bluuebunny/crossref_metadata_2025 huggingface dataset:
533-P: A Ketogenic Diet Reduces Blood Glucose and Restores Exercise Training–Induced Improvements in Aerobic Capacity in Hyperglycemic Mice
Authors: NAVA ROBERTO C. , COONEY EILEEN M. , LESSARD SARAH J.
Published: May 2022

Evidence suggests that hyperglycemia can blunt improvements in aerobic capacity (VO2peak) with exercise training. Accordingly, people with diabetes have lower VO2peak than normoglycemic controls, increasing their risk of complications and mortality. We hypothesized that reducing blood glucose levels with a dietary intervention would restore exercise training-induced improvements in VO2peak in hyperglycemic mice. To test this, we induced hyperglycemia in male CD-1 mice with streptozotocin (STZ) , which increased random blood glucose to 220 ± 31 mg/dL on a standard diet (80% carbohydrate, 10% fat & protein) . A subset of STZ mice was fed a ketogenic (KETO) diet consisting of 90% fat and 10% protein, which reduced blood glucose to 177 ± 26 mg/dL. Eight weeks after starting the dietary intervention, STZ and KETO mice underwent voluntary wheel running or remained sedentary for 8 weeks. Exercise training improved VO2peak and time to exhaustion during a graded exercise test in KETO-fed mice while no significant improvement was observed in STZ mice. Trained STZ and KETO mice had similar fat and lean mass, indicating improved VO2peak in trained KETO mice was independent of body composition. Our data demonstrate that reducing blood glucose using a carbohydrate-restricted diet may restore training-induced improvements in exercise capacity that are prevented by hyperglycemia.

Disclosure

R.C.Nava: None. E.M.Cooney: None. S.J.Lessard: None.

Funding

National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) RDK124258 National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) T32 Postdoctoral Training Fellowship 5T32DK007260-45
549-P: A Premeal Drink of Low-Dose Whey Protein (WP) Microgel Rapidly Increases Bioavailability of Branched Chain Amino Acids (BCAA) in People with Type 2 Diabetes (T2D) : A Randomized, Placebo-Controlled Crossover Study
Authors: NEELAND IAN , AHRÉN BO , CORTHÉSY JOHN V. , GRZYWINSKI YOHAN , MAGOS ZOLTAN , VON EYNATTEN MAXIMILIAN , JOHANSEN ODD ERIK
Published: May 2022

BCAAs are key ingredients of WPs with biomodulatory effects. We recently reported that a highly-concentrated low-dose (10g, 40 Cal) WP pre-meal drink (125 mL) , generated with novel micelle-technology (WP microgel [WPM]) , ingested 15 min ahead of a pizza-meal (622 Cal) , vs placebo (PBO) , reduced the 2h incremental area under the glucose curve (iAUC) by 22%, increased 2h GLP-1 iAUC by 61% and, delayed 1h gastric emptying by 17%, in 26 people with T2D. Here, we analyzed 2h free plasma BCAA trajectories in 25 persons (mean age 62 yrs, HbA1c 7,5%, BMI 29 kg/m2) that completed this single dose study. The pre-meal WPM drink significantly altered the BCAA trajectory vs. PBO (Figure) . For leucine, ΔiAUCWPM vs PBO increased by 267%, with a shorter time to maximum (median ΔTmax [min, max]: -60 [-120,0] min, p<0.0001) , and peak concentration (mean ΔCmax [SD]: 123 [49] umol/L, p<0.0001) . A similar pattern was seen for isoleucine (ΔiAUC +240%, ΔTmax: -60 [-120,0], p<0.0001, ΔCmax: 68 [31], p<0.0001) and valine (ΔiAUC +194%, ΔTmax: -60 [-120, 30], p < 0.0001, ΔCmax: 63 [38], p<0.0001) . We conclude that 10g WPM as a pre-meal drink, induced a rapid plasma increase, and high bioavailibilty, of BCAAs in people with T2D. The rapid BCAA availability might be a likely factor for the metabolic modulatory effects observed with WPM.

Disclosure

I.Neeland: Advisory Panel; Boehringer Ingelheim International GmbH, Merck & Co., Inc., Consultant; Nestlé Health Science. B.Ahrén: Speaker's Bureau; Nestlé, Novo Nordisk, Stock/Shareholder; AstraZeneca, Novo Nordisk A/S. J.V.Corthésy: Employee; Nestlé. Y.Grzywinski: None. Z.Magos: Consultant; Nestlé Health Science. M.Von eynatten: Employee; Nestlé Health Science. O.Johansen: Employee; Boehringer Ingelheim International GmbH, Nestlé Health Science.

Funding

Nestlé Health Science
556-P: The Relationship between Short-Chain Fermentable Carbohydrates (FODMAPs) , Gut Microbiome, and Glucose Intolerance: An Exploratory Analysis
Authors: CHU NATURAL , HE JIE , MA RONALD C. , KONG ALICE P. , CHAN JULIANA C. , CHOW ELAINE
Published: May 2022

Fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs) are fermentable short-chain carbohydrates that include fructans, galactooligosaccharides (GOS) , lactose, excess fructose, mannitol and sorbitol. Low FODMAP diets in irritable bowel syndrome were associated with reductions in metabolically beneficial, short-chain fatty acids (SCFA) - producing bacteria. We examined the interactions between FODMAP, gut microbiota and glucose tolerance in this exploratory analysis. Twenty subjects underwent oral glucose tolerance tests (OGTT) with C peptide measurements. Ten were classified as normal glucose tolerant (mean ±SD 55±years, body mass index (BMI) 22.7­±2.5 kg/m2, 2-hour plasma glucose 5.7±1.0 mmol/L) and with impaired glucose tolerance (58±­5 years, BMI 23.5±2.9 kg/m2, 2-hour glucose 9.0±0.9 mmol/L) . FODMAPs and macronutrients were assessed from 3-day food diaries. Fecal samples were collected for microbiome analysis. Total FODMAPs were positively correlated to presence of Dorea (r=0.49, p=0.027) . For individual FODMAP items, lactose was positively correlated with Akkermansia (r=0.54, p=0.013) , Bifidobacterium (r=0.42, p=0.037) and negatively correlated with Shigella (r=0.35, p=0.031) in both groups. GOS were positively correlated with Lactobacillus (r= 0.21, p=0.006) and negatively with Shigella (r=0.28, p=0.043) . In the whole group, lower insulin resistance as shown by homeostasis model assessment HOMA2-IR was associated with higher abundance of Bifidobacterium logum (r=0.48, p=0.01) . HOMA2-beta showed correlation with Dorea (r=0.43, p=0.056) . FODMAPs increased the health-promoting microbiota (e.g. Dorea, Lactobacillus, Akkermansia, and Bifidobacterium) . These SCFA promoting microbiota were associated with lower insulin resistance and improved beta-cell function while suppressing the growth of opportunistic pathogens, such as Escherichia spp.

Disclosure

N. Chu: None. J. He: None. R.C. Ma: Research Support; AstraZeneca, Bayer AG, Novo Nordisk A/S, Pfizer Inc., Tricida, Inc. Other Relationship; Bayer AG, Boehringer Ingelheim International GmbH. A.P. Kong: Advisory Panel; Abbott, Kyowa Kirin Co., Ltd. Research Support; Boehringer Ingelheim. Speaker's Bureau; AstraZeneca, Bayer, Eli Lilly and Company, Sanofi. Stock/Shareholder; Aptorum Group Limited. Other Relationship; AstraZeneca, Novo Nordisk. J.C. Chan: Board Member; Asia Diabetes Foundation. Consultant; Bayer AG, Boehringer Ingelheim International GmbH, Celltrion, Merck Sharp & Dohme Corp., Roche Diabetes Care, Viatris Inc. Research Support; Applied Therapeutics, AstraZeneca, Eli Lilly and Company, Hua Medicine, Servier Laboratories. Stock/Shareholder; GemVCare Ltd. E. Chow: Research Support; Hua Medicine, Medtronic, Powder Pharmaceuticals Inc. Speaker's Bureau; Novartis AG, Sanofi.

Funding

Health Medical Research Fund (17180431) Hong Kong College of Physicians Young Investigator's Research Grant
583-P: Psychosocial Outcomes among Users and Nonusers of Open-Source Automated Insulin Delivery Systems: Findings from an International Survey of Adults with Type 1 Diabetes
Authors: SCHIPP JASMINE , HENDRIECKX CHRISTEL , BRAUNE KATARINA , O'DONNELL SHANE , BALLHAUSEN HANNE , CLEAL BRYAN , WÄLDCHEN MANDY , KNOLL CHRISTINE , GAJEWSKA KATARZYNA A. , SKINNER TIMOTHY C. , SPEIGHT JANE
Published: May 2022

Background: Use of open-source automated insulin delivery (AID) is associated with improved psychosocial outcomes among people with type 1 diabetes (T1D) . However, research to date has been qualitative or used study-specific single items. There is a need for quantitative research using validated measures in larger samples.

Method: We conducted an international online survey to examine the psychosocial outcomes of open-source AID users and non-users. Validated questionnaires assessed diabetes-specific quality of life (QoL) , impact of the COVID-pandemic on diabetes-specific QoL, diabetes specific-positive well-being, diabetes treatment satisfaction, diabetes distress, fear of hypoglycaemia, general emotional well-being, and subjective sleep quality.

Results: 587 participants completed at least one questionnaire, including 447 adults using open-source AID (mean age 43, 42% women) and 140 non-users (mean age 40, 64% women) . Table 1 shows significant between-group differences for all questionnaire scores.

Discussion: Adults with T1D using open-source AID report significantly better psychosocial outcomes than non-users. Due to the cross-sectional design of this study, we cannot make any causal inferences about the use of these devices. Further research is needed to examine the reasons for these differences.

Disclosure

J.Schipp: None. T.C.Skinner: None. J.Speight: Advisory Panel; Insulet Corporation, Research Support; Novo Nordisk, Sanofi. C.Hendrieckx: None. K.Braune: None. S.O'donnell: None. H.Ballhausen: None. B.Cleal: None. M.Wäldchen: None. C.Knoll: None. K.A.Gajewska: None.

Funding

European Commission Horizon 2020 (823902)
626-P: TheraKey Diabetes 3.0 App: Better Self-Management, Well-Being, Adherence, and Less Diabetes Distress of People with Diabetes
Authors: KULZER BERNHARD , EHRMANN DOMINIC , ROOS TIMM , HERMANNS NORBERT
Published: May 2022

Aim: The TheraKey Diabetes 3.0 app supports people with diabetes (PwD) during diabetes diagnosis and in the further course of the disease by providing personalized content (e.g., information, graphics, educational videos, testimonials, worksheets, interactive elements) , knowledge and skills for better self-management and coping with the diabetes disease or therapy in everyday life. This study examined the effect in terms of patient-reported outcomes.

Methods: Online survey of users of MyTherakey Diabetes 3.0 with a pre-post design at 4 (t1) and 12 weeks (t2) . 185 PwD (15,1% type 1 diabetes (T1D) , 79.5% type 2 diabetes (T2D) , 43,2% female, average age 53.5 years, diabetes duration 3,6 (± 7,2) years, BMI 32,3 (± 7,8) kg/m², 34,6% insulin therapy, HbA1c 8,3 ± 2,5%) . Response rate at t2: 55% (n=105) . Diabetes Self-Management: Diabetes Self-Management Questionnaire (DSMQ) , Problem Areas in Diabetes Scale (PAID-5) . Well-being: WHO-5. Active Patient Participation: Patient Activation Measure (PAM-13D) . Self-efficacy expectancy: General Self-efficacy Scale (GSE) . Health literacy: European Health Literacy Survey (HLS-EU-Q16) . Adherence: MARS D.

Results: (t2) : DSMQ: 10,5 ± 10,8/13,3 ± 9,5, p<.0 (t1 p<.001) . WHO-5: 10,5 ± 4,4/11,7 ± 4,1, p=.0 (t1 p= .006) . PAID-5: 33,4 ± 22,5/29,6 ± 21,5, p=.015 (t1 p=.181) . MARS-D: 6,3 ± 1,7/6,8 ± 2,5, p=.022 (t1 p=.432) . PAM-13D: 42,7 ± 4,8/43,4 ± 5,1, p=.136 (t1 p=.426) . GSE: 21,4 ± 5,1/21,8 ± 5,0, p=.297 (t1 p=.167) . HLS-EU-Q16: 13,8 ± 7,4/12,4 ± 8,1, p=.036 (t1 p=.793) . Subgroup analyses show that PwD with short (< 1 year) and long duration of diabetes (< 5 years) and PwD-T2D benefit most.

Conclusion: After 3 months of using the diabetes app, patient-relevant benefits can be observed in terms of improved self-management, better well-being, reduced diabetes-related burden, and better adherence. It remains unclear why health literacy is declining. The TheraKey 3.0 can positively support PwD in managing their diabetes.

Disclosure

B.Kulzer: Advisory Panel; Bayer AG, Bayer AG, Becton, Dickinson and Company, Becton, Dickinson and Company, Berlin-Chemie AG, Berlin-Chemie AG, Dexcom, Inc., Dexcom, Inc., Insulet Corporation, Novo Nordisk, Roche Diabetes Care, Sanofi, Sanofi-Aventis Deutschland GmbH, Research Support; Novo Nordisk, Roche Diabetes Care. D.Ehrmann: Advisory Panel; Dexcom, Inc., Consultant; mySugr, Roche Diabetes Care, Speaker's Bureau; Berlin-Chemie AG, Dexcom, Inc. T.Roos: None. N.Hermanns: Advisory Panel; Abbott Diabetes, Research Support; Becton, Dickinson and Company, Roche Diagnostics, Speaker's Bureau; Berlin-Chemie AG, Novo Nordisk, Sanofi.
699-P: Time-Restricted Eating Did Not Alter Glycemic Variability in Humans Who Are Overweight and without Diabetes
Authors: MEHFOOZ AYESHA , LEE YEE LIONG , WANG QI , CHOW LISA S.
Published: May 2022

Background: Time-restricted eating (TRE) is increasingly popular for weight loss, yet its effects on glycemic measures remain unclear. Using continuous glucose monitor (CGM) worn for 2 weeks at baseline and end-intervention, we hypothesized that TRE may reduce glycemic variability compared to unrestricted eating (non-TRE) in patients who are overweight and without diabetes.

Method: Participants (17 women and 3 men; mean [SD] age: 45.5 [12.1] years; BMI 34.1 [7.5] kg/m2) without self-reported diabetes (HbA1c 5.5 [0.4]) who had prolonged eating window (15.4 [0.9] hours) were randomized to a 12 week intervention of either TRE (n=11: 8-hour window, unrestricted eating within window) versus non-TRE (n=9: unrestricted eating) . Each participant wore a blinded CGM (Freestyle Libre Pro) for 2 weeks prior to randomization and at end-intervention (week 11-12) . At each time point, multiple measures of glycemic variability were calculated from the raw CGM data. This is a secondary analysis of a previously published study where 12 weeks of TRE did not alter HbA1c.

Result: Between the TRE and non-TRE groups in the pre and end-intervention periods, there was no statistical difference in any of the calculated glycemic variability measures: including, time in range (TIR) , standard deviation (SD) , coefficient of variation (CV) , continuous overlapping net glycemic action (CONGA) , liability, Index, J-index, low and high blood glucose index (LBGI/HBGI) , glycemic risk assessment diabetes equation (GRADE) , mean of daily differences (MODD) , average daily risk range (ADRR) , mean amplitude of glycemic excursions (MAGE) , mean of daily differences (MODD) , Area Under Curve (AUC) , and Glucose Management Indicator (GMI) .

Conclusion: In patients who are overweight without diabetes, TRE did not alter CGM-measured glycemic variability. Further studies regarding TRE effects on glycemic variability should focus on participants with diabetes.

Disclosure

A.Mehfooz: None. Y.Lee: None. Q.Wang: None. L.S.Chow: Other Relationship; Dexcom, Inc.
707-P: Effectiveness of Breathe Well-Being Diabetes Reversal Program in Achieving Diabetes Remission
Authors: GOYAL PAWAN K. , PATRA SURAJEET K. , KAICKER ADITYA , VERMA ROHAN , GOEL SEEMA , REHMAN SALEHA , JANGID RUPALI , MADHUSUDHANA VENUGOPAL
Published: May 2022

Introduction: Breathe Well-being Diabetes Reversal Program (BDRP) provides personalized Lifestyle Management (LSM) including coaching on diet and exercise as needed by individuals with type 2 diabetes mellitus (T2DM) along with tracking their blood glucose levels, weight, and physical activity.

Objective: To evaluate the effectiveness of BDRP for achieving remission in individuals with T2DM in India.

Methodology: This observational study had three cohorts (1:1:1) who were treated with: (1) BDRP with doctor-prescribed medication, (2) BDRP with doctor-prescribed medication and personalized stress reduction module, and (3) Only doctor-prescribed medication (control group) . Program adherence level was categorized as high (H: >70%) , medium (M: ≥50%-<70%) , and low (L: <50%) ; H and M data of cohorts 1 and 2 are presented here. Program was provided for 4 months, and individuals followed up at 7, 10, 13, 16, and 19 months. Informed consent was obtained.

Results: The study included 181 individuals with an average age of 53.1 years, of which 1 (55.8%) were male. Overall, 46.7% (28) and 54.1% (33) individuals in cohorts 1 and 2 showed H and M adherence. Cohorts 1 and 2 showed 1.0% and 1.3% average HbA1c reduction vs. 0.3% with cohort 3 (overall population) after 4 months. At 4 months, in cohort 1, HbA1c levels <6.5% were observed in 32.1% individuals, which increased to 60.7%, 67.9%, and 78.6% at 7, 10, and 19 months vs. 36.4% individuals in cohort 2, which increased to 51.5%, 69.7%, and 81.8% at 7, 10, and 19 months, respectively. In cohorts 1 and 2, medication withdrawal was observed in 89.3% and 90.9% individuals at 13 months which was maintained up to 19 months.

Conclusion: BDRP was effective in achieving remission in individuals with T2DM in India. BDRP with personalized stress reduction module had better outcomes comparatively. Digital therapeutics could be a potential approach in achieving diabetes remission in Indian settings.

Disclosure

P.K.Goyal: None. S.K.Patra: Employee; Breathe Well-being. A.Kaicker: None. R.Verma: None. S.Goel: Employee; Breathe Well-being. S.Rehman: None. R.Jangid: None. V.Madhusudhana: None.
716-P: Systolic Blood Pressure Reduction with Tirzepatide across SURPASS Program: A Mediation Analysis Using Weight Loss as a Factor
Authors: LINGVAY ILDIKO , MOSENZON OFRI , BROWN KATELYN , CUI XUEWEI , LANDO LAURA FERNANDEZ , PATEL HIREN
Published: May 2022

Tirzepatide (TZP) is a novel dual GIP/GLP-1 receptor agonist for the treatment of type 2 diabetes. Across the SURPASS 1-5 clinical studies, TZP 5, and 15 mg demonstrated significant improvements in HbA1c (-1.9 to -2.6%) , body weight (-6.6 to -13.9%) and systolic blood pressure (SBP) (-2.8 to -12.6 mmHg) at primary endpoint. Post-hoc mediation analyses were conducted to evaluate weight loss dependent (WL-D) and independent (WL-IND) effects of TZP on SBP reductions across 5 SURPASS studies. The difference in mean SBP change from baseline at 40-weeks (Total effect) between TZP and comparator group was -1.3 to -5.1 mmHg (TZP 5 mg) , -1.7 to -6.5 mmHg (TZP mg) and -3.1 to -11.5 mmHg (TZP 15 mg) . The contribution of WL-D and WL-IND effects on these treatment differences are presented below (Figure) . In SURPASS-4 study which enrolled patients with established cardiovascular disease, WL-IND effects explained 33% to 57% of difference in SBP change between TZP and insulin glargine groups, with the remainder of 67% to 43% of the effect being WL-D. In a pooled analysis of SURPASS 1-5 studies, there was a significant (p<0.001) but weak correlation (r = 0.18 to 0.22) between change in body weight and SBP. In conclusion, TZP induced SBP reduction was primarily mediated through weight loss, with different degrees of contributions from weight loss independent effects across the different trials.

Disclosure

I. Lingvay: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly, Mannkind, TARGET PharmaSolutions; Valeritas;; Altimmune; DataRevive; Click; Medscape Duke CRI; Janssen Pharma; Bayer; Intercept, Novo Nordisk, Sanofi, Zealand Pharma A/S. Consultant; Novo Nordisk. Research Support; NovoNordisk; Mylan; Merck, Sanofi. O. Mosenzon: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, BOL Pharma, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk, Sanofi. Research Support; AstraZeneca, Novo Nordisk. Speaker's Bureau; AstraZeneca, Bayer AG, Eli Lilly and Company, Novo Nordisk, Sanofi. K. Brown: Employee; Eli Lilly and Company. X. Cui: Employee; Eli Lilly and Company. L. Fernandez Lando: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. H. Patel: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company.

Funding

Eli Lilly and Company
719-P: Tirzepatide Induces Weight Loss in Patients with Type 2 Diabetes Regardless of Baseline BMI: A Post Hoc Analysis of SURPASS-1 through -5 Studies
Authors: KWAN ANITA , MALDONADO JUAN M. , WANG HUI , RASOULI NEDA , WILDING JOHN
Published: May 2022

Tirzepatide (TZP) is a novel once-weekly dual GIP and GLP-1 receptor agonist evaluated in patients with type 2 diabetes (T2D) . Five Phase 3 SURPASS (S) trials have demonstrated safety and shown robust efficacy of TZP in improvement of glycaemic control and body weight (BW) in adults with T2D. To understand whether the weight-lowering effects of TZP are dependent on baseline BMI, we conducted subgroup analyses of S-1 through -5. BW change in the BMI subgroups (Subgroup 1 [<27 or ≥27 kg/m2] and Subgroup 2 [<30; ≥30 to <35; ≥35 kg/m2]) at primary endpoint was assessed in patients while on treatment without rescue medication (efficacy estimand) in the modified intention-to-treat (mITT) population, defined as all randomized patients who received at least one dose of study drug. All TZP doses (5, 10, 15 mg) lowered BW in patients with T2D irrespective of baseline BMI in both subgroups (p<0.001) . The weight reductions were generally dose-dependent and absolute weight change was generally greater in higher BMI categories. TZP-treated patients with T2D experienced weight loss across a spectrum of mean baseline BMI values in S-1 through -5 studies. The most frequent adverse events were GI-related events that were mild to moderate in severity and occurred during the dose-escalation period.

Disclosure

A.Kwan: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. J.M.Maldonado: Employee; Eli Lilly and Company. H.Wang: None. N.Rasouli: Advisory Panel; Eli Lilly and Company, Novo Nordisk, Sanofi, Research Support; Allergan, Eli Lilly and Company, Novo Nordisk. J.Wilding: Advisory Panel; Alnylam Pharmaceuticals, Inc., AstraZeneca, Eli Lilly and Company, Mundipharma, Novo Nordisk A/S, Rhythm Pharmaceuticals, Inc., Sanofi, Research Support; AstraZeneca, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes, Novo Nordisk A/S, Takeda Pharmaceutical Company Limited.

Funding

Eli Lilly and Company
724-P: A First-in-Human Study of RGT-075, a Novel, Orally Bioavailable, Small-Molecule GLP-1 Receptor Agonist, in Healthy Adult Subjects
Authors: PIRNER MARK A. , LIN JING , LIU FENG , YAO LILI , ZETTLER MARJORIE E. , VALACER DAVID J.
Published: May 2022

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a well-characterized and effective class of glucose-lowering agents for the treatment of patients with type 2 diabetes mellitus (T2DM) . To date, all market-authorized GLP-1 RAs are peptides, and only one is administered orally. RGT-075 is a novel, orally bioavailable, small-molecule GLP-1 RA which has shown therapeutic potential in animal models of T2DM. The results of a first-in-human study of RGT-075 are presented.

Methods: A phase 1, randomized, double-blind, placebo-controlled study was conducted to investigate the safety, tolerability, and pharmacokinetics of single escalating oral doses of RGT-075 (15-280 mg) in healthy adult volunteers. Seven cohorts of 8 subjects were enrolled and randomized to treatment with RGT-075 or matching placebo (6 active/2 placebo per cohort) . Plasma and urine samples were collected over 48 hours post-dose and analyzed for RGT-075 concentrations.

Results: A total of 56 healthy adults (64% male, mean age 42.5 years) participated in the study. Treatment-emergent adverse events (TEAEs) were reported by 28 of 56 (50%) subjects (24 subjects treated with RGT-075 and 4 subjects treated with placebo) . There were no serious adverse events, deaths or TEAEs that led to early withdrawal. The majority of TEAEs were considered mild, and the most common TEAEs related to study drug were nausea, vomiting, and headache. Maximum tolerated dose was not reached. Single oral doses of RGT-075 (15-280 mg) resulted in linear increases in Cmax, AUClast, and AUCinf with ascending doses through 240 mg. Mean elimination half-life ranged from 6.3-11.7 hours. Renal clearance of RGT-075 was low to negligible.

Conclusion: Overall, single RGT-075 doses between 15-280 mg were safe and well-tolerated in healthy volunteers. Further clinical development of RGT-075 as a once-daily, oral therapy for T2DM is underway.

Disclosure

M.A.Pirner: Employee; Regor Pharmaceuticals, Inc. J.Lin: None. F.Liu: Employee; Regor Pharmaceuticals Inc. L.Yao: None. M.E.Zettler: Employee; Cardinal Health, Regor Pharmaceuticals Inc. D.J.Valacer: Employee; Regor Pharmaceuticals, Inc.
736-P: Effect of Semaglutide on Liver Steatosis/Fibrosis Indexes in Patients with Diabetes and Obesity
Authors: GOMEZ JUANA CARRETERO , CARRASCO-SÁNCHEZ FRANCISCO JAVIER , FERNANDEZ JOSE MARIA , CASADO PEDRO ,   PANISH SOCIETY OF INTERNAL MEDICINE DIABETES,   NUTRITION AND OBESITY WORKING GROUP OF S, AREVALO LORIDO JOSE CARLOS , GONZÁLEZ JOSE PABLO MIRAMONTES , SEGÍ-RIPOLL JOSÉ MIGUEL , ENA JAVIER
Published: May 2022

Aim: To assess the efficacy of Semaglutide on liver steatosis/fibrosis indexes.

Methods: Observational, multicenter study. Steatosis/fibrosis were determined by HSI (<30 rule out, >36 steatosis) and FIB-4 (<1.3 rule out, >2.67 fibrosis) .

Results: 213 patients (46.9% women) , age 64 (19) years. Variables and 24 wk changes are shown in table 1. 100% of patients had altered steatosis biomarkers (HSI 47.9 (8.2)) , 10.8% fibrosis (FIB-4> 2.76) . A significant reduction in HSI [-2.36 (95%CI 1.83-2.9) p<0.0000] and FIB-4 [-0.075 (95%CI0.015-0.14) p<0.016] were found (Table 1) . There was a correlation between weight loss and HSI, GGT or TyG improvement (figure 1) .

Conclusion: Our results show a beneficial effect of Semaglutide on steatosis that goes beyond glucose control, and it is related mainly with weight loss and decline in biomarkers.

Disclosure

J.Carretero gomez: None. F.Carrasco-sánchez: None. J.Fernandez: Advisory Panel; Boehringer Ingelheim International GmbH, Daiichi Sankyo, Lilly Diabetes, Novartis Pharmaceuticals Corporation, Sanofi Genzyme, Speaker's Bureau; Amgen Inc., Novo Nordisk Foundation. P.Casado: None. P.Diabetes, nutrition and obesity working group of s: n/a. J.Arevalo lorido: None. J.Miramontes gonzález: None. J.Segí-ripoll: None. J.Ena: None.
739-P: iGlarLixi vs. Premixed Insulin Initiation in Adults with Type 2 Diabetes (T2D) Advancing from Basal Insulin (BI) Therapy: SoliComplex Real-World Study
Authors: LAJARA ROSEMARIE , HELLER CAROLINE , PANTALONE KEVIN M. , LEW ELISHEVA , LI XUAN , DEX TERRY A. , KILPATRICK RACHEL
Published: May 2022

Aim: Premixed insulin (premix) , conventionally administered twice daily, is often used in the US to treat T2D that is suboptimally controlled with BI, particularly for people with consistent eating patterns who require affordable treatment. This analysis evaluated use of once daily iGlarLixi vs. premix on T2D outcomes.

Method: This retrospective analysis of the US Optum Clinformatics database compared outcomes in adults (≥18 y) with T2D who previously received BI and newly initiated iGlarLixi or premix. Persistence (primary endpoint) , adherence, healthcare resource utilization (HRU) , costs, any hypoglycemia, and HbA1c change were assessed at 12 months.

Results: After propensity score matching, cohorts (n=834 each) were well balanced with respect to age, HbA1c, use of oral agents, BI, and HRU. The primary endpoint was met with persistence being statistically significantly higher for iGlarLixi vs. premix at 12 months. Adherence and HbA1c reduction were similar between groups, whereas hypoglycemia rates, HRU, and costs were numerically lower for iGlarLixi (Table) .

Conclusion: In this observational study, once daily iGlarLixi was an effective post-BI treatment with higher treatment persistence than premixed insulin, with similar adherence and HbA1c reduction, and numerically lower hypoglycemia rates, HRU, and costs.

Disclosure

R.Lajara: None. C.Heller: Consultant; Sanofi, Employee; Aetion. K.M.Pantalone: Consultant; AstraZeneca, Bayer AG, Corcept Therapeutics, Diasome, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk, Sanofi, Research Support; Bayer AG, Merck & Co., Inc., Novo Nordisk, Speaker's Bureau; AstraZeneca, Corcept Therapeutics, Merck & Co., Inc., Novo Nordisk. E.Lew: Employee; Sanofi. X.Li: Employee; Eisai Co., Ltd., Sanofi. T.A.Dex: Employee; Sanofi, Stock/Shareholder; Pfizer Inc., Teva Pharmaceutical Industries Ltd., Viatris Inc. R.Kilpatrick: Speaker's Bureau; Abbott Diabetes, Amgen Inc., Novo Nordisk, Sanofi.

Funding

Sanofi
751-P: Effect Of Once-Weekly Semaglutide on Weight Change and Metabolic Control in People with Type 1 Diabetes—Six-Months Results from the Real-World STEMT Trial
Authors: MERTENS JONATHAN , DE WINTER HENNAH T. , MAZLOM HADI , PEIFFER FRIDA W. , DIRINCK EVELINE L. , BOCHANEN NIELS , VAN GAAL LUC F. , DE BLOCK CHRISTOPHE
Published: May 2022

Introduction: the SUSTAIN trials have shown significant improvements in weight and HbA1c levels in people with type 2 diabetes, but the effect and safety of semaglutide in people with type 1 diabetes (T1D) has not been explored yet.

Aims & Methods: In this real-world exploratory study 1.0 mg semaglutide once-weekly was started in adults with T1D and overweight/obesity. To be included, people needed to have stable glycemic control (ΔHbA1c < 0.3 %) , bodyweight (Δ < 3 %) , and insulin type and dose (Δ insulin dose < 5 %) in the last year. Pregnancy or pregnancy wish also was an exclusion criterion. Weight, total daily insulin dose (TDI) and HbA1c were assessed at start and at six months.

Results: Twenty subjects (55 % males, mean age 46.3 ± 9.9 y, diabetes duration 29.6 ± 12.5 y, HbA1c 7.4 ± 0.6 %) were included. Body mass index (BMI) was 33.0 ± 4.4 kg/m2 at baseline, with 80 % of subjects being obese. Two subjects discontinued treatment, both due to gastrointestinal intolerance. Mean bodyweight evolution was -8.5 ± 7.8 kg, ranging between +1.5 and -24.7 kg. Three subjects experienced mild weight gain (ranging 0.2 to 1.5 kg) . Relative weight loss ≥ 5 % was attained in 60 % of cases, and 40 % reached ≥ % weight loss. Mean HbA1c reduction was 0.3 ± 0.7 %, with six subjects (30 %) not showing a reduction in HbA1c. An HbA1c reduction of ≥ 0.5 % was seen in 35 % of cases. A moderate correlation was seen between weight loss and HbA1c reduction (r = 0.52, p = 0.020) . Relative TDI reduction was 13.5 % (IQR 17.8) .

Conclusion: Adding semaglutide 1.0 mg once-weekly in people with T1D was safe, well-tolerated and resulted in promising effects on weight, insulin requirement and glycemic control.

Acknowledgements: JM and HDW claim shared first authorship.

Disclosure

J.Mertens: None. H.T.De winter: None. H.Mazlom: None. F.W.Peiffer: None. E.L.Dirinck: None. N.Bochanen: None. L.Van gaal: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk. C.De block: Advisory Panel; Abbott Diagnostics, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Novo Nordisk, Research Support; Indigo Diabetes, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk.
753-P: RGT-075, an Orally Efficacious Small Molecule GLP-1R Full Agonist in Cynomolgus Monkey Models
Authors: LIU FENG , SUN XIANQIANG , HUANG WEI , GUO WEI , LIN JING , ZHONG WENGE
Published: May 2022

Activation of Glucagon-like peptide-1 receptor (GLP-1R) by peptides has been proven clinically to be a very effective treatment approach for type 2 diabetes (T2D) and obesity. Here we describe a small molecule GLP-1R full agonist RGT-075 identified through Computer Accelerated Rational Design (CARD) (Ma et al., Cell Research 2020) with nM potency in G-protein coupled cAMP signaling. RGT-075 displayed much reduced activity in receptor-mediated β-arrestin recruitment and subsequent internalization. It was shown to be selective against other class B G protein-coupled receptors (GPCRs) and was only active for human and monkey GLP-1R. It demonstrated favorable oral bioavailability and pharmacodynamic profile for once-daily oral dosing in monkeys. In food-induced glucose intolerant and prediabetic cynomolgus monkeys, oral administration of RGT-075 improved glucose tolerance to a level comparable to injectable liraglutide. In food-induced type 2 diabetic monkeys, once-daily oral administration of RGT-075 reduced food intake and fasting plasma glucose levels. Together, these data support the development and advancement of RGT-075 into the clinic as a potential therapeutic for T2D and obesity.

Disclosure

F.Liu: Employee; Regor Pharmaceuticals Inc. X.Sun: Employee; AutoDrug Biotech Co. Ltd., Qilu Regor Therapeutics Inc. W.Huang: None. W.Guo: None. J.Lin: None. W.Zhong: None.
761-P: Long-Term Glycemic Control in Adult Participants Using Control-IQ Technology: Real-World Evidence
Authors: GRAHAM RISHI , SINGH HARSIMRAN , ALENCAR GABRIEL , MUELLER LARS , MANNING MICHELLE L. , WHITE KIRSTIN N. , WHEATCROFT ALEX , CARMELO KAREN , ARONOFFSPENCER ELIAH S. , HABIF STEPHANIE , PINSKER JORDAN E.
Published: May 2022

The Control-IQ Observational (CLIO) Study is an ongoing prospective, real-world evaluation of the Tandem Diabetes Care t:slim X2 insulin pump with Control-IQ technology in people with T1D.

We assessed baseline HbA1c and Glucose Management Indicator (GMI) derived from sensor data from adult participants who completed the 12-month CLIO study. Adults ages ≥18 years who had ≥75% overall CGM use during this time were included in the analysis. Outcomes were analyzed using a Wilcoxon test.

In all, 1,1participants (882 prior pump and 225 prior MDI users) , median age 41 years (IQR 30-54) , 57.2% female met the inclusion criteria. Median GMI was significantly lower at 12 months (7.0% [6.7-7.4]) vs. baseline HbA1c (7.2% [6.7-8.1]) (p<0.0001) . Participants ages 18-30 and 46-64 showed the greatest improvement from baseline (0.3% reduction) (p<0.0001) , while older adults (≥65-years) showed the lowest GMI at study end (6.9% [6.6-7.2]) . Prior MDI users reported higher HbA1c at baseline (7.7% [IQR=6.8-9.0]) vs. prior pumpers (7.2% [6.7-8.0]) . However, GMI at 12 months reflected glycemic improvements across all prior therapy modalities (prior MDI=7.0% [6.7-7.3]; prior pump=7.1% [6.7-7.4]) (p<0.0001) .

This real-world evidence demonstrates significant glycemic improvements with Control-IQ technology in adults, regardless of prior therapy modality, that are sustained long-term across diverse groups of users.

Disclosure

R.Graham: Research Support; Tandem Diabetes Care, Inc. S.Habif: Employee; Tandem Diabetes Care, Inc. J.E.Pinsker: Employee; Tandem Diabetes Care, Inc., Stock/Shareholder; Tandem Diabetes Care, Inc. H.Singh: Employee; Tandem Diabetes Care, Inc. G.Alencar: Employee; Tandem Diabetes Care, Inc. L.Mueller: Employee; Tandem Diabetes Care, Inc., Research Support; Dexcom, Inc., Stock/Shareholder; Tandem Diabetes Care, Inc. M.L.Manning: Employee; Tandem Diabetes Care, Inc. K.N.White: Employee; Tandem Diabetes Care, Inc. A.Wheatcroft: Employee; Tandem Diabetes Care, Inc. K.Carmelo: None. E.S.Aronoffspencer: Research Support; Tandem Diabetes Care, Inc.

Funding

Tandem Diabetes Care
77-LB: How the Incidence of Anxiety and Other Psychosocial Factors Impact Quality of Life in Parents of Children with Type 1 Diabetes Who Used a Continuous Glucose Monitor (CGM) —A Systematic Review
Authors: SAWYER BAILEE C. , HUTSON LEANNE M. , CIPRICH AMANDA P.
Published: May 2022

This study aimed to perform a systematic review related to how anxiety and other psychosocial factors impact quality of life in parents and their children with type 1 diabetes (T1D) who utilize a continuous glucose monitor (CGM) . Electronic databases and published references were utilized to establish studies published between 2012 and 2022. There were 29 studies identified that included the search terms T1D, anxiety, parents, CGM. After careful quantitative measurements analysis, seven studies remained. The researchers of the seven studies utilized CGM in children with T1D and surveyed parental anxiety, psychosocial care and quality of life. The results presented in Table 1 and Table 2 show implications for programming and treatment to support parents of T1D children in reducing the psychosocial and quality of life outcomes when utilizing CGM technology.

Disclosure

B. C. Sawyer: None. L. M. Hutson: None. A. P. Ciprich: Other Relationship; DarioHealth Corp., Medtronic.
771-P: Acceptance of Decision Support Recommendations Improves Time in Range for People Living with Type 1 Diabetes on Multiple Daily Injections
Authors: CASTLE JESSICA R. , ESPINOZA ALEJANDRO Z. , TYLER NICHOLE S. , WILSON LEAH M. , MOSQUERA-LOPEZ CLARA M. , PINSONAULT JOSEPH , DODIER ROBERT , OGANESSIAN SOS M. , BRANIGAN DEBORAH , GABO VIRGINIA , EOM JAE H. , EL YOUSSEF JOSEPH , RAMSEY KATRINA , KUSHNER TAISA , WINTERS-STONE KERRI , CAFAZZO JOSEPH A. , JACOBS PETER G.
Published: May 2022

DailyDose is a decision support system developed at Oregon Health & Science University designed for people with T1D on MDI to improve glycemic control. It connects with Dexcom G6 and Medtronic's InPen. DailyDose runs on a smartphone and calculates insulin doses using CGM value and trend, IOB, carbohydrate amount, and exercise information. The system analyzes CGM and insulin data and automatically provides weekly recommendations on insulin settings, such as basal insulin dose and carbohydrate ratios, based on a k-nearest neighbors algorithm. Twenty-four adults with T1D used DailyDose for 8 weeks. The primary outcome was change in % time in range (TIR, 70-180 mg/dL) on CGM comparing the two week run-in period before starting DailyDose vs. final two weeks of DailyDose use. A mixed effects model was used to determine the impact of the % of accepted recommendations on change in % TIR. Users who accepted and followed recommendations showed a mean week-to-week improvement in TIR of 2.0% (Figure) . The mixed effects model shows week-by-week TIR increased by 7.8% when recommendations were accepted compared with not accepted (CI, 3-12%, P=.001) . Overall, there were no significant differences between TIR or time in hypoglycemia comparing the run-in period and the final two weeks of use. Further work is needed to encourage people using decision support systems to follow recommendations.

Disclosure

J.R.Castle: Advisory Panel; Insulet Corporation, Novo Nordisk, Zealand Pharma A/S, Stock/Shareholder; Pacific Diabetes Technologies. V.Gabo: None. J.H.Eom: None. J.El youssef: None. K.Ramsey: None. T.Kushner: Consultant; Tandem Diabetes Care, Inc. K.Winters-stone: None. J.A.Cafazzo: None. P.G.Jacobs: Other Relationship; Pacific Diabetes Technologies, Research Support; Dexcom, Inc. A.Z.Espinoza: None. N.S.Tyler: None. L.M.Wilson: n/a. C.M.Mosquera-lopez: None. J.Pinsonault: None. R.Dodier: None. S.M.Oganessian: None. D.Branigan: None.

Funding

The Leona M. and Harry B. Helmsley Charitable Trust (Grant 2018PG-T1D001) .
782-P: Swimming with Hybrid Closed-Loop: Connectivity Data from Seven Swimmers in the Omnipod 5 Trial
Authors: HUGHES MICHAEL S. , KINGMAN RYAN S. , HSU LIANA , LAL RAYHAN , BUCKINGHAM BRUCE A. , ZAHARIEVA DESSI P.
Published: May 2022

The Omnipod® 5 Automated Insulin Delivery System is a waterproof (IP28) hybrid closed-loop system where the continuous glucose monitor (CGM) communicates directly with the algorithm on the Pod to modulate insulin delivery automatically. However, the system relies on Bluetooth® wireless technology, a radiofrequency with limited underwater transmission ability.

Seven frequent swimmers participating in the Omnipod 5 trial reported 63 separate swimming sessions ranging 25-143 min (mean 75±30 min) . CGM-to-Pod wireless communication during swims had a median (IQR) success rate of 17% (5%, 29%) ; however, the communication success rate was 100% across all swims with CGM-to-Pod distance <8 cm (device edge to edge, n=5) . Despite communication limitations, percent time in automated mode was 99% during swims and automated modulations to insulin delivery continued to occur as needed (Table) .

These results suggest that while in-water communication is challenged, Pod to CGM placement strategies can be practiced to better improve the connectivity. Moreover, the system by design remains in automated mode when CGM values are missed and does not revert the user back to manual mode settings.

Disclosure

M.S.Hughes: Research Support; Insulet Corporation. R.S.Kingman: Research Support; Insulet Corporation. L.Hsu: Research Support; Insulet Corporation, Stock/Shareholder; Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care, Inc. R.Lal: Advisory Panel; Provention Bio, Inc., Consultant; Abbott Diabetes, Biolinq, Capillary Biomedical, Inc., Deep Valley Labs, Gluroo, Morgan Stanley, Tidepool. B.A.Buckingham: Advisory Panel; Arecor, Lilly Diabetes, Medtronic, Other Relationship; Insulet Corporation, Research Support; Insulet Corporation, Lilly Diabetes, Medtronic. D.P.Zaharieva: Research Support; Insulet Corporation, International Society for Pediatric and Adolescent Diabetes, Leona M. and Harry B. Helmsley Charitable Trust.

Funding

Gift funding from Insulet Corporation
81-OR: High Throughput Proteomics Identifies Neurofilament Light Chain (NFL) as a Novel Blood Biomarker for Detection of Diabetic Sensorimotor Polyneuropathy
Authors: MAALMI HAIFA , STROM ALEXANDER , HAUCK STEFANIE M. , ZAHARIA OANA P. , STRASSBURGER KLAUS , BÖNHOF GIDON J. , RATHMANN WOLFGANG , TRENKAMP SANDRA , BURKART VOLKER , SZENDROEDI JULIA M. , ZIEGLER DAN , RODEN MICHAEL , HERDER CHRISTIAN
Published: May 2022

Background: The neurofilament light chain (NFL) is a polypeptide abundant in neuronal axons, reflecting ongoing neuroaxonal degeneration when detected in the blood. However, no previous study has explored NFL as a potential biomarker for diabetic sensorimotor polyneuropathy (DSPN) , a neurodegenerative disease of the peripheral nervous system commonly found in individuals with diabetes. We hypothesized that higher serum NFL levels are associated with DSPN.

Methods: We used data from the German Diabetes Study, a prospective observational study that includes adults with recent-onset diabetes (<1 year) . DSPN was assessed using Toronto consensus criteria. Serum levels of NFL were measured using proximity extension assay, and Poisson regression was used to estimate associations between serum NFL and prevalent DSPN.

Results: From a total of 423 participants, 66 (16%) had DSPN. Serum NFL was inversely correlated with age, eGFR and nerve conduction velocities in motor and sensory nerves (all P Spearman <0.0001) . After adjustment for age, sex, waist circumference, height, HbA1c, diabetes duration, diabetes type, cholesterol, eGFR, hypertension, cardiovascular diseases, use of lipid-lowering drugs, and NSAIDs, higher serum levels of NFL were associated with prevalent DSPN (RR (95% CI) 1.92 (1.50, 2.45) (P < 0.0001) .

Conclusion: NFL might be useful for detecting DSPN in recent-onset diabetes, but validation in other studies will be required. Considering the absence of FDA-approved biomarkers for DSPN, NFL might be a promising biomarker that could improve the management of DSPN.

Disclosure

H. Maalmi: None. A. Strom: None. S.M. Hauck: None. G.J. Bönhof: None. W. Rathmann: Consultant; IQVIA Inc. Speaker's Bureau; Boehringer Ingelheim International GmbH, Novo Nordisk. S. Trenkamp: None. V. Burkart: None. J.M. Szendroedi: Consultant; Boehringer Ingelheim International GmbH. D. Ziegler: None. M. Roden: Advisory Panel; Eli Lilly and Company. Research Support; Boehringer Ingelheim International GmbH, Nutricia. Speaker's Bureau; Novo Nordisk. C. Herder: Research Support; Sanofi.

Funding

DZD (FKZ82DZD02D2G)
832-P: Five-Year Weight and Glycemic Outcomes following a Very-Low-Carbohydrate Intervention Including Nutritional Ketosis in Patients with Type 2 Diabetes
Authors: ATHINARAYANAN SHAMINIE J. , VANTIEGHEM MICHELLE , MCKENZIE AMY L. , HALLBERG SARAH , ROBERTS CAROLINE G.P. , VOLK BRITTANIE M. , ADAMS REBECCA N. , RATNER ROBERT E. , VOLEK JEFF , PHINNEY STEPHEN
Published: May 2022

Objective: We previously reported long term effectiveness of a very low carbohydrate intervention including nutritional ketosis (VLCI) delivered via continuous remote care (CRC) for improving weight and glycemia at 2 years in people with type 2 diabetes (T2D) . We assessed 5-year changes to determine if the intervention is sustainable, durable, and effective over a longer period of time.

Research Design and Methods: Patients with T2D who were initially enrolled in a 2 year non-randomized, controlled clinical trial received a CRC emphasizing a VLCI. These patients were offered to continue for an additional 3 years of prospective follow-up. Of the 200 patients completing 2 years, 169 (84.5%) patients consented to the extension and 122 (72.2%) were retained at 5 years. Among those who extended, baseline versus 5 year differences in weight and glycemic outcomes were assessed using linear mixed effects models in an intent-to-treat analysis. P-values were adjusted using Holm-Bonferroni correction.

Results: At five years, there were persistent improvements in weight from 116.4 to 107.6 kg (-8.8 kg, 95%CI [-11.0, -6.6]) , fasting insulin from 25.8 to 24.5 mIU/L (-7.9 mIU/L, 95%CI [-10.0, -5.8]) , and HOMA-IR from 9.1 to 6.6 (-2.5, 95%CI [-3.5, -1.5]) (all adjusted p-values <0.05) . Total diabetes medications were reduced 46.6%, and 59.9% excluding metformin were deprescribed. The percent of patients prescribed diabetes medications significantly decreased at 5 years (from 85.2% to 71.3%; p<0.01) , including patients taking sulfonylureas (from 27.0% to 4.9%) , insulin (from 26.2% to 13.1%) , and SGLT2i (from 10.7% to 2.5%) . Despite less medication use, HbA1c improved from 7.5 to 7.2% (-0.3%, 95%CI [-0.6, 0.0], unadjusted p-value<0.05) .

Conclusions: Over 5 years follow-up, the VLCI with CRC showed excellent retention, sustained clinically significant weight loss, and stable glycemic control with reduced dependency on antidiabetes medications.

Disclosure

S.J.Athinarayanan: Employee; Virta Health Corp. S.Phinney: Employee; Virta Health Corp. M.Vantieghem: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. A.L.Mckenzie: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. S.Hallberg: Advisory Panel; Atkins Nutritionals Inc., Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. C.G.P.Roberts: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. B.M.Volk: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. R.N.Adams: Employee; Virta Health Corp. R.E.Ratner: Employee; Virta Health Corp. J.Volek: Advisory Panel; Abbott Diagnostics, Simply Good Foods, Stock/Shareholder; Virta Health Corp.
87-LB: Treatment Intensification after Glucagon-Like Peptide-1 Receptor Agonists Therapy in Type 2 Diabetes—The RESTORE-G Real-World Study
Authors: CANDIDO RICCARDO , NICOLUCCI ANTONIO , LAROSA MONICA , ROSSI MARIA CHIARA , NAPOLI RAFFAELE ,   RESTORE-G STUDY GROUP
Published: May 2022

Data on therapeutic approaches after GLP1-RA treatment failure are scant. Intensification strategies include addition of basal insulin to GLP1-RA, as free or fixed-ratio combination, as well as the switch to insulin therapy alone. Aim of the study was to assess treatment intensification approaches after GLP1-RA treatment and their effectiveness and safety in the real-word setting. A retrospective, multicenter study, based on electronic medical records collected between January 2011 and September 2021 was conducted. Overall, data relative to 17.861 patients with at least 1 prescription of GLP1-RA were collected by 32 centers in Italy. Among them, 3.164 (17.7%) needed intensification and were treated according to the three main treatment approaches reported in table. Intensification occurred after a median of 27 months. Data showed clinical inertia during and after GLP1-RA treatment, as documented by high HbA1c levels at intensification and suboptimal basal insulin dosing in all cohorts. Effectiveness and safety were documented in all cohorts, but many patients did not reach the HbA1c target. Low rate of hypoglycemia was documented especially in patients initiating FRC (Table) .

In conclusion, in the years to come, advancing therapy with timely addition and adequate titration of new basal insulin analogues or FRC may contribute to overcome clinical inertia.

Disclosure

R. Candido: None. A. Nicolucci: Board Member; AstraZeneca, Research Support; Novo Nordisk, PIKDARE S. p. A., Sanofi, Shionogi & Co., Ltd., Swedish Orphan Biovitrum AB, Speaker’s Bureau; Eli Lilly and Company. M. Larosa: Employee; Sanofi. M. Rossi: Research Support; AlfaSigma, Novo Nordisk, Sanofi, Shionogi & Co., Ltd., SOBI. R. Napoli: Advisory Panel; Eli Lilly and Company, Novo Nordisk, Sanofi, Speaker’s Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Merck Sharp & Dohme Corp., Novo Nordisk, Sanofi. Restore-g study group: n/a.

Funding

Sanofi