGlarLixi vs. BIAsp 30 (p>0.80) . The advantage of iGlarLixi over BIAsp 30 for Level 2 hypoglycemia was found in all subgroups with no difference in treatment effect (p>0.10) .

Conclusions: The primary findings for iGlarLixi vs. BIAsp 30 were unaffected by baseline age, T2D duration, or renal function.

Disclosure

P.Home: Advisory Panel; Kriya Therapeutics, Consultant; Mundipharma, Sanofi, Other Relationship; AstraZeneca, Sanofi, Research Support; Gan & Lee Pharmaceuticals, Sanofi, Speaker's Bureau; Gan & Lee Pharmaceuticals, Medscape. J.Rosenstock: Consultant; AstraZeneca, Other Relationship; Applied Therapeutics, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Hanmi Pharm. Co., Ltd., Intarcia Therapeutics, Inc., Novo Nordisk, Oramed Pharmaceuticals, Sanofi, Zealand Pharma A/S, Research Support; Genentech, Inc., Merck & Co., Inc., Metacrine, Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc., vTv Therapeutics. F.Giorgino: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk, Consultant; Lilly Diabetes, Sanofi, Research Support; Lilly Diabetes, Roche Diabetes Care, Takeda Pharmaceutical Company Limited. M.Blüher: Consultant; AstraZeneca, Lilly, Novo Nordisk A/S, Pfizer Inc., Sanofi, Speaker's Bureau; Bayer AG, Boehringer Ingelheim International GmbH, Novartis AG. K.Djaballah: Employee; Sanofi. K.Pegelow: Employee; Sanofi-Aventis Deutschland GmbH. L.Melas-melt: None. R.J.Mccrimmon: Advisory Panel; Novo Nordisk, Sanofi, Research Support; Diabetes UK, European Union, MedImmune.

Funding

Sanofi
849-P: Factors Influencing the Selection of Glucose-Lowering Medications among Physicians Treating Patients with Type 2 Diabetes in Real World
Authors: ABUDAHESH JOUD A. , AIJEBREEN JOUD A. , ALHALEES DANAH Z. , ALBRAITHEN GHAIDA , BAMOGADDAM GHADA S. , AL-SOFIANI MOHAMMED
Published: May 2022

Background: Factors considered when selecting a diabetes medication for patients with type 2 diabetes (T2D) in clinical practice may differ from those recommended by professional societies.

Objective: To identify factors that play a major role in guiding the selection of diabetes medications in the real world.

Method: We asked 135 physicians [67% Generalists (Internists and General Practitioners) and 33% Specialists (Endocrinologists and Diabetologists) ] in Saudi Arabia to select a diabetes medication they frequently prescribe in certain clinical scenarios. Then we asked them to rank a set of factors as (“Major,” “Minor,” or “Not” a consideration) according to the degree those factors would typically influence their selection of a particular medication.

Results: Sulfonylurea is the most frequently prescribed second-line agent. Majority (89%) reported prescribing GLP-1 receptor agonists (GLP-1 RA) to “50% of their patients with T2D and ischemic heart disease; and over 2/3 prescribe SGLT-2 inhibitors (SGLT-2i) to <50% of their patients with T2D and heart failure. Strikingly, 41% and 32% of the Generalists did NOT rank “Renal benefits” with SGLT-2i and “cardiovascular benefits” with GLP-1 RA, respectively, as “major consideration” when prescribing these agents. Medication cost was ranked as a “major consideration” by 75% of Specialists and 65% of Generalists when prescribing GLP-1 RA, and by 57% of Specialists and 71% Generalists when prescribing SGLT-2i.

Conclusion: Despite the recent advances in diabetes therapy, medication cost and inadequate awareness of the cardiovascular and renal benefits of novel diabetes agents, particularly among non-specialists, remain major barriers to the wide adoption of recommendations from professional societies. Policies to improve access to novel diabetes medications and disseminate the awareness about the evidence-based benefits of these medications are needed

Disclosure

J.A.Abudahesh: None. J.A.Aijebreen: None. D.Z.Alhalees: None. G.Albraithen: None. G.S.Bamogaddam: None. M.Al-sofiani: None.
850-P: Greater HbA1c Reduction with iGlarLixi vs. Insulin Glargine and Lixisenatide Regardless of Levels at Screening: Subgroup Analysis of the LixiLan-O Asia Pacific Trial
Authors: HE YIFAN , YANG WENYING , XIAOLIN DONG , YUAN GUOYUE , LIU MING , XIAO JIANZHONG , GU SHENGHONG , CHEN LIJUAN , SOUHAMI ELISABETH
Published: May 2022

Introduction: LixiLan-O-AP (NCT03798054) showed greater HbA1c improvement with iGlarLixi vs. iGlar or Lixi in Asian Pacific adults with type 2 diabetes (T2D) . This pre-defined analysis assessed iGlarLixi efficacy by HbA1c levels at screening.

Methods: Adults (N=878) with suboptimally controlled T2D (HbA1c of 7.5-% or 7-% depending on background oral antihyperglycemic drug [OAD] use) on metformin ± a second OAD were randomized 2:2:1 to iGlarLixi, iGlar or Lixi for 24 weeks. Three screening HbA1c subgroups were defined: <8, 8-<9, ≥9 %.

Results: At Week 24, in all HbA1c subgroups, iGlarLixi was associated with greater HbA1c reductions vs. iGlar or Lixi and reached mean HbA1c levels <7 %. iGlarLixi also showed greater 2-h postprandial glucose reductions, and a higher proportion of participants reaching HbA1c <7 % and HbA1c <7 % without weight gain, vs. iGlar or Lixi (Table) . Incidence and rates of documented hypoglycemia ≤70 mg/dL (≤3.9 mmol/L) were similar between iGlarLixi and iGlar in the 8-<9 % and ≥9 % subgroups but were slightly higher with iGlarLixi vs. iGlar in the <8 % subgroup.

Conclusions: Regardless of HbA 1c level at screening, iGlarLixi demonstrated better glycemic control vs. iGlar or Lixi, with over 75% of participants achieving the recommended target HbA 1c (<7 %) with iGlarLixi, even those with HbA1c ≥9 % at screening.

Disclosure

Y. He: None. W. Yang: Other Relationship; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Mer, Merck Sharp & Dohme Corp., Novo Nordisk, Sanofi-Aventis Deutschland GmbH, Servier Laboratories. M. Liu: None. J. Xiao: None. S. Gu: Employee; Sanofi China. L. Chen: None. E. Souhami: Employee; Sanofi. Stock/Shareholder; Sanofi.

Funding

Funding: Sanofi
855-P: PromarkerD Predicts Late-Stage Renal Function Decline in Type 2 Diabetes in the Canagliflozin Cardiovascular Assessment Study (CANVAS)
Authors: PETERS KIRSTEN E. , PRINZIO PATSY DI , BRINGANS SCOTT , DAVIS WENDY A. , DAVIS TIMOTHY , LIPSCOMBE RICHARD J. , HANSEN MICHAEL K.
Published: May 2022

A third of people with type 2 diabetes (T2D) will develop chronic kidney disease (CKD) , the leading cause of end-stage renal disease (ESRD) . Current standard of care tests (urinary albumin:creatinine ratio (ACR) , estimated glomerular filtration rate (eGFR)) have limited ability to predict CKD progression. PromarkerD is a novel blood test that has prognostic value for the onset/progression of early-stage renal function decline in T2D. The ability of PromarkerD to predict later-stage renal decline in participants in the CANVAS trial was explored.

Concentrations of PromarkerD biomarkers (CD5L, ApoA4, IGFBP3) were measured by mass spectrometry at baseline in 3,525 CANVAS participants (n=1,179 placebo arm, n=2,346 canagliflozin arm) and combined with clinical data (age, serum HDL-cholesterol, eGFR) to provide PromarkerD scores (0 to 100%) for adverse renal outcomes. Cox regression was used to assess the ability of PromarkerD to predict three composites: i) ≥40% eGFR decline, ESRD, or renal death ii) outcome 1 or cardiovascular disease death and iii) outcome 2 or progression to macroalbuminuria.

At baseline, the participants (mean age 62.7 years, 67% males, median diabetes duration 12.5 years) had mean eGFR 77 mL/min/1.73m2, median ACR 11.6 mg/g and mean PromarkerD score 34.5%. During a mean 5.6 years of follow-up, 138 (3.9%) , 380 (10.8%) and 427 (12.1%) participants experienced composite outcomes 1 to 3, respectively. After adjusting for allocated treatment, each 10% increase in PromarkerD score was significantly associated with higher rates of adverse outcomes (outcome 1: HR 1.22 [1.to 1.38], outcome 2: HR 1.28 [1.to 1.37], outcome 3: HR 1.13 [1.to 1.21], all P≤0.001) with only modest attenuation after adjustment for both eGFR and ACR (all P≤0.013) .

This post-hoc analysis of CANVAS data shows that PromarkerD can be used to predict late as well as early-stage renal decline in people with T2D.

Disclosure

K.E.Peters: None. P.Di prinzio: None. S.Bringans: None. W.A.Davis: None. T.Davis: Advisory Panel; Merck Sharp & Dohme Corp., Novo Nordisk, Roche Diagnostics, Research Support; Novo Nordisk, Speaker's Bureau; Novo Nordisk. R.J.Lipscombe: Employee; Proteomics International, Stock/Shareholder; Proteomics International. M.K.Hansen: Employee; Janssen Research & Development, LLC.
869-P: Reductions in Traditional Risk Factors Explain Most of the Cardiovascular Benefit of SGLT2 Inhibitors and GLP-1 Receptor Agonists: An Analysis Using the BRAVO Risk Engine
Authors: NIU SHU , GUAN DAWEI , OSPINA NAYKKY SINGH , CUSI KENNETH , FONSECA VIVIAN , SHI LIZHENG , SHAO HUI
Published: May 2022

Several hypotheses have been proposed that SGLT2 inhibitors and GLP-1 receptor agonists may have additional mechanisms to further reduce risks of cardiovascular complications unexplained by traditional risk factors control. This study aimed to examine and quantify the magnitude of additional protective effects of these two drugs on cardiovascular outcomes in individuals with type 2 diabetes (T2D) . Patient characteristics were extracted from four cardiovascular outcomes trials (CVOTs) of SGLT2 inhibitors and four CVOTs of GLP-1 receptor agonists completed before Nov 2021. We used the BRAVO simulation model to translate risk factors reductions from the newer drugs into risk reductions in cardiovascular complications, assuming the simulated risk reductions are only driven by traditional risk factors (i.e., A1c, SBP, LDL, and BMI) . We then derived the relative risk (RR) between observed risk reductions and simulated risk-factor-driven risk reductions in study outcomes to determine whether additional cardiovascular benefit of the newer drugs exist that can be explained by improvement of traditional risk factor control. Controlling for effect from traditional risk factors, SGLT2 inhibitor was associated with an additional risk reduction of hospitalization for heart failure (HHF) (RR: 0.74, 95% confidence interval (CI) : 0.59-0.94) , and a meaningful but not significant reduction in all-cause mortality (RR: 0.90, 95% CI: 0.77-1.03) , but an increased risk of stroke (RR: 1.29, 95% CI: 1.03-1.62) . No additional benefit was observed in preventing MI or CVD mortality from SGLT2 inhibitors. No additional benefit in preventing any study outcomes was associated with GLP-1 receptor agonists. Except for the benefit on HHF by SGLT2i, improvement in traditional CVD risk factors largely account for all the benefit associated with GLP-1 and SGLT2i to reduce CVD.

Disclosure

S.Niu: None. D.Guan: None. N.Singh ospina: None. K.Cusi: Consultant; Altimmune, Arrowhead Pharmaceuticals, Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Eli Lilly and Company, Fractyl Health, Inc., Genentech, Inc., Hanmi Pharm. Co., Ltd., Intercept Pharmaceuticals, Inc., Novo Nordisk. V.Fonseca: Consultant; Abbott, Asahi Kasei Corporation, Bayer AG, Novo Nordisk, Sanofi, Research Support; Fractyl Health, Inc., Jaguar Gene Therapy, Stock/Shareholder; Abbott, Amgen Inc., BRAVO4Health, Mellitus Health. L.Shi: None. H.Shao: Board Member; BRAVO4HEALTH, LLC.
871-P: Weight Change as Mediator for Cardiovascular Benefits of Novel Diabetes Medications: A Meta-Regression Analysis
Authors: RODRIGUEZ-VALADEZ JOSE M. , HUNINK MYRIAM , MASHARANI UMESH , YEBOAH JOSEPH , PARK MEYEON , LI LIHUA , WEBER ELLERIE , LI YAN , BERKALIEVA ASEM , MAX WENDY , FLEISCHMANN KIRSTEN , FERKET BART
Published: May 2022

Background: Prior research suggests cardiovascular (CV) benefits of glucose-lowering interventions are mediated by bodyweight changes, either through changes in fluid retention or body fat mass. For example, a meta-regression analysis of 30 randomized trials on glucose lowering interventions showed a 1 kg weight decrease was associated with a 5.9% (95% CI 3.9 - 8.0) relative reduction of heart failure risk (Ghosh et al., 2020) . We evaluated heterogeneity of CV benefits by weight change for two novel diabetes medications that lower weight: sodium glucose transporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RAs) .

Methods: We performed meta-regression analyses of published CV outcome trials (6 on SGLT2i, 8 on GLP-1RAs) using reported hazard ratios (HRs) and bodyweight difference across study arms. Dependent variables included log HRs for 1) all-cause mortality, 2) major adverse cardiovascular events (MACE) , and 3) hospitalization for heart failure. We ran linear mixed models with weights equal to the inverse of the variance of each study’s log HR.

Results: The slopes from meta-regressions by pooling all trials and by drug type (Figure) were not significant and in some cases demonstrated an inverse relationship (SGLT2i for MACE, slope= -.102; p= .04) .

Conclusion: We could not reproduce findings of increased CV benefits with more weight loss for SGLT2i and GLP-1RAs.

Disclosure

J.M.Rodriguez-valadez: None. W.Max: None. K.Fleischmann: None. B.Ferket: None. M.Hunink: None. U.Masharani: Advisory Panel; Ryse Health, Research Support; Clementia Pharmaceuticals. J.Yeboah: None. M.Park: Advisory Panel; Otsuka America Pharmaceutical, Inc., Reata Pharmaceuticals, Inc., Other Relationship; Merck & Co., Inc. L.Li: None. E.Weber: None. Y.Li: None. A.Berkalieva: None.

Funding

Research reported in this publication was supported by the National Heart, Lung, And Blood Institute of the National Institutes of Health under Award Number R01HL153456. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
876-P: Empagliflozin-Induced Metabolic Changes and Cardiac Function in Patients with Type 2 Diabetes: A Randomized Crossover MRI Study with Insulin as Comparator
Authors: THIRUMATHYAM ROOPAMEERA , GOETZE JENS PETER , HOLST JENS J. , VEJLSTRUP NIELS , MADSBAD STEN , MADSEN PER L. , JØRGENSEN NILS B.
Published: May 2022

Introduction: Empagliflozin reduces cardiovascular risk in type 2 diabetes, possibly through improved cardiac function associated with metabolic changes including lowered glucose and insulin concentrations and elevated free fatty acids (FFA) . We aimed to evaluate the influence of these metabolic changes on cardiac function in type 2 diabetes (T2D) .

Materials and Method: 17 subjects (13 males) with T2D, aged 58±3 years (mean±sem) , BMI 32.9±0.9 kg/m2, HbA1c 52.4±2.4 mmol/L, TD2 duration of 8.9±1.3 years were treated with empagliflozin (E) and NPH-insulin (I) for 5 weeks in a cross-over design with 3 weeks of washout between treatments. Insulin was titrated to produce similar glycemic control as during empagliflozin. Patients were studied before and at the end of each treatment period. Metabolic changes were evaluated with fasting glucose, FFAs and insulin concentrations, cardiac function with cardiac MRI during rest and chronotropic stress on two separate days without and with acute lowering of FFAs with acipimox. Cardiac endpoints were changes in left ventricular peak filling rate (∆LVPFR) and left ventricular ejection fraction (∆LVEF) .

Results: Fasting glucose was reduced from 8.7±0.5 mM during washouts to 7.6±0.3 mM on both treatments, while serum insulin was lower (E: 103±14 pM; I: 141±16 pM, p<0.01) and FFAs higher (E: 0.60±0.03 mM; I: 0.50±0.mM, p=0.02) on empagliflozin compared with insulin treatment. Cardiac function did not differ between treatments in rest or during stress (rest: ∆LVPFR E: -2±19;I: -11±20 ml/s, p=1.0; ∆LVEF -1 ±1, -1±1%, p=0.8; stress: ∆LVPFR E:-32±20, I: -14±24 ml/s; ∆LVEF E: 1±2, I: 0±2%) . Acipimox reduced FFAs by ∼35% at all visits but did not reveal any cardiac effects of treatments.

Conclusion: Neither empagliflozin nor insulin treatment change cardiac function in patients with T2D. Treatment specific metabolic effects play no role for cardiac function under the studied conditions.

Disclosure

R.Thirumathyam: None. J.Goetze: Consultant; Novo Nordisk A/S. J.J.Holst: Advisory Panel; Novo Nordisk, Board Member; Antag Therapeutics, Bainan Biotech. N.Vejlstrup: None. S.Madsbad: None. P.L.Madsen: None. N.B.Jørgensen: Advisory Panel; Novo Nordisk A/S, Research Support; Boehringer Ingelheim International GmbH, Speaker's Bureau; Novo Nordisk A/S, Stock/Shareholder; Eli Lilly and Company, Novo Nordisk A/S.

Funding

Boehringer Ingelheim Gmbh. Investigator initiated study grant.
890-P: Health Care Economic Burden and Resource Utilization in Adults with Type 2 Diabetes and Stroke
Authors: KING AARON A. , RAJPURA JIGAR J. , LIANG YUANJIE , PAPROCKI YUREK M. , UZOIGWE CHIOMA
Published: May 2022

Objectives: To evaluate health care resource utilization and all-cause healthcare costs in adults with type 2 diabetes mellitus (T2DM) and stroke.

Methods: Patients ≥ 18 years of age with T2DM, with or without incident stroke, were identified between January 1, 2012 and December 31, 2020 using the Optum® Clinformatics® Data Mart database. Healthcare utilization and cost were measured for the 12 months after stroke (T2DM + stroke) or random ICD-9/ICD-code (T2DM only) . Stroke was defined as overnight hospitalization with a primary discharge code for hemorrhagic or ischemic stroke. We compared patient cohorts using an inverse probability of treatment weighting approach.

Results: The incidence rate of stroke in the year following T2DM diagnosis was 0.9% (n = 16,034) . Weighted analysis compared 11,021 patients with T2DM and incident stroke (mean age, 75.1; mean Charlson comorbidity index, [CCI] 4.6) and 11,1patients with T2DM alone (mean age, 75.2; mean CCI, 4.7) . Compared to patients with T2D alone, patients with T2DM and stroke were more likely to have an IP visit (adjusted rate ratio [ARR], 5.4; 95% CI, 5.3-5.6; p < 0.01) , outpatient (OP) visit (ARR, 1.6; 95% CI, 1.6-1.6; p < 0.01) , ER visit (ARR, 1.7; 95% CI, 1.6-1.7; p < 0.01) , and longer hospital stay (ARR, 5.9; 95% CI, 5.8-5.9; p < 0.01) . Pharmacy, IP, OP, and ER costs were higher in patients with T2DM and stroke compared to patients with T2DM alone (Total costs, $8,864 per patient per month [PPPM] vs. $2,902 PPPM; p < 0.01) . IP visits (+$4,062) and OP visits (+$1,642) accounted for the biggest differences in healthcare costs. In a hypothetical population of one million patients with T2DM, we project an initial cost difference of +$615 million annually for patients with T2DM + stroke compared to T2DM alone.

Conclusions: In adults with T2DM, copresence of stroke was associated with higher healthcare utilization and cost compared to adults with T2DM alone. Treatments that lower risk of stroke in patients with T2DM should be considered in this population.

Disclosure

A.A.King: Advisory Panel; Novo Nordisk, Board Member; JDRF, Speaker's Bureau; Abbott, Dexcom, Inc., Lilly Diabetes, MannKind Corporation, Medtronic, Novo Nordisk. J.J.Rajpura: Employee; Novo Nordisk. Y.Liang: Employee; Novo Nordisk. Y.M.Paprocki: Employee; Novo Nordisk, Stock/Shareholder; Novo Nordisk. C.Uzoigwe: Employee; Novo Nordisk, Stock/Shareholder; Novo Nordisk.
894-P: The Potential Value of Clustering-Based Type 2 Diabetes Subgroups for Guiding Intensive Treatment: A Maximum Cost-Based Comparison with Threshold-Based Classifications
Authors: LI XINYU , VAN GIESSEN ANOUKH , ALTUNKAYA JAMES , SLIEKER RODERICK , BEULENS JOLINE , PEARSON EWAN , ELDERS PETRA J.M. , FEENSTRA TALITHA , LEAL JOSE
Published: May 2022

Aim: To quantify and compare the performance of setting priority for intensive treatment by novel clustering-based subgroups to threshold-based classifications using systematic coronary risk evaluation (SCORE) and HbA1c levels.

Methods: We divided 2,935 patients from the Hoorn diabetes care system cohort into five clustering-based subgroups: severe insulin-deficient (SIDD) , severe insulin-resistant (SIRD) , mild obesity-related (MOD) mild (MD) , and mild with high HDL-cholesterol (MDH) diabetes, and four risk threshold-based subgroups. The United Kingdom Prospective Diabetes Study Outcomes Model was used to simulate lifetime health outcomes in the U.S. and U.K. settings. Gains from hypothetical treatment scenarios based on clinical guidelines were compared to “care-as-usual” and expressed in incremental quality-adjusted life-expectancy (QALE) and complication costs.

Results: The SIRD and MOD subgroup had the lowest absolute and age-sex-standardized QALE, respectively (7.90; 9.07) . Threshold-based classifications better discriminated between patients with higher and lower absolute and standardized QALE than clustering-based subgroups. For MOD, hypothetical interventions costing up to $1973 (95%CI $1444-$2603) and £463 (95%CI £345-£603) per year would be cost-effective at $100,000 and £20,000 per QALY thresholds in the U.S. and U.K., respectively. The MOD, SIDD and SIRD subgroups had the best potential cost-effectiveness alongside the subgroup with high HbA1c and high SCORE.

Conclusions: Intensified treatment could be cost-effective at higher-than-average costs for three out of five of the clustering-based subgroups and two out of four of the threshold-based classifications. Both classification methods support priority setting for intensive treatment, but the threshold-based method may better identify those who have the most potential to benefit from intensified treatment.

Disclosure

X.Li: None. A.Van giessen: None. J.Altunkaya: None. R.Slieker: None. J.Beulens: None. E.Pearson: Speaker's Bureau; Sanofi. P.J.M.Elders: None. T.Feenstra: Research Support; Dutch Healthcare Institute (ZIN) , European Union/IMI Rhapsody. J.Leal: None.

Funding

RHAPSODY (115881)
9-LB: Increased Islet Expression of Somatostatin and Glucagon in Male Rats with Insulin-Dependent Type 2 Diabetes
Authors: HOFFMAN EMILY G. , ATHERLEY SARA C. , AKBARIAN NICKY , DSOUZA NINOSCHKA , LIGGINS RICHARD , RIDDELL MICHAEL
Published: May 2022

Background: Pancreatic islet remodelling in type 1 diabetes increases somatostatin (SST) expression, which inhibits glucagon counterregulation to hypoglycemia. Here, we characterized islet morphology and hormone composition in a rodent model of insulin-deficient type 2 diabetes (T2D) .

Methods: Hypoinsulinemic T2D was induced in 8-9-week-old, male, Sprague-Dawley rats (n=4) via 3 weeks of high-fat feeding and a low-dose injection of streptozotocin (STZ; 35 mg/kg) . After 2 weeks of basal insulin treatment, pancreas tissue was extracted from T2D and healthy control (n=5) rats for immunohistochemical staining of representative islets.

Results: Fasted plasma C-peptide levels of hyperglycemic (24.8±3.3 mmol/l) T2D rats were reduced by ∼44% (624±64 vs. 1107±121 pmol/l; p<0.001) , while glucagon was unchanged (75±31 vs. 98±39 pg/ml) . Fractional islet area of glucagon and SST were elevated by 40% (21±15 vs. 15±10%; p<0.001) and 83% (11±8 vs. 6±5%; p<0.001) , respectively, as compared to control rats (Figure) , which was most pronounced in small and medium-sized islets.

Conclusions: Fractional area expression of glucagon and SST increased per islet in insulin-treated rats with advanced T2D. These findings may help account for the increase in SST signaling that underscores defective glucagon counterregulation to hypoglycemia in insulin-deficient diabetic states.

Disclosure

E. G. Hoffman: None. S. C. Atherley: None. N. Akbarian: None. N. Dsouza: None. R. Liggins: Employee; Zucara Therapeutics, Stock/Shareholder; Zucara Therapeutics. M. Riddell: Advisory Panel; Zealand Pharma A/S, Zucara Therapeutics, Consultant; Eli Lilly and Company, Jaeb Center for Health Research, Speaker’s Bureau; Dexcom, Inc., Eli Lilly and Company, Novo Nordisk.

Funding

GlycoNet
903-P: Health Care Economic Burden and Resource Utilization in Adults with Type 2 Diabetes and Peripheral Artery Disease
Authors: UZOIGWE CHIOMA , RAJPURA JIGAR J. , LIANG YUANJIE , PAPROCKI YUREK M. , KING AARON A.
Published: May 2022

Objectives: To evaluate health care utilization and cost in adults with type 2 diabetes mellitus (T2DM) and peripheral artery disease (PAD) .

Methods: Patients ≥ 18 years of age with T2DM, with or without PAD, were identified between January 1, 2012 and December 31, 2020 using the Optum® Clinformatics® Data Mart database. Healthcare utilization and cost was measured for the 12 months after PAD (T2DM + PAD) or random T2DM-related ICD-9/ICD-code (T2DM alone) . PAD was defined as ICD-9/ICD-code of atherosclerosis or artery thrombosis of the lower extremities from ≥ 1 hospitalization, ≥ 2 physician evaluations, or hospitalization or physician visit with relevant current procedural terminology codes. Patient cohorts were compared using an inverse probability of treatment weighting approach.

Results: PAD incidence was 4.1% (n = 68,479) in the year after T2DM diagnosis. The weighted analysis compared 54,080 patients with T2DM and incident PAD (mean age, 74.0; mean Charlson comorbidity index, [CCI] 3.9) and 54,758 patients with T2DM alone (mean age, 74.2; mean CCI, 4.0) . Compared to patients with T2DM alone, patients with T2DM and PAD were more likely to have an inpatient (IP) visit (adjusted rate ratio [ARR], 2.4; 95% CI, 2.4-2.4; p < 0.01) , outpatient (OP) visit (ARR, 1.5; 95% CI, 1.5-1.5; p < 0.01) , or emergency room (ER) visit (ARR, 1.5; 95% CI, 1.4-1.5; p < 0.01) and a longer IP stay (ARR, 2.6; 95% CI, 2.6-2.7; p < 0.01) . Compared to patients with T2DM alone, patients with T2DM and PAD had higher mean healthcare costs (Total costs, $5,068 per patient per month [PPPM] vs. $2,416 PPPM; p < 0.01) . In a health plan covering one million patients with T2DM, we project annual costs +$1.3B higher for patients with T2DM and PAD compared to patients with T2DM alone.

Conclusions: Patients with T2DM and PAD had higher healthcare utilization and costs. Further research could investigate cost effectiveness of treatments for patients with T2DM that lower risk of PAD.

Disclosure

C.Uzoigwe: Employee; Novo Nordisk, Stock/Shareholder; Novo Nordisk. J.J.Rajpura: Employee; Novo Nordisk. Y.Liang: Employee; Novo Nordisk. Y.M.Paprocki: Employee; Novo Nordisk, Stock/Shareholder; Novo Nordisk. A.A.King: Advisory Panel; Novo Nordisk, Board Member; JDRF, Speaker's Bureau; Abbott, Dexcom, Inc., Lilly Diabetes, MannKind Corporation, Medtronic, Novo Nordisk.
904-P: Trends in Out-of-Pocket Cost for Glucagon 2010–2020
Authors: ZUPA MARGARET , FELDMAN ROBERT , LUO JING
Published: May 2022

The ADA Standards of Care recommend that all patients with diabetes at risk of hypoglycemia have glucagon available for emergency use. However, glucagon prescriptions are filled by only a small minority of patients with type 1 and type 2 diabetes in the United States each year. While there are multiple barriers to glucagon use, the extent to which out-of-pocket medication costs contributes to low uptake is not clear.

Using administrative claims from Optum’s de-identified Clinformatics® Data Mart Database (2007-2019) for adults with commercial or Medicaid insurance from 2010-2020, we sought to describe the trends in out-of-pocket costs for glucagon over time. Analyzed claims included all fills of glucagon, based on National Drug Codes, from 20through 9/30/2020. Our primary outcome was total out-of-pocket costs defined as the sum of copays and deductibles. Costs were adjusted for inflation based on 2020 dollars and scaled per single-use kit. Insurance type was based on the primary payor at the time of the glucagon fill.

The median (IQR) out-of-pocket cost of unmixed glucagon was $27.42 (15.09-37.98) in 2010, $33.58 (5.60-41.97) in 2015, and $30.42 (15.21-40.56) in 2020 for commercially insured beneficiaries. For Medicare beneficiaries, cost for unmixed glucagon was $0 (0-25.35) in 2010, $0 (0-33.58) in 2015, and $0 (0-40.56) in 2020. After introduction in 2019, the 2020 out-of-pocket cost of intranasal glucagon was $15.21 (7.60-35.49) for commercially insured beneficiaries and $10.14 (0.99-23.83) for Medicare beneficiaries.

Out-of-pocket costs for unmixed glucagon was stable for most commercially insured patients, and $0 for most Medicare beneficiaries from 20through 2020; therefore, cost should not serve as the primary barrier to accessing glucagon for most patients. However, for the subset of patients (4th quartile) with the highest out-of-pocket costs in both insurance groups, the cost of unmixed glucagon has increased over time. Novel intranasal glucagon had lower out-of-pocket cost compared to unmixed glucagon for most commercially insured patients immediately after introduction.

Disclosure

M.Zupa: None. R.Feldman: None. J.Luo: None.

Funding

NCATS KL2 (TR001856)
905-P: Simulation Model Estimating Lifetime Health and Economic Outcomes of Prediabetes Screening by One-Hour Plasma Glucose
Authors: ANDELLINI MARTINA , MANCO MELANIA , ESPOSITO MARIA TERESA , TOZZI ALBERTO EUGENIO , BERGMAN MICHAEL , RITROVATO MATTEO
Published: May 2022

Background: One of the current methods to diagnose prediabetes and predict diabetes incidence is based on 2-h plasma glucose (2-hPG) value following 75-g oral glucose tolerance test. Evidence demonstrates that 1-hour post-load plasma glucose (1-hPG) ≥ 155 mg/dl (8.6 mmol/L) in those with normal glucose tolerance at 2-hPG is highly predictive for T2D incidence. We conducted a health economic analysis to estimate long-term cost-effectiveness of using 1-hPG as compared to 2-hPG to screen and assess diabetes risk.

Methods: The main outcome of the study was cost per quality-adjusted life-year (QALY) gained. We used a Monte Carlo-based Markov simulation model to simulate long-term effects of the two screening strategies on clinical and cost-effectiveness outcomes. The base case model included 20.000 simulated patients over 35-years. Transition probabilities were retrieved from landmark studies. Direct medical costs were sourced from the literature and inflated to 20Euros.

Results: In the lifetime analysis, 1-hPG was projected to increase the number of years free from disease (2yr/patient) ; to delay the onset of T2D (1yr/patient) ; to reduce the incidence of T2D complications (0.6 Relative Risk/patient) and to increase the QALY gained (0.58/patient) . Though testing the 1-hPG resulted in higher initial costs owing to a larger number of preventive treatments, long-term diabetes and complications costs were reduced leading to -31,225,719.82€ saving over a lifetime as compared to 2-hPG. The incremental cost-effectiveness ratio was -8,214.7€ per each QALY gained for the overall population.

Conclusions: Screening prediabetes by using 1h-PG is feasible and cost-effective resulting in QALYs gained and reduced costs. Notwithstanding the higher initial costs of 1-hPG compared to 2-hPG, due to the incremental number of preventive treatments, long-term diabetes and complications costs were reduced expecting an overall cost saving of -8,214.7€ per each QALY gained.

Disclosure

M.Andellini: None. M.Manco: None. M.Esposito: None. A.Tozzi: None. M.Bergman: None. M.Ritrovato: None.
907-P: Michigan Collaborative for Type 2 Diabetes: Mixed Methods Change Readiness Assessment of Provider Organizations and Clinical Champions
Authors: RAU JACQUELINE , REISS JACOB , OSHMAN LAUREN , DIEZ HEIDI L. , AIKENS JAMES E. , RICHARDSON CAROLINE R.
Published: May 2022

Optimal glycemic control and avoiding cardiovascular, renal, and metabolic complications are important treatment goals in Type 2 Diabetes (T2D) . The Michigan Collaborative for Type 2 Diabetes (MCT2D) is a state-wide collaborative quality initiative launched in 2021 and supported by Blue Cross Blue Shield of Michigan. A total of 27 physician organizations (POs) enrolled 238 primary care practices along with collaborating specialists across the state with the goal of improving T2D care. MCT2D has identified optimizing use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA) , low carbohydrate diets (LCD) , and continuous glucose monitoring (CGM) as initial quality initiatives. We conducted a mixed methods study of POs and practices to understand factors that will influence successful implementation.

We conducted qualitative interviews with leaders from all 27 POs using the Consolidated Framework for Implementation Research (CFIR) to assess anticipated barriers and needs. We then surveyed clinical champions at each participating practice on confidence for implementing these initiatives. Of the 238 practices, 202 consented to de-identified use of their responses.

Qualitative results identified common barriers: patient activation, motivation, and engagement; clinician engagement and change fatigue; busy physician schedules; clinician education needs; lack of resources; access to dieticians for LCD counseling; access to diabetes education; cost of GLP1-RAs and SGLT2is; CGM insurance coverage limitations; and impact to risk sharing contracts. The percentage of clinical champions who responded as moderately, mostly or very confident that their practice could increase use were, 88.1% for GLP1-RAs and SGLT2is, 86.1% for CGMs, and 89.6% for LCDs. Several practical barriers will need to be addressed to successfully implement MCT2D’s initial quality initiatives.

Disclosure

J.Rau: None. J.Reiss: n/a. L.Oshman: Stock/Shareholder; Abbott, AbbVie Inc., Johnson & Johnson, Lilly, Merck & Co., Inc., Procter & Gamble. H.L.Diez: None. J.E.Aikens: None. C.R.Richardson: n/a.