Basal Bolus Research Articles

Safety and Efficacy of Exenatide Therapy for the Management of Hospitalized Patients with Type 2 Diabetes—Exenatide Hospital Trial

This pilot multi-center, open-label, randomized trial determined the safety and efficacy of exenatide alone or in combination with basal insulin in medicine and surgery patients with type 2 diabetes (T2D). A total of 150 patients with blood glucose (BG) between 140-400 mg/dl on home therapy with oral agents or insulin ≤ 0.5 U/kg/day were treated with exenatide, exenatide+basal, or basal-bolus (BB) regimen. Exenatide was started at 5 mcg BID, basal insulin at 0.25 U/kg/d, and BB at 0.5 U/kg/d given half as glargine and half as lispro before meals. At discharge, pre-admission therapy was restarted and patients were randomized to exenatide (titrated to 10 mcg BID) or basal insulin, and followed for up to 3 months. The combination of exenatide and basal insulin resulted in lower hospital mean daily BG and higher proportion of target BG 70-180 mg/dl compared to exenatide or BB, p<0.01 (Table). There were no differences in hospital hypoglycemia, gastrointestinal (GI) adverse events or study withdrawal between groups. After discharge, there was no difference in BG control (p=0.65) but exenatide group had more GI adverse events (p<0.001) compared to basal group.Exenatide (n=47)Exe+Basal (n=51)Basal-Bolus (n=52)P valueRandomization BG, mg/dl196±61195±51201±580.91Admission HbA1c, %8.9±2.28.3±2.08.5±1.70.22Length-of-stay, days, median Q1-Q34.0 (2.0-8.0)5.0 (3.0-7.0)4.0 (2.0-5.0)0.23Mean daily BG, days 2-10, mg/dl177±41154±39166±400.01BG at target 70-180 mg/dl, %61±3978±3163±310.02BG < 54 mg/dl, n (%)0 (0)1 (2.1)2 (4.1)0.77Nausea/vomiting, n (%)5 (10.6)5 (9.8)1 (1.9)0.17Withdrawal due to AE, n (%)3 (6.4)0 (0)0 (0)0.029Post-Discharge DataExenatide (n= 48)Basal Insulin (n= 55)Mean daily BG, mg/dl156±63141.±270.65BG < 54 mg/dl, n (%)*4 (10)4 (11)1.0Hospital re-admission, n (%)17%13%0.59Nausea/vomiting, n (%)20 (53)1 (3)<0.001Withdrawal due to AE, n (%)5 (13)0 (0)0.05HbA1c at 3 months, %8.2±1.97.3±10.07 These preliminary results indicate that inpatient and post-discharge treatment with exenatide in combination with basal insulin is safe and effective for the management of general medicine and surgery patients with T2D. Disclosure M. Fayfman: None. D.L. Mize: None. D.J. Rubin: Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc.. I. Anzola: None. M.A. Urrutia: None. C. Ramos: None. F.J. Pasquel: Consultant; Self; Merck Sharp & Dohme Corp., Sanofi, Boehringer Ingelheim Pharmaceuticals, Inc.. J. Haw: None. P. Vellanki: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., AstraZeneca. H. Wang: None. K.E. Joyce: None. A. Karunakaran: None. B.S. Albury: None. R. Weaver: None. L. Viswanathan: None. S. Jaggi: None. R.J. Galindo: None. G.E. Umpierrez: Research Support; Self; Sanofi US, Merck & Co., Inc., Novo Nordisk Inc., AstraZeneca. Advisory Panel; Self; Sanofi, Intarcia Therapeutics, Inc..

Effectiveness of Insulin Glargine U300 Used as Part of Basal Bolus Therapy in People with T2DM—Toujeo 6 Months Real-World Data From Hungary

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<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.

Liraglutide-Based Therapy Shows More Prominent Effect than Conventional Insulin Therapy to Achieve HbA1c Target, Especially in Patients with Short Duration

Objective: Despite advanced new medications, the rate of achieving HbA1c target <7% is only around 50%. The aim of study is to evaluate the ability of GLP-1 receptor agonist to achieve this target compared to insulin therapy. Methods: A total of 154 type 2 diabetic (T2DM) patients on liraglutide (LIRA) based therapy and 124 T2DM patients on insulin based therapy were randomly recruited. The rate of patients achieving the target and background characteristics were compared. Results: 1) The rate of achieving HbA1c<7% was 41.6% on insulin vs. 61.0% on LIRA. HbA1c<6% was only 7.3% on insulin, but 19.4% on LIRA, although self-blood glucose monitoring (SMBG) was equally done (52.4% vs. 51.9%). 2) Divided into 3 regimes: LIRA mono-injection, LIRA+basal insulin, LIRA+basal bolus (BBT)/pre-mixed insulin therapy, achieving HbA1c<7% rate much varied: 76.3%, 56.9%, and 35.0%. Achieving HbA1c<6% rate was 21.8%, 21.5%, and 5.0% without hypoglycemia. In mono-injection group, the rate of SMBG (30.9%) was lower than other 2 groups (58.2%, 80.0%), and less cost. Moreover, prominent effect was attained in this group, HbA1c improved from 9.9±2.9 to 6.6±0.9% (p<0.01), and BMI improved from 24.5±5.9 to 23.6±5.3kg/m2 (p<0.05) by adding LIRA. In background characteristics, the duration of diabetes was shortest (6.6±6.3 year) in this group, compared with LIRA+basal (11.2±8.8 year) or LIRA+BBT/pre-mixed (15.6±10.6 year) group. But ischemic heart disease (12.7%), chronic kidney disease (30.9%), and obesity (30.9%) complication rates were still high. 4) In one of the patients with a year duration of diabetes, after changing the regime from BBT into LIRA+basal insulin, marked improvement in HbA1c from 8.2% to 5.6% with narrowing blood glucose range 126∼349mg/dL into 79∼145mg/dL was found, and durability for 3 years was confirmed. Conclusion: Since T2DM is a complex metabolic disorder, LIRA should be started early years to get its maximum benefit of LIRA. Disclosure K. Kashima: None. H. Shimizu: Speaker's Bureau; Self; Eli Lilly and Company, MSD K.K., Daiichi Sankyo Company, Limited, Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk Inc.. M. Yamada: None.

Mobile-Based Artificial Intelligence Significantly Improves Type 1 Diabetes Management

Background: Type 1 diabetes involves a multiple decision making process on a daily basis.Mobile technology has been widely spread not only as a mean of communication, but also as multi-usage tool involving a large variety of applications, making everyday life more convenient. “D-Partner” (Diabetes Innovations Ltd) is a mobile based application that serves as a self-management tool for type 1 diabetes, including a bolus wizard (with food database),a basal insulin titration manager, as well as, a large number of automated notifications, warnings or reward messages, according to the data imported by the patient. In addition,“D-Partner” serves as a telemedicine tool, as information of meals, insulin dosage, measurements of glucose, blood pressure, body weight, and lab values, may be monitored by the physician through an on-line, web-based platform. Aim: To investigate the efficacy of "D-Partner" mobile application, in glucose management, in patients with type 1 diabetes. Methods: 24 patients with type 1 diabetes (14 male, 10 female), with diabetes duration of 14,2±8,8 years, mean age of 37.4±11,7 years and HBA1c >7%, on basal bolus insulin therapy, were randomized to receive either standard care, or standard care plus the ‘D-Partner” application usage. HBA1c, somatometric data, blood pressure, heart rate and hypoglycemia frequency data, were obtained at baseline and 3 months after the intervention. Results: The intervention group presented a significantly improved glucose control as recorded by HBA1c reduction, compared to the control group (p=0.01). Additionally, hypoglycemia incidence was significantly lower in the intervention group (p=0.04). There were no significant changes in somatometric data blood pressure, and heart rate, among the 2 groups. Concusion: D-partner, is a mobile based self-management application, that may contribute to a better management of type 1 diabetes, potentially improving the life quality of the patient. Disclosure J. Doupis: Consultant; Self; Novo Nordisk Inc., Eli Lilly and Company, Sanofi, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc.. V. Papandreopoulou: None. S. Glykofridi: None. V. Andrianesis: None.

Basal-Bolus Insulin Therapy May Not Be the Optimal Strategy in a "Real-World" Hospital Setting for Inpatient Hyperglycemia Management

Basal bolus insulin therapy (BB) is recommended for glucose control in noncritically ill inpatients based on two small RABBIT2 trails. However, BB is complex and has limited data in large scale “real world” settings. This is a retrospective analysis of 4,558 noncritical, medical-surgical admissions from 1/2013 to 9/2015 in patients ≥18 years who received SC but not IV insulin for ≥ 75% of the stay. Insulin therapy was identified within the first 2 days as BB (long + rapid, n=2319), sliding scale (SS, rapid only, n=1855) or Basal Only (BO, long only, n=384). A propensity score analysis adjusted for clinical, demographic and physician variables affecting choice of therapy. Point of care glucose (mg/dl) was used to define patient days as hypo- (any <70), hyper- (mean >180) or euglycemic (no <70 AND mean ≤180). Negative binomial regression analyzed glucose outcomes (number of hypo-, hyper- and euglycemic days, mean glucose); linear regression modeled log of length of stay (LOS); logistic regression modeled odds of 30 and 60 day readmission. All analyses were conducted overall and by medical or surgical DRG. BB had worse glucose control but less LOS in medical DRG. BO had better hyper-, euglycemic and mean glucose. BB and BO had more hypo- days. This suggests that BO may be superior and simpler than BB for hyperglycemia but medical patients may benefit from BB for reasons beyond glucose control. Insulin groupsOVERALL (n= 4,558)MEDICAL DRG (n =3,211)SURGICAL DRG (n= 1,347)Length of stay*BB vs SS0.97 (0.141)0.94 (0.003)1.02 (0.540)BO vs SS1.01 (0.711)0.99 (0.741)1.03 (0.665)Hyperglycemic days*BB vs SS0.99 (0.700)0.97 (0.416)1.00 (0.922)BO vs SS0.69 (<0.001)0.69 (<0.001)0.69 (<0.001)Hypoglycemic days*BB vs SS2.45 (<0.001)2.29 (<0.001)2.78 (<0.001)BO vs SS2.71 (<0.001)2.37 (<0.001)3..40 (<0.001)Euglycemic days*BB vs SS0.91 (0.008)0.85 (<0.001)1.01 (0.823)BO vs SS1.15 (0.012)1.11 (0.151)1.20 (0.063)Mean glucose*BB vs SS1.01 (0.415)1.69 (0.266)-1.18 (0.589)BO vs SS-17.27 (<0.001)-17.95 (<0.001)-15.91 (<0.001)1Results for 30 and 60 day readmission are not significantly different across the groups and are not presented in the table;*Results above shown as: Estimate (p-value) Disclosure A.R. Sadhu: None. B. Patham: None. A. Vadhariya: None. M.L. Johnson: None.

Is It Possible to Predict the Onset of Nocturnal Severe Asymptomatic Hypoglycemia Using CGM Data of Previous Day and Next Morning in Type 1 Diabetic Patients Receiving Insulin Degludec?

The aim of this study to investigate whether the occurrence of nocturnal severe asymptomatic hypoglycemia (NH) may be predicted based on glycemic variability on the previous day and next morning on the day of onset. This study examined patients with type 1 diabetes (T1D) who underwent CGM assessments and received basal bolus therapy of insulin degludec (IDeg) in outpatient setting. NH was defined as glucose levels < 54 mg/dL detected between 12:00 and 6:00 AM. The subjects were evaluated for fasting glucose level, the range of post-breakfast glucose elevation, and glucose level at bedtime (12:00 AM) on the previous day. For comparison, the patients were divided into those with NH and those without by using t-test. Optimal cut-off values for the relevant parameters were determined in order to predict NH using ROC analysis. Thirty-one patients (mean HbA1c values, 7.8 ± 0.7 %) were selected for analysis. NH occurred in 8 patients (26%). Fasting glucose level was significantly lower in those with NH than in those without (61 ± 13 mg/dL vs. 130 ± 68 mg/dL; P = 0.001). The range of post-breakfast glucose elevation was significantly greater in those with NH. Again, the glucose level at bedtime was significantly lower in those with NH than in those without (88 ± 44 mg/dL vs. 144 ± 69 mg/dL; P = 0.044). The cut-off values for predicting NH determined for the relevant factors were as follows: fasting glucose level < 69 mg/dL (sensitivity 0.83/ specificity 0.75/ AUC 0.86, P = 0.003) and bedtime glucose level < 90 mg/dL (0.83/ 0.75/ 0.79, P = 0.017). The results suggest that fasting glucose level of < 69 mg/dL and bedtime glucose level < 90 mg/dL had approximately 80% probability of predicting the occurrence of NH in T1D receiving IDeg. While the post-breakfast glucose levels and the pre- and post-dinner glucose levels were not significantly different, the range of post-breakfast glucose increase was greater in those with NH than in those without. Disclosure H. Takahashi: None. R. Nishimura: Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Astellas Pharma US, Inc., Eli Lilly and Company, Abbott, Medtronic, MSD K.K., Novo Nordisk A/S, Sanofi, Takeda Development Center Asia, Pte. Ltd., Kissei Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd.. K. Utsunomiya: None.

Euglycemic DKA as an Initial Presentation of Immunotherapy-Induced Insulin-Dependent Diabetes

New onset insulin dependent diabetes (DM) has been reported in cancer patients (pts) receiving immunotherapy (IO). Typically, pts have Grade 3 hyperglycemia (CTCAE) and sometimes DKA. Euglycemic DKA has been reported in pts on empagliflozin (Empa). We present a unique case of euglycemic DKA as initial presentation for immunotherapy induced insulin dependent DM. Pt is a 68 year old man without preexisting DM started on nivolumab for metastatic prostate cancer. Following 2 doses of nivolumab, he developed fatigue, weight loss and Grade 2 hyperglycemia for which he was started on metformin, glipizide, and Empa by his outside physician. His BG levels ranged from 130-200 mg/dL on these therapies. Nivolumab treatment was stopped due to significant adverse effects. On return visit to our clinic, approximately 3 months after initial hyperglycemia, pt complained of persistent fatigue, weight loss and a new fruity odor in his breath. Labs revealed BG of 134mg/dl, bicarb of 19 mEq/L (23-30mEq/L), anion gap (AG) of 17mEq/L (4-14mEq/L). Urine ketones were positive and c-peptide level was 0.3ng/ml (0.8- 3.85ng/ml). Pt was advised to immediately stop Empa and follow-up with local ER. When he presented to local ER, approximately 4 days later, he was hyperglycemic with glucose 316 mg/dL, and labwork consistent with classic DKA. Pt was initiated on basal bolus insulin regimen and had resolution of DKA.IO mediated DM results from immune mediated islet cell destruction leading to rapidly progressive insulin deficiency. When suspected, these pts should be evaluated for beta cell dysfunction and insulin should be used for glycemic control. This case highlights that SGLT2 therapy should be used with caution in patients with hyperglycemia on immunotherapy as it could mask the diagnosis of DKA. In addition, this case shows that patients taken off of immunotherapy may develop delayed glycemic complications and may need long term monitoring. Disclosure P. Iyer: None. S.N. Thosani: Consultant; Spouse/Partner; Boston Scientific Corporation, Medtronic. Speaker's Bureau; Spouse/Partner; AbbVie Inc..

Durability of Combination Therapy with Exenatide and Pioglitazone vs. Basal Bolus Insulin in Poorly Controlled T2DM Patients—Three-Year Follow-Up of the QATAR Study

Background: We previously demonstrated that addition of exenatide (EXEN) plus pioglitazone (PIO) in poorly controlled T2DM patients on maximal dose of metformin plus sulfonylurea produced a greater A1c reduction at 1 year than basal-bolus insulin. Here we report the 3-year follow-up data. Methods: 274 poorly controlled T2DM patients (age=56 y; BMI=31; Diabetes duration=11 y, HbA1c=10.1%) on maximal doses of metformin plus SU were randomized to receive: (1) Exenatide once weekly (2 mg) plus pioglitazone (n=142) or (2) basal (glargine)-bolus (aspart) insulin (n=132) to maintain HbA1c below 7%. Results: In subjects receiving EXEN + PIO, A1c decreased to 6.5% at 6 months, and remained at 6.6% after 36 months. With Insulin Therapy, A1c declined to 7.5% at 6 months and remained 7.3 at 36 months (P<0.001) (Figure 1). More subjects receiving Insulin Therapy failed to achieve the A1c goal <7% (63% vs. 22%, p<0.0001). Despite lower A1c, subjects receiving EXEN + PIO had lower rate of hypoglycemia (P<0.001) compared to subjects receiving Insulin Therapy. Lastly, subjects receiving Insulin Therapy gained 4.1 kg vs. 1.7 kg (p=0.0002) vs. subjects treated with EXEN + PIO. Conclusion: Addition of EXEN + PIO in poorly controlled T2DM patients on MET/SU produces greater and more durable HbA1c reduction with lower rate of hypoglycemia compared to Insulin Therapy. Disclosure M. Abdul-Ghani: None. O. Migahid: None. A. Megahed: None. M.F. Mohammad: None. R.A. DeFronzo: Speaker's Bureau; Self; AstraZeneca, Novo Nordisk Inc.. Advisory Panel; Self; AstraZeneca, Novo Nordisk Inc., Janssen Pharmaceuticals, Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Elcelyx Therapeutics, Inc., Intarcia Therapeutics, Inc.. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Takeda Pharmaceuticals U.S.A., Inc.. A. Jayyousi: None.

Simplified Transition Algorithm from Intravenous to Subcutaneous Insulin in Nondiabetic Cardiac Surgery Patients with Stress Hyperglycemia

Intravenous (IV) insulin is recommended to treat stress hyperglycemia (SH) in nondiabetic (non-DM) patients after cardiac surgery. Many patients with SH require transition to subcutaneous (SQ) insulin after stopping IV drip in the ICU. We report a simplified protocol for the transition from IV to SQ insulin in cardiac surgery patients with SH. Patients requiring IV insulin >2 U/hour were transitioned to SQ basal bolus regimen at 70% of calculated daily insulin requirement. Patients requiring ≤ 2 U/hour were treated with sliding scale insulin (SSI), if >2 episodes of BG > 140 mg/dl patients were started on rescue therapy with basal insulin. Among 150 non-DM patients with SH in the ICU, 30 patients (20%) required >2 U/hour and were transitioned to SQ basal/bolus at a mean SQ dose of 0.34 U/kg/day for a duration of treatment of 5.5±3.6 days. A total of 120 (80%) patients required ≤ 2 U/hour and were transitioned to SSI. Of them, the mean blood glucose (BG) was 129.8±16 mg/dl and only 3 (2.5%) patients required a single dose of basal insulin during the hospital stay. There were no differences in LOS or in a composite of complications between groups. Our results indicate that cardiac surgery patients with SH requiring continuous IV insulin ≤ 2 U/hour in the ICU can be safely transitioned to SSI; however, patients requiring > 2 U/hour should be transitioned to basal insulin to maintain glycemic targets. Transition to SSITransition to Basalp-valuePatients, n (%)120 (80)30 (20)BMI, Kg/m228.8 ± 6.530.3 ± 5.40.15HbA1c, %5.6 ± 0.45.8 ± 0.70.047ICUDaily BG during IV insulin drip, mg/dl133.9 ± 17142.9 ± 150.004Total insulin in the ICU, U/day57.4 ± 8973.8 ± 640.005TRANSITIONAverage BG after transition, mg/dl123.4 ± 12129.8 ± 160.022Patients who required SQ SSI99 (83)30 (100)<0.001Patients with BG < 70 mg/dl, n (%)13 (10.8)2 (6.7)0.74Composite of complications53 (44)14 (47)0.81Data are n (%) or mean ± SD. Composite complications: major CV events, infections, respiratory failure and acute kidney injury. Disclosure S. Cardona: None. R.J. Galindo: None. K.G. Tsegka: None. M.A. Urrutia: None. P. Vellanki: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., AstraZeneca. M. Fayfman: None. J. Haw: None. F.J. Pasquel: Consultant; Self; Merck Sharp & Dohme Corp., Sanofi, Boehringer Ingelheim Pharmaceuticals, Inc.. L. Peng: None. G.E. Umpierrez: Research Support; Self; Sanofi US, Merck & Co., Inc., Novo Nordisk Inc., AstraZeneca. Advisory Panel; Self; Sanofi, Intarcia Therapeutics, Inc..

The effect of basal-bolus therapy varies with baseline 1,5-anhydroglucitol level in people with Type 2 diabetes: a post hoc analysis.

AimsTo investigate the impact of baseline 1,5‐anhydroglucitol on the treatment effect of basal–bolus therapy in people with Type 2 diabetes.Methods Post hoc analysis of onset 3, an 18‐week, randomized, phase 3 trial evaluating the efficacy and safety of fast‐acting insulin aspart in basal–bolus therapy (n = 116) vs. basal insulin‐only therapy (n = 120) in people with Type 2 diabetes. The estimated treatment difference in change from baseline in HbA1c was investigated for different cut‐off values of baseline 1,5‐anhydroglucitol (2, 3, 4, 5 and 6 μg/ml).ResultsThe estimated treatment difference in change from baseline in HbA1c between basal–bolus therapy and basal insulin‐only therapy was statistically significantly greater in participants with baseline 1,5‐anhydroglucitol ≤3 μg/ml (n = 34) vs. >3 μg/ml (n = 198) [estimated treatment difference (95% CI): −1.53% (−2.12; −0.94) vs. −0.82% (−1.07; −0.57); P‐value for interaction = 0.03]. The estimated treatment difference became more pronounced when comparing participants with 1,5‐anhydroglucitol ≤2 μg/ml (n = 15) vs. >2 μg/ml (n = 217) [estimated treatment difference (95% CI): −2.26% (−3.15; −1.36) vs. −0.85% (−1.08; −0.62); P‐value for interaction = 0.003]. For cut‐off values ≥4 μg/ml, estimated treatment differences were numerically greater below the cut‐off compared with above, although the interaction terms were not statistically significant.ConclusionThis analysis indicates that people with Type 2 diabetes with low 1,5‐anhydroglucitol have an added treatment benefit with basal–bolus therapy compared with people with higher 1,5‐anhydroglucitol. Further research is needed to clarify any clinical utility of these findings. Clinical Trials Registry No: NCT01850615

Protocol for Meal-time Administration of Exenatide for Glycaemic Control in Type 1 Diabetes Cases (The MAG1C trial): a randomised, double-blinded, placebo-controlled trial

IntroductionPersons with type 1 diabetes require intensive insulin therapy to achieve glycaemic control, but side effects, including hypoglycaemia and weight gain, may reduce treatment compliance. We hypothesise that add-on treatment...

Multinational Consensus: Insulin Initiation with Insulin Degludec/Aspart (IDegAsp).

Insulin degludec/aspart (IDegAsp) is the first soluble insulin co-formulation, combining a long-acting insulin degludec (IDeg) and rapid-acting insulin aspart (IAsp). In type 2 diabetes patients with oral antidiabetes agent (OAD) inadequacy, insulin initiation with IDegAsp once daily provides superior long-term glycemic control compared to insulin glargine, with similar fasting plasma glucose (FPG) and insulin doses, and numerically lower rates of overall and nocturnal hypoglycemia. Furthermore, in patients with uncontrolled type 2 diabetes previously treated with insulins, IDegAsp twice daily effectively improves glycated hemoglobin and FPG, with fewer hypoglycemic episodes versus premix insulins and basal bolus therapy. In patients with type 1 diabetes mellitus, IDegAsp once daily with two doses of IAsp is a convenient, yet effective, regimen as compared to the conventional 4-5 injection-based basal bolus therapy. IDegAsp is an appropriate and reasonable option for initiation of insulin therapy in both type 1 and type 2 diabetes.

DEVOTE 5: Evaluating the Short-Term Cost-Utility of Insulin Degludec Versus Insulin Glargine U100 in Basal-Bolus Regimens for Type 2 Diabetes in the UK.

IntroductionThe aim of this study was to evaluate the short-term cost-utility of insulin degludec (degludec) versus insulin glargine 100 units/mL (glargine U100) for the treatment of type 2 diabetes in the basal–bolus subgroup of the head-to-head cardiovascular (CV) outcome trial, DEVOTE.MethodsA cost-utility analysis was conducted over a 2-year time horizon using a decision analytic model to compare costs in patients receiving once daily degludec or glargine U100, both as part of a basal–bolus regimen, in addition to standard care. Clinical outcomes and patient characteristics were taken exclusively from DEVOTE, whilst health-related quality of life utilities and UK-specific costs (expressed in 2016 GBP) were obtained from the literature. The analysis was conducted from the perspective of the National Health Service.ResultsDegludec was associated with mean cost savings of GBP 28.78 per patient relative to glargine U100 in patients with type 2 diabetes at high CV risk. Cost savings were driven by the reduction in risk of diabetes-related complications with degludec, which offset the higher treatment costs relative to glargine U100. Degludec was associated with a mean improvement of 0.0064 quality-adjusted life-years (QALYs) compared with glargine U100, with improvements driven predominantly by lower rates of severe hypoglycemia with degludec versus glargine U100. Improvements in quality-adjusted life expectancy combined with cost neutrality resulted in degludec being dominant over glargine U100. Sensitivity analyses demonstrated that the incremental cost-utility ratio was stable to variations in the majority of model inputs.ConclusionThe present short-term modeling analysis found that for the basal–bolus subgroup of patients in DEVOTE, with a high risk of CV events, degludec was cost neutral (no additional costs) compared with glargine U100 over a 2-year time horizon in the UK setting. Furthermore, there were QALY gains with degludec, particularly due to the reduction in the risk of severe hypoglycemia.FundingNovo Nordisk A/S.Trial RegistrationClinicalTrials.gov identifier, NCT01959529.Electronic supplementary materialThe online version of this article (10.1007/s13300-018-0430-4) contains supplementary material, which is available to authorized users.

DIABEO App Software and Telemedicine Versus Usual Follow-Up in the Treatment of Diabetic Patients: Protocol for the TELESAGE Randomized Controlled Trial.

BackgroundSelf-management of diabetes minimizes the risk of macrovascular and microvascular complications, but understanding and/or adherence to self-management recommendations is often suboptimal. DIABEO is a smartphone app (downloaded via the internet) used to calculate bolus insulin doses. A previous study (TELEDIAB 1) showed that the use of DIABEO was associated with a significant improvement in glycemic control in patients with poorly controlled type 1 diabetes mellitus, particularly when combined with teleconsultations with physicians.ObjectiveHere, we present the protocol for a new study (Suivi A Grande Echelle d’une cohorte de diabétiques de type 1 et de type 2 sous schéma insulinique basal bolus par la TELEmédecine; abbreviated TELESAGE), conducted in a larger population of diabetic patients with poorly controlled basal-bolus insulin levels.MethodsTELESAGE is a multicenter, double-randomized, open-label, three parallel–arms study, conducted in approximately 100 centers in France. The study will compare a control group (arm 1: usual follow-up) with two DIABEO telemedicine systems: (1) physician-assisted telemedicine (arm 2), and (2) nurse-assisted telemonitoring and teleconsultations by a diabetologist’s task delegation (arm 3). Initial randomization will allocate the study arms in 12 French regions. A second randomization will assign patients in the groups allocated to each studied region. The primary objective of TELESAGE will be to investigate the effect of the DIABEO telemedicine system versus usual follow-up, with respect to improvements in the glycated hemoglobin levels of approximately 696 diabetic patients with poorly controlled basal-bolus insulin levels.ResultsThe TELESAGE study is sponsored by Sanofi (Gentilly, France). A primary completion date is expected in June 2018, and publication of results is expected within 6 months of work completion.ConclusionsThe TELESAGE study is expected to confirm the previous results of the TELEDIAB 1 study using a larger sample of diabetic patients. It is also expected to evaluate a nurse-assisted telemonitoring system. We will assess the potential of the DIABEO telemedicine service in terms of its utility and explore whether it can become an integral part of diabetes care for patients.Trial RegistrationClinicalTrials.gov NCT02287532; https://clinicaltrials.gov/ct2/show/NCT02287532 (Archived by WebCite at http://www.webcitation.org/6ykajhJKd)

Managing Diabetes in Patients Hospitalized in Internal Medicine Units.

Diabetes and hyperglycemia are present in over one-third of inpatients in internal medicine units and are associated with worse prognosis in multiple morbidities. Treatment of inpatient hyperglycemia is usually with basal bolus insulin in a dose calculated by the patient’s weight, with lower doses recommended in patients who are at a higher risk for hypoglycemia. Other antihyperglycemic medications and insulin regimens can be used in selected patients. There are no adequately powered studies on the effect of improving glycemic control on hospitalization outcomes in non-critically ill patients in internal medicine units, and in most patients a modest glucose target of 140–180 mg/dL is recommended. A structured discharge plan should intensify antihyperglycemic treatment as needed and include an outpatient follow-up appointment shortly after discharge.

Clinical application of intelligent patient-controlled pump for labor analgesia

Objective To evaluate the efficiency of intelligent patient-controlled pump for labor analgesia, and its influence on mothers and neonates. Methods One hundred and twenty primiparas were randomly divided into two groups(n=60), respectively utilizing intelligent(group I) and traditional(group T) patient-controlled pumps to deliver 0.1% ropivacaine plus 0.5 mg/L sufentanil for constant epidural analgesia. Both groups received an initial bolus of 12 ml analgesic solution, and the basic pump settings were 5 ml/h, 5 ml, 15 min for basal infusion rate, bolus dose, and lock time, respectively. In group T, the basic pump settings were used. In group I, the doses of analgesics were adjusted once every hour to meet patients demands for adequate analgesia. The pumps were stopped by the end of the second stage of labor. The follow outcome measures, including the VAS scores before maternal analgesia(T0), 15 min(T1), 30 min (T2), 2 h (T3) after analgesia, the full cervical dilatation(T4), and forced delivery at the second stage of labor(T5), delivery mode, the time of the second stage of labor, total duration of labor, total analgesia time, the usage of analgesics, hourly dosage, local anesthetic background infusion rate at delivery, the number of breakthrough pain, 1 min, 5 min Apgar score of the neonatal, the neonatal weight, side-effects as well as the maternal satisfaction, were recorded. Results We analyzed valid data from 113 parturient women(57 in group I and 56 in group T). Compared with group T, the VAS score at full cervical dilatation and the incidence of breakthrough pain in group I were significantly decreased(P<0.05), the infusion rate of analgesics during forced labor in group I was increased with better analgesia(P<0.05), there was no significant difference between two groups in, the usage of analgesics, the duration of labor, the mode of delivery, the condition of neonates, and the incidence of side-effects as well. Conclusions The intelligent patient-controlled analgesia pump is effective for labor analgesia. It lowers incidence of breakthrough pain and improves maternal satisfaction without increasing the dosage of analgesics and the risk of side-effects. Key words: Analgesia, obstetrical; The intelligent patient controlled analgesia pump; Patient controlled analgesia

Basal-Bolus Insulin Therapy with Gla-300 During Hospitalization Reduces Nocturnal Hypoglycemia in Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Study.

IntroductionAlthough reduction in the incidence of nocturnal hypoglycemia, as estimated by symptom or self-monitored plasma glucose, was shown to be more pronounced with 300 units/mL insulin glargine (Gla-300) than with 100 units/mL insulin glargine (Gla-100) in type 2 diabetes patients, the exact frequency of nocturnal hypoglycemia estimated with continuous glucose monitoring (CGM) has not been reported.MethodsForty patients with type 2 diabetes who were admitted for glycemic control with basal–bolus insulin therapy (BBT) were randomized into the Gla-100 and Gla-300 groups. Insulin doses were adjusted to maintain blood glucose levels within 100–120 mg/dL at each meal. Plasma glucose and C-peptide profiles were estimated serially after admission and before discharge. Daily CGM was also performed before discharge.ResultsIn the Gla-100 and Gla-300 groups, the mean duration of hospitalization was 15 ± 2 and 15 ± 1 days, respectively, and the mean basal insulin dose before discharge was 13 ± 7 and 15 ± 10 units, respectively. The dose of meal-time insulin was not different between the two groups. Compared with the Gla-300 group, the Gla-100 group had significantly lower nocturnal profiles of plasma glucose and C-peptide, but significantly higher frequency of CGM-estimated nocturnal hypoglycemia (10.7% ± 18.4% versus 1.2% ± 3.6%, P = 0.033).ConclusionIn type 2 diabetic patients, reduction in the incidence of CGM-estimated nocturnal hypoglycemia by BBT under tightly controlled diet therapy was higher with Gla-300 than with Gla-100.Trial RegistrationUMIN clinical trials registry (UMIN000023360).

Abstract #239 Insulin Degludec/Liraglutide (Ideglira) Achieved Non-Inferior A1c Reduction; Weight Loss and Fewer Hypoglycemic Episodes while Using a Simple Regimen with Fewer Injections and Dose Adjustments Compared with Basal–Bolus Therapy: An Analysis of Dual VII

Abstract #239 Insulin Degludec/Liraglutide (Ideglira) Achieved Non-Inferior A1c Reduction; Weight Loss and Fewer Hypoglycemic Episodes while Using a Simple Regimen with Fewer Injections and Dose Adjustments Compared with Basal–Bolus Therapy: An Analysis of Dual VII

Reduction of glycemic variability with Degludec insulin in patients with unstable diabetes

SummaryIntroductionDegludec (IDeg) is an ultralong-acting insulin, with stable pharmacodynamic profile which leads to lower fluctuations in glucose levels. The effect of IDeg has not been specifically assessed in patients with unstable diabetes, defined as increased glycemic variability (GV).MethodsA prospective before-after pilot study was conducted, including patients managed at Hospital Universitario San Ignacio in Bogotá, Colombia. The impact of the switch from a Glargine or Detemir insulin to a basal insulin regimen with IDeg for 12 weeks on GV measured by continuous glucose monitoring, on A1c levels, and on the incidence of episodes of global and nocturnal hypoglycemia was assessed in a group of patients with (coefficient of variation >34%) or without increased basal GV using a Generalised Estimating Equation (GEE) analysis.Results60 patients with basal bolus therapy and history of hypoglycemia were included. 18 patients had High GV (HGV). In this group a significant reduction of 11.1% of CV (95% CI: 6.3, 15.9, p = 0.01) was found. GEE analysis confirmed a higher impact over time on patients with HGV (p < 0.001). The percentage of patients with at least 1 episode of hypoglycemia decreased from 66.6% to 22.2% (p = 0.02) and from 37.14% to 5.71% (p < 0.01) for global and nocturnal hypoglycemia, respectively. Changes were not significant in patients with low GV. A reduction of A1c was observed in both groups (p < 0.001).ConclusionsThe results suggest that treatment with IDeg reduces GV, A1c levels and the incidence of global and nocturnal hypoglycemia events in patients with HGV, but not in patients with low GV.

The effectiveness of lixisenatide as an add on therapy to basal insulin in diabetic type 2 patients previously treated with different insulin regimes: a multi-center observational study

IntroductionThis observational study aimed to assess the effectiveness of lixisenatide as add on therapy to basal insulin in diabetic type 2 patients previously treated with different insulin regimes.MethodsPatients with diabetes type 2, prescribed with lixisenatide and basal insulin were divided in three groups (premixed insulin, basal bolus insulin and basal oral therapy (BOT). Difference in mean change in HbA1c, body mass index, total insulin doses, fasting blood glucose (FPG) and prandial blood glucose (PPG) were assessed after 3–6-months of follow-up.ResultsThe primary outcomes were assessed in 111 patients. Lixisenatide added to basal insulin, reduced HbA1c and body weight significantly in all three groups of patients (p < 0.001 for all), with the most prominent reduction in the basal bolus group of patients which had the highest baseline HbA1c compared to premix and BOT treatment groups. Regarding a difference in total insulin dose the reduction was statistically significant in the basal bolus (p = 0.006) and premix group (p < 0.001). FPG and PPG were also significantly reduced over time in all three groups (p < 0.001 for all). A composite outcome (reduction of HbA1c below 7% (53 mmol/mol) with any weight loss) was achieved in 27% of total patients included in the study, reduction of HbA1c below 7% was observed in 30% of patients, while 90% of patients experienced weight reduction.ConclusionThese results indicate that lixisenatide add on basal insulin treatment (BIT) can improve glycemic control in a population with long-standing type 2 diabetes and previously uncontrolled on other insulin therapy.