bluuebunny/crossref_metadata_2025 huggingface dataset:
1051-P: Improving Glycemic Outcomes in T1D Using an Automated Decision Support Recommender System: Evaluation In Silico and Compared with Physician Recommendations
Authors: TYLER NICHOLE S. , MOSQUERA-LOPEZ CLARA M. , WILSON LEAH M. , RESALAT NAVID , DODIER ROBERT , BRANIGAN DEBORAH , GABO VIRGINIA , YOUSSEF JOSEPH EL , CASTLE JESSICA R. , JACOBS PETER G.
Published: June 2019

Most people with type 1 diabetes use multiple daily injections (MDI) therapy, yet there are limited decision support tools for this population. We designed and evaluated a K-nearest-neighbors decision support system (KNN-DSS) that utilizes continuous glucose data and Bluetooth-enabled insulin dose capture devices to detect problematic glycemic patterns and recommend insulin dosage adjustments to maximize time-in-range (70-180 mg/dL) and minimize hypoglycemia (< 70 mg/dL). The KNN-DSS employs distance and class weighting, a carb ratio aggressiveness algorithm, and an expert-opinion quality-control algorithm to filter erroneous recommendations.

The KNN-DSS was evaluated both in silico and in comparison with physician recommendations. In silico virtual patients (n=30) of varying weight, total daily insulin requirement, insulin sensitivity, and compliance with care were evaluated in a 1-year study whereby they received weekly recommendations. The primary outcome measures were the % time-in-range and % time-in-hypoglycemia. The KNN-DSS was further evaluated for accuracy compared with endocrinologist recommendations collected during a 4-week, at-home clinical trial of CGM-augmented MDI therapy (N = 12, 7 female, 30.8 ± 5 years, 79.6 ± 18.9 kg), and compared using Dice similarity coefficient.

In silico, the KNN-DSS improved time-in-range from 66.8% at baseline to 81.0% (21% relative improvement, p <0.005), and reduced time-in-hypoglycemia from 3.14% at baseline to 1.37% (56% relative improvement, p < 0.005) after one year. Compared to endocrinologists, the KNN-DSS recommendations to real-world patients were within acceptable agreement 75% of the time, 6% contraindicated, and 19% whereby KNN-DSS gave a recommendation when the physician gave no recommendation. KNN-DSS improves glycemic outcomes in silico and exhibits acceptable agreement with physician recommendations. Future clinical studies are planned.

Disclosure

N.S. Tyler: None. C.M. Mosquera-Lopez: None. L.M. Wilson: None. N. Resalat: None. R. Dodier: None. D. Branigan: None. V. Gabo: None. J. El Youssef: None. J.R. Castle: Advisory Panel; Self; Novo Nordisk Inc., Zealand Pharma A/S. Consultant; Self; Dexcom, Inc. Research Support; Self; Dexcom, Inc., Xeris Pharmaceuticals, Inc. P.G. Jacobs: Stock/Shareholder; Self; Pacific Diabetes Technologies.

Funding

The Leona M. and Harry B. Helmsley Charitable Trust (2018PG-T1D001)
1057-P: Performance Enhancement of Fully Closed-Loop Insulin Delivery in Type 2 Diabetes by Automatized Bolusing
Authors: ORNETZEDER CLEMENS , REITERER FLORIAN , CHRISTENSEN MERETE B. , NØRGAARD KIRSTEN , DEL RE LUIGI
Published: June 2019

Introduction: Systems for fully closed loop insulin delivery (AP) lack bolus administration at mealtimes, resulting in higher postprandial glucose excursions than hybrid APs. In order to mitigate this disadvantage an algorithm can be used for the automatic delivery of bolus insulin (BI) in case a meal is recognized from the CGM recordings. The use of a full AP with automatic BI delivery is tested in simulations against a hybrid AP with manual bolusing and a full AP without any meal boluses.

Methods: The simulation approach used for this purpose combines data from real clinical trials with mathematical models. A cohort of five insulin-treated T2D patients is used to test the feasibility of the different AP concepts.

Results: Using a full AP with automatized bolusing more patients were able to achieve their therapeutic goals (defined here as HbA1c < 7%) than for the case without meal boluses (4/5 vs. 1/5). Time in hypoglycemia is at a comparably low level for both considered full AP versions (0.9±1.5% vs. 0.4±0.8%), whereas time in hyperglycemia (21.9±5.4% vs. 30.9±7.9%) and HbA1c (6.8±0.3% vs. 7.4±0.5%) is significantly reduced for the case with automatized bolusing. However, as can be expected, a hybrid AP approach with manual bolusing does result in even better glycemic outcomes.

Conclusion: Results show that automatized bolusing does indeed lead to enhanced glycemic outcomes in full AP systems.

Disclosure

C. Ornetzeder: None. F. Reiterer: None. M.B. Christensen: None. K. Nørgaard: Advisory Panel; Self; Abbott, Medtronic, Novo Nordisk A/S. Speaker's Bureau; Self; Bayer US, Medtronic, Roche Diabetes Care, Rubin Medical, Sanofi, Zealand Pharma A/S. Stock/Shareholder; Self; Novo Nordisk A/S. L. del Re: None.
1062-P: Insulin Requirement Profiles of Short-Term Continuous Subcutaneous Insulin Infusion Therapy in Chinese Patients with Type 2 Diabetic Nephropathy
Authors: LIN SHUO , ZHANG KUIXING , LI PING , FANG KE , ZENG LONGYI
Published: June 2019

Our study aims to explore the insulin requirement profiles of short-term intensive continuous subcutaneous insulin infusion (CSII) in Chinese patients with type 2 diabetic nephropathy. CSII was applied in 68 patients with diagnosed type 2 diabetic nephropathy (using Paradigm 712, Medtronic). Daily insulin doses were titrated and recorded to achieve and maintain target glucose levels (FPG<7.0mmol/L and 2hPBG<10mmol/L) for 8-12 days. The patients were 60.0±13.1 years in age, 45.6% female (n=31), mean duration 11.3±7.2 years, BMI 25.0±3.3 kg/m2, mean HbA1c of 9.4±2.5%, median urinary microalbumin/creatine 78.2 mg/g (inter-quartile range 36.0-274.6 mg/g), and median creatine 72.0umol/l (inter-quartile range 53.5-110.8 umol/l). At the first day after the glycemic targets were achieved (Day1), total daily insulin dose (TDD), total basal and premeal dose were 44.3±17.5 IU (0.67±0.27 IU/kg), 19.6±9.2 IU (0.30±0.14 IU/kg) and 24.7±10.3 IU (0.37±0.15 IU/kg), respectively. At the end of CSII therapy, TDD was 43.7±18.1 IU (0.66±0.28 IU/kg). Total basal dose and total pre-meal dose were 19.2±9.0 IU (0.29±0.14 IU/kg, P>0.05 compared with Day1) and 24.5±11.2 (0.37±0.17 IU/kg, P > 0.05 compared with Day1), respectively. The ratio of basal insulin dose to TDD were 44%±11% at Day1 and 44%±12% at the end, respectively. The ratio of basal insulin dose to TDD at day 1 were 45%±11% and 40%±9% in subjects with eGFR >60ml/min (n=48) or eGFR <60ml/min (n=20), respectively (P=0.11). The ratio of basal insulin dose to TDD at day 1 were 49%±18% and 39%±12% in subjects with eGFR 60-90 ml/min or eGFR <30ml/min, respectively (P=0.041). The TDD at Day1 were 45.8±12.4 IU in subjects with 40.9±26.1 IU in subjects with eGFR >60ml/min or eGFR <60ml/min, respectively (P>0.05). These results suggested the ratio of basal insulin dose to TDD might be decreased while eGFR declined in patients with type 2 diabetic nephropathy.

Disclosure

S. Lin: None. K. Zhang: None. P. Li: None. K. Fang: None. L. Zeng: None.

Funding

Science and Technology Planning Project of Guangdong Province (2017A020215026); Medical Scientific Research Foundation of Guangdong Province (A2017314)
1072-P: Comparison of the Efficacy between a Needle-Free Insulin Injector and Conventional Insulin Pen in Glycemic Control in Insulin-treated Type 2 Diabetic Patients in China
Authors: GAO LEILI , JI LINONG , GUO LIXIN , WANG YANGANG , CHEN LIMING , WANG GUIXIA , RAN XINGWU , XU XIANGJIN , SUN ZILIN , MA ZHONGSHU , SHAN ZHONGYAN
Published: June 2019

Background: Needle free insulin injector is designed for diabetics with needle anxiety or fear of injection pain resulting in reluctance to initiate insulin therapy when it is actually indicated. This device has faster absorption of insulin and has better glycemic control compared with conventional insulin pen. But the efficacy of glycemic control was only evaluated by postprandial blood glucose or the area under blood glucose curve.

Objective: To investigate the efficacy of needle free insulin injector by HbA1c level compared with conventional insulin pen in insulin treated type 2 diabetic patients in multicenter, prospective, randomized, open-label trial.

Methods: A total of 427 patients with HbA1c levels of ≥7.5% to ≤11% while receiving basal or premixed insulin were randomized 1:1 to needle free insulin injector group (NFII) or conventional insulin pen group (CIP). The primary efficacy endpoint was change of HbA1c leve after 16 weeks treatment. The change of 7-point blood glucose profile and the percentage of patients with HbA1c level <7% were also observed.

Results: Of the 412 patients (mean age 57.92±10.03ys; BMI 28.33±2.96kg/m2; HbA1c 8.25±1.00%) who completed the study, 206 patients were insulin treated via NFII and 206 via CIP. There were no significant differences in baseline characteristics between the two groups (P> 0.05). The HbA1c reduction 0.55% (95% CI: -0.71, -0.39) at week 16 in NFII group was non-inferior and statistically superior compared with that of 0.26% (95% CI: -0.42, -0.11) in CIP group. There were no differences between two groups in the percentages of patients achieving the HbA1c target (27.32% vs. 24.26%; P> 0.05) or in the change of 7-point blood glucose profile at week 16.

Conclusions: The device non-inferior and statistically superior efficacy in glycemic control compared to conventional insulin pen in insulin-treated type 2 diabetic Patients in China.

Disclosure

L. Gao: None. L. Ji: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Eli Lilly and Company, Merck KGaA, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi, Takeda Pharmaceutical Company Limited. Research Support; Self; AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Roche Pharma, Sanofi. L. Guo: None. Y. Wang: None. L. Chen: Research Support; Self; Becton, Dickinson and Company. G. Wang: None. X. Ran: None. X. Xu: None. Z. Sun: None. Z. Ma: None. Z. Shan: None.
1073-P: A Study of Flat and Circadian Insulin infusion Rates in Continuous Subcutaneous Insulin Infusion (CSII) in Adults with Type 1 Diabetes (FIRST1D)
Authors: RILSTONE SIAN K. , REDDY MONIKA , OLIVER NICK
Published: June 2019

Background and Aims: Initiation of continuous subcutaneous insulin therapy (CSII) in people with type 1 diabetes (T1D) requires conversion of a basal insulin dose to a continuous infusion regimen. There are limited data to guide the optimal insulin profile to rapidly achieve target glucose and minimize healthcare professional input. The aim of this study was to compare circadian and flat insulin infusion rates in CSII naïve adults with T1D.

Materials and Methods: Adults with T1D who met the NICE criteria for CSII were recruited. Participants were randomized to either a circadian profile or a flat basal rate, each calculated from the total daily dose. Basal rate testing was undertaken on days 7, 14 and 28 of CSII and basal rates were adjusted according to protocol. The primary outcome was the between group difference in absolute change in insulin basal rate over 24 hours following 3 rounds of basal testing. Secondary outcomes included the number of basal rate changes and the time blocks. Data from blinded continuous glucose monitoring were also collected.

Results: Seventeen participants (mean age 33.3 (SD 8.6)) were recruited. There was no significant difference in absolute change in insulin basal rates between the two groups (p=0.85) from baseline to the end of the study. In the circadian basal group, there was significant variation in the number of changes made across the 24 one-hour blocks with the most changes early in the morning (p=0.005). In the flat basal group, there were no significant variation in the number of changes made across the time points (p=0.09).

Conclusion: Commencing CSII with a flat or circadian profile does not impact on the magnitude of basal rate insulin changes during optimization in the first 28 days. The circadian profile requires changes at specific time points, while the flat basal rate requires even optimization throughout the 24-hour period. Further development of the circadian profile early in the morning may address this.

Disclosure

S.K. Rilstone: None. M. Reddy: None. N. Oliver: Advisory Panel; Self; Roche Diabetes Care. Research Support; Self; Dexcom, Inc., Roche Diabetes Care. Speaker's Bureau; Self; Dexcom, Inc., Sanofi.

Funding

Roche
1074-P: Performance of an Artificial Pancreas System in Swine during Severe Hypo- and Hyperglycemic Provocations
Authors: DEJOURNETT JEREMY , DEJOURNETT LEON
Published: June 2019

Introduction: Intensive care unit (ICU) patients develop stress induced insulin resistance causing hyperglycemia, large glucose variability and hypoglycemia, all of which increase mortality rates. Tight glucose control (TGC) in the ICU is challenging, and usually significantly increases the risk for treatment induced hypoglycemia. The only way to achieve safe TGC will be through use of an artificial pancreas (AP) system. Our goal with the present study was to assess the safety and performance of an AP system, composed of the EIRUS (Getinge AB) continuous glucose monitor (CGM) and novel artificial intelligence-based (AI-based) glucose control software, in a swine model using unannounced hypo- and hyperglycemia challenges.

Methods: Fourteen piglets (6 control, 8 treated) underwent sequential unannounced (to the AP system) hypoglycemic and hyperglycemic challenges with 3 U of insulin aspart and a large glucose infusion over the course of 5 hours. In the control animals an ICU physician used every 30-minute arterial blood glucose values to maintain control to a range of 4.4 - 9 mmol/L through use of 20% dextrose for hypoglycemia and insulin aspart for hyperglycemia. In the treated group the AP system attempted to maintain blood glucose control to a range of 4.4 - 6.6 mmol/L in a fully autonomous mode.

Results: Five of six control animals and none of eight treated animals experienced severe hypoglycemia (< 2.22 mmol/L). The area under the curve 3.5 mmol/L was 28.9 (21.1 - 54.2) for control and 4.8 (3.1 - 5.2) for the treated animals. The percent time in range 4.4 - 6.6 mmol/L was 32.8 (32.4 - 47.1) for the control and 55.4 (52.9 - 59.4) for the treated animals. After the start of the experiment the control animals underwent 4 (3-5) human interventions to maintain control whereas the treated animals underwent none. Data are median (25-75).

Conclusions The AP system abolished severe hypoglycemia and outperformed the ICU physician both in avoiding hypoglycemic excursions and maximizing time in range.

Disclosure

J. DeJournett: Employee; Self; Ideal Medical Technologies. L. DeJournett: Stock/Shareholder; Self; Ideal Medical Technologies.
1076-P: Increased Time-in-Range (TIR) Observed after Introduction of a Connected Insulin Pen
Authors: ADOLFSSON PETER , HARTVIG NIELS V. , KAAS ANNE , NYGÅRD KNUDSEN NIKOLINE , MÅRDBY ANN-CHARLOTTE , HELLMAN JARL
Published: June 2019

The capture and visualization of insulin injection patterns together with blood glucose data has potential to improve dialogue between patients and HCPs about dose, injection time and missed injections. This may improve glycemic control. The objective of this non-interventional study was to investigate how a connected insulin pen (NovoPen®6) influences glycemic control in patients with T1DM in a real-world setting. Patients were recruited from 12 Swedish diabetes clinics. At baseline patients received a NovoPen®6, which logs time of injection and number of insulin units. HCP visits were conducted according to clinical practice. At each visit, pen data were downloaded at the clinic to support patient-HCP dialogue. Adults with T1DM (n=94) using NovoPen®6 for basal and/or bolus and CGM were included in the analyses. The effect on TIR was based on a 14-day interval after each visit using a linear mixed-effects model. A significant increase in TIR from baseline to after ≥5 HCP visits (median time in study 6 months) of 1.9 hours/day (9.2 to 11.1 hours/day) was found (p=0.0009). Accordingly, significant reduction in time spent in hyper- and L2 hypoglycemia (-1.8 hours/day p=0.003; -0.3 hours/day p=0.005) was observed. There was no change in time in L1 hypoglycemia (p=0.181). These real-world findings in patients with T1DM highlight the potential benefit on glycemic control when accurate connected pen data contribute to patient-HCP dialogue.

Disclosure

P. Adolfsson: Advisory Panel; Self; Eli Lilly and Company, Novo Nordisk A/S, Roche Pharma. Employee; Self; Region Halland. Research Support; Self; Region Halland. N.V. Hartvig: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. A. Kaas: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. N. Nygård Knudsen: Employee; Self; Novo Nordisk A/S. A. Mårdby: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. J. Hellman: Advisory Panel; Self; Abbott, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk A/S, Sanofi.

Funding

Novo Nordisk A/S
1081-P: Incidence of Hypoglycemia within 24 Hours of Hospital Admission in Patients Using Insulin Pumps
Authors: HALSTROM AMANDA , MOLEDINA IRAM , PERAGALLO-DITTKO VIRGINIA , ANCONA KARENA , ISLAM SHAHIDUL , ROTHBERGER GARY , KLEK STANISLAW P.
Published: June 2019

Background: Insulin pumps have become an increasingly popular alternative to traditional forms of insulin therapy for patients with type 1 and type 2 diabetes. Despite the increasing prevalence of insulin pumps, the safety of their use in hospitalized patients has not been well studied. In this study, we aim to determine the incidence of hypoglycemia in hospitalized patients using insulin pumps within 24 hours of admission prior to any adjustments of their insulin pump settings.

Methods: This is a retrospective analysis of adult patients with diabetes (type 1 and 2) who used insulin pumps during the first 24 hours of admission to NYU Winthrop Hospital and did not make any adjustments to the pump settings during that time. Patients <18 years of age, pregnant patients and those who were electively admitted for surgery were excluded from this study. Demographic data and clinical data were collected, which included the presence of steroid use, total daily dose of basal insulin, creatinine level, HbA1c level, and serum and capillary blood glucose values. Hypoglycemia was defined as blood glucose <70mg/dL and severe hypoglycemia was defined as blood glucose <40mg/dL.

Results: Two hundred and fifty-seven patients were included in the study. The mean age was 56 years, 152 (59%) patients were male, and 130 (55%) had type 1 diabetes. The mean hemoglobin A1c was 7.9%. A total of 2097 finger stick blood glucose values were obtained, and 1290 (62%) were <180 mg/dL. There were 88 episodes of hypoglycemia (4.1% of all finger stick blood glucose values) and 2 episodes of severe hypoglycemia (0.1% of all finger stick blood glucose values).

Conclusion: Insulin pumps are safe and effective for the treatment of both type 1 and type 2 diabetes in the first 24 hours of hospital admission.

Disclosure

A. Halstrom: None. I. Moledina: None. V. Peragallo-Dittko: None. K. Ancona: None. S. Islam: None. G. Rothberger: None. S.P. Klek: None.
109-LB: Potent Weight Loss Mechanism by a Novel Long-Acting Glucagon Analog, HM15136, in Animal Models
Authors: LEE JONG SUK , KIM JUNG KUK , KIM JINYOUNG , PARK EUNJIN , LEE SANG HYUN , BAE SUNGMIN , CHOI IN YOUNG
Published: June 2019

Clinical use of glucagon (GCG) has long been limited to the acute treatment of insulin-induced hypoglycemia. However, recent studies demonstrate that GCG also plays a central role in the regulation of lipid metabolism and body weight, suggesting its potential application in managing obesity. Consistent with this new concept, we observed that chronic treatment with the novel long-acting glucagon analog, HM15136, led to body weight loss (BWL) with minimized effects on blood glucose control (BG). To further explore the therapeutic potential of HM15136 in obesity, the present study compared the BWL effects of HM15136 with various incretin therapeutics targeting obesity, and investigated the potential BWL mechanism in vivo. In DIO mice, HM15136 showed greater BWL effects than GLP-1 agonists such as liraglutide, dulaglutide, and semaglutide. Of note, more BWL was also confirmed even under pair-feeding conditions with liraglutide, indicating appetite-independent BWL by HM15136. As to the postulated mechanism, HM15136 increased the expression of PGC-1α and UCP-1 in white adipose tissue (WAT). Consistent with these results, HM15136 enhanced the energy expenditure in DIO mice. Taken together with the reduced respiratory exchange ratio, these results suggested that HM15136 may induce WAT browning a mechanism through which energy expenditure can increase. We then evaluated a flexible dosing regimen for HM15136, and similar BWL effects were confirmed for human weekly- and monthly-mimetic dosing groups. Most interestingly, BWL achieved by HM15136, but not liraglutide, was maintained after 4 weeks without drug treatment. No abnormal changes in BG and HbA1c were observed. Based on these results, we propose that the novel long-acting glucagon analog, HM15136, could be a potential therapeutic option for the management of obesity. Human studies are needed to confirm these therapeutic benefits and to evaluate the safety of HM15136.

Disclosure

J. Lee: None. J. Kim: None. J. Kim: None. E. Park: None. S. Lee: Employee; Self; Hanmi Pharm. Co., Ltd. S. Bae: None. I. Choi: Employee; Self; Hanmi Pharm. Co., Ltd.
1093-P: The Prevalence and Clinical Characteristics of Insulin Antibody Formation in Patients with Type 2 Diabetes Treated with Insulin
Authors: ZHOU LINGLI , LUO YINGYING , CAI XIAOLING , HAN XUEYAO , JI LINONG
Published: June 2019

Objective: To investigate the prevalence of insulin antibody (IA) formation among patients with type 2 diabetes receiving insulin therapy and their clinical characteristics.

Research Design and Methods: IA formation was evaluated using a polyethylene glycol (PEG) precipitation assay in 726 patients with type 2 diabetes (396 on insulin therapy and 330 who had never used insulin), and 87 nondiabetes controls. Risk factors for IA formation were analyzed by logistic regression.

Results: IAs were detected in 154 of the 396 type 2 diabetes patients on insulin therapy (38.9%). IA formation was independently associated with fasting insulin concentration or insulin/C-peptide ratio, IA titers and the incidence of hypoglycemia. The area under ROC curve for fasting insulin/C-peptide ratio in predicting IA formation was 0.830, indicating good diagnostic performance. The insulin/C-peptide ratio cutoff value of 9.3 uIU/ng(Figure 1)showed a sensitivity of 78% and specificity of 73% for predicting the presence of IAs.

Conclusions: Our findings suggest that IA formation should be suspected if insulin-treated diabetes patients experience frequent hypoglycemia, and that the fasting insulin/C-peptide ratio can be used to detect IA formation. Our study thus provides the foundation for developing more clinically convenient methods for identifying IAs in insulin-treated type 2 diabetes patients.

Disclosure

L. Zhou: None. Y. Luo: None. X. Cai: None. X. Han: None. L. Ji: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Eli Lilly and Company, Merck KGaA, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi, Takeda Pharmaceutical Company Limited. Research Support; Self; AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Roche Pharma, Sanofi.
1096-P: Determining the Optimal Fasting Glucose Target for Patients with Type 2 Diabetes: Results of the FPG Goal Trial
Authors: YANG WENYING , MA JIANHUA , YUAN GUOYUE , LI LING , ZHANG MIN , LU YIBING , YE XINHUA , SONG WEIHONG , LIU MING , WU JUN , CHEN RIQIU , CUI NAN , LI YUNGUANG , ZHANG XIA , YANG JIN-KUI
Published: June 2019

Background: The optimal fasting glucose target to achieve an HbA1c <7.0% in patients with T2D remains controversial.

Methods: This open-label RCT conducted in China (ClinicalTrials.gov, NCT02545842), randomly assigned (1:3:3) adults (aged 18-65 years) with uncontrolled T2D (HbA1c >7% to ≤10.5%) on 1-3 OADs to 1 of 3 self-monitored fasting blood glucose (FBG) target groups: ≤5.6 mmol/L (Group 1), ≤6.1 mmol/L (Group 2), or ≤7.0 mmol/L (Group 3). The lowest of 3 consecutive FBG values was used for insulin glargine 100 U/ml titration decisions. Primary endpoint was the proportion of patients achieving an HbA1c <7.0% at 24 weeks.

Results: Of 947 patients randomized (Group 1, n=136; Group 2, n=405; Group 3, n=406), 914 were analyzed (mean age 53.9 years; 56.2% male; mean HbA1c 8.59%), and 885 (93.4%) completed the study. At 24 weeks, 44.4%, 46.1%, and 37.7% of patients achieved an HbA1c <7.0% in Group 1, 2, and 3, respectively (p=0.017; Group 2 vs. Group 3). Significantly more patients in Group 2 than in Group 3 (45.0% vs. 36.5%; p=0.014) achieved an HbA1c <7% without hypoglycemia (BG ≤3.0 mmol/L). Confirmed hypoglycemia (BG ≤3.9 mmol/L) was significantly more frequent in Group 1 vs. Group 3 (38.9 vs. 23.3%, p<0.001) but not in Group 2 vs. Group 3 (27.5% vs. 23.3%; p=0.177). Based on the lowest of 3 consecutive FBG values, the proportions of patients achieving an FBG within their target range at 24 weeks were 70.1%, 67.6% and 79.0% in Groups 1, 2 and 3, respectively. However, based on laboratory fasting plasma glucose (FPG) measurements, these proportions were 31.9%, 39.5% and 47.7%. After re-dividing by actual FPG level at 24 weeks, significantly more patients with an FPG ≤5.6 mmol/L (68.7%, p<0.001) and 5.6< FPG ≤6.1mmol/L (58.2%, p=0.013) achieved an HbA1c <7.0% than those with 6.1< FPG ≤7.0 mmol/L (43.6%).

Conclusions: The optimal FBG target for the majority of patients with T2D appears to be ≤6.1 mmol/L. However, for patients at lower risk of hypoglycemia, an FBG target of ≤5.6 mmol/L may be appropriate.

Disclosure

W. Yang: Speaker's Bureau; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck & Co., Inc., Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi, Servier. J. Ma: None. G. Yuan: None. L. Li: None. M. Zhang: None. Y. Lu: None. X. Ye: Speaker's Bureau; Self; AstraZeneca, Merck Sharp & Dohme Corp., Novo Nordisk Inc. W. Song: None. M. Liu: None. J. Wu: None. R. Chen: None. N. Cui: Employee; Self; Sanofi. Y. Li: Employee; Self; Sanofi. X. Zhang: None. J. Yang: None.
1101-P: The Effect of Smoke on Short-Term Insulin Intensive Therapy for Male Patients with New Diagnosis Type 2 Diabetes
Authors: WAN XUESI , HUANG ZHIMIN , LIU LIEHUA , LI YANBING
Published: June 2019

Our previous study showed that short-term intensive insulin therapies (SIIT) can improve insulin resistance by eliminating glucolipotoxicity and induce remission in newly diagnosed T2DM patients. It's interesting that smokers seem to recover worse than non-smokers. The purpose of this study is to clarify the effect of smoking on T2DM remission from SIIT. 103 male patients (aged 47±10 ys, HbA1C 11.2±2.1%, 59 smokers) after 2-week SIIT therapy were studied. At the 1-year follow-up, the remission rate was much lower in the smokers than non-smokers (36/59 vs. 35/44). Though their insulin secretion and HbA1C were similar at the end of therapy, the smokers have statistically higher TG and worse HOMA-IR. These results indicated that smoking might affect the remission rate mainly by the weaker improved metabolism of lipids.

Disclosure

X. Wan: None. Z. Huang: None. L. Liu: None. Y. Li: None.
1110-P: Use of IDegLira Is Associated with High Persistency Rates Up to 12 Months (M) and Improved A1C after 6M in Swedish Clinical Practice
Authors: ELIASSON BJORN , EKELUND JAN , SVENSSON ANN-MARIE , MIFTARAJ MERVETE , MÅRDBY ANN-CHARLOTTE , ROCHA FERNANDES JOAO DIOGO DA
Published: June 2019

This retrospective study examines outcomes associated with use of IDegLira - a fixed-ratio insulin degludec/liraglutide combination - in a large real-world cohort of patients with type 2 diabetes in Sweden. Data were obtained from the Swedish National Diabetes Registry on patients who initiated IDegLira (index date) until the end of 2017 (or 30 June/1 January 2017 for 6M/12M for persistency analyses). Persistency at 6M was defined as ≥1 more IDegLira withdrawal within 6M of index date, and 12M persistency was ≥1 more withdrawal in M6-12. Clinical variables were assessed at baseline (closest measurement to index date in previous 12M) and 6M ± 45 days after IDegLira initiation. Mean daily IDegLira dose was calculated from volume withdrawn during defined time periods of ≥6M. Baseline characteristics for overall cohort (N=3000) are in Table. At 6 and 12M, 2281/2432 (94%) and 1482/1760 (84%) patients were persistent, respectively. In persistent patients, least squares mean [95% CI] change in A1C and body mass index was -0.9% [-1.0; -0.8] and -0.3 kg/m2 [-0.5; -0.2] at 6M, respectively and mean daily IDegLira dose was 32-35 U at all 180-day periods assessed (Table). After 6M, IDegLira use in Sweden is associated with improved A1C and no clinically significant change in BMI at a moderate mean daily insulin dose, and 84% were persistent at 12M.

Disclosure

B. Eliasson: Advisory Panel; Self; Amgen Inc., AstraZeneca, Merck Sharp & Dohme Corp. Speaker's Bureau; Self; Boehringer Ingelheim International GmbH. Other Relationship; Self; Eli Lilly and Company, Novo Nordisk A/S, Sanofi. J. Ekelund: Employee; Spouse/Partner; AstraZeneca. Stock/Shareholder; Spouse/Partner; AstraZeneca. A. Svensson: None. M. Miftaraj: None. A. Mårdby: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. J. da Rocha Fernandes: Employee; Self; Novo Nordisk A/S.

Funding

Novo Nordisk A/S
1123-P: Reduction of Mortality and Major Adverse Cardiovascular Events (MACE) in Men with Hypogonadism and Type 2 Diabetes (T2DM) Receiving Long-Term Treatment with Injectable Testosterone Undecanoate (TU): Ten-Year Data from a Urological Registry Study
Authors: HAIDER KARIM S. , HAIDER AHMAD , SAAD FARID
Published: June 2019

Background: Potential cardiovascular risk as a result of testosterone therapy is controversially discussed.

Methods: In a registry of 823 men with hypogonadism, 324 men (39%) had T2DM. 152 received TU 1000 mg/12 weeks (T-group), 172 opted against treatment (CTRL). Changes over time between groups were compared by mixed effects model for repeated measures with random effect for intercept and fixed effects for time, group and their interaction, and adjusted for age, weight, WC, fasting glucose, blood pressure, lipids and quality of life to account for baseline differences between the two groups.

Results: Mean age: T-group: 61.8±5.1, CTRL: 63.6±4.9 years.

Follow-up: T-group (CTRL): mean: 7.4 (8.3), median: 8 (9) years. T-group: 54 patients (35.5%) had had a previous cardiovascular disease (CVD, defined as myocardial infarction, stroke, or diagnosis of coronary artery disease). CTRL: 68 patients (39.5%) (p=0.4574). 64 men (42.1%) had been smokers at baseline (T-group), 66 (38.4%) in CTRL (p=0.4939). Most classical risk factors were significantly higher at baseline in the T-group compared to CTRL: BMI (36.4±4.5 vs. 33.3±5.3 kg/m²), systolic blood pressure (162.6±13.1 vs. 145.4±14.7 mmHg), diastolic blood pressure (97.2±10.7 vs. 84.7 vs. 10.3 mmHg), LDL (4.6±0.7 vs. 4.0±1.4 mmol/L), with no significant difference in HDL. Glycemic control was worse in the T-group: HbA1c 9.1±1.2 vs. 7.8±0.7%, HOMA-IR 10.2±2.1 vs. 7.5±1.3. Mortality: during the entire observation time, 12 patients (7.8%) died in the T-group and 43 (25%) in CTRL (p<0.0001). MACE: in the T-group, there were no myocardial infarctions or strokes. In CTRL, 49 myocardial infarctions (28.5%) and 42 strokes (24.4%) occurred.

Conclusions: Mortality, myocardial infarctions and strokes were reduced in men with hypogonadism and T2DM receiving long-term testosterone therapy.

Disclosure

K.S. Haider: Speaker's Bureau; Self; Bayer AG. A. Haider: Research Support; Self; Bayer AG. Speaker's Bureau; Self; Bayer AG. F. Saad: Employee; Self; Bayer AG. Stock/Shareholder; Self; AbbVie Inc., Amgen Inc., Bayer AG.

Funding

Bayer AG
1125-P: Effect of High Dose vs. Conventional Dose Angiotensin Receptor Blockers in 175 T2DM with Microalbuminuria on CV (NT-ProBNP) and Renal Biomarkers
Authors: GUPTA VISHAL , TELI VAISHALI
Published: June 2019

Methodology: 175 T2DM patients on regular follow-up with microalbuminuria (eUACR >30), aged <75 years, irrespective of their A1c, on standard glucose, lipid and blood pressure lowering therapy using ARB (valsartan or telmisartan) were followed-up for 2 years. 2 groups were identified, Control group (Cn) on conventional dose CDARB’s and case (Cs) group on high dose HDARB’s. Renal (creatinine, eGFR, UACR) and CV (SBP, DBP, BMI, Lipid profile, hs-CRP) parameters were evaluated in both groups at 3-6 monthly intervals. NT-ProBNP was evaluated in both groups at the end of the study. Patients with history of any revascularization, IHD or hospitalization in last 1 year, eGFR <45, hyperkalemia >5.5 were excluded. Data was analysed using PSPP version 1.0.1 and represented as Mean (Standard deviation), independent sample t-test and paired t test was used. P-value of 0.05 was considered significant.

Results: Both groups Cs and Cn were well matched for treatment and clinical characteristics except DBP, higher mean in Cs (81 ±11.39) vs. Cn (76.80 ± 11.58, p 0.025). Mean CDARB dose in Cn group (Telmisartan 55.15mg (SD ± 24) and valsartan 115.76 (SD ±47.82) vs. Cs group HDARB (telmisartan 222.22mg (SD±49.22) and valsartan 334.58 (SD±77.81). Within the cases there was a significant reduction seen in A1c, SBP, hs-CRP, lipid parameters and UACR over 2 years. Within the control group there was a significant reduction seen in A1c, lipid parameters, UACR. At the end of the follow-up there was significant reduction seen in Cs in LDL (Cs 51.34 ±19.73 vs. Cn 63.82 ± 25.97, p-0.005) and non-HDL (Cs 66.77 ±34.74 vs. Cn 51.70 ±44.56, p-0.023). There was a trend towards reduction in hs-CRP in Cs (Cs 1.74 ± 1.92 vs. Cn 2.53 ± 3.70, p-0.066). The NT-ProBNP remained high in both groups (142.86 ±232.32 vs. 192.61 ±260.93, p-0.203).

Conclusion: HDARB may be associated with better vascular protection as shown by improvements in LDL, non-HDL and hs-CRP compared to CDARB in T2DM with microalbuminuria.

Disclosure

V. Gupta: None. V. Teli: None.
1128-P: SGLT2 Inhibition Increases Serum Copeptin in Adults with Type 1 Diabetes (T1D)
Authors: LYTVYN YULIYA , BJORNSTAD PETTER , KATZ ALEXANDRA , SINGH SUNITA K. , GODOY LUCAS C. , CHUNG LINH T. , VINOVSKIS CARISSA L. , PERKINS BRUCE A. , CHERNEY DAVID
Published: June 2019

Elevated copeptin, a stable surrogate of vasopressin, is recognized to be higher in T1D and predicts diabetic kidney disease and cardiovascular (CV) mortality. Vasopressin increases renal oxygen consumption through enhanced sodium reabsorption and may result in renal hypoxia. Given the natriuretic and cardiorenal protective effects of SGLT2 inhibition (SGLT2i) in clinical trials, our aim was to: 1) examine serum copeptin in adults with T1D after SGLT2i with empagliflozin (EMPA) for 8-weeks; and 2) determine the relationship between copeptin and metabolic, renal and system hemodynamic parameters.

In this post hoc, exploratory analysis, serum copeptin concentration, glomerular filtration rate (GFR) by inulin clearance, effective renal plasma flow (ERPF) by PAH clearance, vascular stiffness parameters, plasma RAAS markers, HbA1c, 24-hour urine volume and sodium and glucose excretion were measured in 40 participants with T1D (24.1±5.0 years, HbA1c 8.0±0.9%) during eu- and hyperglycemia at baseline and after 25 mg of daily EMPA.

Copeptin concentrations increased under both eu- and hyperglycemic conditions (4.0±2.1 to 5.1±6.0 pmol/L, p=0.005 and p<0.0001, respectively) in response to EMPA. Higher copeptin concentrations were associated with higher HbA1c (β±SE: 0.97±0.30, p=0.003), lower 24h urine volume (β±SE: -3.08±1.05, p=0.006) and fractional sodium excretion (β±SE: -8.30±2.73, p=0.004), after correcting for age, sex, systolic blood pressure (SBP), and HbA1c. There were no significant relationships between copeptin and RAAS markers, vascular stiffness, renal or systemic hemodynamic parameters in fully adjusted models.

SGLT2i increased serum copeptin concentrations, which positively correlated with HbA1c and inversely with urine output and natriuresis, but not with renal or system hemodynamic parameters. Further work is required to evaluate the clinical implications of elevated copeptin with SGLT2i; whether it is simply a marker of diuresis or may contribute to CV disease long-term.

Disclosure

Y. Lytvyn: None. P. Bjornstad: Advisory Panel; Self; Horizon, XORTX. Consultant; Self; Bayer US, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company. A. Katz: None. S.K. Singh: None. L.C. Godoy: None. L.T. Chung: None. C.L. Vinovskis: None. B.A. Perkins: Advisory Panel; Self; Abbott, Boehringer Ingelheim International GmbH, Boehringer Ingelheim International GmbH, Insulet Corporation. Research Support; Self; Boehringer Ingelheim International GmbH. Other Relationship; Self; Abbott, Boehringer Ingelheim International GmbH, Lilly Diabetes, Medtronic, Novo Nordisk Inc., Sanofi. D. Cherney: Other Relationship; Self; AbbVie Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, Prometic Life Sciences Inc., Sanofi.
113-LB: Effects of Liraglutide and Empagliflozin Add-On to Insulin Therapy in Patients with Type 2 Diabetes: ELLENA-IT, a Randomized Controlled Study
Authors: NAKAGUCHI HIROTATSU , KONDO YOSHINOBU , TERAUCHI YASUO
Published: June 2019

Liraglutide (Lira) and empagliflozin (Empa) have been reported to suppress cardiovascular events in large-scale clinical trials. However, reports of their long-term combined use with insulin therapy or direct comparisons of both drugs are limited. This open-label, parallel-group, randomized controlled trial aimed to compare the effects of Lira and Empa used in combination with insulin therapy in patients with type 2 diabetes (T2D). Adult outpatients with T2D undergoing stable insulin therapy with HbA1c level of 7.0%-9.5% were eligible for participation. Subjects received 0.9 mg/day Lira or 10 mg/day Empa for 24 weeks. The primary endpoint was the change in HbA1c levels from baseline to week 24. Body composition was assessed using the dual energy X-ray absorptiometry method (UMIN-CTR 000027614). Overall, 66 insulin-treated patients with T2D were randomized to receive Lira or Empa; 57 patients completed 24 weeks of weekly administration of Lira (n = 29) or Empa (n = 28). HbA1c and glycated albumin (GA) levels were lower in the Lira group than in the Empa group (HbA1c, Lira, −1.23 ± 0.85% vs. Empa, −0.32 ± 0.68%, p < 0.001; GA, Lira, −4.3 ± 3.1% vs. Empa, −2.2 ± 2.9%, p = 0.01). There was no difference between the two groups in terms of change in body weight (∆BW: Lira, −1.4 ± 1.9 kg vs. Empa, −1.4 ± 1.9 kg, p = 0.97) or in body fat mass/lean tissue mass. There was no difference between the groups in terms of change in urinary albumin excretion [∆UAE (median, IQR): Lira, −6.2 (−63.5, −10.1) mg/g-creatinine vs. Empa, −20.4 (−69.7, −2.0) mg/g-creatinine, p = 0.28]. There was no significant difference in the frequency of hypoglycemia between the groups over 24 weeks (p = 0.46).

In conclusion, the addition of Lira to ongoing insulin therapy significantly reduced HbA1c and GA levels to a larger extent than the addition of Empa in patients with inadequately controlled T2D.

Disclosure

H. Nakaguchi: None. Y. Kondo: None. Y. Terauchi: Advisory Panel; Self; AstraZeneca, Daiichi Sankyo Company, Limited, Eli Lilly and Company, Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk A/S, Sanofi. Research Support; Self; Daiichi Sankyo Company, Limited, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Sanofi, Shionogi & Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd. Speaker's Bureau; Self; Astellas Pharma Inc., AstraZeneca, Bayer Yakuhin, Ltd., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho, Shionogi & Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd.
1136-P: Chemical Pancreatectomy as a Revolutionary Therapy for Chronic Pancreatitis and Prevention of Type 3C Diabetes
Authors: SALEH MOHAMED , KALSI RANJEET S. , GITTES GEORGE
Published: June 2019

Background: Chronic pancreatitis (CP) is a debilitating disease that leads to chronic pain, pancreatic endocrine and exocrine dysfunction. CP affects > 140,000 in the U.S. and millions worldwide. Type 3C diabetes, a brittle form of diabetes, constitutes 9% of those hospitalized with diabetes. Total pancreatectomy with auto islet cell transplantation (TPIAT) may treat CP and preserve endocrine function, but it is major surgery, the outcomes are variable, and islet yield is questionable.

Methods: An intrapancreatic infusion of 150 µL of acetic acid or sham was performed on 8-week old CD1 mice. Serum enzymes, GTT, GSIS, behavioral pain assessment, histology and IHC were done 4 weeks and 8 weeks after surgery.

Results: There was no significant difference between the two groups in serum amylase and lipase, GTT, GSIS, and pain parameters. IHC revealed negative staining for amylase and normal insulin staining while histology showed intact islets, replacement of acinar cells with fat cells, and no signs of inflammation.

Conclusion: This procedure may be a revolutionary non-invasive therapy for CP able to relieve pain and preserve endocrine function. It may rescue ailing islets by removing the source of injury (exocrine tissue) without major surgery. The loss of the exocrine tissue is trivial because it is not functional, and most patients with CP require enzyme replacement therapy.

Disclosure

M. Saleh: None. R.S. Kalsi: None. G. Gittes: None.
1145-P: Acarbose-Induced Glucagon-Like Peptide-1 Secretion Contributes to the Glucose-Lowering Effect of Acarbose
Authors: DALSGAARD NIELS B. , GASBJERG LÆRKE S. , HANSEN LAURA S. , HANSEN NINA L. , STENSEN SIGNE , HARTMANN BOLETTE , HOLST JENS J. , VILSBØLL TINA , KNOP FILIP K.
Published: June 2019

The glucose-lowering alpha-glucosidase inhibitor acarbose, is believed to act by delaying digestion and absorption of dietary carbohydrates. It has been shown that acarbose increases circulating glucagon-like peptide 1 (GLP-1). Using the GLP-1 receptor antagonist exendin(9-39)NH2, we investigated the effect of acarbose-induced GLP-1 secretion on postprandial glucose metabolism in patients with type 2 diabetes (T2D). In a double-blinded, placebo-controlled, randomized, cross-over study, 15 participants with metformin-treated T2D (age 57-85 years, BMI 23.6-34.6 kg/m2, HbA1c 40-74 mmol/mol (5.8-8.9%)) were subjected to two 14-day treatment periods with acarbose (uptitrated to 100 mg TID) and placebo treatment, respectively, with an interposed 6-week wash-out period. At the end of each treatment period, we performed two randomized 4-hour mixed meal tests (including acetaminophen for evaluation of gastric emptying) with concomitant infusion of exendin(9-39)NH2 (1000 pmol/kg/min for 20 min followed by 450 pmol/kg/min for 240 min) and saline, respectively. Acarbose treatment lowered fasting plasma glucose (P<0.0001) and postprandial plasma glucose excursions (P<0.0001) compared to placebo. Furthermore, acarbose almost doubled the postprandial GLP-1 response (P=0.0032), reduced postprandial glucose-dependent insulinotropic polypeptide (P<0.0001) and delayed gastric emptying (P=0.0395). No absolute difference was seen in exendin(9-39)NH2-induced postprandial plasma glucose changes between treatment periods (P=0.54), but relative to postprandial glucose tolerance during exendin(9-39)NH2 infusions, the change (i.e., contribution of GLP-1) was significantly higher during acarbose (56±26%) compared to placebo treatment (37±15%) (P=0.042). We conclude that acarbose treatment robustly stimulates GLP-1 secretion in patients with T2D and that acarbose-induced GLP-1 secretion contributes to the glucose-lowering effect of acarbose.

Disclosure

N.B. Dalsgaard: None. L.S. Gasbjerg: Stock/Shareholder; Self; Antag Therapeutics. L.S. Hansen: None. N.L. Hansen: None. S. Stensen: None. B. Hartmann: None. J.J. Holst: Advisory Panel; Self; Novo Nordisk A/S. T. Vilsbøll: None. F.K. Knop: Advisory Panel; Self; AstraZeneca, MedImmune, Merck Sharp & Dohme Corp., Mundipharma, Novo Nordisk A/S, Sanofi. Consultant; Self; Amgen Inc., Carmot Therapeutics, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Novo Nordisk A/S. Speaker's Bureau; Self; AstraZeneca, MedImmune, Merck Sharp & Dohme Corp., Mundipharma, Norgine, Novo Nordisk A/S.
1149-P: A1C Goal Attainment after Metformin (MET) Uptitration With and Without Sitagliptin (SITA): Impact of Baseline and Target A1C
Authors: CRUTCHLOW MICHAEL , LIN JIANXIN , LAM RAYMOND L. , O'NEILL EDWARD A. , KAUFMAN KEITH D. , ENGEL SAMUEL S.
Published: June 2019

MET is generally recommended as the initial AHA for T2D, but many patients do not achieve glycemic goal at an initial, sub-maximal dose (500-1000 mg/day) and should intensify therapy. Typically, MET dose is first maximized, followed by addition of a second AHA as needed. This sequential approach can result in prolonged exposure to hyperglycemia. Therefore, addition of a second AHA during MET up-titration may be appropriate for some patients. In a recent study, patients with T2D not at glycemic goal on 1000 mg/day MET initiated SITA or PBO while increasing MET dose to 2000 mg/day. Study participants had entry A1C ≥7.5% (mean = 8.6%) and baseline characteristics were balanced. SITA provided greater improvement in glycemic control and likelihood of A1C goal attainment, with similar safety and tolerability compared to PBO. In a post hoc analysis characterizing the impact of baseline A1C, A1C goal, and treatment on A1C goal attainment, the likelihood of A1C goal attainment decreased as distance to goal at baseline increased (Table). Compared to MET increase alone, MET increase + SITA was generally more effective in achieving glycemic targets across a range of goals and baseline A1C. These results suggest that the distance to A1C goal should be considered throughout the process of MET up-titration to inform AHA intensification strategy, including the potential benefit of early SITA initiation.

Disclosure

M. Crutchlow: Consultant; Spouse/Partner; Crinetics, Novartis Pharmaceuticals Corporation, ProSciento, Soleno Therapeutics, Zealand Pharma A/S. Employee; Self; Merck & Co., Inc. Research Support; Spouse/Partner; Dexcom, Inc. J. Lin: Employee; Self; Merck & Co., Inc. Stock/Shareholder; Self; Merck & Co., Inc. R.L. Lam: Employee; Self; Merck & Co., Inc. E.A. O'Neill: Employee; Self; Merck & Co., Inc. Stock/Shareholder; Self; Merck & Co., Inc. K.D. Kaufman: Employee; Self; Merck & Co., Inc. Stock/Shareholder; Self; Merck & Co., Inc. S.S. Engel: Employee; Self; Merck & Co., Inc. Stock/Shareholder; Self; Merck & Co., Inc.

Funding

Merck & Co., Inc.