Similar HbA1c Reduction Research Articles

Twelve-months treatment with dapagliflozin improves endothelial glycocalyx and cardiovascular function in patients with type 1 diabetes mellitus

Abstract Background Individuals diagnosed with type 1 diabetes mellitus (T1DM) exhibit indications of vascular and endothelial dysfunction earlier in comparison to healthy individuals. Evidence shows that SGLT-2 inhibitors (SGLT-2i) have a beneficial impact on cardiovascular health in individuals with type 2 diabetes mellitus (T2DM). We investigated the effects of dapagliflozin on endothelial and cardiovascular function in patients with T1DM. Methods We recruited in total 40 patients with T1DM and pour glycemic control who were treated with insulin and received dapagliflozin (n=20) or intensification of insulin treatment (n=20) (control group). We measured at baseline and at twelve months post-treatment the: a) Carotid-femoral pulse wave velocity (PWV-Complior; ALAM Medical) b) Central systolic blood pressure (cSBP) c) Perfused boundary region (PBR) of the sublingual arterial microvessels (marker of endothelial glycocalyx thickness) and d) Left ventricular global longitudinal strain (GLS) using speckle-tracking echocardiography. Results At baseline, patients among the two groups had similar age, sex, HbA1c and markers of endothelial and cardiovascular function (p>0.05). After 12 months of treatment, patients who received dapagliflozin displayed an improvement in PBR5–25 (−16%, p<0.05), in PWV (−9.3%, p<0.05), in cSBP (−6%, p<0.05) and in GLS (+4%, P<0.05) compared to baseline. However, no statistically significant changes in PBR5–25, in PWV, in cSBP and in GLS were observed after intensification of insulin treatment (PBR5–25: +0.4%, PWV: -1%, cSBP: −2%, GLS: −1% at 4 months, P>0.05), despite a similar HbA1c reduction (Table 1). Changes of PBR after one year treatment with dapagliflozin correlated with a concomitant reduction of PWV and cSBP (P<0.05). Conclusions Twelve months treatment with dapagliflozin improves endothelial glycocalyx and cardiovascular function in patients with T1DM, independently of glycemic control.

Efficacy and safety of oral semaglutide monotherapy vs placebo in a predominantly Chinese population with type 2 diabetes (PIONEER 11): a double-blind, Phase IIIa, randomised trial

Aims/hypothesisThe aim of this study was to evaluate the efficacy and safety of oral semaglutide monotherapy vs placebo in a predominantly Chinese population with type 2 diabetes insufficiently controlled with diet and exercise alone.MethodsThe Peptide Innovation for Early Diabetes Treatment (PIONEER) 11 trial was a double-blind, randomised, Phase IIIa trial conducted across 52 sites in the China region (mainland China and Taiwan), Hungary, Serbia and Ukraine. Eligible participants were ≥18 years (≥20 years in Taiwan), had a diagnosis of type 2 diabetes with HbA1c 53–86 mmol/mol (7.0–10.0%) and were not receiving any glucose-lowering drugs. After a 4-week run-in period in which participants were treated with diet and exercise alone, those who fulfilled the randomisation criteria were randomised (1:1:1:1) using a web-based randomisation system to receive once-daily oral semaglutide 3 mg, 7 mg or 14 mg or placebo for 26 weeks (using a 4-week dose-escalation regimen for the higher doses). Randomisation was stratified according to whether participants were from the China region or elsewhere. The primary and confirmatory secondary endpoints were change from baseline to week 26 in HbA1c and body weight (kg), respectively. Safety was assessed in all participants exposed to at least one dose of the trial product.ResultsBetween October 2019 and October 2021, a total of 774 participants were screened and 521 participants were randomised to oral semaglutide 3 mg (n=130), 7 mg (n=130), 14 mg (n=130) or placebo (n=131); most participants (92.5%, n=482) completed the trial, with 39 participants prematurely discontinuing treatment. The number of participants contributing to the trial analyses was based on the total number of participants who were randomised at the beginning of the trial. The majority of participants were male (63.7%), and the mean age of participants was 52 years. At baseline, mean HbA1c and body weight were 63 mmol/mol (8.0%) and 79.6 kg, respectively. Oral semaglutide resulted in significantly greater reductions in HbA1c than placebo at week 26 (p<0.001 for all doses). The estimated treatment differences (ETDs [95% CIs]) for oral semaglutide 3 mg, 7 mg and 14 mg vs placebo were –11 (–13, –9) mmol/mol, –16 (–18, –13) mmol/mol and –17 (–19, –15) mmol/mol, respectively. The corresponding ETDs in percentage points (95% CI) vs placebo were –1.0 (–1.2, –0.8), –1.4 (–1.6, –1.2) and –1.5 (–1.8, –1.3), respectively. Significantly greater reductions in body weight were also observed for oral semaglutide 7 mg and 14 mg than for placebo at week 26 (ETD [95% CI] –1.2 kg [–2.0 kg, –0.4 kg; p<0.01] and –2.0 kg [–2.8 kg, –1.2 kg; p<0.001], respectively), but not for oral semaglutide 3 mg (ETD [95% CI] –0.0 kg [–0.9 kg, 0.8 kg; not significant]). Similar reductions in HbA1c and body weight were observed in the Chinese subpopulation, which represented 74.9% of participants in the overall population. Adverse events (AEs) occurred in between 65.4% and 72.3% of participants receiving oral semaglutide (for all doses) and 57.3% of participants with placebo. Most AEs were mild to moderate in severity, with few serious AEs reported; the most commonly reported AEs were gastrointestinal-related and were more frequent with semaglutide (all doses) than with placebo. The proportion of AEs was slightly higher in the Chinese subpopulation.Conclusions/interpretationOral semaglutide resulted in significantly greater reductions in HbA1c across all doses and in significant body weight reductions for the 7 mg and 14 mg doses when compared with placebo in predominantly Chinese participants with type 2 diabetes insufficiently controlled by diet and exercise alone. Oral semaglutide was generally well tolerated, with a safety profile consistent with that seen in the global PIONEER trials.Trial registrationClinicalTrials.gov NCT04109547.FundingNovo Nordisk A/S.Graphical

Effectiveness of Continuous Glucose Monitoring on Metrics of Glycemic Control in Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

To provide a systematic review and meta-analysis synthesizing the findings of randomized controlled trials (RCTs) of continuous glucose monitors (CGMs) in the management of adults with type 2 diabetes mellitus (T2DM) on glucose control and clinical outcomes. MEDLINE, Embase, and Cochrane were searched for RCTs that assessed the effectiveness of real-time CGM (rt-CGM) or flash CGM (FGM) in adults (≥18 years) with T2DM that reported on at least 1 of the following outcomes: hemoglobin A1c (HbA1c), time in range, time in hyperglycemia, or time in hypoglycemia. The GRADE approach was used to assess certainty of evidence for primary outcomes. Fourteen RCTs assessing CGM were included, with 825 patients in 9 RCTs using rt-CGM and 822 in 5 RCTs using FGM. Moderate certainty of evidence indicated that use of CGM had a modest but statistically significant reduction in HbA1c levels of about 0.32%. Our analyses of each device type separately showed similar reductions in HbA1c (0.34% and 0.33%, respectively, for rt-CGM and FGM), with trends for improvement in other glucose metrics favoring rt-CGM over self-monitored blood glucose. Both rt-CGM and flash CGM led to modest but statistically significant declines in HbA1c among individuals with T2DM, with little heterogeneity in the results. However, the duration of the included RCTs was relatively short and few studies reported on important clinical outcomes, such as adverse events, emergency department use, or hospitalization. Longer term studies are needed to determine if the short-term improvements in glucose control leads to improvements in clinically important outcomes.

The real-world observational prospective study of health outcomes with dulaglutide and liraglutide in patients with type 2 diabetes (TROPHIES): Final, 24-month analysis of time to first significant treatment change, treatment persistence and clinical outcomes.

To present the final results of the TROPHIES study (The real-world observational prospective study of health outcomes with dulaglutide and liraglutide in patients with type 2 diabetes). The prospective, real-world TROPHIES study included patients with type 2 diabetes initiating their first injectable glucose-lowering medication (GLM), dulaglutide or liraglutide, in France, Germany and Italy. The primary endpoint was the time spent on dulaglutide or liraglutide until a significant treatment change over 24 months. Other endpoints measured persistence with treatment, clinical outcomes (glycated haemoglobin [HbA1c] and weight) and treatment patterns. Kaplan-Meier estimates of time to first significant treatment change and persistence with treatment were generated. Propensity-score-based inverse probability of treatment weighting (IPTW) was used to adjust for baseline imbalances in the comparison between cohorts. The 286 of 1014 patients (28.2%) in the dulaglutide cohort and 448 of 991 patients (45.2%) in the liraglutide cohort had a significant treatment change over 24 months. By IPTW analysis, dulaglutide-initiating patients were less likely to have a significant treatment change (hazard ratio [HR] 0.54, 95% confidence interval [CI] 0.46-0.63) and more likely to be persistent with treatment (HR 0.69, 95% CI 0.56-0.86) over 24 months than liraglutide-initiating patients. Dulaglutide and liraglutide yielded similar HbA1c (-11.80 mmol/mol [1.08%] and -11.91 mmol/mol [1.09%]) and weight (-3.5 kg and -3.3 kg) reductions from baseline to 24 months. Few changes in patterns of treatment with other GLMs were observed in the two cohorts. Dulaglutide-initiating patients had a longer time spent without any significant treatment change and higher persistence than those initiating liraglutide. Treatment with either glucagon-like peptide-1 receptor agonist yielded similar and clinically meaningful reductions in HbA1c and body weight.

Disparities in Hemoglobin A1c Levels in the First Year After Diagnosis Among Youths With Type 1 Diabetes Offered Continuous Glucose Monitoring

Continuous glucose monitoring (CGM) is associated with improvements in hemoglobin A1c (HbA1c) in youths with type 1 diabetes (T1D); however, youths from minoritized racial and ethnic groups and those with public insurance face greater barriers to CGM access. Early initiation of and access to CGM may reduce disparities in CGM uptake and improve diabetes outcomes. To determine whether HbA1c decreases differed by ethnicity and insurance status among a cohort of youths newly diagnosed with T1D and provided CGM. This cohort study used data from the Teamwork, Targets, Technology, and Tight Control (4T) study, a clinical research program that aims to initiate CGM within 1 month of T1D diagnosis. All youths with new-onset T1D diagnosed between July 25, 2018, and June 15, 2020, at Stanford Children's Hospital, a single-site, freestanding children's hospital in California, were approached to enroll in the Pilot-4T study and were followed for 12 months. Data analysis was performed and completed on June 3, 2022. All eligible participants were offered CGM within 1 month of diabetes diagnosis. To assess HbA1c change over the study period, analyses were stratified by ethnicity (Hispanic vs non-Hispanic) or insurance status (public vs private) to compare the Pilot-4T cohort with a historical cohort of 272 youths diagnosed with T1D between June 1, 2014, and December 28, 2016. The Pilot-4T cohort comprised 135 youths, with a median age of 9.7 years (IQR, 6.8-12.7 years) at diagnosis. There were 71 boys (52.6%) and 64 girls (47.4%). Based on self-report, participants' race was categorized as Asian or Pacific Islander (19 [14.1%]), White (62 [45.9%]), or other race (39 [28.9%]); race was missing or not reported for 15 participants (11.1%). Participants also self-reported their ethnicity as Hispanic (29 [21.5%]) or non-Hispanic (92 [68.1%]). A total of 104 participants (77.0%) had private insurance and 31 (23.0%) had public insurance. Compared with the historical cohort, similar reductions in HbA1c at 6, 9, and 12 months postdiagnosis were observed for Hispanic individuals (estimated difference, -0.26% [95% CI, -1.05% to 0.43%], -0.60% [-1.46% to 0.21%], and -0.15% [-1.48% to 0.80%]) and non-Hispanic individuals (estimated difference, -0.27% [95% CI, -0.62% to 0.10%], -0.50% [-0.81% to -0.11%], and -0.47% [-0.91% to 0.06%]) in the Pilot-4T cohort. Similar reductions in HbA1c at 6, 9, and 12 months postdiagnosis were also observed for publicly insured individuals (estimated difference, -0.52% [95% CI, -1.22% to 0.15%], -0.38% [-1.26% to 0.33%], and -0.57% [-2.08% to 0.74%]) and privately insured individuals (estimated difference, -0.34% [95% CI, -0.67% to 0.03%], -0.57% [-0.85% to -0.26%], and -0.43% [-0.85% to 0.01%]) in the Pilot-4T cohort. Hispanic youths in the Pilot-4T cohort had higher HbA1c at 6, 9, and 12 months postdiagnosis than non-Hispanic youths (estimated difference, 0.28% [95% CI, -0.46% to 0.86%], 0.63% [0.02% to 1.20%], and 1.39% [0.37% to 1.96%]), as did publicly insured youths compared with privately insured youths (estimated difference, 0.39% [95% CI, -0.23% to 0.99%], 0.95% [0.28% to 1.45%], and 1.16% [-0.09% to 2.13%]). The findings of this cohort study suggest that CGM initiation soon after diagnosis is associated with similar improvements in HbA1c for Hispanic and non-Hispanic youths as well as for publicly and privately insured youths. These results further suggest that equitable access to CGM soon after T1D diagnosis may be a first step to improve HbA1c for all youths but is unlikely to eliminate disparities entirely. ClinicalTrials.gov Identifier: NCT04336969.

Tirzepatide as a novel therapeutic option for patients with type 2 diabetes: A pooled analysis of subgroups of SURPASS 1-5 trials

Abstract Aim: The aim of this study was to evaluate the impact of patients’ characteristics on the efficacy and the safety of subcutaneous tirzepatide once-weekly in patients with uncontrolled type 2 diabetes mellitus (T2DM). Materials and Methods: This post hoc analysis of pooled SURPASS 1-5 randomized controlled trials narratively examined changes from baseline in hemoglobin A1c (HbA1c) and body weight and the proportions of patients who achieved the endpoint composite HbA1c with tirzepatide (5, 10, and 15 mg) across the following subgroups; baseline HbA1c (≥ 7.5% to ≤8.0% [≥48 ≤ 64 mmol/mol], ≥8.0% to ≤8.5% [≥64 ≤68 mmol/mol], and ≥ 8.5% to ≤9.0% [≥68 ≤75 mmol/mol]), baseline diabetes durations (≤ 5 years, 5–10 years, and ≥ 10 years), and age (non-elderly ≤ 60 years and elderly ≥ 60 years). Results: Based on diabetes duration, the mean HbA1c reduced from baseline (≥–1.87 % to ≤–2.24% [≥–20.57 to ≤–24.64 mmol/mol]) for tirzepatide 5 mg (P = 0.308), –1.89 % to –2.43% (–20.79 to –26.73 mmol/mol) with tirzepatide 10 mg (P = 0.015) and ≥–2.07 % to≤ –2.58 % (≥–22.77 to ≤–28.38 mmol/mol) with tirzepatide 15 mg (P = 0.010). Similar HbA1c and body weight reductions were observed across other subgroups (baseline HbA1c and age). Conclusion: Tirzepatide was consistently efficacious and safe in the broad spectrum of patients with T2DM subgroups across the SURPASS 1-5 trials.

Safety and efficacy analyses across age and body mass index subgroups in East Asian participants with type 2 diabetes in the phase 3 tirzepatide studies (SURPASS programme).

To assess the safety and efficacy of tirzepatide in people of East Asian descent based on age and body mass index (BMI). Data of participants enrolled in East Asian countries in the SURPASS-1, -3, -4, -5, J-mono and J-combo phase 3 clinical trials were included. Participants with type 2 diabetes with a baseline HbA1c of 7.0% up to 11.0% and a BMI of 23 kg/m2 or greater or 25 kg/m2 or greater were included. Participants treated with tirzepatide 5, 10 or 15 mg were evaluated to assess the safety and efficacy of tirzepatide in people of East Asian descent (94% from Japan) based on age (< 65 and ≥ 65 years) and BMI (< 25 and ≥ 25 kg/m2 ). Key safety and efficacy outcomes were assessed. At baseline, 73% of East Asian participants had a BMI of 25 kg/m2 or greater and 74% were younger than 65 years. At week 52, tirzepatide induced a similar dose-dependent reduction in HbA1c, waist circumference and BMI across subgroups. Across all BMI and age subgroups, mean absolute HbA1c reductions across the three doses ranged from 2.3% to 3.0%, and mean waist circumference reductions ranged from 4.3 to 9.8 cm. Improvements in absolute insulin sensitivity, assessed by homeostatic model assessment for insulin resistance, were greater in those with a baseline BMI of ≥ 25 kg/m2 . Improvements in lipid profiles were similar across subgroups. While the safety profile of tirzepatide was broadly similar across BMI and age subgroups, drug discontinuation because of adverse events was higher in participants with a baseline age of ≥ 65 years. This post hoc analysis showed that once-weekly tirzepatide had a similar safety and efficacy profile across BMI and age subgroups in East Asian participants.

Four-months treatment with dapagliflozin improves endothelial glycocalyx and cardiovascular function in patients with type 1 diabetes mellitus

Abstract Background/Introduction Patients with type 1 diabetes mellitus (T1DM) present signs of vascular and endothelial dysfunction earlier compared to healthy individuals. According to clinical studies, SGLT-2i favorably affect cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM). However, the data regarding the efficacy of SGLT-2i on cardiovascular markers in patients with T1DM are scarce. Purpose We investigated the effects of dapagliflozin on endothelial and cardiovascular function in patients with T1DM. Methods We recruited in total 30 patients with T1DM and pour glycemic control who were under medication with insulin and received dapagliflozin (n=15) or intensification of insulin treatment (n=15) (control group). We measured at baseline and at four months post-treatment the: a) Carotid-femoral pulse wave velocity (PWV-Complior; ALAM Medical) b) Central systolic blood pressure (cSBP) c) Perfused boundary region (PBR) of the sublingual arterial microvessels (marker of endothelial glycocalyx thickness) and d) Left ventricular global longitudinal strain (GLS) using speckle-tracking echocardiography. Results At baseline, patients among the two groups had similar age, sex, HbA1c and markers of endothelial and cardiovascular function (p&amp;gt;0.05). After four months treatment, patients who received dapagliflozin displayed an improvement in PBR5–25 (−41%, p&amp;lt;0.05), in PWV (−10%, p&amp;lt;0.05), in cSBP (−6%, p&amp;lt;0.05) and in GLS (+5%, P&amp;lt;0.05) compared to baseline. However, no statistically significant changes in PBR5–25, in PWV, in cSBP and in GLS were observed after intensification of insulin treatment (PBR5–25: +3%, PWV: +2%, cSBP: −2%, GLS: −3% at 4 months, P&amp;gt;0.05), despite a similar HbA1c reduction (Table 1). Changes of PBR after four months treatment with dapagliflozin correlated with a concomitant reduction of PWV and cSBP (P&amp;lt;0.05). Conclusions Four-months treatment with dapagliflozin improves endothelial glycocalyx and cardiovascular function in patients with T1DM, independently of glycemic control. Funding Acknowledgement Type of funding sources: None.

Four-month treatment with long-acting glucagon-like peptide-1 receptor agonists (GLP-1) or sodium-glucose co-trasporter-2 inhibitors (SGLT-2i) improves vascular function in type 2 diabetes mellitus

Abstract Background/Introduction Patients with type 2 diabetes mellitus (T2DM) and ischemic stroke present impaired markers of vascular and endothelial function. Glucagon-like peptide-1 receptor agonists (GLP-1) and sodium-glucose contrasporter-2 inhibitors (SGLT-2) are novel antidiabetic agents reducing the risk of cardiovascular complications. Purpose The aim of the study is to investigate the effect of treatment with GLP-1 or SGLT2 on arterial stiffness and endothelial glycocalyx in patients with T2DM and ischemic stroke. Methods We recruited in total 81 patients with T2DM and ischemic stroke who received dulaglutide (n=27), dapagliflozin (n=27) or insulin (n=27). We measured at baseline and at four months post-treatment the: a) Carotid-femoral pulse wave velocity (PWV-Complior; ALAM Medical), b) Augmentation index (Aix), c) Central systolic blood pressure (cSBP), and d) Perfused boundary region (PBR) of the sublingual arterial microvessels(marker of endothelial glycocalyx thickness), e) Left ventricular global longitudinal strain (GLS) using speckle-tracking echocardiography. Results At baseline, patients among the three groups had similar age, sex, HbA1c and markers of endothelial and cardiovascular function (p&amp;gt;0.05). Dapagliflozin and dulaglutide showed a greater reduction of PBR, PWV and central SBP than insulin, despite a similar HbA1c reduction (p&amp;lt;0.05). After four months treatment, patients on dapagliflozin and on dulaglutide displayed a greater reduction of PWV (−10% and −8% vs −1%), of cSBP (−9% and −8% vs +1%), of Aix (−65% and −13% vs −3%) and of GLS (+11% and +7% vs +5%) compared to patients on insulin (p&amp;lt;0.05 for all comparisons) (Table 1). PBR values were improved only in patients who received dulaglutide (−4% vs dapagliflozin: −2% vs insulin +1%). Conclusions Dulaglutide and dapagliflozin improve cardiovascular function, but only dulaglutide improves endothelial glycocalyx in patients with T2DM and ischemic stroke after four months treatment. Funding Acknowledgement Type of funding sources: None.

A randomized clinical trial of genetic testing and personalized risk counselling in patients with type 2 diabetes receiving integrated care -The genetic testing and patient empowerment (GEM) trial

AimsWe evaluated the effect of personalized risk counseling incorporating clinical and genetic risk factors on patient empowerment and risk factor control in diabetes. MethodsPatients with type 2 diabetes (T2D) with suboptimal glycaemic control (HbA1c ≥ 7.5%) were randomized to a genetic counselling (GC) or control group. All patients underwent genetic testing for alleles at three loci associated with diabetic complications. The GC group received additional explanation of the joint associations of genetic and modifiable risk factors on risk of complications. All patients were reassessed at 12 months including validated questionnaires for patient reported outcomes. The primary outcome was proportion of patients reaching ≥ 3 of 5 predefined treatment targets (HbA1c < 7%, BP < 130/80 mmHg, LDL-C < 2.6 mmol/L, Triglyceride < 2.0 mmol/L, use of renin-angiotensin system inhibitors). Secondary outcomes included new-onset chronic kidney disease or microalbuminuria and patient reported outcome measures. ResultsA total of 435 patients were randomized and 420 patients were included in the modified intention-to-treat analysis. At 12 months, the proportion of patients who attained ≥ 3 targets increased from 41.6% to 52.3% in the GC group (p = 0.007) versus 49.5% to 62.6% in the control group (p = 0.003), without between-group difference. Both groups had similar reduction in HbA1c, LDL-C and increased use of medications. In per protocol analysis, the GC group had higher diabetes empowerment, with reduced diabetes distress. In the GC group, the greatest improvement in positive attitude and self-care activities was observed in the intermediate to high genetic risk score (GRS) groups. ConclusionsIn patients with T2D receiving integrated care, additional counselling on genetic risk of complications did not further improve risk factor control, although the improvement in self-efficacy warrants long-term evaluation.

733-P: Initiation of iGlarLixi vs. Basal-Bolus Insulin (BB) in Adults with Type 2 Diabetes (T2D) Advancing from Basal Insulin (BI) Therapy: The SoliComplex Real-World Study

Aim: When T2D is suboptimally controlled with BI, 1-3 daily injections of prandial insulin are commonly added (BB regimen) . Once daily iGlarLixi is an alternative treatment. This analysis evaluated the use of iGlarLixi vs. BB on T2D outcomes. Methods: 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 BB between Jan 1, 2017, and Jun 30, 2020. Persistence (primary endpoint) , adherence, healthcare resource utilization (HRU) , costs, any hypoglycemia, and HbA1c change were assessed at 12 months. Results: Propensity score matching generated cohorts (n=1070 each) that were well balanced with similar mean ± SD age (iGlarLixi: 63.9 ± 11.0 y; BB: 64.5 ± 11.3 y) , HbA1c (iGlarLixi: 9.2 ± 1.7%; BB: 9.2 ± 1.8%) , oral agent use, BI use, and HRU. The primary endpoint was met with treatment persistence being statistically significantly higher for iGlarLixi vs. BB at 12 months. Adherence was numerically higher for iGlarLixi, and hypoglycemia rates, HRU and costs, numerically lower. HbA1c reduction was similar between groups (Table) . Conclusions: In this observational study, initiation of once daily iGlarLixi vs. BB insulin was associated with higher persistence and similar HbA1c reduction without increasing HRU or costs. Disclosure K.M. Pantalone: Consultant; AstraZeneca, Bayer AG, Corcept Therapeutics, Diasome, Eli Lilly and Company, Merck &amp; Co., Inc., Novo Nordisk, Sanofi. Research Support; Bayer AG, Merck &amp; Co., Inc., Novo Nordisk. Speaker's Bureau; AstraZeneca, Corcept Therapeutics, Merck &amp; Co., Inc., Novo Nordisk. C. Heller: Consultant; Sanofi. Employee; Aetion. R. Lajara: None. 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

739-P: iGlarLixi vs. Premixed Insulin Initiation in Adults with Type 2 Diabetes (T2D) Advancing from Basal Insulin (BI) Therapy: SoliComplex Real-World Study

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 &amp; Co., Inc., Novo Nordisk, Sanofi, Research Support; Bayer AG, Merck &amp; Co., Inc., Novo Nordisk, Speaker's Bureau; AstraZeneca, Corcept Therapeutics, Merck &amp; 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

Comparing clinical outcomes between two continuous glucose monitors: similar diabetes-related events, all-cause hospitalizations and HbA1c reductions in type 1 and type 2 diabetes

ObjectivesWe compared clinical outcomes after acquiring a FreeStyle Libre© Flash Continuous Glucose Monitoring System (FSL) or Dexcom (DEX) continuous glucose monitoring (CGM) device in individuals with type 1 diabetes (T1D) and type 2 diabetes (T2D) treated with intensive insulin therapy. Design and MethodsThis retrospective analysis of the IBM® MarketScan® Research Databases and IBM® Explorys® Electronic Health Records Database assessed differences in acute diabetes-related events (ADE), all-cause hospitalizations (ACH) and glycated hemoglobin (HbA1c) in T1D and T2D populations 6 months post CGM acquisition. Analyses were conducted in two study cohorts (Cohort 1, n = 7,494; Cohort 2, n = 678). Participants were T1D or T2D, age ≥ 18 years, treated with short or rapid-acting insulin and naïve to CGM, who acquired a CGM system. Users were propensity score matched on demographics and clinical factors. ResultsCohort 1: Post-CGM ADE-free rates at 6 months ranged from 94.8 to 96.7% and ACH-free rates ranged from 90.4 to 95.4%, for both T1D and T2D groups, with no significant differences between CGM systems. Cohort 2: Significant HbA1c reductions were associated with use of the DEX and FSL devices in the T1D (-0.35% and -0.37%, respectively) and T2D (-0.73% and -0.79%, respectively) cohorts, both p < 0.001, with no significant differences in the magnitude of reduction between systems (T1D p = 0.99 and T2D p = 0.84). ConclusionsAcquisition of the FSL and DEX systems was associated with similar rates of acute diabetes-related events and all-cause hospitalizations and similar HbA1c reductions in adults with T1D and T2D.

Effect of chiglitazar and sitagliptin on glucose variations, insulin resistance and inflammatory-related biomarkers in untreated patients with type 2 diabetes

AimsTo evaluate glycemic variations, changes in insulin resistance and oxidative stress after chiglitazar or sitagliptin treatment in untreated patients with type 2 diabetes mellitus (T2DM). MethodsBased on the study inclusion and exclusion criteria, 81 patients with T2DM were randomly divided to receive chiglitazar or sitagliptin treatment for 24 weeks. Continuous glucose monitoring (CGM) systems were conducted for 72 h in eligible patients. We analyzed the following glycemic variation parameters derived from the CGM data and measured the serum levels of hemoglobin A1c (HbA1c), fasting blood glucose (FBG), 2-h postprandial blood glucose (2-h PBG), fasting insulin (Fins) and inflammatory-related indicators at baseline and the end of the study. ResultsAfter treatment for 24 weeks, our data showed a similar reduction in HbA1c between chiglitazar and sitagliptin. The 24-h mean blood glucose (MBG), standard deviation (SD) and mean amplitude of glycemic excursion (MAGE) were significantly decreased, and the time in range (TIR) was increased after chiglitazar and sitagliptin therapy. Chiglitazar administration led to significant improvement in insulin resistance/insulin secretion (HOMA-IR, HOMA-IS), interleukin-6 (IL-6), prostaglandin F2α (PGF-2α), 17-hydroxyprogesterone (17-OHP) and adiponectin (ADP) score values compared with sitagliptin administration. ConclusionsChiglitazar therapy effectively reduced glucose variation and showed a larger improvement in insulin resistance and inflammatory parameters than sitagliptin.

Clinical outcomes in high-hypoglycaemia-risk patients with type 2 diabetes switching to insulin glargine 300U/mL versus a first-generation basal insulin analogue in the United States : Results from the DELIVER High Risk real-world study.

AimsTo compare 12‐month clinical effectiveness of insulin glargine 300 units/mL (Gla‐300) versus first‐generation basal insulin analogues (BIAs) (insulin glargine 100 units/mL [Gla‐100] or insulin detemir [IDet]) in patients with type 2 diabetes (T2D) who were at high risk of hypoglycaemia and switched from one BIA to a different one (Gla‐300 or Gla‐100/IDet) in a real‐world setting.MethodsDELIVER High Risk was a retrospective observational cohort study of 2550 patients with T2D who switched BIA to Gla‐300 (Gla‐300 switchers) and were propensity score‐matched (1:1) to patients who switched to Gla‐100 or IDet (Gla‐100/IDet switchers). Outcomes were change in glycated haemoglobin A1c (HbA1c), attainment of HbA1c goals (<7% and <8%), and incidence and event rates of hypoglycaemia (all‐hypoglycaemia and hypoglycaemia associated with an inpatient/emergency department [ED] contact).ResultsHbA1c reductions were similar following switching to Gla‐300 or Gla‐100/IDet (−0.51% vs. −0.53%; p = .67), and patients showed similar attainment of HbA1c goals. Patients in both cohorts had comparable all‐hypoglycaemia incidence and event rates. However, the Gla‐300 switcher cohort had a significantly lower risk of inpatient/ED‐associated hypoglycaemia (adjusted odds ratio: 0.73, 95% confidence interval: 0.60–0.89; p = .002) and experienced significantly fewer inpatient/ED‐associated hypoglycaemic events (0.21 vs. 0.33 events per patient per year; p < .001).ConclusionIn patients with T2D at high risk of hypoglycaemia, switching to Gla‐300 or Gla‐100/IDet achieved similar HbA1c reductions and glycaemic goal attainment, but Gla‐300 switchers had a significantly lower risk of hypoglycaemia associated with an inpatient/ED contact during 12 months after switching.

Efficacy and Safety of Once-Weekly Semaglutide 2.0 mg vs 1.0 mg by Baseline HbA1c and BMI: SUSTAIN FORTE Subgroup Analyses

Once-weekly subcutaneous semaglutide 2.0 mg showed superior efficacy with similar safety vs 1.0 mg in 961 participants with type 2 diabetes (HbA1c 8.0-10.0%) after 40 weeks in SUSTAIN FORTE. We assessed the effect of semaglutide 2.0 mg vs 1.0 mg on HbA1c and body weight (BW) in prespecified baseline (BL) HbA1c (<9.0%, ≥9.0%) and BMI (<35, ≥35 kg/m2) subgroups. Mean BL HbA1c was 8.9% and BMI 34.6 kg/m2. For HbA1c and BW, estimated treatment differences favored semaglutide 2.0 mg vs 1.0 mg across all BL HbA1c and BMI subgroups. Treatment-by-subgroup interactions were nonsignificant (HbA1c, p=0.55 and p=0.41; BW, p=0.40 and p=0.13; Figures A-D). Greater mean HbA1c reductions were observed for both doses in the higher vs lower BL HbA1c subgroup (Figure A). Conversely, greater mean BW reductions were observed for both doses in the lower vs higher BL HbA1c subgroup (Figure C). Similar mean HbA1c reductions were observed across BL BMI subgroups (Figure B), while greater mean BW reductions were observed for both doses in the higher vs lower BL BMI subgroup (Figure D). Overall, the incidence of adverse events was similar for both doses and across BL HbA1c and BMI subgroups with no new safety concerns identified. In line with the results in the overall population, semaglutide 2.0 mg provided consistently greater reductions in HbA1c and BW vs 1.0 mg across BL HbA1c and BMI subgroups.

665-P: Efficacy and Safety of Once-Weekly Semaglutide 2.0 mg vs. 1.0 mg by Baseline HbA1c and BMI: SUSTAIN FORTE Subgroup Analyses

Once-weekly subcutaneous semaglutide 2.0 mg showed superior efficacy with similar safety vs. 1.0 mg in 961 participants with type 2 diabetes (HbA1c 8.0-10.0%) after 40 weeks in SUSTAIN FORTE. We assessed the effect of semaglutide 2.0 mg vs. 1.0 mg on HbA1c and body weight (BW) in prespecified baseline (BL) HbA1c (<9.0%, ≥9.0%) and BMI (<35, ≥35 kg/m2) subgroups.Mean BL HbA1c was 8.9% and BMI 34.6 kg/m2. For HbA1c and BW, estimated treatment differences favored semaglutide 2.0 mg vs. 1.0 mg across all BL HbA1c and BMI subgroups. Treatment-by-subgroup interactions were nonsignificant (HbA1c, p=0.55 and p=0.41; BW, p=0.40 and p=0.13; Figure A-D). Greater mean HbA1c reductions were observed for both doses in the higher vs. lower BL HbA1c subgroup (Figure A). Conversely, greater mean BW reductions were observed for both doses in the lower vs. higher BL HbA1c subgroup (Figure C). Similar mean HbA1c reductions were observed across BL BMI subgroups (Figure B), while greater mean BW reductions were observed for both doses in the higher vs. lower BL BMI subgroup Figure D). Overall, the incidence of adverse events was similar for both doses and across BL HbA1c and BMI subgroups with no new safety concerns identified.In line with the results in the overall population, semaglutide 2.0 mg provided consistently greater reductions in HbA1c and BW vs. 1.0 mg across BL HbA1c and BMI subgroups.View largeDownload slideView largeDownload slide DisclosureJ. B. Buse: Consultant; Self; Cirius Therapeutics, CSL Behring, Fortress Biotch, Mellitus Health, Moderna, Pendulum Therapeutics, Praetego Inc., Stability Health, Zealand Pharma A/S, Other Relationship; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk, vTv Therapeutics, Research Support; Self; NovaTarg Therapeutics, Novo Nordisk, Sanofi, Tolerion, Inc., vTv Therapeutics, Stock/Shareholder; Self; Mellitus Health, Pendulum Therapeutics, PhaseBio Pharmaceuticals, Inc., Stability Health. J. P. Frias: Consultant; Self; 89bio, Inc., Altimmune, Axcella Health Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk, Pfizer Inc., Sanofi, Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, CymaBay Therapeutics, Eli Lilly and Company, Intercept Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Madrigal Pharmaceuticals, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Pfizer Inc., Sanofi, Speaker’s Bureau; Self; Merck & Co., Inc., Sanofi. P. Auerbach: Employee; Self; Novo Nordisk A/S. H. S. Bajaj: Other Relationship; Self; Eli Lilly and Company, Novo Nordisk, Research Support; Self; Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., Kowa Pharmaceuticals America, Inc., Merck & Co., Inc., Sanofi, Tricida, Inc. Y. Fukushima: None. I. Lingvay: Advisory Panel; Self; Bayer Healthcare Pharmaceuticals Inc., Lilly Diabetes, Consultant; Self; TARGET PharmaSolutions, Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk, Pfizer Inc., Zealand Pharma A/S, Research Support; Self; Mylan N. V., Sanofi. S. Macura: Employee; Self; Novo Nordisk A/S. A. L. Søndergaard: Stock/Shareholder; Self; Novo Nordisk A/S, Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. T. Tankova: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Medtronic, Novartis AG, Sanofi, Wörwag Pharma, Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes, Merck Sharp & Dohme Corp., Novo Nordisk Pharma Ltd., Sandoz International GmbH, Sanofi, Servier Laboratories. N. Tentolouris: None.FundingNovo Nordisk A/S

672-P: The Real-World Observational Prospective Study of Health Outcomes with Dulaglutide and Liraglutide in Type 2 Diabetes Patients (TROPHIES): Twelve-Month Data Analysis

TROPHIES is a 24-month, prospective, non-comparative, observational study in adult patients with T2D initiating their first injectable glucose-lowering treatment with once-weekly dulaglutide (DU) or once-daily liraglutide (LIRA) in France, Germany, and Italy. Patient disposition, clinical characteristics, and GLP-1 RA persistence at 12-months are described for 1112 DU and 1039 LIRA patients eligible for analysis. The 12-month mean HbA1c (SD) change from baseline was -1.2 (1.4)% (baseline, 8.2 (1.2)%) in the DU cohort and -1.2 (1.5)% (baseline, 8.3 (1.3)%) in the LIRA cohort. At 12-months, 35% DU and 29% LIRA patients reached their individualized HbA1c target set by the physician at baseline. The mean weight change for DU and LIRA from baseline to 12-months was -3.3 (5.5) kg and -3.4 (6.1) kg, respectively. Probability (95%CI) of GLP-1 RA persistence was high in both DU and LIRA cohorts at 12-months: DU, 0.88 (0.86-0.90); LIRA 0.82 (0.79-0.84); (Figure).In summary, these data show similar HbA1c and weight reductions for DU and LIRA at 12-months with good persistence, consistent with known clinical trial results.View largeDownload slideView largeDownload slide DisclosureB. Guerci: Advisory Panel; Self; Abbott, Novartis Pharmaceuticals Corporation, Board Member; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk, Sanofi, Consultant; Self; AstraZeneca, Intercept Pharmaceuticals, Inc. M. O. Orsini federici: Employee; Self; Eli Lilly and Company. F. Giorgino: Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes, Novo Nordisk, Roche Diabetes Care, Sanofi, Research Support; Self; Lilly Diabetes, Roche Diabetes Care. L. Garcia: Employee; Self; Eli Lilly and Company. K. Boye: Employee; Self; Eli Lilly and Company, Employee; Spouse/Partner; Eli Lilly and Company. K. Norrbacka: Employee; Self; Oy Eli Lilly Finland Ab, Stock/Shareholder; Self; Eli Lilly and Company. H. Sapin: Employee; Self; Eli Lilly and Company. E. Heitmann: Employee; Self; Lilly Diabetes. J. Lebrec: Consultant; Self; Eli Lilly and Company. A. Dib: Advisory Panel; Spouse/Partner; Boehringer Ingelheim Pharmaceuticals, Inc., Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company.

Real-World Use of Insulin Glargine U100 and U300 in Insulin-Naïve Patients with Type 2 Diabetes Mellitus: DosInGlar Study.

IntroductionIn the EDITION clinical trial programme, patients with type 2 diabetes mellitus (T2DM) receiving insulin glargine (IGlar) U300 required 10–15% more insulin than those receiving IGlar U100. This study sought to determine whether this difference was apparent in real-world practice.MethodsIn this observational, retrospective cohort study, electronic medical records in the Big-Pac® database (Real Life Data) relating to adult insulin-naïve patients with T2DM who initiated IGlar U100 or U300 treatment in Spain in 2016–2017 and remained on treatment for 18 months were selected. IGlar U100- and U300-treated patients were matched 1:1 (propensity score matching). The primary analysis compared changes from baseline in mean daily IGlar dose (U and U/kg) at 6 (± 2), 12 (± 2) and 18 (± 2) months between cohorts (paired t tests). Changes in glycated haemoglobin (HbA1c) and weight were analysed descriptively.ResultsThe IGlar U100 and U300 cohorts included 556 matched pairs (46.9% female) with the following mean (standard deviation) values at baseline, respectively: age 63.6 (12.8) versus 63.7 (11.9) years; years since diagnosis 9.5 (1.4) versus 9.5 (1.3); HbA1c 8.8 (1.3) versus 8.7 (1.5) %; weight 84.6 (16.9) versus 84.7 (17.1) kg. Mean IGlar dose at baseline was 0.19 U/kg/day (both cohorts). Patients receiving IGlar U300 showed a greater increase from baseline in IGlar dose at 6, 12 and 18 months [mean dose (U/kg/day) 5.1%, 10.3% and 12.8% greater, respectively, in IGlar U300-treated patients]. Mean HbA1c was 8.1% in both cohorts at 18 months. Mean (SD) weight at 18 months with IGlar U100 and IGlar300 was 86.8 (17.0) kg and 85.0 (17.1) kg, respectively.ConclusionIn real-world practice, insulin dose was significantly higher in IGlar U300-treated than U100-treated patients at 6, 12 and 18 months, with similar reductions in HbA1c. At equal IGlar price/unit in Spain, the increased dose requirements of IGlar U300 would result in higher costs.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-021-01773-z.

Efficacy and safety of LY2963016 insulin glargine versus insulin glargine (Lantus) in Chinese adults with type 2 diabetes: A phase III, randomized, open-label, controlled trial.

AimTo compare the efficacy and safety of LY2963016 insulin glargine (LY IGlar) with insulin glargine (Lantus; IGlar) combined with oral antihyperglycaemic medications (OAMs) in insulin‐naive Chinese patients with type 2 diabetes (T2D).Materials and MethodsIn this phase III, open‐label trial, adult patients with T2D receiving two or more OAMs at stable doses for 12 weeks or longer, with HbA1c of 7.0% or more and 11.0% or less, were randomized (2:1) to receive once‐daily LY IGlar or IGlar for 24 weeks. The primary outcome was non‐inferiority of LY IGlar to IGlar at a 0.4% margin, and a gated secondary endpoint tested non‐inferiority of IGlar to LY IGlar (−0.4% margin), assessed by least squares (LS) mean change in HbA1c from baseline to 24 weeks.ResultsPatients assigned to LY IGlar (n = 359) and IGlar (n = 177) achieved similar and significant reductions (p < .001) in HbA1c from baseline. LY IGlar was non‐inferior to IGlar for change in HbA1c from baseline to week 24 (−1.27% vs. −1.23%; LS mean difference: −0.05% [95% CI, −0.19% to 0.10%]) and IGlar was non‐inferior to LY IGlar. The study therefore showed equivalence of LY IGlar and IGlar for the primary endpoint. At week 24, there were no between‐group differences in the proportion of patients achieving an HbA1c of less than 7.0%, seven‐point self‐measured blood glucose, insulin dose or weight gain. Adverse events, allergic reactions, hypoglycaemia and insulin antibodies were similar in the two groups.ConclusionsOnce‐daily LY IGlar and IGlar, combined with OAMs, provide effective and similar glycaemic control with comparable safety profiles in insulin‐naive Chinese patients with T2D.