Low Rate Of Hypoglycaemia Research Articles

1045-P: Basal Insulins in Advanced Renal Failure: Time for a Paradigm Shift

Aim: To compare efficacy and safety of IDeg and IGlarU100 in T2DM patients with Stage 3 or 4 CKD. Methods: This single-centered, retrospective, observational study evaluates efficacy and safety of insulin glargine and insulin degludec in CKD with eGFR 60 and below. T2DM patients with DKD receiving IGlarU100 or IDeg for 24 weeks and beyond were included. Data relating to anthropometry, blood pressure, renal parameters, and glycaemic control were analysed. Results: In advanced renal failure, IDeg caused statistically significant less hypoglycemia than IGlarU100. Ironically, reverse occurred in CKD stage 3A which may be contributed by concomitant usage of SUs. Both drugs were found to be similarly efficacious in this population. Conclusion: IDeg has lower rate of hypoglycemia in advanced renal failure T2DM patients and may be a safer option to use in this scenario. Disclosure S. Roy Chaudhuri: None. A. Majumder: None. D. Sanyal: None.

388-P: Real-World Associations between Glucose Management Indicator and CGM-Derived Metrics of Hypoglycemia

Early randomized controlled trials (RCTs) showed a strong inverse relationship between A1C and severe hypoglycemia (SH) risk, which could potentially limit therapy intensification and resulted in some guidelines suggesting increased A1C goals in at-risk patients. Subsequently, RCTs demonstrated that real-time continuous glucose monitoring (CGM) alters this relationship and attenuates SH risk associated with low A1C values ≥6.5%. The glucose management indicator (GMI) reflects average CGM glucose and correlates with A1C. This analysis uses real-world evidence to explore the relationship between GMI and hypoglycemia exposure. Data were from an anonymized convenience sample of 151,315 U.S.-based Dexcom G6 CGM app users with good device adherence evidenced by having uploaded ≥80% of possible CGM values in 3Q 2019. Hypoglycemia exposure was reported as the percentage of glucose values <70 or <54 mg/dL (level 1 or level 2 hypoglycemia, respectively). The Figure shows hypoglycemia and the number of users in six GMI categories. Although there are small, incremental increases in hypoglycemia until GMI is <6.5%, time spent in level 1 and level 2 hypoglycemia remains below the consensus goals of <4% and <1% for users with GMI values ≥6.5%. On average, CGM users with GMI values ≥6.5% have acceptably low rates of hypoglycemia, obviating the need to relax GMI goals as a strategy to reduce the risk of SH. Disclosure T.C. Walker: Employee; Self; Dexcom, Inc. J. Welsh: Employee; Self; CSL Behring. G.J. Norman: Employee; Self; Dexcom, Inc. A. Parker: Employee; Self; Dexcom, Inc. Stock/Shareholder; Self; Dexcom, Inc. D.A. Price: Employee; Self; Dexcom, Inc.

Benefits of insulin degludec/liraglutide are maintained even in patients discontinuing sulphonylureas or dipeptidyl peptidase-4 inhibitors upon initiation of degludec/liraglutide therapy: A post hoc analysis of the DUAL II and DUAL IX trials.

AimTo investigate the efficacy and safety of initiating insulin degludec/liraglutide (IDegLira) in patients with type 2 diabetes (T2D) who had discontinued pretrial sulphonylureas (SUs) or dipeptidyl peptidase‐4 inhibitors (DPP4is) versus patients not previously treated with these regimens.Materials and MethodsIn DUAL II, patients with T2D uncontrolled on basal insulin and metformin ± SU/glinides were randomized to insulin degludec or IDegLira (both capped at 50 U). In DUAL IX, patients were randomized to insulin glargine U100 (no maximum dose) or IDegLira, as add‐on to sodium‐glucose co‐transporter‐2 inhibitors ± oral antidiabetic drugs. In this post hoc analysis, patients were grouped according to pretrial use of SU (DUAL II) or DPP4i (DUAL IX).ResultsRegardless of pretrial SU/DPP4i use, IDegLira was favourable versus insulin comparators with respect to change in HbA1c and body weight. Lower hypoglycaemia rates and comparable end‐of‐trial daily insulin dose were achieved with IDegLira, regardless of pretrial regimen. There was no clinically relevant increase in mean self‐measured blood glucose in the early weeks after IDegLira initiation. There was no statistically significant interaction between the randomized treatments and previous SU/DPP4i use.ConclusionsIDegLira was more favourable compared with degludec or glargine U100 in terms of change in HbA1c and body weight, regardless of antecedent treatment. Clinicians should be aware of a potential transient rise in self‐measured blood glucose when transitioning therapy in patients. This shows that SUs/DPP4is can be safely discontinued, without deterioration in glycaemic control when initiating IDegLira, allowing a simplified treatment regimen.

Efficacy and safety of long-acting glucagon-like peptide-1 receptor agonist dulaglutide in patients with type 2 diabetes: a systematic review and meta-analysis of 21 randomized controlled trials.

To assess the efficacy and safety of once weekly glucagon-like peptide-1 receptor agonist (GLP-1 RA) dulaglutide for the treatment of type 2 diabetes mellitus (T2DM). We searched PubMed, Embase, and Cochrane Library from inception to August 18, 2019. Revman5.3 and Stata13.0 software were used for meta-analysis. Twenty-one trials including 20,367 patients were analyzed. Compared with control group, hemoglobin A1c (HbA1c) in 0.75 mg dulaglutide group and 1.5 mg dulaglutide group were reduced by 0.29% and 0.55%, respectively. More patients treated with 0.75 mg dulaglutide [RR 1.24, 95% CI (1.08, 1.42), p = 0.002] and 1.5 mg dulaglutide [RR 1.66, 95% CI (1.40, 1.99), p < 0.00001] had reached the target of HbA1c 7.0%. In patients with T2DM, 0.75 mg dulaglutide and 1.5 mg dulaglutide had a statistically higher adverse events (AEs) incidence than control, whereas the risk of hypoglycaemia was lower in 0.75 mg dulaglutide group and 1.5 mg dulaglutide group than in control group. Based on the current evidence, 0.75 and 1.5 mg dulaglutide are associated with better glycemic control and lower rate of hypoglycemia in patients with T2DM.

Insulin degludec/liraglutide (IDegLira) maintains glycaemic control and improves clinical outcomes, regardless of pre-trial insulin dose, in people with type 2 diabetes that is uncontrolled on basal insulin.

AimsTo assess whether people with type 2 diabetes transferring from higher basal insulin doses (> 20 units) to a starting dose of 16 units of insulin degludec/liraglutide (IDegLira) benefit from IDegLira with/without transient loss of glycaemic control.Methods Post hoc analysis of DUAL V and VII assessed fasting self‐measured blood glucose (SMBG) over weeks 1–8, changes in HbA1c, body weight and mean insulin dose over 26 weeks, and percentage of participants achieving HbA1c < 53 mmol/mol (7.0%) by end of trial in participants with type 2 diabetes uncontrolled with basal insulin. IDegLira was compared with continued up‐titration of insulin glargine (IGlar U100) in DUAL V, or switching to basal–bolus therapy in DUAL VII (IGlar U100 and insulin aspart), across pre‐trial insulin dose groups (20–29, 30–39 and 40–50 units/day).ResultsIn all subgroups, participants treated with IDegLira experienced significant improvements in HbA1c by end of trial, which were greater than with IGlar U100 up‐titration (estimated treatment difference –5.86, –6.59 and –6.91 mmol/mol for pre‐trial insulin doses of 20–29, 30–39 and 40–50 units/day, respectively) and similar to basal–bolus therapy (estimated treatment difference –0.16, –1.0 and –0.01 mmol/mol for pre‐trial insulin doses of 20–29, 30–39 and 40–50 units/day, respectively). Compared with IGlar U100 and basal–bolus therapy, IDegLira participants experienced weight loss vs. weight gain, lower rates of hypoglycaemia and a lower mean end of trial total daily insulin dose. In both trials, mean fasting SMBG decreased from weeks 1 to 8 across all subgroups, despite a temporary increase in mean fasting SMBG in the 40–50 units pre‐trial insulin dose group during week 1 [mean increase (sd) +1.1 (2.0) mmol/l for DUAL V and +1.1 (2.1) mmol/l for DUAL VII], which reverted to baseline by week 4.ConclusionsRegardless of pre‐trial insulin dose, IDegLira resulted in improved clinical outcomes, even in participants transferring from 40–50 units of basal insulin, despite a transient (< 4 weeks), clinically non‐relevant, elevation in pre‐breakfast SMBG. (Clinical Trial Registry Number NCT01952145 and NCT02420262).

Long-Acting Basal Insulins: A Review of the More Recently Approved Agents.

Long-acting basal insulins are used for the management of both type 1 and type 2 diabetes mellitus. Long-acting basal insulins were developed utilizing recombinant DNA technology and have been available since 2000 with the approval of insulin glargine U-100 followed by insulin detemir in 2005. In recent years, diabetes management has become more complex with the approval of insulin glargine U-300 and insulin degludec U-100 and U-200. Both insulin glargine U-300 and insulin degludec have been compared with insulin glargine U-100 and have demonstrated longer durations of action, as well as lower rates of hypoglycemia. This review discusses the Food and Drug Administration-approved long-acting insulins with a focus on recently approved agents and their efficacy and safety compared with the first long-acting basal insulins.

Insulin glargine compared to neutral protamine Hagedorn (NPH) insulin in patients with type-2 diabetes uncontrolled with oral anti-diabetic agents alone in Hong Kong: a cost-effectiveness analysis

BackgroundInternational guidelines recommend using basal insulin in patients with type-2 diabetes mellitus if glycaemic target cannot be attained on non-insulin anti-diabetic drugs. Available choices of basal insulin include intermediate-acting neutral protamine Hagedorn (NPH) insulin and long-acting insulin analogues like insulin glargine U100. Despite clear advantages of glargine U100, the existing practice in Hong Kong still favours NPH insulin due to lower immediate drug costs.ObjectivesThe objective of this study was to assess the cost-effectiveness of insulin glargine U100 compared to NPH insulin in patients with type-2 diabetes uncontrolled with non-insulin anti-diabetic agents alone in Hong Kong.MethodsThe IQVIA™ Core Diabetes Model (CDM) v9.0 was used to conduct the cost-effectiveness analysis of glargine U100 versus NPH. Baseline characteristics were collected from the Hong Kong Diabetes Registry. Efficacy rates were extracted from a published study comparing glargine U100 and NPH in Asia, utilities from published literature, and costs constructed using the Hong Kong Hospital Authority (HA) Gazette (public healthcare setting). The primary outcome was an incremental cost-effectiveness ratio (ICER).ResultsInsulin glargine U100 resulted in an ICER of HKD 98,663 per Quality Adjusted Life Year (QALY) gained. The incremental gains in QALY and costs were 0.217 years and HKD 21,360 respectively. Results from scenario and probabilistic sensitivity analyses were consistent with that from base case analysis.ConclusionInsulin glargine U100 is a cost-effective treatment for patients with type 2 diabetes compared to NPH insulin in setting in Hong Kong. This was mainly driven by the significantly lower rates of hypoglycaemia of insulin glargine U100 than NPH insulin.

122-LB: iSage: Successful Basal Insulin Titration Managed by a Prescription-Only Digital Therapy for T2DM

Ideally, initiating and titrating basal insulin should quickly achieve A1C and fasting glucose targets without significant hypoglycemia. In practice, it’s often not so simple. iSage Rx (iSage) is the first FDA-cleared digital therapy for basal insulin titration that is prescribed by providers and easily downloaded to patients’ mobile phones. In less than a minute, the provider personalizes their patient’s glycemic targets and configures a titration algorithm for use with any basal insulin. The iSage app automatically manages the patient’s titration plan and provides ongoing education regarding insulin administration. We tested the efficacy of iSage in 27 T2DMs (59±7.6 year, 12M/15F). Entry criteria included T2DM patients treated solely with detemir, glargine or delgudec insulin, fluency in English, and generally healthy. T2DMs with stage 4 or 5 kidney disease, active malignancies, variable glucocorticoid doses, severe visual impairment and dementia were excluded. The study aims included changes in both insulin dose and A1C values while achieving low rates of hypoglycemia. The average (SD) starting and app-directed final doses of insulin were 33.6 (20) and 46.8 (27) U/d, p=0.047, respectively. Initial mean A1c was 8.2 (1.4)% that dropped to 7.3 (0.95)%, p=0.002 at study termination (79-139 days). Among those with an initial A1c &amp;gt;8.0, (mean A1c 9.3%) the final mean A1c was 7.4% (1.0) p=0.005. Of the 2,257 fasting blood glucose readings (BG) recorded in the mobile app, only 27 were &amp;lt;70 mg/dL (1.64% of total fasting BGs). Participants required almost no unexpected visits or phone consultations to manage their insulin doses. The iSage digital therapy, while prescribed by a provider, requires minimal provider demands, is patient self-directed, and produces significant reductions in A1C with low rates of hypoglycemia. Disclosure K. Grdinovac: None. D.C. Robbins: None. T.A. Lavenbarg: None. P. Levin: Research Support; Self; MannKind Corporation, Novartis AG, Novo Nordisk Inc. Speaker’s Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Lilly Diabetes, Merck &amp; Co., Inc., Sanofi. R. Sysko: Employee; Self; iSage Rx, LLC. Funding Amalgam Rx, Inc.; Blue KC

1083-P: Comparison of Hyperglycemia Management Protocols in the ICU: Standard Protocol vs. Electronic Glycemic Management System

A variety of continuous insulin infusion (CII) algorithms are available to improve and maintain glycemic control in the ICU. In December of 2016, our institution, a community based academic hospital of 900 beds, acquired an electronic glycemic management system (eGMS, GlucommanderTM) for the management of ICU patients with hyperglycemia. We present our experience and compared glycemic control between patients managed with eGMS and standard care between December 2016 and December 2018. The standard care group included patients who were not on eGMS with at least 2 blood glucose readings &amp;gt;180 mg/dl during their ICU stay. The primary endpoint was a proportion of blood glucose (BG) readings between 70-180 mg/dl. Secondary outcomes included rates of hyperglycemia &amp;gt; 250 mg/dl, as well as rates of hypoglycemia &amp;lt; 70 mg/dl, &amp;lt; 54 mg/dl and &amp;lt;40 mg/dl, and patient-day rates for hypoglycemia. Among a total of 2897 ICU patients, 1971(68%) were treated with standard care and 926(32%) with eGMS. eGMS resulted in improved glycemic control with lower rates of hypoglycemia, Table. Conclusion: Treatment with eGMS significantly lowered the incidence of hypoglycemia and severe hyperglycemia compared to standard care in the ICU. eGMS is a safe and effective way to manage hyperglycemia in the ICU of an academic medical center. Disclosure G.E. Umpierrez: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc. Research Support; Self; AstraZeneca, Merck &amp; Co., Inc., Novo Nordisk Inc., Sanofi US. J. Messler: Employee; Self; Glytec, LLC.

374-P: Reduced Rates of Hypoglycemia Irrespective of the Definition Used When Switching to Insulin Degludec (degludec) from Other Basal Insulins in Routine Clinical Care: The ReFLeCT Study

ReFLeCT was a multicenter, prospective, observational study designed to investigate the safety and effectiveness of switching to degludec from other basal insulins in patients with type 1 (T1D) or type 2 diabetes (T2D). ReFLeCT comprised a 4-week baseline period (pre-switch basal insulin) and 12-month follow-up period (degludec). The primary endpoint of overall hypoglycemia reported in patient diaries was reduced during follow-up vs. baseline in T1D and T2D without compromising glycemic control. As different hypoglycemia definitions can impact study outcomes, the previous (pre-specified) and updated (post hoc) American Diabetes Association (ADA) hypoglycemia definitions were analyzed and presented here (Figure). Definitions consisted of, documented asymptomatic and symptomatic, pseudo, probable symptomatic, and Level 1, 2 and 3 (severe) (Figure). Hypoglycemic events were analyzed using fully adjusted, negative binomial regression models. In T1D (n=556) and T2D (n=611), the estimated rate ratios across the previous and the updated ADA hypoglycemia definitions were significantly lower during the 12-month follow-up vs. baseline, except for asymptomatic hypoglycemia in T1D (Figure). Overall, switching to degludec from other basal insulins is associated with lower rates of hypoglycemia across a range of definitions. Disclosure H.W. de Valk: Advisory Panel; Self; Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S. M. Feher: Advisory Panel; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk A/S, Sanofi. Research Support; Self; Amgen Inc., Novo Nordisk A/S. Speaker's Bureau; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk A/S, Sanofi. T.K. Hansen: None. J.H. Jendle: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Merck &amp; Co., Inc., Novo Nordisk A/S, Sanofi. Board Member; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Merck &amp; Co., Inc., Novo Nordisk A/S, Sanofi. Consultant; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Merck &amp; Co., Inc., Novo Nordisk A/S, Sanofi. Research Support; Self; Abbott, Dexcom, Inc., Medtronic, Novo Nordisk A/S. Speaker's Bureau; Self; Eli Lilly and Company, Medtronic, Nordic Infucare, Novo Nordisk A/S, Sanofi. Á. Merchante: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Research &amp; Development, Mundipharma International, Novo Nordisk A/S, Nutricia, Persan Pharma. Consultant; Self; Eli Lilly and Company, Novo Nordisk A/S. M.M. Koefoed: Employee; Self; Novo Nordisk A/S. E. Parvaresh Rizi: Employee; Self; Nestlé, Novo Nordisk A/S. E. Zimmermann: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. G. Fadini: Consultant; Self; AstraZeneca, Novo Nordisk A/S, Sanofi. Research Support; Self; AstraZeneca, Novo Nordisk A/S, Sanofi. Speaker's Bureau; Self; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck &amp; Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Sanofi. Funding Novo Nordisk A/S

1044-P: Insulin Intensification with a 24-Hour Wearable Insulin Delivery Device in Patients Inadequately Controlled with Basal Insulin Therapy

A stepwise approach for the addition of prandial insulin is recommended when intensification from basal to basal-bolus therapy is required. Rationale for this approach includes patient resistance to multiple daily injections and a stepwise approach has been associated with lower rates of hypoglycemia. Unfortunately, evidence suggests within a year of initiating prandial insulin, up to 75% of patients require full basal-bolus therapy. This results in the ongoing need to address the same barriers that initially delayed intensification to full basal-bolus therapy. In light of these considerations, insulin delivery options that simplify basal-bolus therapy while offering clinical benefit without increased safety risk may be an attractive option. This study retrospectively evaluated the use of a wearable basal-bolus insulin delivery device (V-Go) in 73 patients with type 2 diabetes inadequately controlled with basal insulin. Change in A1C, insulin basal and total daily doses (TDD) and prevalence of hypoglycemia were analyzed. Mean ± SD characteristics at baseline included duration of diabetes 12 ± 7 years, A1C 9.6 ± 1.5%, basal TDD 52 ± 34 u/day (range 10 to 170), and basal TDD 0.53 ± 0.35 u/kg. Concomitant anti-hyperglycemic agents were prescribed in 93% of patients. After a mean of 5 months of V-Go use, mean ± SD reductions in A1C (-1.3 ± 1.5%; p&amp;lt;0.0001) and basal TDD (-22 ± 30 u/day; p&amp;lt;0.0001 and -0.24 ± 0.31 u/kg; p&amp;lt;0.0001) were observed. Compared to baseline, TDD was similar on V-Go, 52 ± 18 u/day; p=0.946, however, insulin dose was redistributed to incorporate prandial coverage (22 ± 9 u/day) and basal coverage (30 ± 13 u/day). With V-Go use, severe hypoglycemia was reduced from 10% at baseline to 3% and fewer concomitant agents were prescribed. Intensification from basal insulin to basal-bolus therapy with V-Go was effective and resulted in a lower prevalence of hypoglycemia. Disclosure T. Zeidan: Advisory Panel; Self; Corcept Therapeutics. Research Support; Self; Valeritas, Inc. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Valeritas, Inc. C.C. Nikkel: Employee; Self; Valeritas, Inc. Stock/Shareholder; Self; Valeritas, Inc. E.A. Dziengelewski: Employee; Self; Valeritas, Inc. Stock/Shareholder; Self; Valeritas, Inc.

964-P: CGM-Tele Monitoring in Older Adults with T1D: Results of a Pilot Study

T1D management in older individuals can be difficult due to an increased risk for hypoglycemia and other co-morbidities. CGM can help lower rates of hypoglycemia; however, in practice, patient data is only reviewed at clinic visits, rather than in near real-time by the diabetes care team. This pilot study tested if patients could be remotely monitored daily through a CGM system (Dexcom G5/6) that communicated via smart phone to a Tidepool designed dashboard. Alerts were set for: ≥4 hours without CGM signal, ≥2 hours 54-70 mg/dl, and 15 mins &amp;lt;54 mg/dl. If alerts occurred, the CDE performed telemedicine outreach following a protocol. Ten individuals with T1D ≥65 years were enrolled. Patients were 72+5.3 years; duration of diabetes 39.1+16.5 years; 50% were on CSII. At baseline, the CGM was connected to the monitoring system, followed by 2 weeks of system checks. Remote monitoring was activated at week 2 continuing to week 14. Three patients didn’t complete the study. One had connection issues, one didn't want to wear the CGM; the third had spousal health issues. The CDE/system was capable of identifying the desired findings (Table). An A1C was measured at baseline and 14 weeks. The A1C didn’t change, 7.2% +0.95 vs. 7.3% +0.99. This trial proved it was possible to monitor well-controlled seniors with T1D using an automated system with daily alerts to identify episodes of hypoglycemia and time off CGM. Further research is needed to assess the alert system efficacy. Disclosure M.D. Harmel: Advisory Panel; Spouse/Partner; Abbott, Becton, Dickinson and Company, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Lexicon Pharmaceuticals, Inc., MannKind Corporation, Merck &amp; Co., Inc., Novo Nordisk Inc., Omada Health, Inc., OptumRx, Inc., Sanofi, Zafgen, Inc. Consultant; Self; MannKind Corporation. Research Support; Spouse/Partner; AstraZeneca, Dexcom, Inc., MannKind Corporation. Speaker's Bureau; Spouse/Partner; Novo Nordisk Inc. V.F. Ruelas: None. E.T. Nykaza: None. A.L. Peters: Advisory Panel; Self; Abbott, Becton, Dickinson and Company, Bigfoot Biomedical, Eli Lilly and Company, Lexicon Pharmaceuticals, Inc., Livongo Health, MannKind Corporation, Medscape, Merck &amp; Co., Inc., Omada Health, Inc., OptumRx, Inc., Sanofi US, Zafgen, Inc. Research Support; Self; AstraZeneca, Dexcom, Inc., Jaeb Center for Health Research, MannKind Corporation, National Institute of Diabetes and Digestive and Kidney Diseases. Speaker's Bureau; Self; Novo Nordisk Inc.

148-OR: IDegLira Improves Glycemic Control in Japanese Patients with Type 2 Diabetes (T2D) Uncontrolled on Premixed Insulin Therapy

Diabetes management is moving towards choosing therapies that reduce treatment burden, risk of hypoglycemia and weight gain. DUAL VII showed that IDegLira, a fixed-ratio insulin degludec (degludec)/liraglutide combination, had non-inferior A1C lowering, lower hypoglycemia rates, no weight gain and less treatment burden vs. basal-bolus therapy. In contrast, there are no trial data on the efficacy and safety of switching patients (pts) from premixed insulin therapy (with basal and bolus components) to a fixed-ratio combination such as IDegLira. DUAL II Japan (NCT02911948) - a 26 week phase 3a multicenter, randomized, double-blind, treat-to-target trial - compared the efficacy and safety of IDegLira vs. ≤50 U degludec in 210 Japanese pts with uncontrolled T2D (A1C 7.5-11.0%) on 20-50 U basal or premixed insulin therapy + metformin ± an oral antidiabetic drug. Primary analysis confirmed superior change in A1C with IDegLira vs. degludec ≤50, and post hoc analyses found the treatment effect was independent of insulin type at baseline (basal or premixed; interaction test, p=0.5229). This post hoc evaluation describes novel data in a subset of 39 pts who switched from premixed insulin to IDegLira. Mean (standard deviation [SD]) A1C was 8.3% (0.73) at baseline and 6.7% (0.93) at Week 26. Mean (SD) body weight reduced by 1.5 (2.9) kg. Daily insulin dose was 14.1 (3.4) U at baseline and 34.2 (11.5) U at Week 26. Rate of hypoglycemic events (defined as severe or plasma glucose &amp;lt;56 mg/dL) was 2.6 events/patient-year of exposure (52 events in 17 pts). No pts withdrew. This post hoc study is the first to evaluate the switch from premixed insulin to IDegLira, in pts with uncontrolled T2D. IDegLira initiation resulted in improved A1C and weight loss with most pts not experiencing hypoglycemic events. This study offers insight into the effectiveness and safety of switching pts from premixed insulin therapy to IDegLira, and provides a support for further investigation into this transition. Disclosure H. Watada: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Kissei Pharmaceutical Co., Ltd., Merck Sharp &amp; Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Pfizer Inc., Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited. Speaker's Bureau; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Sanofi, Takeda Pharmaceutical Company Limited, Terumo Medical Corporation. Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Kowa Pharmaceutical Europe Co. Ltd., Merck Sharp &amp; Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd., Sanwa Chemical Industry Co. Ltd., Takeda Pharmaceutical Company Limited. B.F. Agner: Employee; Self; Novo Nordisk A/S. A. Doshi: Advisory Panel; Self; Pfizer Inc. Employee; Self; PrimeCare Medical Group. R. Grøn: Employee; Self; Novo Nordisk A/S. M.F. Ranthe: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. L.K. Billings: Advisory Panel; Self; Novo Nordisk A/S, Sanofi-Aventis. Consultant; Self; Novo Nordisk A/S. Research Support; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Novo Nordisk A/S. Funding Novo Nordisk A/S

144-OR: Ultra Rapid Lispro (URLi) Improves Postprandial Glucose (PPG) Control vs. Humalog (Lispro) in T1D: PRONTO-T1D Study

URLi is a novel prandial insulin lispro formulation developed to more closely match physiological insulin secretion. This phase 3, 26-week trial evaluated the efficacy and safety of URLi vs. lispro in 1222 adults with T1D. The primary endpoint was A1C change from baseline after 26 weeks of treatment, with multiplicity adjusted objectives for PPG excursions (PPGE) after test meal. After an 8-week lead-in to optimize basal insulin glargine or degludec, patients were randomized to double-blind URLi (n=451) or lispro (n=442) given at the start of the meal, or open-label URLi (n=329) given 20 minutes after the meal (URLi +20). A1C was reduced for URLi and lispro and non-inferiority (NI) was shown: estimated treatment difference (ETD) -0.08 [-0.16; 0.00] p=0.06 (Figure). NI for URLi +20 vs. lispro was also shown: ETD +0.13 [0.04; 0.22] p=0.003. URLi was superior to lispro in controlling 1- and 2-h PPGE during the test meal (Figure). No significant differences were seen between URLi vs. lispro in rate or incidence of severe hypoglycemia; overall daily or postprandial hypoglycemia (&amp;lt;54 mg/dL) ≤4 h after meals, but URLi had a 37% lower hypoglycemia rate in the period &amp;gt;4 h, (p=0.013). Overall, the incidence of treatment-emergent adverse events was similar between groups. URLi was efficacious with a similar safety profile to lispro and, when given at start of the meal, provided superior PPG control vs. lispro. Disclosure L.J. Klaff: Research Support; Self; Abbott, Ascensia Diabetes Care, Cnoga Medical, Gan &amp; Lee Pharmaceuticals, Lilly Diabetes, Medtronic MiniMed, Inc., Novo Nordisk Inc., REMD Biotherapeutics, Sanofi, Senseonics, Xeris Pharmaceuticals, Inc., Zealand Pharma A/S. D. Cao: Employee; Self; Eli Lilly and Company. M.A. Dellva: Employee; Self; Eli Lilly and Company. J. Tobian: Employee; Self; Eli Lilly and Company. J. Miura: None. D. Dahl: None. J.M. Bue-Valleskey: Employee; Self; Eli Lilly and Company. Funding Eli Lilly and Company

A Retrospective Study of Early vs Delayed Home Dose Basal Insulin in the Acute Management of Diabetic Ketoacidosis.

BackgroundInsulin via continuous intravenous infusion (ICII) is a standard of care for treating patients with diabetic ketoacidosis (DKA). Once DKA is resolved, ICII is transitioned to subcutaneous therapy. However, recent guidelines recommend continuation of home dose subcutaneous basal insulin (HDBI) in patients with DKA. The objective of this study was to evaluate outcomes in patients who received early vs delayed HDBI.MethodsThis is a retrospective cohort study of patients ≥16 years old admitted to the medical intensive care unit between 1 July 2012 and 30 June 2015 with a primary diagnosis of DKA who received ICII and HDBI. Patients were stratified into early or delayed groups if they received HDBI before or after resolution of DKA, respectively. The primary outcome was incidence of transitional failure, defined as resumption of ICII or recurrence of DKA after initial ICII discontinuation.ResultsA total of 106 admissions were included for analysis; 33 (31.1%) received early HDBI. The incidence of transitional failure was similar between the early and delayed groups (OR, 0.60; 95% CI, 0.26 to 1.44; P = 0.72). In the early group, ICII duration was shorter at 13.8 hours [interquartile range (IQR), 10.1 to 16.5] vs 17.1 hours (IQR, 12.6 to 21.1; P = 0.04), with a trend toward lower rates of hypoglycemia (OR, 0.41; 95% CI, 0.16 to 1.05; P = 0.058).ConclusionThere was no significant difference in incidence of transitional failure between early and delayed HDBI. Early HDBI was associated with a shorter duration of ICII and a trend toward less hypoglycemia. A prospective analysis is needed to confirm these findings.

Glucose Management Technologies for the Critically Ill.

Hyperglycemia is common in the intensive care unit (ICU) both in patients with and without a previous diagnosis of diabetes. The optimal glucose range in the ICU population is still a matter of debate. Given the risk of hypoglycemia associated with intensive insulin therapy, current recommendations include treating hyperglycemia after two consecutive glucose >180 mg/dL with target levels of 140-180 mg/dL for most patients. The optimal method of sampling glucose and delivery of insulin in critically ill patients remains elusive. While point of care glucose meters are not consistently accurate and have to be used with caution, continuous glucose monitoring (CGM) is not standard of care, nor is it generally recommended for inpatient use. Intravenous insulin therapy using paper or electronic protocols remains the preferred approach for critically ill patients. The advent of new technologies, such as electronic glucose management, CGM, and closed-loop systems, promises to improve inpatient glycemic control in the critically ill with lower rates of hypoglycemia.

Evaluation of the long-term cost-effectiveness of once-weekly semaglutide versus dulaglutide for treatment of type 2 diabetes mellitus in the UK.

AimsGlucagon‐like peptide‐1 (GLP‐1) receptor agonists are appealing as glucose‐lowering therapy for individuals with type 2 diabetes mellitus (T2DM) as they also reduce body weight and are associated with low rates of hypoglycaemia. This analysis assessed the long‐term cost‐effectiveness of semaglutide 0.5 and 1 mg vs dulaglutide 1.5 mg (two once‐weekly GLP‐1 receptor agonists) from a UK healthcare payer perspective, based on the head‐to‐head SUSTAIN 7 trial, to inform healthcare decision making.Materials and MethodsLong‐term outcomes were projected using the IQVIA CORE Diabetes Model (version 9.0). Baseline cohort characteristics, changes in physiological parameters and adverse event rates were derived from the 40‐week SUSTAIN 7 trial. Costs to a healthcare payer were assessed, and these captured pharmacy costs and costs of complications. Utilities were taken from published sources.ResultsOnce‐weekly semaglutide 0.5 and 1 mg were associated with improvements in quality‐adjusted life expectancy of 0.04 and 0.10 quality‐adjusted life years, respectively, compared with dulaglutide 1.5 mg. Clinical benefits were achieved at reduced costs, with lifetime cost savings of GBP 35 with once‐weekly semaglutide 0.5 mg and GBP 106 with the once‐weekly semaglutide 1 mg, resulting from fewer diabetes‐related complications due to better glycaemic control. Therefore, both doses of once‐weekly semaglutide were considered dominant vs dulaglutide 1.5 mg (improving outcomes and reducing costs).ConclusionsCompared with treatment with dulaglutide, once‐weekly semaglutide represents a cost‐effective option for treating individuals in the UK with T2DM who are not achieving glycaemic control with metformin, projected to both improve clinical outcomes and reduce costs.

Improved Glycemic Control with Insulin Glargine 300U/mL (Toujeo®) in Patients with Type 2 Diabetes: Real-World Effectiveness in Switzerland.

IntroductionInsulin glargine 300 U/mL (Gla-300, Toujeo®) is a long-acting, once-daily basal insulin with improved—more stable and smoother—pharmacokinetic and pharmacodynamic profiles compared to insulin glargine 100 U/mL (Gla-100) and insulin degludec (IDeg). These properties have been shown to translate into an effective HbA1c reduction with the advantage of a lower risk of hypoglycemia in randomized controlled trials of Gla-300 versus Gla-100. In this study, we assessed the effectiveness and safety of Gla-300 under real-world conditions in Switzerland.MethodsThe prospective, observational, open-label, multicenter study TOP-2 explored the effectiveness of Gla-300 in adult patients with type 2 diabetes (T2D) uncontrolled (HbA1c 7.5–10%) on their previous basal insulin in Germany, Austria, and Switzerland. The primary endpoints were the percentages of patients achieving a fasting plasma glucose (FPG) of ≤ 6.1 mmol/L after 6 and 12 months. Secondary endpoints included changes in HbA1c, FPG, body weight, and insulin dose as well as hypoglycemia incidence and safety. Here we report the results for the Swiss patient cohort after 12 months of treatment with insulin glargine 300 U/mL.ResultsThe 62 patients (33 men) had a mean age of 65 years, a mean diabetes duration of 14 years, a mean body mass index (BMI) of 31 kg/m2, and were mainly switched from Gla-100 (44%) to Gla-300. The most common concomitant oral anti-diabetes therapy was metformin (65%). The mean individual HbA1c target chosen by the investigators was 7.4%. After 12 months of therapy, Gla-300 significantly reduced mean HbA1c from 8.2% to 7.6% (p < 0.0001). Likewise, Gla-300 significantly reduced mean FPG from 9.1 mmol/L to 7.4 mmol/L (p < 0.0001). At study end, 32% of patients achieved FPG ≤ 6.1 mmol/L, 55% achieved FPG ≤ 7.2 mmol/L , and 57% achieved their individual HbA1c target. Gla-300 was uptitrated to a mean dose of 40 units per day. Symptomatic hypoglycemia incidence after 12 months was low at 9.7% and a rate of 0.23 events per patient year. Body weight remained stable and was not significantly altered during the study.ConclusionUpon switching basaI insulin to Gla-300, overall glucose control significantly improved and glycemic targets were achieved with a low rate of hypoglycemia in T2D patients under real-world conditions in Switzerland.FundingSanofi–Aventis (Suisse) SA.

Safety of once-weekly glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been shown to be efficacious in lowering HbA1c in patients with type 2 diabetes (T2D) and are associated with reduction in meal-related hyperglycemia and bodyweight, low rates of hypoglycemia, and most recently, with reduction of major adverse cardiovascular events for all of them. This narrative review compares the safety of the existing once-weekly (OW) GLP-1RAs with other currently available antidiabetic treatments. Key safety data from 29 sponsor-led trials of albiglutide, dulaglutide, exenatide extended-release (ER), and semaglutide were included in the analysis. Once-weekly GLP-1RAs were associated with lower rates of hypoglycemic events compared with most other antidiabetic agents. Gastrointestinal adverse events were common, tended to dissipate with time, and tended to be less frequent with albiglutide and exenatide ER compared with semaglutide. Of the currently approved OW GLP-1RAs as of Q4 2018, exenatide ER is the only one without an indication for patients with T2D with comorbid severe renal impairment or end-stage renal disease. Implications for practice: OW GLP-1RAs offer a well-tolerated therapeutic option for T2D. Further studies are needed to further differentiate the safety profiles of OW GLP-1RAs.

A safe and efficacious preventive strategy in the high-risk surgical neonate: cycled total parenteral nutrition.

Hepatic dysfunction in patients reliant on total parenteral nutrition (TPN) may benefit from cycled TPN. A concern for neonatal hypoglycemia has limited the use of cycled TPN in neonates less than 1 week of age. We sought to determine both the safety and efficacy of cycled TPN in surgical neonates less than 1week of age. A retrospective chart review was conducted on surgical neonates placed on prophylactic and therapeutic cycled TPN from January 2013 to March 2016. Specific emphasis was placed on identifying incidence of direct hyperbilirubinemia and hypoglycemic episodes. Fourteen neonates were placed on cycled TPN; 8 were prophylactically cycled and 6 were therapeutically cycled. Median gestational age was 36 weeks (34, 37). Sixty-four percent (n = 9) had gastroschisis. There was no difference between the prophylactic and therapeutic groups in incidence of hyperbilirubinemia > 2mg/dL (3 (37%) vs 5 (83%), p = 0.08) or the length of time to development of hyperbilirubinemia [24 days (4, 26) vs 27 days (25, 67), p = 0.17]. Time on cycling was similar though patients who were prophylactically cycled had a shorter overall time on TPN. Three (21%) infants had documented hypoglycemia, but only one infant became clinically symptomatic. Prophylactic TPN cycling is a safe and efficacious nutritional management strategy in surgical neonates less than 1week of age with low rates of hypoglycemia and a shorter total course of TPN; however, hepatic dysfunction did not appear to be improved compared to therapeutic cycling.