Greater Reduction In HbA1c Research Articles

Effectiveness and Safety of Once-Weekly Semaglutide in Japanese Patients with Type2 Diabetes in Treatment Intensification: A Retrospective Observational Single-Center Study.

IntroductionOnce-weekly (OW) glucagon-like peptide 1 receptor agonist (GLP-1RA) semaglutide has been shown to have a more potent glycated hemoglobin (HbA1c)-lowering effect than other oral hypoglycemic agents and existing GLP-1RAs in global randomized controlled trials. The study aim was to evaluate the safety and effectiveness of OW semaglutide in Japanese patients with type 2 diabetes mellitus (T2DM) in a real-world clinical setting and identify pre- and post-treatment predictors of good response.MethodsWe investigated the change in HbA1c, percentage of patients achieving < 7% HbA1c, and factors contributing to the effect 6 months after OW semaglutide use in Japanese patients with T2DM. We also examined differences in effectiveness between patients with different backgrounds.ResultsAt baseline, the 77 patients had a mean baseline HbA1c of 8.1% ± 1.23%, 74% of the patients were injecting another GLP-1RA, and 42.9% of the patients were being treated with insulin. HbA1c decreased by 0.89% and by 0.66% in the other GLP-1RA users. The rate of achievement of < 7% HbA1c increased from 21% to 43%. There were no differences in effect by age, sex, or body mass index. Higher baseline HbA1c and shorter duration of diabetes were associated with greater HbA1c reduction. OW semaglutide was tolerable for the majority of our study population.ConclusionThis study provided real-world evidence showing that OW semaglutide significantly reduced HbA1c in Japanese patients with T2DM who had inadequate HbA1c control.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-022-01313-0.

Weight loss improves β-cell function independently of dietary carbohydrate restriction in people with type 2 diabetes: A 6-week randomized controlled trial.

BackgroundCarbohydrate restriction may benefit β-cell function and glucose metabolism in type 2 diabetes (T2D) but also leads to weight loss which in itself is beneficial.MethodsIn order to determine the additional effect of carbohydrate restriction in addition to a fixed body weight loss, we randomly assigned 72 adults with T2D and obesity (mean ± SD HbA1c 7.4 ± 0.7%, BMI 33 ± 5 kg/m2) to a carbohydrate-reduced high-protein diet (CRHP; energy percent from carbohydrate/protein/fat: 30/30/40) or an isocaloric conventional diabetes diet (CD; 50/17/33) for 6 weeks. All foods were provided free of charge and total energy intake was tailored individually, so both groups lost 6% of baseline body weight.ResultsDespite significantly greater reductions in HbA1c (mean [95% CI] −1.9 [−3.5, −0.3] mmol/mol) after 6 weeks, the CRHP diet neither improved glucose tolerance, β-cell response to glucose, insulin sensitivity, during a 4-h oral glucose tolerance test, nor basal proinsulin secretion when compared to the CD diet, but increased C-peptide concentration and insulin secretion rate (area under the curve [AUC] and peak) significantly more (~10%, P ≤ 0.03 for all). Furthermore, compared with the CD diet, the CRHP diet borderline increased basal glucagon concentration (16 [−0.1, 34]%, P = 0.05), but decreased glucagon net AUC (−2.0 [−3.4, −0.6] mmol/L ×240 min, P < 0.01), decreased basal triglyceride and total AUC (~20%, P < 0.01 for both), and increased gastric inhibitory polypeptide total AUC (14%, P = 0.01).ConclusionA moderately carbohydrate-restricted diet for 6 weeks decreased HbA1c but did not improve β-cell function or glucose tolerance beyond the effects of weight loss when compared with a conventional diabetes diet in people with T2D.Clinical trials registrationwww.Clinicaltrials.gov, Identifier: NCT02472951.

Predictors of HbA1c reduction and hypoglycemia in type 2 diabetes mellitus individuals switching from premixed to basal insulin: an exploratory analysis of optimization study

Objective To identify population with type 2 diabetes mellitus (T2DM) who are more likely to benefit from switching to basal insulin (BI) treatment from premixed insulin. Methods This secondary analysis included data from a previously published study (Optimization: NCT00693771) which was a single-arm, multicenter, 16 weeks, phase IV study. The analysis included participants with T2DM inadequately controlled with premixed insulin plus oral hypoglycemic drugs (OADs) who switched to BI plus OADs. Results Among the 297 participants included for analysis, subjects with fasting C-peptide (FCP)>1.2 nmol/L group showed a trend for greater reduction in HbA1c [Least square mean difference (LSMD), −0.59; 95% confidence interval (CI), −0.98 to −0.21; p = 0.003] and FPG (LSMD, −1.36; 95% CI, −2.20 to −0.53; p = 0.002) than those with FCP ≤ 0.4 nmol/L. The baseline insulin glargine 100 U/mL (Gla-100) dose increased significantly in 0.4 to ≤ 1.2 nmol/L group with LS mean difference (SE) of 0.16 (0.01) U/kg/day (p = 0.008) compared to FCP ≤ 0.4 nmol/L group. When combined with Diabetes Treatment Satisfaction Questionnaire (DTSQ) score, participants with a C-peptide level of 0.4 to ≤1.2 nmol/L (OR, 4.05; 95% CI, 1.08 to 15.22; p = 0.039) had significantly higher odds of achieving HbA1c <7%. The number of participants experiencing documented symptomatic hypoglycaemia (≤3.9 mmol/L) was higher in the FCP ≤0.4 nmol/L group compared to those in 0.4 to ≤1.2 nmol/L FCP group at any time of the day (31.6 vs. 17.1%) and during night (00:00 ∼ 05:59) (17.1 vs. 7.5%). Conclusion The findings from this study proposed that FCP is an important biomarker to identify T2DM participants who experience improved glucose control without compromising on hypoglycemia levels during switch from premixed insulin to BI. Participants especially with FCP levels >1.2 nmol/L may respond better in terms of HbA1c reduction without increased hypoglycemia risk compared to those with lower FCP values.

High engagement in mobile peer support is associated with better glycemic control in type 1 diabetes: A real-world study.

Peer support for diabetes has become convenient and interactive after the emergence of mobile health (mHealth). We aimed to evaluate the association between engagement in peer support through the mHealth app and glycemic control in type 1 diabetes patients. This retrospective study included adults with type 1 diabetes who had joined the mobile community "TangTangQuan" since May 2018 for at least 1 year. "Like", "comment" and "share" were the major interaction indicators of the mobile community and were used to assess engagement in peer support. The patients were divided into four engagement groups by quartile. The primary outcome was the change in glycosylated hemoglobin (HbA1c ), mean fasting blood glucose (FBG) and postprandial blood glucose (PBG) from baseline to the 12th month. Other outcomes included the change of self-monitoring of blood glucose frequency, hypoglycemia frequency and the proportion of reaching optimal glycemic control. Among the 693 individuals, the HbA1c , mean FBG and PBG improved in the 12th month. Multiple regression analysis showed that higher engagement in peer support was associated with a greater reduction of HbA1c (β = -0.45, P < 0.001) and mean FBG (β = -0.82, P < 0.001). In the subgroup of poor glycemic control, the association between engagement in peer support and glycemic improvement still remained (HbA1c : β = -0.86, P = 0.002; FBG: β = -1.36, P = 0.001). The engagement in mobile peer support was positively correlated with educational level (odds ratio 1.42, P = 0.042), household income (odds ratio 1.43, P = 0.013) and the use of continuous subcutaneous insulin infusion (odds ratio 1.73, P = 0.009). High engagement in mobile peer support was associated with better glycemic control in adults with type 1 diabetes.

Impact of pharmacist participation in the patient care team on value-based health measures.

To evaluate whether pharmacist engagement on the interdisciplinary team leads to improved performance on diabetes-related quality measures. This was a retrospective observational study of patients seen in primary care and specialty clinics from October 2014 to October 2020. Patients were included if they had a visit with a physician, nurse practitioner, physician's assistant, or clinical pharmacist practitioner (CPP) within the study period and had a diagnosis of diabetes. The intervention group included patients with at least one visit with a CPP, while the control group consisted of patients who were exclusively managed by non-CPP providers. The primary outcome of this study was the median change in glycosylated hemoglobin (HbA1c) from baseline to follow-up at 3, 6, and 12 months. The secondary outcome was the probability of achieving the HbA1c targets of <7% and <8% at 3, 6, and 12 months. Patients referred to a CPP had higher HbA1c levels at baseline and were more likely to have concomitant hypertension (P < 0.01). Patients seen by a CPP had 0.31%, 0.41%, and 0.44% greater reductions in HbA1c compared to patients in the control group at 3, 6, and 12 months, respectively (P < 0.01). Patients managed by a CPP were also more likely to achieve the identified HbA1c targets of <7% and <8%. Patients referred to a CPP were more complex, but had greater reductions in HbA1c and were more likely to achieve HbA1c goals included in the organization's quality measures. This study demonstrates the value of pharmacists in improving patient care and their role in supporting an organization's achievement of value-based quality measures.

Metabolic and cardiovascular benefits with combination therapy of SGLT-2 inhibitors and GLP-1 receptor agonists in type 2 diabetes.

Both GLP-1 receptor agonists (GLP-1RA) and SGLT-2 inhibitors (SGLT-2I) are newer classes of anti-diabetic agents that lower HbA1c moderately and decrease body weight and systolic blood pressure (SBP) modestly. Combination therapy with GLP-1RA plus SGLT-2I have shown a greater reduction in HbA1c, body weight, and SBP compared to either agent alone without any significant increase in hypoglycemia or other side effects. Since several agents from each class of these drugs have shown an improvement in cardiovascular (CV) and renal outcomes in their respective cardiovascular outcome trials (CVOT), combination therapy is theoretically expected to have additional CV and renal benefits. In this comprehensive opinion review, we found HbA1c lowering with GLP-1RA plus SGLT-2I to be less than additive compared to the sum of HbA1c lowering with either agent alone, although body weight lowering was nearly additive and the SBP lowering was more than additive. Our additional meta-analysis of CV outcomes with GLP-1RA plus SGLT-2I combination therapy from the pooled data of five CVOT found a similar reduction in three-point major adverse cardiovascular events compared to GLP-1RA or SGLT-2I alone, against placebo. Interestingly, a greater benefit in reduction of heart failure hospitalization with GLP-1RA plus SGLT-2I combination therapy was noted in the pooled meta-analysis of two randomized controlled trials. Future adequately powered trials can confirm whether additional CV or renal benefit is truly exerted by GLP-1RA plus SGLT-2I combination therapy.

Texting Older Sisters to Step to Manage Obesity in Older Black Women: A Feasibility Study

Black women are disproportionately classified as overweight or obese and physically inactive. Social support and culturally relevant and age-appropriate physical active interventions are needed to reduce inactivity and to prevent weight gain among this group. Mobile-health text messages have shown to be an acceptable, feasible and interactive way to promote physical activity among older Black women. This feasibility, 12-week RCT, deployed between August 2020 and December 2020, aimed to determine the feasibility and effectiveness of a mobile health intervention that focused on increasing physical activity behaviors among community-dwelling, older Black women who were age ≥60 years and classified with overweight or obesity. Community-dwelling, older Black women. The intervention group received physical activity promotion text messages daily, whereas the control group received 1 neutral message related to general health information weekly. At baseline and post intervention assessments, researchers obtained HbA1c levels, weight, BMI, waist circumference, and questionnaires related to physical activity. Post-intervention satisfaction was also collected through a survey. The intervention group had an average increase of approximately 700 steps per day more than the control group, lost more waist circumference inches (2.2) than the controls, and averaged more pound loss (2.5) than controls. The control group had a greater HbA1c reduction, whereas the intervention group remained stable. The text messages were 100% readable, and 95% of the women stated the study was motivational. Overall, 12% of participants suggested that future studies should include more in-person social support, and 8.3% said that daily text messages were too much. Findings suggest that a mobile health physical activity intervention that uses self-monitoring techniques in conjunction with motivational cues, is an acceptable delivery method and a promising strategy to increase physical activity behaviors among this population, which is feasible, potentially efficacious, and low cost. NCT04114071.

1138-P: Impact of Continuous Glucose Monitoring (CGM) on Glycemic Control and Acute Complications in Type 2 Diabetes (T2D) in the Veterans Health Administration (VHA)

Use of CGM in T2D is rising rapidly, yet little is known regarding its effects on glucose management in the VHA. We thus identified new CGM users (new CGM sensor prescriptions for T2D on insulin) and non-users (T2D receiving glucose strips) during the years 2015-2020 and used national VHA healthcare data from visit encounters to compare change over 12 months in glucose control and new emergency room (ER) or hospital admissions. Changes in HbA1c and acute admissions were compared by linear mixed models and generalized linear models, respectively. Compared with 36,082 non-users, CGM users (n=16,013) differed in many ways but were well-balanced with overlap weighting from propensity score modeling. CGM users had a greater reduction in HbA1c over 12 months (-0.25%; 95% CI -0.21-0.29, p&amp;lt;0.0001) and a decline in hypoglycemia related ER visits/hospitalizations (OR = 0.78; CI 0.62-0.97) . Among CGM users, those &amp;lt; 65 years old or with initial HbA1c &amp;gt; 8. 4% (median) had greater reductions in HbA1c, while those at higher hypoglycemia risk had reduced hypoglycemia and hyperglycemia related ER visits/hospitalizations and all-cause hospitalizations (Table) . In this large national study in T2D, CGM initiation was linked with better glucose control and reduced ER and/or hospital admissions for hypoglycemia and showed even greater benefits in subsets of CGM users. Disclosure P.Reaven: Research Support; AstraZeneca, Dexcom, Inc. M.Newell: Research Support; Dexcom, Inc. S.Rivas: None. X.Zhou: None. G.J.Norman: Employee; Dexcom, Inc. J.Zhou: Research Support; Dexcom, Inc. Funding DexCom, Inc

850-P: Greater HbA1c Reduction with iGlarLixi vs. Insulin Glargine and Lixisenatide Regardless of Levels at Screening: Subgroup Analysis of the LixiLan-O Asia Pacific Trial

Introduction: LixiLan-O-AP (NCT03798054) showed greater HbA1c improvement with iGlarLixi vs. iGlar or Lixi in Asian Pacific adults with type 2 diabetes (T2D) . This pre-defined analysis assessed iGlarLixi efficacy by HbA1c levels at screening. Methods: Adults (N=878) with suboptimally controlled T2D (HbA1c of 7.5-% or 7-% depending on background oral antihyperglycemic drug [OAD] use) on metformin ± a second OAD were randomized 2:2:1 to iGlarLixi, iGlar or Lixi for 24 weeks. Three screening HbA1c subgroups were defined: &amp;lt;8, 8-&amp;lt;9, ≥9 %. Results: At Week 24, in all HbA1c subgroups, iGlarLixi was associated with greater HbA1c reductions vs. iGlar or Lixi and reached mean HbA1c levels &amp;lt;7 %. iGlarLixi also showed greater 2-h postprandial glucose reductions, and a higher proportion of participants reaching HbA1c &amp;lt;7 % and HbA1c &amp;lt;7 % without weight gain, vs. iGlar or Lixi (Table) . Incidence and rates of documented hypoglycemia ≤70 mg/dL (≤3.9 mmol/L) were similar between iGlarLixi and iGlar in the 8-&amp;lt;9 % and ≥9 % subgroups but were slightly higher with iGlarLixi vs. iGlar in the &amp;lt;8 % subgroup. Conclusions: Regardless of HbA 1c level at screening, iGlarLixi demonstrated better glycemic control vs. iGlar or Lixi, with over 75% of participants achieving the recommended target HbA 1c (&amp;lt;7 %) with iGlarLixi, even those with HbA1c ≥9 % at screening. Disclosure Y. He: None. W. Yang: Other Relationship; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Mer, Merck Sharp &amp; Dohme Corp., Novo Nordisk, Sanofi-Aventis Deutschland GmbH, Servier Laboratories. M. Liu: None. J. Xiao: None. S. Gu: Employee; Sanofi China. L. Chen: None. E. Souhami: Employee; Sanofi. Stock/Shareholder; Sanofi. Funding Funding: Sanofi

523-P: The Results of Virtual Diabetic “Boot Camp”

Introduction: The use of telemedicine exponentially increased during the COVID-pandemic as it provided easier access as well as the provision of safety via social distancing. A 12-week intense telemedicine diabetic Bootcamp was therefore launched for patients with uncontrolled DM intended for high-quality outpatient diabetic care. Methods: Patients with DM seen at ambulatory clinics with HbA1c &amp;gt; 8.0%, were voluntarily enrolled from September 2020 to November 2021. The dietitians and diabetic educators conducted biweekly visits via telehealth. Patient demographics, HbA1c, BMI, BP were compared before and after the intervention. Results: A total of 134 patients were included for analysis and 94 patients (70.2%) completed the visits. Mean HbA1c change was -2.09% ± 2.4%, and HbA1c reduction was similarly observed across different age groups, gender, ethnicity, BMI, referred clinic types [Table 1]. A greater HbA1c reduction in patients who completed the visits was noted although it was not statistically significant. We found a negative correlation between the initial HbA1c and the change of HbA1c (coefficient -0.7709, p&amp;lt;0.0001, r2= 0.3899) . No significant BMI or MAP change was observed. Conclusions: This quality improvement project demonstrated an improvement in HbA1c for all poorly controlled diabetic patients, regardless of patient characteristics. Moreover, higher initial HbA1c was associated with a greater HbA1c reduction. Disclosure Y.Chen: None. U.C.Udeh: None. K.Rajak: None. A.Amirian: None. A.Atrash: None. K.Yari: None. R.Joshi: n/a.

95-OR: Impact of Flash Glucose Monitoring in People with Type 2 Diabetes Inadequately Controlled with Noninsulin Antihyperglycemic Therapy: IMMEDIATE study

Continuous glucose monitoring (CGM) has been shown to improve glycemic outcomes in people with diabetes using insulin therapies. In this multi-site, randomized trial, we studied adults with T2D inadequately controlled with non-insulin antihyperglycemic therapy to evaluate the impact of flash glucose monitoring (FGM) on glycemic and patient-reported outcomes. Participants received FGM + diabetes self-management education (DSME) or matched DSME alone for 16 weeks. Primary outcome was assessed by a blinded CGM device worn at baseline and at outcome. Among 116 participants enrolled (age 58.4 ± 10.1 years; T2D duration 10.1 ± 6.1 years; HbA1c 8.6 ± 1.1%) , the initial 82 completers (41 FGM + DSME, 41 DSME) showed time in range significantly greater in the FGM + DSME arm (76.1 ± 16.9%) compared to DSME arm (64.3 ± 23.2%) (p&amp;lt;0.01) . Time above range was similarly lower in the FGM + DSME arm (21.5 ± 17.8% vs. 31.3 ± 25.6%, p=0.03) . Hypoglycemia was rare in both arms. Glucose monitoring satisfaction scores improved in the FGM + DSME arm only (0.6 ± 0.5 vs. 0.0 ± 0.5, p&amp;lt;0.01) . Change in HbA1c was also greater in the FGM + DSME arm (-0.9 ± 0.9% vs. -0.5 ± 0.9%, p=0.03) . In this interim analysis, FGM users with T2D using non-insulin therapies had significantly greater time in range, satisfaction with glucose monitoring, and a greater reduction in HbA1c. Disclosure R.E.Brown: None. R.Aronson: Consultant; AstraZeneca, Becton, Dickinson and Company, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Gilead Sciences, Inc., HTL Strefa, Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc., Novo Nordisk, Sanofi, Research Support; AstraZeneca, Bausch Health, Canada, Bayer AG, Becton, Dickinson and Company, Boehringer Ingelheim International GmbH, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Janssen Pharmaceuticals, Inc., Kowa Pharmaceuticals America, Inc., Medpace, Novo Nordisk, Sanofi, Tandem Diabetes Care, Inc., Xeris Pharmaceuticals, Inc., Zealand Pharma A/S. Funding Abbott Diabetes Care, Inc.

90-LB: Characterization of Tirzepatide-Treated patients achieving HbA1c &amp;lt;5.7% in the SURPASS 1-4 Trials

Tirzepatide, a novel dual GIP/GLP-1 receptor agonist, demonstrated clinically meaningful improvements in glycemic control with 23% to 62% of patients achieving a normal HbA1c (&amp;lt;5.7%) at the primary endpoints in addition to robust weight loss in adults with type 2 diabetes (T2D) in the SURPASS program. Herein we report results from exploratory analyses to better characterize subsets of tirzepatide-treated patients who achieved different HbA1c targets (&amp;lt;5.7%, 5.7-6.5%, or &amp;gt;6.5%) in the SURPASS 1-4 clinical trials. Baseline characteristics and change from baseline to Week 40 for several efficacy parameters were analyzed for compliant patients (≥75% doses received) , on treatment without rescue medication. Background medication at baseline included metformin only (63%) , combination of oral antidiabetic medication (OAM) (26%) , and no treatment (9%) . Those achieving HbA1c &amp;lt;5.7% were noted to be slightly younger, with shorter duration of T2D, and lower HbA1c at baseline. Furthermore, greater reductions in HbA1c, FSG, BW, BMI, waist circumference, BP, liver enzymes as well as greater improvement in lipid parameters were observed at Week 40 in the HbA1c &amp;lt;5.7% subset (Table) . In conclusion, patients who achieved HbA1c &amp;lt;5.7% showed greater improvements in several biomarkers which may be associated with a reduced risk of long-term cardiometabolic complications. Disclosure J. Rosenstock: Consultant; AstraZeneca, Other Relationship; Applied Therapeutics, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Hanmi Pharm. Co., Ltd., Intarcia Therapeutics, Inc., Novo Nordisk, Oramed Pharmaceuticals, Sanofi, Zealand Pharma A/S, Research Support; Genentech, Inc., Merck &amp; Co., Inc., Metacrine, Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc., vTv Therapeutics. S. Del prato: Advisory Panel; Applied Therapeutics, Eli Lilly and Company, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Sanofi, Consultant; Menarini Group, Research Support; AstraZeneca, Boehringer Ingelheim International GmbH, Speaker’s Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck &amp; Co., Inc., Sanofi, Stock/Shareholder; Novo Nordisk A/S. D. R. Franco: Advisory Panel; Abbott Diabetes, Medtronic, Novo Nordisk, Sanofi, Research Support; Eli Lilly and Company, Speaker’s Bureau; Abbott Diabetes, AstraZeneca, Medtronic, Roche Diabetes Care, Sanofi. L. A. Vázquez: Advisory Panel; Eli Lilly and Company, Research Support; Eli Lilly and Company, Novo Nordisk, Speaker’s Bureau; Eli Lilly and Company, Novo Nordisk, Stock/Shareholder; Eli Lilly and Company. B. Dai: None. G. J. Weerakkody: None. L. Fernandez lando: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. Á. Rodríguez: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. B. Bergman: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. Funding Eli Lilly and Company

743-P: Effect of Once-Weekly TZP on Glycemic Control by Baseline Age in Patient Subpopulations from the SURPASS Trials

Tirzepatide (TZP) is a dual GIP and GLP-1 receptor agonist developed for the treatment of patients with type 2 diabetes (T2D) . The SURPASS clinical trials demonstrated efficacy and safety of TZP 5, 10, and 15 mg, administered once weekly in patients with T2D. This post-hoc analysis of the 5 SURPASS studies was undertaken to assess the efficacy of TZP in subgroups of subjects &amp;lt;65 years and ≥65 years of age. Prespecified subgroup analyses were conducted on the mITT population in all 5 global Phase 3 trials to assess the effects of treatment (TZP vs. placebo or active comparator) on change from baseline in HbA1c. End of treatment HbA1c was evaluated at week 40 or 52. Efficacy estimands, based on data collected from participants on treatment and without rescue medication, were utilized for all analyses reported here. For all 5 studies, analyses of change from baseline in HbA1c at 40 or 52 weeks for both age subgroups were consistent with the primary study results, with the treatment differences favoring all 3 doses of TZP compared with placebo (SURPASS-1 and -5) or active comparator (SURPASS-2, -3 and -4) (Figure) . The most frequent adverse events with TZP were mild-to-moderate, gastrointestinal-related and occurred during the dose-escalation period. In all 5 trials and for subjects in both prespecified age subgroups, TZP demonstrated significantly greater reductions in HbA1c versus placebo or active comparator. Disclosure C.H.Wysham: Research Support; Abbott, Corcept Therapeutics, Eli Lilly and Company, Mylan N.V., Novo Nordisk. S.Tofe: Advisory Panel; Lilly Diabetes, Novo Nordisk, Research Support; Lilly Diabetes, Novo Nordisk, Speaker's Bureau; Lilly Diabetes, Novo Nordisk. H.Sapin: Employee; Eli Lilly and Company. R.Malik: None. L.M.Neff: Employee; Eli Lilly and Company, Research Support; Amryt Pharma Plc, Novo Nordisk, Stock/Shareholder; Eli Lilly and Company.

74-LB: Real-World Glycemic Outcomes in Adult Patients with Type 1 Diabetes Using a Real-Time Continuous Glucose Monitor Compared with an Intermittently Scanned Glucose Monitor and Self-Measured Blood Glucose—A Retrospective Observational Study from the Canadian

Real-time continuous glucose monitoring (rtCGM) and intermittently scanned CGM (isCGM) have both been shown to improve glycemic outcomes in people with T1D. In this retrospective analysis, we propensity score matched CGM naïve adults with T1D who initiated a rtCGM or an isCGM device. HbA1c and CGM metrics were assessed at 6-12-months. Among the 143 matched patients/cohort (age 43 ± 14 years; T1D duration 22 ± 14 years; HbA1c 8.4 ± 1.0%) , rtCGM users had a significantly greater change in HbA1c (-0.7 ± 0.1%) compared to isCGM users (-0.4 ± 0.1%) (p=0.01) . There was a significantly greater change in HbA1c for rtCGM compared to isCGM when baseline HbA1c was &amp;lt;8.5% (difference -0.4% [-0.6 to -0.2], p&amp;lt;0.001) , and in MDI users (difference -0.3% [-0.5 to 0.0], p=0.04) . Compared to isCGM users, rtCGM users had significantly greater time in range (58.3 ± 16.1% vs. 54.5 ± 17.1%, p=0.03) , lower time below range (2.1 ± 2.7% vs. 6.1 ± 5.0%, p&amp;lt;0.001) and lower glycemic variability (Table) . In this real-world analysis of adults with T1D, rtCGM users had a significantly greater reduction in HbA1c at 6-12 months, significantly greater time in range, lower time below range, and lower glycemic variability, compared to a matched cohort of isCGM users. Disclosure R. E. Brown: None. L. Chu: None. G. J. Norman: Employee; Dexcom, Inc. A. Abitbol: Consultant; Amgen Inc., AstraZeneca, Bayer Inc., Boehringer Ingelheim International GmbH, Dexcom, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Novo Nordisk, Other Relationship; AstraZeneca, Bayer Inc., Boehringer Ingelheim International GmbH, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc., Novo Nordisk, Novo Nordisk, Sanofi, Senseonics. Funding DexCom Canada, Co.

537-P: Timing of Moderate-to-Vigorous Physical Activity Is Associated with Improvements in Glycemic Control in Type 2 Diabetes in the Look AHEAD Study

Background: We examined the association of time-of-day bout-related moderate-to-vigorous physical activity (bMVPA) with changes in glycemic measures and use of antidiabetic medications in adults with type 2 diabetes. Methods: Look AHEAD participants were randomly assigned to a lifestyle intervention or a control group, in which the most intensive intervention occurred in Year 1. Among 1755 participants (age, mean ± SD 60 ± 7 years; 57% women) with 7-day waist-worn accelerometry data at Year 1, we grouped them by the timing of bMVPA (≥3 METs in ≥min bouts) : ≥50% of bMVPA during the same time period (Morning, Midday, Afternoon, or Evening; N=191-258) , &amp;lt;50% of bMVPA in any time period (Mixed; N=379) , and ≤1 day with bMVPA per week (Inactive; N=485) . Analyses were adjusted for covariates including socio-demographic factors, randomization arm, and clinics; then further adjusted for weekly bMVPA volume and intensity. Findings: Timing of bMVPA was associated with changes in HbA1c across Year 1 (P=0.01) , independent of weekly bMVPA volume and intensity. Participants in the afternoon group as compared to the inactive group had a greater HbA1c reduction (mean: -0.16%; 95%CI: -0.33% to 0%) . Among non-insulin users the odds of discontinuation vs. maintaining or initiating antidiabetic medications across Year 1 trended to differ between the bMVPA timing groups (P=0.09) , with the afternoon group having the highest odds of discontinuation (OR vs. inactive group: 1.86; 1.14 to 3.02) . Interpretation: Timing of bMVPA may be linked with improvements in glycemic control in adults with type 2 diabetes. While regular physical activity remains to be the cornerstone for blood glucose management in diabetes, our findings suggested that exercise interventions aimed to increase glycemic control in patients with diabetes can be enhanced by engaging in physical activity at specific times of the day. Experimental protocols are needed to test the causality. Disclosure J.Qian: None. R.Middelbeek: Research Support; Novo Nordisk. Q.Xiao: None. M.P.Walkup: None. M.Coday: None. M.Erickson: None. J.L.Unick: None. J.M.Jakicic: Advisory Panel; Spark360, Wondr Health, WW International, Inc. K.Hu: None. F.A.Scheer: None. Funding National Institutes of Health (K99HL148500, DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135, DK56992, R01HL140574, RF1AG059867, RF1AG064312)

1169-P: Circulating MicroRNA-378a-5p and Improvement in Glucose Homeostasis in Response to Weight-Loss Diets: The Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) Trial

Background: MicroRNA-378a (MiR-378a) has been identified as a key regulator of glucose homeostasis and emerging as a promising target for the improvement of glycemic dysregulation including type 2 diabetes. Hypothesis: We assessed associations of circulating miR-378a-5p with improvements in insulin sensitivity and glucose metabolism in a 2-year dietary intervention trial. Methods: Circulating miR-378a-5p levels were measured at baseline and 6 months among 5participants with overweight or obesity. Outcome measurements including fasting glucose, hemoglobin A1c (HbA1c) , fasting insulin, and homeostasis model assessment-of-insulin resistance (HOMA-IR) were assessed at baseline, 6 and 24 months. Results: Higher level of miR-378a-5p was associated with greater fasting glucose (p =0.031) at baseline. Greater decrease in miR-378a-5p was significantly associated with greater improvements in fasting insulin (p =0.012) and HOMA-IR (p =0.017) over 6 months. The initial (6-months) decrease of miR-378a-5p was also significantly related to long-term (24-months) improvements in glucose, insulin, and HOMA-IR (p &amp;lt;0.for all) . Individuals in the lowest tertile group of the baseline miR-378a-5p showed consistently improved fasting insulin and HOMA-IR over 2 years, as compared to those with higher levels of miR-378a-5p (p time*miR-378a-5p =0.015 and 0.007, respectively) . We also found significant interactions between baseline miR-378a-5p and dietary fat in the 6-months change in HbA1c (p = 0.003) ; a lower level of baseline miR-378a-5p showed a greater reduction of HbA1c at 6 months among participants who consumed a low-fat diet. Conclusions: In conclusion, decreased circulating miR-378a-5p levels were related to significant improvements in insulin sensitivity and glucose metabolism in response to dietary weight-loss interventions; and dietary fat intake modified such associations. Disclosure Q.Xue: None. Y.Heianza: None. X.Li: None. H.Deng: None. J.Rood: None. G.Bray: None. F.Sacks: None. L.Qi: None. Funding National Heart, Lung, and Blood Institute (HL071981, HL034594, and HL126024) ;National Institute of Diabetes and Digestive and Kidney Diseases (DK115679, DK091718, and DK100383) ;Fogarty International Center (TW010790)

858-P: Predictors of HbA1c and Weight Response to Sodium–Glucose Cotransporter 2 Inhibitors (SGLT2i) in the Association of British Clinical Diabetologist (ABCD) UK Nationwide Audit

SGLT2i treatment is associated with weight and Hba1c reduction. Previous work has demonstrated clinical predictors of HbA1c and weight reduction with canagliflozin. We aim to analyse predictors of HbA1c and weight change across the class. Methods: People with type 2 diabetes treated with any SGLT2i in the ABCD nationwide audit and available baseline and follow-up data were included. Multiple linear regression model was used to assess independent predictors of Hba1c and weight change. Analysis was performed using Stata 16. Results: Data for 275individuals were included (n=13925 Empagliflozin, n=106Dapagliflozin, n=2976 Canagliflozin) . Baseline (mean±SD) were: age 59.8±10.5 years, baseline Hba1c 9.1±1.6%, weight 97.7±22.2kg, BMI 33.8±6.9kg/m2 and eGFR 81.8±13.6. Median (IQR) diabetes duration was 8.3 years (4.4-12.7) and follow-up time 1.5 years (0.7-2.7) . 61.3% were men. HbA1c fell by 0.87% (95%CI 0.85-0.89; p&amp;lt;0.01) . Factors associated with greater Hba1c reductions include: older age (ß=0.01, p&amp;lt;0.01) ; shorter diabetes duration (ß=-0.01, p&amp;lt;0.01) ; higher HbA1c (ß=0.65, p&amp;lt;0.01) ; greater weight loss (ß=0.02, p&amp;lt;0.01) ; higher alanine aminotransferase (ALT) (ß=0.005, p&amp;lt;0.01) ; higher baseline eGFR (ß=0.002, p&amp;lt;0.01) and canagliflozin or empagliflozin use (vs. dapagliflozin; p&amp;lt;0.05) . Weight fell by 3.0kg (95%CI 2.2-3.8; p&amp;lt;0.01) . Predictors of greater weight reductions include: older age (ß=0.05, p&amp;lt;0.01) ; lower HbA1c (ß=-0.29, p&amp;lt;0.01) ; higher weight (ß=0.03, p&amp;lt;0.01) or BMI (ß=0.17, p&amp;lt;0.01) and larger HbA1c reductions (ß=0.41, p&amp;lt;0.01) . Empagliflozin was superior to dapagliflozin (p=0.01) - no other differences between drugs were noted. Conclusion: Our models demonstrate that baseline characteristics can help predict clinical outcomes with SGLT2i. Individual patient levels factors appear to provide only weak predictive value but may still be useful in assisting therapeutic choices. Disclosure T.S.J. Crabtree: Other Relationship; Abbott Diabetes, Novo Nordisk, Sanofi. A. Gallagher: Other Relationship; Dexcom, Inc. S. Sivappriyan: None. K. Dhatariya: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH. R.P. Raghavan: Speaker's Bureau; Novo Nordisk. Other Relationship; Lilly Diabetes, Novo Nordisk. A. Bickerton: None. J. Elliott: Advisory Panel; Abbott. Speaker's Bureau; Abbott, Dexcom, Inc., Insulet Corporation, Novo Nordisk. G. Rayman: None. I.W. Gallen: None. I.R. Idris: None. R.E. Ryder: None. Funding The ABCD SGLT2 audits are funded by unrestricted grants from Boehringer Ingelheim, AstraZeneca and Napp Pharmaceuticals

Efficacy and safety outcomes of dulaglutide by baseline HbA1c: A post hoc analysis of the REWIND trial.

AimTo assess cardiovascular, glycaemic, weight and safety outcomes of long‐term treatment with dulaglutide 1.5 mg compared with placebo in patients with a baseline HbA1c of less than 7% versus 7% or higher.Materials and MethodsIntention‐to‐treat analyses were performed on REWIND participants with a baseline HbA1c measurement, using Cox proportional hazards regression and mixed model for repeated measures. Subgroup analyses with factors for baseline HbA1c categories and their interaction with treatment group, as well as analyses within the HbA1c subgroups, were conducted. Additionally, sensitivity analyses were performed for baseline HbA1c subgroups of 6.5% or less and more than 6.5%.ResultsOf the 9876 eligible participants, 3921 and 5955 had a baseline HbA1c of less than 7% and 7% or higher, respectively. Mean baseline HbA1c was 6.3% and 8.0% and the mean duration of diabetes was 9.0 and 11.6 years in the respective subgroups. The less than 7% subgroup was slightly older and less frequently insulin‐treated. There was no evidence of a differential dulaglutide treatment effect on body mass index (BMI) reduction, cardiovascular or safety outcomes of interest between the baseline HbA1c subgroups. Treatment‐by‐baseline HbA1c group interaction was significant for HbA1c change from baseline (P < .001), with a greater reduction in the subgroup with higher baseline HbA1c values. Sensitivity analyses by baseline HbA1c subgroups of 6.5% or less and more than 6.5% showed similar results.ConclusionsThe reduced incidence of cardiovascular events, and the reduction in BMI in participants treated with once‐weekly dulaglutide, were independent of the baseline HbA1c level. Conversely, participants with a higher baseline HbA1c level had greater reductions in HbA1c. Dulaglutide has a positive benefit–risk profile and can be considered in patients with comparatively well‐controlled HbA1c levels seeking optimal metabolic control and cardiovascular benefits.

Efficacy and safety benefits of iGlarLixi versus insulin glargine 100 U/mL or lixisenatide in Asian Pacific people with suboptimally controlled type 2 diabetes on oral agents: The LixiLan-O-AP randomized controlled trial.

To compare the efficacy and safety of iGlarLixi with insulin glargine 100 units/mL (iGlar) and lixisenatide (Lixi), in Asian Pacific people with suboptimally controlled type 2 diabetes (T2D) on metformin with or without a second oral antihyperglycaemic drug (OAD). LixiLan-O-AP (NCT03798054) was a 24-week multicentre study in adults (n=878, mean age 56.0 years, mean body mass index 26.0 kg/m2 ) with glycated haemoglobin (HbA1c) levels ≥53 mmol/mol (7%)and ≤97 mmol/mol (11%) on OAD(s), randomized (2:2:1) to open-label once-daily iGlarLixi, iGlar or Lixi while on continued metformin ± sodium-glucose cotransporter-2 inhibitors. The primary efficacy endpoint was change in HbA1c. After 24 weeks, greater reductions in HbA1c from baseline (67 mmol/mol; 8.3%) were seen with iGlarLixi (-21 mmol/mol; -1.9%) compared with iGlar (-16 mmol/mol; -1.4%; P< 0.0001) and Lixi (-10 mmol/mol; -0.9%; P< 0.0001). Greater proportions of participants achieved HbA1c <53 mmol/mol (<7%) with iGlarLixi versus iGlar or Lixi (79%, 60% and 30%, respectively), overall and as composite endpoints including weight and hypoglycaemia. iGlarLixi improved 2-hour postprandial glucose versus iGlar and Lixi and mitigated the weight gain seen with iGlar (least squares mean difference -1.1 kg; P< 0.0001). Documented ≤3.9 mmol/L (≤70 mg/dL) hypoglycaemia was similar between iGlarLixi and iGlar (both 3.38 events per participant-year). The incidence rates of nausea and vomiting were lower with iGlarLixi (14% and 6%) than Lixi (21% and 11%). iGlarLixi achieved significant HbA1c reductions, to near-normoglycaemic levels, compared with iGlar or Lixi, with no meaningful additional risk of hypoglycaemia and mitigated body weight gain versus iGlar, with fewer gastrointestinal adverse events versus Lixi. iGlarLixi with specifically adapted ratios may provide an efficacious and well-tolerated treatment option for Asian Pacific people with T2D.

Uptake and impact of the English National Health Service digital diabetes prevention programme: observational study

Introduction‘Healthier You’, the National Health Service (NHS) diabetes prevention programme (DPP) offers adults in England at high risk of type 2 diabetes (T2DM) an evidence-based behavioral intervention to prevent or...