bluuebunny/crossref_metadata_2025_split huggingface dataset:
781-P: Efficacy and Safety of Switching to iGlarLixi from Twice-Daily (BID) Premixed Insulin (PI) Administration in People with Type 2 Diabetes (T2D)—Subanalysis of Soli-SWITCH Study
Authors: HALUZIK MARTIN , MIN KYUNGWAN , CYPRYK KATARZYNA , ALVAREZ AGUSTINA , LAUAND FELIPE , REN YAN , BAKINER OKAN 
Published: June 2024

Introduction & Objective: iGlarLixi is a once-daily injectable fixed-ratio combination of insulin glargine 100 U/mL plus lixisenatide. This sub-analysis of Soli-SWITCH (EudraCT number 2021-003711-25) assessed the efficacy and safety of switching from BID administration to once-daily iGlarLixi in people with T2D.
Methods: In this phase 4, 24-week, single-arm study, participants switched from PI to iGlarLixi at baseline. Key inclusion criteria included participants aged ≥18 years who had been diagnosed with T2D for ≥6 months and had received PI for ≥3 months and &lt;10 years. In this sub-analysis we assessed the change in HbA1c (baseline to Week 24) in participants with previous BID PI dosing. The analyses also included the proportion of participants achieving HbA1c &lt;7% at Week 24 and safety.
Results: Overall, 162 participants received iGlarLixi (88.3% BID PI dosing). In the overall population, mean PI dose at baseline was 39.5 units (U) (standard deviation [SD] 13.4), mean iGlarLixi dose at Week 24 was 40.6 U (SD 13.3). In evaluable participants with BID PI dosing at baseline and at Week 24 (n=126), mean HbA1c reduced from baseline to Week 24 by 1.2% (standard deviation [SD] 0.9%); similarly, in the total population, mean HbA1c reduced from baseline to Week 24 (n=145) by 1.2% ([SD] 0.9%). At Week 24, 36.2% of participants with prior BID PI dosing and 37.6% of participants in the total population achieved a HbA1c target of &lt;7%. Confirmed symptomatic hypoglycemia occurred in 38.3% of all participants (ADA level 1: 35.8%; ADA level 2: 15.4%; ADA level 3: 0.0%). No new safety signals were observed in overall population.
Conclusion: iGlarLixi demonstrated improved glycemic outcomes in participants switching to iGlarLixi from BID PI dosing. These data suggest that iGlarLixi may be a potentially simplified treatment alternative for people with T2D currently receiving two daily injections of PIs.

Disclosure
M. Haluzik: Advisory Panel; Sanofi, Novo Nordisk, Eli Lilly and Company, AstraZeneca, Bayer Inc., Johnson & Johnson Medical Devices Companies. Consultant; Merck & Co., Inc., Sanofi, Novo Nordisk, Eli Lilly and Company, AstraZeneca, Bayer Inc., Boehringer-Ingelheim, Johnson & Johnson Medical Devices Companies, Novatin. Research Support; Sanofi. Speaker's Bureau; Sanofi, Novo Nordisk. K. Min: None. K. Cypryk: Research Support; Novo Nordisk, Sanofi. Speaker's Bureau; Novo Nordisk, Eli Lilly and Company, Sanofi, Merck & Co., Inc. A. Alvarez: Employee; Sanofi. Stock/Shareholder; Sanofi. F. Lauand: Employee; Sanofi. Stock/Shareholder; Sanofi. Y. Ren: Consultant; Sanofi. Employee; Aixial. O. Bakiner: None.

Funding
Sanofi
782-P: Insulin Therapy Deintensification with iGlarLixi—The IDEAL Randomized Controlled Trial
Authors: NOVODVORSKY PETER , THIEME LENKA , LANKOVA IVANA , VESELÁ ALICA , ZAHUMENSKY EMIL , EDELSBERGER TOMAS , LÖBLOVÁ MARIE , HRUBÝ FILIP , MRAZ MILOS , HALUZIK MARTIN 
Published: June 2024

Introduction: Multiple daily injection (MDI) insulin therapy in people with type 2 diabetes (PwT2D) often leads to weight gain, increased risk of hypoglycemia and lower QoL. The Insulin therapy DE-intensificAtion with iglarLixi (IDEAL) trial examined the efficacy and safety of MDI de-intensification into once-daily administered FRC of insulin glargine U100 and GLP-1 RA lixisenatide (iGlarLixi) in PwT2D.
Methods: IDEAL was a 5-centre, open-label, parallel-group, phase 4 RCT with a 24-week treatment period. Eligible individuals (age 18-80 years, total daily dose of insulin [TDD] ≤ 0.8 IU/kg and fasting c-peptide above the lower limit of normal) were randomized in a 1:1 fashion into once-daily administered iGlarLixi or continuation with MDI, both titrated to fasting plasma glucose (FPG) ≤ 6 mmol/L (108 mg/dL). Primary outcome was HbA1c change at 24 weeks. Secondary outcomes were change in body weight (BW), TDD, FPG, postprandial glycemia (PPG), hypoglycemia, CGM-related metrics and QoL.
Results: Altogether 91 individuals (20/91, 22% women) with mean (SD) age 66 (9) years, diabetes duration 17 (9) years and BMI 33.5 (5.5) kg/m2 were analyzed. Mean change in HbA1c in the iGlarLixi group was non-inferior to the MDI group (-0.47 [0.91] % vs (-0.37 [0.77] %, p = 0.01 for non-inferiority, p = 0.25 for superiority). Mean reduction in BW in the iGlarLixi group was higher in comparison to the MDI group (-4.8 [4.3] kg vs -0.5 [3.7] kg, p &lt; 0.001). TDD reduced in the iGlarLixi group (p &lt; 0.0001) and remained unchanged in the MDI group (p = 0.233). The proportion of study visits at which hypoglycemia was reported was lower in the iGlarLixi vs MDI group (5.5% vs 9.6%, p = 0.029). No differences in FPG and PPG were observed.
Conclusion: Insulin therapy de-intensification from MDI into iGlarLixi is an efficient and safe treatment option for PwT2D that provides comparable glycemic control with the benefits of reduction of BW, TDD, number of insulin injections and lower proportion of visits as which hypoglycemia was reported.

Disclosure
P. Novodvorsky: Speaker's Bureau; Sanofi, Boehringer-Ingelheim. Advisory Panel; Boehringer-Ingelheim. Speaker's Bureau; Novo Nordisk A/S. Research Support; Sanofi. Speaker's Bureau; Abbott, Medtronic, Berlin-Chemie AG, Viatris Inc., Novartis AG. L. Thieme: None. I. Lankova: None. A. Veselá: None. E. Zahumensky: None. T. Edelsberger: None. M. Löblová: None. F. Hrubý: None. M. Mraz: None. M. Haluzik: Advisory Panel; Sanofi, Novo Nordisk, Eli Lilly and Company, AstraZeneca, Bayer Inc., Johnson & Johnson Medical Devices Companies. Consultant; Merck & Co., Inc., Sanofi, Novo Nordisk, Eli Lilly and Company, AstraZeneca, Bayer Inc., Boehringer-Ingelheim, Johnson & Johnson Medical Devices Companies, Novatin. Research Support; Sanofi. Speaker's Bureau; Sanofi, Novo Nordisk.

Funding
Sanofi
791-P: The Impact of Age on Response to Injectable Semaglutide—Insights from the Association of British Clinical Diabetologists’ Audit Programme
Authors: CRABTREE THOMAS S.J. , ADAMSON KAREN , BICKERTON ALEX , EVANS ALISON , PHILLIPS SUZANNE M. , GALLAGHER ALISON , BARNES DENNIS , DHATARIYA KETAN , FIELD BENJAMIN C.T. , IDRIS ISKANDAR R. , RYDER ROBERT E. 
Published: June 2024

The ABCD Semaglutide (Ozempic) audit launched in 2019 to capture real-world outcomes in the UK. Pooled analysis from the SUSTAIN trials has demonstrated similar HbA1c and weight reducing efficacy in older populations compared younger. We report the impact of age on weight and HbA1c response to semaglutide.
Methods: Routinely collected clinical data was entered by participating centres into a secure online tool and included provided baseline and follow-up data were available. Age groups at commencement were defined as &lt;40years, 40-64.9 years and ≥65years. Changes between baseline and follow-up were assessed using multivariate regression analysis to correct for potential confounders, with Bonferroni corrections for multiple comparisons. Analysis performed in Stata 16.
Results: In total 1,623 individuals (49.9% female) were included with baseline mean±SD age 58.9±11.0 years, HbA1c 9.4±1.7% and 107.1±23.5kg. Over a median follow-up of 0.7 years (IQR 0.4-1.0), HbA1c reduced by 1.2% (95%CI 1.1-1.3, P&lt;0.001) and weight reduced by 4.7kg (95%CI 4.1-5.3, P&lt;0.001). Baseline HbA1c levels were similar across age groups, but baseline weight was significantly lower with increasing age (mean±SD youngest group 115.5±28.6 vs. 101.8±19.5 in the oldest group, P&lt;0.001). In those aged &lt;40years HbA1c fell by 1.4% (95% 0.9-1.9) and weight reduced by 4.4kg (1.4-7.4); in age 40-64.9years HbA1c fell by 1.2% (1.0-1.3) and weight by 4.3kg (3.7-5.0) and in age ≥65years HbA1c reduced by 1.2% (1.0-1.4) and weight by 4.7kg (3.8-5.6) (P&lt;0.001 for all). No significant differences between groups were noted for either change in HbA1c or weight.
Conclusions: Semaglutide is associated with HbA1c reductions across all ages. Weight reductions are also similar despite differences in baseline weight; this may be variably desirable in older individuals where weight maintenance may be preferred to prevent frailty.

Disclosure
T.S.J. Crabtree: Speaker's Bureau; Abbott, Novo Nordisk, Dexcom, Inc., Sanofi, Insulet Corporation, Lilly Diabetes. K. Adamson: Speaker's Bureau; Lilly Diabetes. A. Bickerton: None. A. Evans: None. S.M. Phillips: None. A. Gallagher: None. D. Barnes: None. K. Dhatariya: Other Relationship; AstraZeneca, Menarini, Boehringer-Ingelheim, Abbott Diagnostics, Eli Lilly and Company, Novo Nordisk. B.C.T. Field: Speaker's Bureau; AstraZeneca, Boehringer-Ingelheim, Eli Lilly and Company, Novo Nordisk, Sanofi. Consultant; Tape Specialities Limited. I.R. Idris: None. R.E. Ryder: Speaker's Bureau; Abbott, Besins Healtcare, BioQuest, GI Dynamics. Consultant; GI Dynamics. Other Relationship; Novo Nordisk.

Funding
Funded by ABCD
830-P: No Evidence of Increased Physical Activity–Related Hypoglycemia with Once-Weekly Insulin Icodec vs. Once-Daily Basal Insulin in Type 2 Diabetes—ONWARDS 1–5
Authors: RIDDELL MICHAEL C. , HELLER SIMON R. , ASONG MARISSE , CARSTENSEN LISBETH , WATT SARA K. , WOO VINCENT C. 
Published: June 2024

Introduction & Objective: The ONWARDS (ON) phase 3a trials showed the efficacy and safety of once-weekly (OW) basal insulin icodec (icodec) vs once-daily (OD) basal insulin comparators. This post hoc analysis examined physical activity (PA)-related hypoglycemia, based on self-reported data, in adults with T2D in ON 1-5.
Methods: Hypoglycemia occurrence was evaluated in insulin-naive (ON 1, 3, 5) and insulin-treated (ON 2, 4) adults with T2D receiving icodec vs OD comparators. In each trial, participants who experienced hypoglycemic episodes were instructed to note any relation to PA in a digital diary.
Results: The number of PA-related level 2 or level 3 hypoglycemic episodes was low in all trials, except ON 4 (basal-bolus trial). The proportion of hypoglycemic episodes that were related to PA trended higher or was comparable with icodec vs OD comparators in insulin-naive T2D and trended lower or was comparable in insulin-treated T2D (Table). There were no statistically significant differences in the odds of experiencing a PA-related level 2 or level 3 hypoglycemia for icodec vs OD comparators.
Conclusion: The incidence of PA-related level 2 or level 3 hypoglycemia in T2D was low in these trials of basal insulins and was not worsened by treatment with icodec vs OD basal insulin comparators. Despite some uncertainty due to low incidences, these data are reassuring.

Disclosure
M.C. Riddell: Consultant; Eli Lilly and Company. Speaker's Bureau; Novo Nordisk. Advisory Panel; Supersapiens. Consultant; Dexcom, Inc. Speaker's Bureau; Sanofi. Advisory Panel; Zealand Pharma A/S. Speaker's Bureau; Dexcom, Inc. Stock/Shareholder; Zucara Therapeutics. S.R. Heller: Research Support; Dexcom, Inc. Speaker's Bureau; Novo Nordisk. Other Relationship; Eli Lilly and Company. Speaker's Bureau; Medtronic. Advisory Panel; Zealand Pharma A/S, Zucara Therapeutics, Vertex Pharmaceuticals Incorporated. M. Asong: Employee; Novo Nordisk A/S. Stock/Shareholder; Novo Nordisk A/S. L. Carstensen: Employee; Novo Nordisk A/S. Stock/Shareholder; Novo Nordisk A/S. S.K. Watt: Employee; Novo Nordisk. V.C. Woo: Advisory Panel; Novo Nordisk. Speaker's Bureau; Abbott. Advisory Panel; Boehringer-Ingelheim, Lilly Diabetes.

Funding
Novo Nordisk A/S
834-P: A Prospective Study on Switching from Basal Insulin to Insulin Degludec/Insulin Aspart, in Patients with Type 2 Diabetes Whose FPG Levels Are Lower Than Those Predicted by Their HbA1c
Authors: HONG EUNSHIL , NA JANG HAN , LEE SEONGOK , SEUL YANG YE , HEON KWAK SOO , SOO PARK KYONG , CHUL JANG HAK , SEUNG JUNG HYE 
Published: June 2024

Objective: Benefits of once-daily insulin degludec/aspart (IDegAsp) compared with basal insulin in patients with type 2 diabetes (T2D) have not been established. As we have observed that a low ratio of fasting plasma glucose (FPG) to mean glucose was associated with superior response to IDegAsp by a retrospective study, we aimed to confirm it by a prospective design.
Methods: A randomized, open-label, cross-over trial was conducted in patients on a basal insulin therapy with FPG lower than predicted FPG (=12.6 x HbA1c (%) + 30, drawn from our previous study). Participants were assigned 1:1 ratio to IDegAsp or insulin glargine (IGlar) arm. After 20 weeks, the treatments were exchanged for the next 20 weeks. The primary endpoint was treatment difference of HbA1c changes from the baseline. Additionally, self-reported hypoglycemic events were collected, and a professional CGM was applied for 1 week prior to completion of each treatment.
Results: The study included 55 subjects (male 40 %, age 64.6 ± 9.5 years, FPG 102.6 ± 19.5 mg/dL, HbA1c 8.3 ± 0.6 %). After 20 weeks, the HbA1c significantly decreased to 7.8 ± 0.8 % by IDegAsp (0.40 ± 0.17 U/kg) and to 8.0 ± 0.7 % by IGlar (0.39 ± 0.18 U/kg). The mean estimated treatment difference of changes in HbA1c was not statistically significant (-0.22% point, 95% CI [-0.52, 0.08], p=0.078). In the CGM analyses, IDegAsp significantly reduced glucose levels after breakfast and before lunch, compared to IGlar. TIR, TBR, and hypoglycemic events were not significantly different between the treatments.
Conclusion: Compared to basal insulin, once-daily IDegAsp demonstrated a marginal benefit in reducing HbA1c in patients with lower FPG than predicted by their HbA1c, though the glycemic excursions after breakfast were significantly improved. More indices would be needed to tell those expected to have significant benefits by switching from basal insulin to IDegAsp. UTN#: U1111-1241-6269

Disclosure
E. Hong: None. H. Jang: None. S. Lee: None. Y. Yang: None. S. Kwak: Employee; SNUH Venture. K. Park: None. H. Jang: Consultant; Novo Nordisk. H. Jung: Research Support; Novo Nordisk.

Funding
Novo Nordisk, NRF (2022R1A2C2004570)
851-P: Whole Body Digital Twin (WBDT) Enabled Diabetes Reversal—U.S. Real-World Findings
Authors: SHAH LISA , JOSHI SHASHANK R. , MOHAMMED JAHANGIR , MOHAMED MALUK , THAJUDEEN MOHAMED , KAUFMAN FRANCINE R. , WILLIS BREE 
Published: June 2024

The WBDT is a digital model of metabolism, created using sensors, the Internet of Things, artificial intelligence and machine learning, providing an individualized comprehensive lifestyle intervention to improve and reverse T2D and its comorbidities. With an easy-to-use app, patients (pts) and the care team are given daily individualized guidance across nutrition, sleep, and activity. This study assessed medication (meds) use and metabolic markers over 1 yr in 256 T2D pts using WBDT commercial program data. Continuous variables were analyzed with paired t-test or Wilcoxon signed-rank test. At 1 yr, A1C decreased from 7.73±1.38 to 6.22±0.62; 71.9% had A1C &lt;6.5%. T2D reversal (A1C &lt;6.5% with no T2D meds except metformin) was achieved by 55.5%. At entry, 5.9% were not on T2D meds, 32.8% on 1, 35.9% on 2, and 25.4% on ≥3. At 1 yr, 29.7% were not on T2D meds, 37.5% on 1, 25.8% on 2, and 7.0% on ≥3. The Table shows the 1 yr changes in metabolic parameters. These data suggest the WBDT program leads to diabetes reversal, reduction in meds, and improvement or normalization of multiple metabolic parameters. The WBDT program may be an effective strategy to reduce the overall burden of T2D and its comorbidities.

Disclosure
L. Shah: Employee; Twin Health. S.R. Joshi: Consultant; Twin Health, Marico, Franco Indian, Zydus Cadila, Glenmark Pharmaceuticals. Other Relationship; Novo Nordisk, Sanofi, MSD, Abbott Nutrition, Abbott, Biocon, Alkem, USV Private Limited, Boehringer-Ingelheim. J. Mohammed: Employee; Twin Health. M. Mohamed: None. M. Thajudeen: None. F.R. Kaufman: Employee; Senseonics. Consultant; Twin Health. B. Willis: Employee; Twin Health.
857-P: Real-World Impact of Once-Weekly Injectable Semaglutide on Weight, BMI, and HbA1c Outcomes in Type 2 Diabetes—An Observational Study (PAUSE)
Authors: AMAMOO JAMES , DOSHI RIDDHI P. , NOONE JOSHUA , XIE LIN , GAMBLE CORY L. , GUEVARRA MICO , DIVINO VICTORIA , CHEN JUSTIN , KING AARON A. 
Published: June 2024

Introduction & Objective: This study aimed to determine the real-world effectiveness of injectable semaglutide once weekly (sema OW) on weight and HbA1c outcomes among people with type 2 diabetes (T2D) in the US.
Methods: This observational cohort study involved adults with uncontrolled T2D (HbA1c ≥7%) initiating sema OW from January 2018—February 2022 (first prescription = index) using IQVIA PharMetrics® Plus and Ambulatory Electronic Medical Records databases. Change in weight, BMI and HbA1c outcomes from baseline to 1-year post-index were descriptively compared overall, as well as for subgroups of those persistent (≤60-day gap in treatment, subgroup 1), those receiving maintenance dose ≥1 mg (subgroup 2), and those who were persistent and receiving dose ≥1 mg (subgroup 3).
Results: Among the final sample (n=772) and all subgroups, a significant mean change from baseline was seen in weight, BMI and HbA1c (all p&lt;0.0001; Fig.). Mean changes in weight and BMI were numerically greatest in subgroup 3 (Fig.). The proportion of patients with obesity (BMI ≥30 kg/m2) significantly decreased from 84.0% at baseline to 77.1% post-index (p&lt;0.0001).
Conclusion: Adults with T2D initiating sema OW had statistically significant decreases in weight, BMI and HbA1c after 1 year, with better weight outcomes in patients persistent to treatment and receiving maintenance dose ≥1 mg.

Disclosure
J. Amamoo: None. R.P. Doshi: None. J. Noone: Employee; Novo Nordisk. L. Xie: None. C.L. Gamble: Employee; Novo Nordisk. M. Guevarra: Stock/Shareholder; Novo Nordisk. V. Divino: Employee; IQVIA Inc. J. Chen: None. A.A. King: Speaker's Bureau; Abbott, MannKind Corporation, Novo Nordisk. Advisory Panel; Novo Nordisk. Speaker's Bureau; Lilly Diabetes. Advisory Panel; Lilly Diabetes. Speaker's Bureau; Dexcom, Inc. Advisory Panel; Dexcom, Inc. Speaker's Bureau; Astellas Pharma Inc.

Funding
Novo Nordisk
862-P: Efficacy and Safety of Orlistat in People with Overweight/Obese and Hyperuricemia—Results of a Randomized, Double-Blind, Placebo-Controlled Trial
Authors: LIU SHUANG , QU SHEN , CHEN HAIBING 
Published: June 2024

Objective: Obesity is associated with elevated serum uric acid (SUA) and frequent gout flares. Losing weight can lower SUA and reduce gout flares. In this study, we investigated the effects of orlistat on SUA and gout flares compared to placebo in people with overweight/obese and hyperuricemia (HUA).
Methods: A total of 72 Chinese people with overweight/obese and HUA were randomly divided into placebo group and orlistat group for 12 weeks. The primary endpoints were relative changes in SUA, as well as gout flares.
Results: All participants with overweight/obesity and HUA were randomly assigned to placebo group (35, 48.61%) and orlistat group (37, 51.39%). There were 26 (74.29%) and 29 (78.38%) participants with gout in the two groups, respectively. Orlistat was associated with a significantly lower proportion of people with gout flares (log-rank p = 0.023, hazard rate = 0.31, 95% CI 0.11-0.85). There was no significant change in SUA levels in both groups. The weight loss of participants in the orlistat group (2.85kg) was significantly higher than that in the placebo group (0.76kg).
Conclusions: This study demonstrates for the first time that orlistat has no direct effect on SUA levels in people with overweight/obese and HUA. The value of orlistat as an adjunct therapy to prevent gout flares during weight loss in people with HUA was emphasized.

Disclosure
S. Liu: None. S. Qu: None. H. Chen: None.

Funding
National Natural Science Foundation of China (81870606)
863-P: Genetically Proxied GLP-1 Receptor Agonism Improves Kidney Function—A Mendelian Randomization Study
Authors: CHOI JAEWON , LEE HYUNSUK , LEE JEONGEUN , PARK JONGSEOK , JO YEEUN , SUNG JOOHON , LEE SEUNGGEUN , HEON KWAK SOO , KHO MINJUNG 
Published: June 2024

Recently, the use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) has been associated with prevention of kidney function decline and reducing the risk of chronic kidney disease (CKD). However, it is not clear whether GLP-1 receptor agonism has a direct causal effect on renal function. We aimed to investigate the causal association between GLP-1 receptor agonism, kidney function, and the risk of CKD using the Mendelian randomization approach. We constructed genetic instruments for GLP-1 receptor agonism using expression quantitative trait loci (eQTL), focusing on those with significant associations between genetic variants and gene expression in pancreatic tissue from the GTEx database. The inverse variance weighted model was utilized to estimate causal associations, and summary genetic association estimates for the estimated glomerular filtration rate (eGFR)(N=33,152) and CKD (N=117,165) were obtained from a mixed-ancestry genome-wide association study (GWAS) from the CKD Gen Consortium. We identified 7 genetic variants, or eQTL, that were significantly associated with GLP1 receptor mRNA expression in pancreatic tissue. Using these as instrumental variables we observed that genetically predicted GLP1 receptor agonism was significantly associated with improved kidney function as estimated by eGFR (beta 1.97×10-3, 95% CI 6.08×10-4-3.33×10-3, P=5.38×10-3). However, we were not able to find any causal association between genetically predicted GLP1 receptor agonism and reduction in risk of CKD (OR=0.99, 95% CI 0.95-1.03, P=0.65). There was no evidence of horizontal pleiotropy, as indicated by MR-Egger intercept and no obvious heterogeneity (all P&gt;0.05) was observed in each analysis.
In conclusion, genetic evidence suggests that GLP-1 receptor agonism is likely to improve kidney function in the general population. Further studies are warranted to determine the impact of GLP-1 receptor agonism on reducing the risk of CKD especially in people with diabetes.

Disclosure
J. Choi: None. H. Lee: None. J. Lee: None. J. Park: None. Y. Jo: None. J. Sung: None. S. Lee: None. S. Kwak: Employee; SNUH Venture. M. Kho: None.

Funding
National Research Foundation of Korea grant funded by the Korean Ministry of Science and ICT (RS-2023-00262002)