bluuebunny/crossref_metadata_2025_split huggingface dataset:
Continuous Glucose Monitoring Guided Assessment of Concentrated U200 r-DNA Human Premix 30/70 Insulin
Authors: THACKER HEMANT , KESAVADEV JOTHYDEV , SINGH GURSIMRAN , SHUKLA KIRTI , PUPPALWAR GAURAV , SHRIMANKER RUPAL 
Published: June 2018

Objective: With increasing longevity, obesity and late insulin initiation being common in type 2 diabetes mellitus (T2DM), concentrated insulin formulations could evolve as a choice in a subgroup of these subjects. Globally, 30% of T2DM use more than 60 units of insulin daily. U200 (r-DNA Human Insulin Premix 30/70 200IU/mL) insulin has been developed to provide sustained glucose-lowering effect and enhanced compliance without increasing the risk of hypoglycaemia. This study was conducted to assess the efficacy and safety of U200 insulin in terms of 24-hour glucose profiling using Continuous Glucose Monitoring (CGM) in T2DM.
Methods: Prospective, single-arm, open-label, multi-centre study evaluating glycaemic profile in 60 adults with T2DM administered with U200 was undertaken using CGM (iPro2, Medtronic USA) for 7 days. The endpoints assessed were time spent within acceptable glycaemic range, mean amplitude of glucose excursions (MAGE), and the duration and frequency of hypo/hyper-glycaemic periods.
Results: Mean age of subjects was 55.47 ± 9.68 (26-70) years. Mean blood glucose level was 151±23.93 (105.73-231.69) mg/dl. Blood glucose levels were within the normal limits (70-150 mg/dL) for 62.35% of time. Average numbers of hyperglycaemic and hypoglycaemic episodes observed were 2.64 and 0.22 with mean duration of 165.16 and 27.35 minutes respectively. MAGE was 77.24±22.50 (37.47-153.00) mg/dl. Medication adherence rate was 100% with no adverse event other than minor hypoglycemia reported.
Discussion and Conclusion: CGM provides 24-hour profiling of glycometabolic control and identifies fluctuations. U-200 premixed insulin demonstrated low intraday variability as measured by MAGE of 77.24 mg/dl and patients spending 62.35% of time within normal glucose limits, allowing for a more constant action with less frequent hypoglycaemic or hyperglycaemic excursions. U200 human premix insulin is effective, safe and well tolerated in T2DM patients.

Disclosure
H. Thacker: Research Support; Self; Wockhardt LTD. J. Kesavadev: Advisory Panel; Self; Novo Nordisk India Private Limited. Speaker's Bureau; Self; Novo Nordisk India Private Limited. Advisory Panel; Self; Medtronic. Speaker's Bureau; Self; Medtronic. Advisory Panel; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Research Support; Self; MSD. Speaker's Bureau; Self; MSD. Advisory Panel; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca. G. Singh: Employee; Self; Wockhardt LTD. K. Shukla: Employee; Self; Wockhardt Ltd. G. Puppalwar: Employee; Self; Wockhardt Limited, India. R. Shrimanker: Research Support; Self; Wockhardt LTD.
Treatment Patterns in Patients with Type 2 Diabetes Treated with Human Regular U-500 Insulin—A Retrospective Claims Database Analysis
Authors: CHEN JIELING , HE XUANYAO , KAO CHRISTI Y. , JACKSON JEFFREY A. 
Published: June 2018

Human regular U-500 insulin (U-500R) is highly concentrated with both basal and prandial activity. It can be used as insulin monotherapy. This study sought to provide a better understanding of treatment patterns in a real-world environment for patients treated with U-500R.
Patients with type 2 diabetes initiating U-500R between 2010 and 2013 (N=1582) were selected from Truven Health MarketScan® database. The study had 3 periods: pre-index (12 month before initiation), post-index (12 month after initiation or until U-500R discontinuation), and follow-up (12 month after post-index). U-500R treatment patterns, medication possession ratio (MPR), and persistence with its contributing baseline factors were examined. The resumption of U-500R was studied during follow-up (i.e., after a gap ≥ 60 days between ends of supply from one fill to the next).
During post-index, 74.1% of patients had U-500R claims that did not overlap with other insulins. Only 7.6% had continuous U-500R claims overlapping ≥ 60 days with continuous claims of other insulins. The median U-500R average daily dose was 333 units. Among 12patients with more than one U-500R fill, 54.39% had MPR ≥80% and 26.08% patients between 60% and 80%. Within one year, 849 patients discontinued U-500R. Median time to discontinuation was 264 days. Patients 45 to 75 years old, treated with more types of insulins, or with rapid acting insulin use during pre-index were less likely to have a U-500R treatment gap (P &lt;0.05). During follow-up, 602 (70.9%) of patients resumed U-500R. The median time from end of post-index to U-500R restart was 135 days. Out of the 733 patients with U-500R use beyond one year, 286 patients discontinued U-500R in the second year and 447 continued U-500R beyond two years.
The study suggests that U-500R is commonly used as insulin monotherapy. The observed adherence/persistence could be the result of the simplicity of U-500R regimen, which might benefit high-dose insulin-treated patients.

Disclosure
J. Chen: None. X. He: None. C.Y. Kao: None. J.A. Jackson: Other Relationship; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company.
Once-Weekly Dulaglutide (DU) and Canagliflozin (CAN) Combination Therapy in Obese T2 Diabetes (T2D) Patients—One Year Real-World Evidence from India
Authors: NIGAM ANANT 
Published: June 2018

Objective: To assess the effects of addition of a combination of GLP-1 receptor agonist (GLP-1RA), injection DU 1.5 mg weekly and SGLT2 inhibitor (SGLT2i), CAN 100mg/day in T2 D obese Asian Indian patients sub-optimally controlled on metformin and other agents [sulfonylurea (SU) 71%, insulin 29%].
Methods: Impact of DU and CAN on HbA1c (A1c), weight (wt.), systolic blood pressure (SBP), lipids and dose of previous antidiabetic agents at week 16, 32 and 52 was analyzed retrospectively.
Results: Fifty-five patients (31M/24F, age 51±5.8 y, wt. 92.6±3.4 kg, BMI 31.1±2.1kg/m2, SBP 142.4±3.9mmHg, eGFR 62± 5mL/minutes/1.73m2, with 8.4±3.3 years duration of diabetes) met the inclusion criteria. In 71% subjects, A1c decreased by 1.6% [8.5±0.4 to 7.1±0.2, P&lt;0.0001] at week 16 and dropped to 6.8±0.3 (P=0.0002) in 18% (week 32) but rose by 0.26% (P=0.0056) in 11% (week 40-52). At week 16, wt. was - 4.1 kg (92.6±3.4 to 88.5±3.6, P&lt;0.0001). By week 32, 68% lost another 3.3±0.7 kg (P&lt;0.0001) while 10% regained 1.1±0.6 kg (P=0.077). A drop in SBP of 4.1±0.8 mmHg (P&lt;0.0001) was seen in 74.5% patients and 53% of these needed reduction in doses. A decrease in triglyceride (189.6±8.1 to 168.4±6.9 mg/dL, P&lt;0.0001) and LDL-cholesterol (107.5±4.7 to 104.2±4.9 mg/dl, P=0.0004) occurred. At week 16, 50% required reduction in insulin dose and 15% stoppage. Increase in basal insulin dose/addition of prandial insulin was needed in 5% (week 39-52). By week 16, SU dose had to be halved in 56% and discontinued in others because of minor episodes of hypoglycemia. With CAN, genital and urinary tract infections were seen in 5.9% (2 F/1M) and 3.6% respectively. None had to stop therapy. With DU, nausea (18.1%), vomiting (14.5%) and diarrhea (7.2%) occurred but none had to stop therapy.
Conclusion: Combination Therapy of GLP-1 RA and SGLT2i in obese T2D patients provides statistically significant and durable glycemic control, with favorable effects on weight, BP and lipids and is also well tolerated.

Disclosure
A. Nigam: None.
Glycemic Management as the Primary Determinant of One-Year Mortality after CABG
Authors: HELLER LUCAS , ZUPA MARGARET , PERREIAH PETER L. , HARSHA RAO R. 
Published: June 2018

Factors linked to mortality after coronary artery bypass graft (CABG) include post-operative hypoglycemia and graft source. However, it is unknown if there is an interaction between these two factors, namely whether arterial grafts withstand hypoglycemia better than veins after CABG. In a cohort of 1323 patients undergoing CABG with intensive insulin therapy (IIT) in the ICU, we identified graft sources, ICU glucometrics, diabetes (DM) status and one-year mortality. Glucometrics included mean BG in ICU, and hypoglycemic excursions (Incidence, Severity [nadir &lt;40, 40-69mg/dl], Repetitive Frequency [number of excursions/patient]). The impact of different factors, individually and in combination, was analyzed by Chi-squared Automatic Interaction Detection (CHAID). One year mortality was highest in those with BG&lt;40mg/dl in the ICU (12/26, 46%) vs. those without (67/1283, 5%, p&lt;0.001). No other factor was significant in those with BG&lt;40. Of those without BG&lt;40, repetitive (≥2) excursions with BG&lt;70mg/dL had the highest mortality (17/96, 17%, p&lt;0.001), vs. those with one (13/190, 7%) or no excursions (37/997, 4%). Graft source was dominated by other factors in one year mortality, except for the left internal thoracic artery which was protective only in patients who had no hypoglycemia. Hyperglycemia was a contributor to mortality in patients who had a single hypoglycemic excursion &lt;70 (ICU Mean BG&gt;152mg/dl 4/17, 24% vs. ≤152 9/173, 5%, p=0.039) Preexisting DM was protective in patients with repetitive hypoglycemia (DM 2/43, 5% vs. 15/53 28%, p=0.003). Hypoglycemia in the ICU has a durable impact on one-year mortality post-CABG, superseding graft source, which is only significant without hypoglycemia. Severe hypoglycemia poses the greatest risk, but even mild repetitive BG&lt;70 is a threat to one year survival.
In conclusion, hypoglycemia erases the survival benefit from arterial grafts, suggesting that it may be equally damaging, regardless of graft source, and far more durable than hitherto envisioned.

Disclosure
L. Heller: None. M. Zupa: None. P.L. Perreiah: None. R. Rao: None.
Comparison of Different Self-Adjustment Regimens of Basal Insulin in Outpatients with T2DM
Authors: HU XILING , YANG XUBIN , XU WEN , DENG HONG R. , GUO XIAODI , YAO BIN , ZENG LONGYI , WENG JIANPING 
Published: June 2018

Self-adjustment of basal insulin dose were proved to be effective and widely used in clinical practice. However, no study compares the efficacy and safety of different self-adjustment regimens of basal insulin in T2DM.
T2DM with inadequate glucose control on OADs who were to start basal insulin from our outpatient clinics were enrolled and randomized to two groups. Patients in Group A were guided to adjust insulin dose 2-6U weekly; those in Group B adjusted insulin dose 2-3U every 3 days. Dose titration was based on self-monitored blood glucose (SMBG) to achieve a target FBG of 6.1mmol/L. The titration regimen is shown in Table.
A total of 648 patients aged 53.9 years old finished the 12-week visits. The baseline characteristics were even between groups. The FBG achieving rates were similar between Group A (75.7%) and Group B (74.4%). Compared with baseline, FBG and HbA1c decreased in both groups (FBG:10.7mmol/L vs. 6.6mmol/L in Group A, 10.8mmol/L vs. 6.5mmol/L in Group B; HbA1c:9.3% vs. 6.9% in group A, 9.5% vs. 6.8% in Group B, respectively, All P&lt;0.001). The reduction of FBG (-4.1mmol/L vs. -4.2mmol/L) and HbA1c (-2.4% vs. -2.7%) were similar between groups, so as the hypoglycemic incidences (17.9% vs. 20.1%). The frequency of SMBG was higher in Group B (5.21 times/week vs. 4.69 times/week, p=0.02).
In conclusion, both self-adjustment regimens in this study are effective and safe in T2DM.Table. Insulin Titration Protocol.Fasting blood glucose(mmol/L)Dose adjustment (U)Group AGroup B&lt;4.4-2U-2∼3U4.4-6.1No changeNo change6.2-7.8+2U+2∼3U7.9-9.9+4U+2∼3U&gt;10.0+6U+2∼3U

Disclosure
X. Hu: None. X. Yang: None. W. Xu: None. H.R. Deng: None. X. Guo: None. B. Yao: None. L. Zeng: None. J. Weng: None.
Effectiveness of Insulin Glargine U300 Used as Part of Basal Bolus Therapy in People with T2DM—Toujeo 6 Months Real-World Data From Hungary
Authors: HIDVEGI TIBOR , STELLA PETER 
Published: June 2018

The EDITION program demonstrated similar efficacy with lower risk of hypoglycemia (HG) of insulin glargine U300 (Gla-300) compared to insulin glargine U100 in T2DM. Data prospectively collected on real world use of Gla-300 are still of scarce. This single-arm, non-interventional, observational study aimed to describe the effectiveness of Gla-300 in real world setting in people with advanced T2DM. Data on HbA1c, fasting BG, weight (BMI), insulin doses and HG were collected for 6 months in routine clinical care in Hungary from 229 people with T2DM (age: 60.9 years±10.4, diabetes duration:13.4 years±7.9, being on insulin for: 7.4 years±6.2, HbA1c: 8.9%±1.5, BMI: 32.5kg/m2±5.7 (mean±SD)) previously treated with human basal-bolus (BB) regime (NPH+regular insulin) who were switched to analogue BB with Gla-300 and insulin glulisine. Data on safety and efficacy were available for 217 (95%) and 189 (83%) patients, respectively. Reasons for switching were: uncontrolled diabetes (68%), HG (15%), combination of the two (17%). By Month 6, HbA1c decreased by 1.36% (-1.55; -1.17), (mean+95% CI), fasting BG by 47 mg/dl (-57; -37), (p&lt;0.001 for both), while BMI decreased by 0.28 (-0.68; 0.13, NS). An HbA1c of 8.0%, the glycemic target for long term reimbursement for insulin analogues was achieved in 78% of the patients. Daily basal dose (U) was increased from 34.5 to 41.0, bolus dose remained the same (+0.13, (+0.3%)). From safety perspective, proportion of patients with documented (severe/non-severe) HG (BG≤70mg/dl) decreased from 44.2% to 27.6% (change in HG incidence: patients with HG within the preceding 3 months before switching vs. patients with HG during follow-up). The effectiveness of Gla-300 in routine clinical care was consistent with results from the EDITION program. When used concomitantly with glulisine, Gla-300 provided a clinically significant HbA1c reduction alongside with a decreased risk of hypoglycemia allowing 78% of patients to reach an HbA1c goal ≤8%.

Disclosure
T. Hidvegi: None. P. Stella: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi.
The Challenges and Potential of Digital Therapeutic Solutions for Long-Acting Insulin Management
Authors: KANCHI ARATI , PARKS LINDA , SHENG TONG , SMITH JANE LEA , GREENFIELD MICHAEL 
Published: June 2018

Starting on long acting insulin (LAI) can be difficult for people with type 2 diabetes (PWT2D). Delayed treatment initiation, imprecise titration, and poor adherence to therapy can lead to inadequate glycemic control. While emerging digital therapeutic solutions aim to help clinicians and PWT2D achieve optimal individualized LAI regimens, real world use of these solutions remains unknown. In this human factors validation study, we present findings on the Mobile Insulin Dosing System (MIDS), a mobile app module designed to reduce the manual burden of LAI titration. Sixteen PWT2Ds (age: 35-70 years) participated in the study. Participants were introduced to MIDS without training. Six real world use scenarios related to LAI management were presented with simulated data. Participants worked through each task using MIDS without assistance. Task performance was measured. Three out of six tasks had 100% success rates and the remaining three tasks had success rates from 73.3-87.5%. Three participants had 100% success rate despite having no prior experience with insulin therapy. All participants endorsed MIDS to be straightforward, easy to use, and effective for insulin management. Among unsuccessful tasks, the individual’s mental model of LAI adjustment was the common root cause. Some PWT2Ds did not understand that LAI is adjusted based on the fasting blood glucose (BG) only and assumed that non-fasting BG readings should also be included. Confidence in self titration was also a risk factor. Overall, MIDS proved to be simple, effective, and easy to use for PWT2Ds of varying ages, LAI experience, and smartphone use. Observed failure risks were related to poor understanding of diabetes and insulin regimens in general and not with the mobile implementation per se. Minimizing these risks, in addition to those inherent to manual recall and entry of BG readings, can enhance the use of digital therapeutic solutions for LAI therapy management.

Disclosure
A. Kanchi: Employee; Self; Glooko, Inc. L. Parks: Employee; Self; Glooko, Inc. T. Sheng: Employee; Self; Glooko, Inc.. J. Smith: None. M. Greenfield: Stock/Shareholder; Self; Glooko, Inc..
Impact of Insulin Therapy Assistance Program, a Patient Support Program, on 10,426 Indian T2DM Patients to Assess Safety and Efficacy with Biosimilar Insulin
Authors: JABEEN SARAH , PAWAR DILIP , SHIVARAM VS , RAJ PRAVEEN 
Published: June 2018

Introduction: Insulin Therapy Assistance Program (iTAP) is a structured Patient Support Program (PSP) designed by Biocon for T2DM patients receiving insulin therapy. The contact program trained the patients on essentials of diabetes, life style management including diet, importance of exercise and general care by trained and certified health care providers.
The aim of this study is to understand efficacy and safety of insulin (Biosimilar) treatment in patients with T2DM with PSP.
Method: A total of 10,426 patients were enrolled over a four-year period. These patients were observed at 3, 6 and 9 months post-initiation. This study presents the improvements in the glycaemic parameters—blood glucose, glycated haemoglobin (HbA1c) and body weight in patients on insulin therapy over 9 months follow-up period. Patients in the PSP received either human insulin (Insugen) or basal insulin (Basalog). The mean blood glucose, glycated haemoglobin and body weight were analysed for any differences with respect to the type of insulin.
Results: The mean (SD) blood glucose (mg%) significantly reduced (p&lt;0.05) with insulin initiation from 183.78 (54.74) at baseline to 145.15 (33.79) at 3 months and 132.80 (29.38) at 6 months and 133.98 (25.13) at 9 months. Similarly, the HbA1c reduced (p&lt;0.05) from 10.10% (1.75) at baseline to 7.85% (1.06) at the end of 9 months. Minimal changes were observed in the bodyweight.
Conclusion: It was observed with iTAP, there was an overall significant improvement in the glycaemic parameters when therapy was aided with a PSP. Insulin therapy in this study proved to be safe and well tolerated in patients with T2DM. The preponderance of evidence that is glycaemic control and low risk of hypoglycaemia suggest a positive impact of PSP on clinical outcomes which aid patients stand to benefit from participation.

Disclosure
S. Jabeen: Employee; Self; Biocon. D. Pawar: Employee; Self; Biocon. S. Vs: Employee; Self; Biocon. P. Raj: Employee; Self; Biocon.
Relative Contribution of Basal and Postprandial Hyperglycemia Stratified by A1C Categories Before and After Treatment Intensification with Dulaglutide
Authors: UMPIERREZ GUILLERMO E , PANTALONE KEVIN M , ATISSO CHARLES , LANDO LAURA FERNANDEZ , PATEL HIREN 
Published: June 2018

Dulaglutide (DU) has demonstrated non-inferiority vs. liraglutide (LIR) and superiority vs. exenatide BID (EXE) in A1c reduction. No data are available on how GLP-1RAs affect the relative contribution of basal hyperglycemia (BHG) and post-prandial hyperglycemia (PPHG) to overall hyperglycemia (OHG) across A1c categories. Data from five phase 3 studies (N=673) were pooled to assess the change in relative contributions of BHG and PPHG to diurnal OHG across different A1c categories after 6 months of treatment intensification with DU 1.5 mg as monotherapy or with oral medication(s) in patients with type 2 diabetes. BHG and PPHG were calculated using the area under the curve of the 7-point SMPG profiles. As a secondary objective, overall change in BHG for DU vs. LIR and DU vs. EXE was assessed by individual studies. At baseline, relative contributions of BHG increased and PPHG decreased with increasing A1c levels (Figure). After 6 months of treatment with DU, this pattern was maintained, despite 1.3% overall mean A1c reduction. At 6 months, the relative contribution of BHG and PPHG were similar between LIR and DU, whereas DU had lower BHG but higher PPHG contribution than EXE. The trend of relative contribution of PPHG and BHG across A1c categories is similar before and after DU treatment intensification, implying its effect on both BHG and PPHG to lower A1c.

Disclosure
G.E. Umpierrez: Research Support; Self; Sanofi US, Merck & Co., Inc., Novo Nordisk Inc., AstraZeneca. Advisory Panel; Self; Sanofi, Intarcia Therapeutics, Inc. K.M. Pantalone: Consultant; Self; Merck & Co., Inc.. Speaker's Bureau; Self; Merck & Co., Inc.. Research Support; Self; Merck & Co., Inc.. Speaker's Bureau; Self; AstraZeneca. Consultant; Self; Novo Nordisk Inc.. Speaker's Bureau; Self; Novo Nordisk Inc.. Research Support; Self; Novo Nordisk Inc.. Consultant; Self; Sanofi. Speaker's Bureau; Self; Sanofi. C. Atisso: Employee; Self; Eli Lilly and Company. L. Fernandez Lando: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. H. Patel: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company.
Achieving Composite Endpoint of A1C &lt;7.0% without Weight Gain or Hypoglycemia with Once-Weekly Dulaglutide in Chinese Patients with Type 2 Diabetes—Post-Hoc Analysis
Authors: XIAO XINHUA , WANG CHANGJIANG , WANG FENG , LI PENGFEI , GU LIQUN 
Published: June 2018

This post-hoc analysis of 2 randomized trials of the once weekly glucagon-like peptide-1 receptor agonist dulaglutide (DU) assessed the proportion of Chinese patients with type 2 diabetes (T2D) achieving a composite endpoint of glycated hemoglobin (A1C) &lt;7.0%, no weight gain (≤0 kg), and no hypoglycemia (confirmed glucose ≤3.9 mmol/L or report of severe hypoglycemia) after 26 or 52 weeks of treatment with DU 1.5 mg or 0.75 mg vs. glimepiride (GLIM) or insulin glargine (GLAR). Patients in the DU vs. GLIM study (n = 556) were treatment-naive or discontinued from oral monotherapy; those in the DU vs. GLAR study (n = 591) continued on metformin and/or sulfonylurea. Analyses in each trial were on modified intent—to-treat population; missing values were imputed using last observation carried forward. Significantly (p&lt;.001, Fisher’s exact test) more patients achieved the composite endpoint with DU 1.5 mg or 0.75 mg vs. GLIM after 26 weeks (47.8% and 39.2% vs. 19.9%), as well as vs. GLAR after 26 weeks (39.5% and 30.1% vs. 14.9%) and after 52 weeks (26.0% and 23.0% vs. 6.7%). Similar results were observed for composite endpoints of A1C &lt;7.0% and no weight gain, and A1C &lt;7.0% and no hypoglycemia. Dulaglutide is an effective treatment option for Chinese patients with T2D, resulting in a large proportion of patients reaching A1C targets without weight gain or hypoglycemia.

Disclosure
X. Xiao: None. C. Wang: None. F. Wang: None. P. Li: Employee; Self; Eli Lilly and Company. L. Gu: Employee; Self; Eli Lilly and Company.