Teva Pharmaceutical Industries Research Articles

345-OR: A Retrospective U.S. Real-World Evidence Study on Glycemic Goal Achievement within 2 Years Post-Basal Insulin Initiation

The probability of reaching the glycemic goal of A1C <7.0% in T2D patients, who initiated basal insulin (BI) after being uncontrolled on oral therapy, was investigated using real-world data extracted from the Optum Humedica EMR database. The cohort comprised 70,288 patients whose baseline A1C was obtained ≤90 days prior to BI initiation (index date). Baseline characteristics were mean age (59 years), mean BMI (34.1 kg/m2), mean A1C (9.8%), mean FPG (190.6 mg/dL), gender (53% males), and race (74.8% Caucasian, 14.2% African American, 2.3% Asian American). Mean A1C increased from 8.5% to 9.8% in the 6 months prior to BI initiation while still on oral therapy, declined to about 8.2% at 3 months post index date, and then remained steady for 24 months. The Kaplan-Meier curve for reaching the glycemic goal (A1C <7.0%) had a steep increasing slope in the first 12 months but remained flat during the following 12 months. Achieving the glycemic goal was less likely in patients with higher baseline A1C. Lower baseline A1C correlated with persistence of index medications (mean duration 574.1, 489.3, and 479.3 days for sub-cohorts with baseline A1C 7.0-8.0%, 8.0-9.0%, and ≥9.0%, respectively). Adjusted proportional hazards analyses showed a higher probability of reaching A1C <7.0% with ages 18-34 years or 55-64 years, male gender, Caucasian race, and non-Hispanic ethnicity. Lower probability of reaching the glycemic goal was seen in patients with A1C ≥8.0% or coronary heart disease, neuropathy, peripheral vascular disease, or retinopathy comorbidities (potentially indicative of longer disease duration). These results suggest that if an A1C goal <7.0% is not achieved within 12 months post BI initiation, the likelihood of achieving glycemic control diminishes thereafter. Clinicians should consider additional therapeutic options for their patients if T2D is still inadequately controlled 12 months after BI initiation. Disclosure X.V. Peng: Employee; Self; Sanofi. Stock/Shareholder; Spouse/Partner; AbbVie Inc. Stock/Shareholder; Self; AbbVie Inc., Sanofi. P.R. Hunt: Consultant; Self; AstraZeneca, Sanofi. T.A. Dex: Stock/Shareholder; Self; Merck & Co., Inc., Pfizer Inc., Sanofi US. R. Lubwama: Employee; Self; Merck & Co., Inc., Sanofi. N. Skolnik: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., GlaxoSmithKline plc., Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Mylan, Sanofi, Teva Pharmaceutical Industries Ltd. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., GlaxoSmithKline plc., Sanofi. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc. L. Blonde: Consultant; Self; Gilead Sciences, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc., Sanofi US. Research Support; Self; Janssen Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc., Sanofi US. Speaker's Bureau; Self; Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi US. Funding Sanofi U.S.

1841-P: Fasting Test Distinguished Organic from Functional Hypoglycemia

Nondiabetic hypoglycemia may be caused by hepatic or renal failure, drugs, malnutrition, malignancy or functional changes. The fasting test may be used to distinguish organic hypoglycemia by insulinoma from functional (reactive) hypoglycemia. The aim was to compare if clinical and biochemical characteristics could clearly differentiate both diagnoses during fasting test. In total, 84 patients (mean age 50 ± 16 years; 54 females) with history of unclear hypoglycemia were examined at our department in the last 8 years. Their liver and renal functions were normal. All patients underwent a 72-hour fasting test. The test was stopped earlier when neuroglycopenic symptoms developed. Blood samples were taken for glucose (BG), insulin (Ins) and C peptide measurements at the beginning, in 6-hour intervals and at the end of the test. Fasting test was positive (F+ group) in 43 persons developing neuroglycopenic symptoms and thus it was stopped earlier (duration 24 ± 17 hours) as compared to F- group (41 persons) without these symptoms during the whole 72-hours of fasting. Both groups were similar in age, BMI or arterial pressure. Significant differences between F+ and F- group were observed at the end of the test (BG: 2.0 ± 0.4 vs. 3.8 ± 0.8 mmol/l, p<0.0001; Ins: 61 (11; 111) vs. 13 (5; 22) mU/L, p<0.0001; C peptide: 1.4 (0.5; 2.1) vs. 0.4 (0.1; 0.6) nmol/L, p<0.0001). All patients in F+ group developed spontaneous hypoglycemia <2.5 mmol/l during fasting but it was not true in F- group. The insulin/BG ratio (normal value <5.0 mU/mmol) could significantly distinguish both groups at the end of fasting (29.7 vs. 3.5 mU/mmol, p<0.0001). Insulinoma was then confirmed in all F+ patients at surgery. Fasting test represents the most important diagnostic tool in the evaluation of unclear nondiabetic hypoglycemia. Neuroglycopenic symptoms together with spontaneous hypoglycemia by fasting are the most sensitive indicators of insulinoma. In addition, the insulin/BG ratio seems to be of highest benefit in distinguishing organic and functional hypoglycemia. Disclosure J. Skrha: Advisory Panel; Self; Boehringer Ingelheim International GmbH. Speaker's Bureau; Self; Lilly Diabetes. M. Prazny: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi-Aventis, Takeda Pharmaceutical Company Limited. Board Member; Self; Bayer AG. Consultant; Self; Medtronic, Roche Diabetes Care. Speaker's Bureau; Self; Abbott, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Sanofi-Aventis, Servier, Teva Pharmaceutical Industries Ltd. J. Krizova: None. J. Skrha: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Lilly Diabetes, Novo Nordisk A/S, Sanofi. Funding RVO-VFN00064165

2331-PUB: Effectiveness of Insulin Glargine 300 units/mL in Treating Patients with T2DM Uncontrolled by Basal Insulin in Real-Life Settings in the Czech Republic (TOPAZ Study)

Objective: To evaluate the clinical effectiveness of Gla-300 units/mL (Gla-300) in the treatment of patients with type 2 diabetes (T2DM) uncontrolled by basal insulin in real-life clinical settings in the Czech Republic (TOPAZ study). Methods: TOPAZ was a prospective, multi-centric, non-interventional, 6-month study. Of the 312 patients screened, 289 were evaluated at month 6. The primary objective was the change of HbA1c after 6 months. The proportion of patients with HbA1c <7% DCCT (<53 mmol/mol), and those with a decrease of at least 0.5% of HbA1c at month 6, change in FPG, body weight and insulin dose at months 3 and 6 were analysed as secondary objectives. Incidence of hypoglycaemia, adverse events and patient treatment satisfaction (DTSQ) were also assessed. Results: HbA1c decreased significantly after 6 months (mean change 0.9 ± 1.1% DCCT [-9.9 ± 11.6 mmol/mol], p < 0.0001). HbA1c target < 7% DCCT was achieved in 17.6% of patients, 66.1% of patients showed mean HbA1c decrease of -1.5 ± 0.8%. At month 6, FPG decreased (mean change from baseline -1.8 ±3.1 mmol/L) as well as the incidence of hypoglycaemia decreased by 49% (p ˂ 0.0001) while no weight gain was observed. No significant safety signals were identified. Patients reported significantly better satisfaction with the treatment with Gla-300 (p < 0.0001). Conclusion: In a real-world setting, switching to Gla-300 in T2DM patients uncontrolled with any other basal insulin was associated with improved glycemic control and reduced risk of hypoglycaemia without weight gain, while patients′ satisfaction with treatment increased. Disclosure M. Prazny: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi-Aventis, Takeda Pharmaceutical Company Limited. Board Member; Self; Bayer AG. Consultant; Self; Medtronic, Roche Diabetes Care. Speaker's Bureau; Self; Abbott, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Sanofi-Aventis, Servier, Teva Pharmaceutical Industries Ltd. M. Flekac: None. P. Jelinek: Employee; Self; Sanofi. J. Maskova: Other Relationship; Self; Sanofi-Aventis. Funding Sanofi; Neox Clinical Research

Safety and efficacy of pridopidine in patients with Huntington's disease (PRIDE-HD): a phase 2, randomised, placebo-controlled, multicentre, dose-ranging study

Previous trials have shown that pridopidine might reduce motor impairment in patients with Huntington's disease. The aim of this study was to ascertain whether higher doses of pridopidine than previously tested reduce motor symptoms in a dose-dependent manner while maintaining acceptable safety and tolerability. PRIDE-HD was a randomised, placebo-controlled, phase 2, dose-ranging study in adults (aged ≥21 years) with Huntington's disease at outpatient clinics in 53 sites across 12 countries (Australia, Austria, Canada, Denmark, France, Germany, Italy, Poland, Russia, the Netherlands, the UK, and the USA). Eligible patients had clinical onset after age 18 years, 36 or more cytosine-adenine-guanine repeats in the huntingtin gene, motor symptoms (Unified Huntington's Disease Rating Scale total motor score [UHDRS-TMS] ≥25 points), and reduced independence (UHDRS independence score ≤90%). Patients were randomly assigned (1:1:1:1:1) with centralised interactive-response technology to receive one of four doses of pridopidine (45, 67·5, 90, or 112·5 mg) or placebo orally twice a day for 52 weeks. Randomisation was stratified within centres by neuroleptic drug use. The primary efficacy endpoint was change in the UHDRS-TMS from baseline to 26 weeks, which was assessed in all randomised patients who received at least one dose of study drug and had at least one post-baseline efficacy assessment (full analysis set). Participants and investigators were masked to treatment assignment. This trial is registered with EudraCT (2013-001888-23) and ClinicalTrials.gov (NCT02006472). Between Feb 13, 2014, and July 5, 2016, 408 patients were enrolled and randomly assigned to receive placebo (n=82) or pridopidine 45 mg (n=81), 67·5 mg (n=82), 90 mg (n=81), or 112·5 mg (n=82) twice daily for 26 weeks. The full analysis set included 397 patients (81 in the placebo group, 75 in the 45 mg group, 79 in the 67·5 mg group, 81 in the 90 mg group, and 81 in the 112·5 mg group). Pridopidine did not significantly change the UHDRS-TMS at 26 weeks compared with placebo at any dose. The most frequent adverse events across all groups were diarrhoea, vomiting, nasopharyngitis, falls, headache, insomnia, and anxiety. The most common treatment-related adverse events were insomnia, diarrhoea, nausea, and dizziness. Serious adverse events occurred in the pridopidine groups only and were most frequently falls (n=5), suicide attempt (n=4), suicidal ideation (n=3), head injury (n=3), and aspiration pneumonia (n=3). No new safety or tolerability concerns emerged in this study. One death in the pridopidine 112·5 mg group due to aspiration pneumonia was considered to be possibly related to the study drug. Pridopidine did not improve the UHDRS-TMS at week 26 compared with placebo and, thus, the results of secondary or tertiary analyses in previous trials were not replicated. A potentially strong placebo effect needs to be ruled out in future studies. Teva Pharmaceutical Industries.

Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals.

Stable heavy isotopes of hydrogen, carbon, and other elements have been incorporated into drug molecules, largely as tracers for quantitation during the drug development process. Studies involving the human use of drugs labeled with deuterium suggest that these compounds may offer some advantages when compared with their nondeuterated counterparts. Deuteration has gained attention because of its potential to affect the pharmacokinetic and metabolic profiles of drugs. Deutetrabenazine (Austedo, Teva Pharmaceutical Industries, Ltd) is the first deuterated drug to receive Food and Drug Administration approval. This deuterated form of the drug tetrabenazine is indicated for the treatment of chorea associated with Huntington's disease as well as tardive dyskinesia. Ongoing clinical trials suggest that a number of other deuterated compounds are being evaluated for the treatment of human diseases and not merely as research tools. A search of the MEDLINE (1946 to present) database was undertaken using the Ovid interface. The search was conducted using the heading deuterium and then limited to Administration & Dosage, Adverse Effects, Pharmacokinetics, Pharmacology, Poisoning, Therapeutic Use, and Toxicity. All articles were reviewed and those with human information were included. Review articles were likewise interrogated for additional published human data. Deuterated compounds may, in some cases, offer advantages over nondeuterated forms, often through alterations in clearance. Deuteration may also redirect metabolic pathways in directions that reduce toxicities. The approval of additional deuterated compounds may soon follow. Clinicians will need to be familiar with the dosing, efficacy, potential side effects, and unique metabolic profiles of these new entities.

Massachusetts, Other States Ratchet Up Legal Action Against Opioid Manufacturers

Back to table of contents Previous article Next article Legal NewsFull AccessMassachusetts, Other States Ratchet Up Legal Action Against Opioid ManufacturersNick ZagorskiNick ZagorskiSearch for more papers by this authorPublished Online:31 Jul 2018https://doi.org/10.1176/appi.pn.2018.7b23AbstractGroups across the nation are targeting Purdue Pharma and other companies with lawsuits alleging misleading claims about the safety of opioid painkillers.Over the past year, opioid manufacturers have faced a growing barrage of lawsuits from states and municipalities over the role the companies played in the opioid crisis.Massachusetts in June filed a lawsuit against Purdue Pharma, maker of OxyContin, as well as 16 current and former executives at the company.As with the numerous other cases of opioid litigation, the basis for Massachusetts’ suit is that Purdue and its executives deceptively promoted opioid-based pain medications (particularly OxyContin) despite knowing about the risks associated with long-term use of the medication. “We found that Purdue engaged in a multibillion-dollar enterprise to mislead us about their drugs,” Massachusetts Attorney General Maura Healey said at a news conference announcing the suit. “Purdue pushed prescribers to give higher doses to keep patients on drugs for longer periods of time, without regard to the very real risks of addiction, overdose, and death.”The Massachusetts suit came one month after six other states (Florida, Nevada, North Carolina, North Dakota, Tennessee, and Texas) filed suits against Purdue. In total, Purdue now faces lawsuits by 24 states and the territory of Puerto Rico. Similarly, more than 1,000 additional lawsuits from cities, counties, and Native American tribes have been brought against companies that make or distribute opioid medications. Besides Purdue, companies such as Janssen Pharmaceuticals (makers of Duragesic), Endo Health Solutions Inc. (makers of Percocet), and Teva Pharmaceutical Industries (makers of Actiq) have been named in lawsuits. To expedite the proceedings, over 400 of these lawsuits were combined by the Judicial Panel on Multidistrict Litigation (MDL) in December 2017 and handed over to the federal court for the Northern District of Ohio. The MDL panel chose this district in part because this region has been heavily affected by the opioid crisis. The presiding judge, Dan Polster, scheduled the first trial—for the governments of the city of Cleveland and Ohio’s Cuyahoga and Summit counties against 11 opioid manufacturers/distributors—for March 18, 2019. In the meantime, he ordered both sides to begin settlement talks.This forthcoming trial is not the first time Purdue has been in the legal crosshairs. Following years of legal battles with many states, Purdue eventually reached a settlement in 2007 and pled guilty to charges of misleading the public about the drug’s risks. Purdue and executives paid $634 million in fines, which were distributed to federal and state agencies, as well as individuals who had sued the company.During the plea, company executives noted that since 2002—when Florida became the first state to probe Purdue’s marketing practices—they had implemented new training, monitoring, and compliance procedures to ensure that its employees would not misrepresent any drugs in the future. The recent lawsuits from Massachusetts and other states contend otherwise, stating that Purdue and other drug companies have continued to place profits over public health.“We are disappointed that after months of good faith negotiations working toward a meaningful resolution to help these states address the opioid crisis, this group of attorneys general have unilaterally decided to pursue a costly and protracted litigation process,” the company said in the statement. ■ ISSUES NewArchived

The Teva Case: A Tale of a Race to the Bottom in Global Securities Regulation

This article tells how a shareholder class action against Teva Pharmaceutical Industries, the largest generic drug maker in the world, ended the practice of hiding individual executive pay figures by companies crosslisted in Israel and the United States. That practice relied on a tenuous reading of the law, according to which crosslisted issuers are exempt from the pay disclosure requirements in both countries. It had nevertheless persisted with no regulatory response because both countries maintained a hands-off attitude toward crosslisted companies. While the class action prompted Israel to ensure crosslisted issuers disclose individual executive pay, crosslisted issuers continue to be less transparent in other areas. The story serves as an important reminder of the powerful race to laxity in the global competition for securities listings.

BioChaperone Glucagon (BCG), a Stable Ready-to-Use Liquid Glucagon Formulation, Is Well Tolerated and Quickly Restores Euglycemia after Insulin-Induced Hypoglycemia

BCG is a stable, ready-to-inject, aqueous formulation of human glucagon for hypoglycemia rescue therapy. In this randomized, double-blind, crossover trial we investigated the safety and efficacy of two BCG formulations vs. a commercially available glucagon (GlucaGen® HypoKit, GEN) in 27 patients with type 1 diabetes who received single subcutaneous doses of 1 mg of BCG1, BCG2 or GEN under insulin-induced hypoglycemic conditions (plasma glucose (PG)<60 mg/dl). Both BCG formulations were safe and well tolerated with the most frequent adverse event being mild nausea with both BCGs and GEN. Both BCGs quickly restored PG of ≥ 70 mg/dl after hypoglycemia (BCG1 11.5±5.0 min; BCG2 10.0±3.5 min; GEN 7.3±1.8 min, p<0.001 vs. BCG1 and BCG2). PG≥70 mg/dl was reached within 30 minutes by all but one patient with both BCGs and the mean PG increase at 15 minutes was 29±17 mg/dl with BCG1, 36±16 mg/dl with BCG2 and 47±11 mg/dl with GEN (p<0.001 vs. BCG1 and BCG2). In conclusion, the BioChaperone technology allows the formulation of stable ready-to-use liquid formulations of human glucagon suited for rescue therapy of severe hypoglycemia with only slightly slower effects than GEN. Disclosure S. Glezer: Stock/Shareholder; Self; Sanofi. Stock/Shareholder; Spouse/Partner; Sanofi. Employee; Self; ADOCIA, Novo Nordisk Inc.. Employee; Spouse/Partner; Pfizer Inc., Teva Pharmaceutical Industries Ltd.. Stock/Shareholder; Spouse/Partner; Teva Pharmaceutical Industries Ltd.. U. Hovelmann: None. S. Teng: Employee; Self; ADOCIA. D. Lamers: None. M. Odoul: Employee; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. J. Correia: Employee; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. E. Zijlstra: Speaker's Bureau; Self; Novo Nordisk A/S. Other Relationship; Self; Novo Nordisk A/S. M. Gaudier: Employee; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. O. Soula: Board Member; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. Employee; Spouse/Partner; ADOCIA. D. Duracher: Employee; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA.

Better Postprandial Glucose (PPG) Control with BioChaperone Combo (BC Combo) than with Lispro Mix25 (LMx) or Separate Glargine and Lispro (G+L) Administrations in Subjects with Type 2 Diabetes (T2DM)

BC Combo is a co-formulation of prandial insulin lispro (25%) and basal insulin glargine (75%) with a rapid “prandial“ insulin component and prolonged flat “basal“ component compared to LMx. In this study the effects of BC Combo on PPG vs. LMx and G+L were investigated. Thirty-nine T2DM subjects (mean±SD age 60.8±7.5 years and HbA1c 7.97±0.6%) were randomized to receive the three insulin combinations immediately before a standardized solid meal test (MMT, 20% protein 30% fat 50% carbohydrates) in a double-blind, double-dummy, cross-over design. The individual insulin dose was the same for each visit day (mean 0.62 U/kg). BC Combo demonstrated improved PPG compared to LMx (Figure, reduction ∆AUCBG,0-2h of 18%, p=0.0009) and G+L (reduction ∆AUCBG,0-2h of 10%, p=0.0450). The proportion of subjects experiencing documented symptomatic hypoglycemic events (plasma glucose <70 mg/mL) over 24h was numerically lower with BC Combo (15.8%) vs. LMx (32.4%) and G+L (21.6%). The total insulin PK profile of BC Combo showed a faster time to insulin peak and a lower exposure in the late prandial phase (2-6 h) than LMx and G+L. In conclusion, BC Combo demonstrated superior PPG control in T2DM subjects with numerically fewer subjects experiencing symptomatic hypoglycemia compared to both LMx and separate G+L. Disclosure T. Heise: Research Support; Self; ADOCIA, Boehringer Ingelheim GmbH, Dance Biopharm, Eli Lilly and Company, Janssen Research & Development, MedImmune, Merck Sharp & Dohme Corp., Mylan, Nordic Bioscience, Novo Nordisk A/S, Poxel SA, Roche Diagnostics Corporation, Saniona, Sanofi, Senseonics, Zealand Pharma A/S. Advisory Panel; Self; Novo Nordisk A/S, Mylan. Speaker's Bureau; Self; Dexcom, Inc., Eli Lilly and Company, Novo Nordisk A/S, Sanofi. L. Plum-Moerschel: None. C. Mégret: Employee; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. T. Herbrand: None. V. Vacher: Employee; Self; ADOCIA. E. Anastassiadis: None. O. Klein: None. M. Gaudier: Employee; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. O. Soula: Board Member; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. Employee; Spouse/Partner; ADOCIA. S. Glezer: Stock/Shareholder; Self; Sanofi. Stock/Shareholder; Spouse/Partner; Sanofi. Employee; Self; ADOCIA, Novo Nordisk Inc.. Employee; Spouse/Partner; Pfizer Inc., Teva Pharmaceutical Industries Ltd.. Stock/Shareholder; Spouse/Partner; Teva Pharmaceutical Industries Ltd.. B. Alluis: None. G. Meiffren: Employee; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA.

Pooled Analysis of Clinical Trials Investigating the Pharmacokinetics (PK) of Ultra-rapid Insulin BioChaperone Lispro (BCLIS) vs. Lispro (LIS) in Subjects with Type 1 (T1D) and Type 2 (T2D) Diabetes

BCLIS is an ultra-rapid insulin lispro formulation designed to accelerate the time-action profile vs. conventional short-acting insulin analogs. PK characteristics of single doses of BCLIS and LIS were characterized in four randomized, double-blind, crossover studies in altogether 112 T1D and 51 T2D subjects who received BCLIS and LIS (0.2 U/kg in studies 1 and 2, individualized doses in studies 3 and 4) subcutaneously by syringe. Insulin absorption was consistently faster with BCLIS than with LIS as indicated by reaching early half-maximum insulin levels (early t50%max) 8.4 (95% confidence interval [-9.6;-7.2]) and time to maximum levels (tmax) 10.0 [-14.3;-5.8] min earlier (p<0.0001 for both comparisons). Early insulin exposure was significantly greater for BCLIS for up to 2 hours after administration (Figure). BCLIS also showed faster offset of exposure, with a 22.3 [-28.8;-15.7] min earlier time to late half-maximum insulin levels (late t50%max) (p<0.0001) and a 24% lower late exposure (AUC2-6h; Figure). Total exposure (AUC0-6h) was similar for both formulations in all studies (treatment ratio in pooled analysis 0.99 [0.95;1.03], p=NS). In conclusion, BCLIS consistently shows faster onset and offset of exposure than conventional LIS in both T1D and T2D. Disclosure T. Heise: Research Support; Self; ADOCIA, Boehringer Ingelheim GmbH, Dance Biopharm, Eli Lilly and Company, Janssen Research & Development, MedImmune, Merck Sharp & Dohme Corp., Mylan, Nordic Bioscience, Novo Nordisk A/S, Poxel SA, Roche Diagnostics Corporation, Saniona, Sanofi, Senseonics, Zealand Pharma A/S. Advisory Panel; Self; Novo Nordisk A/S, Mylan. Speaker's Bureau; Self; Dexcom, Inc., Eli Lilly and Company, Novo Nordisk A/S, Sanofi. A. Ranson: Employee; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. M. Gaudier: Employee; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. O. Soula: Board Member; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. Employee; Spouse/Partner; ADOCIA. B. Alluis: None. E. Zijlstra: Speaker's Bureau; Self; Novo Nordisk A/S. Other Relationship; Self; Novo Nordisk A/S. S. Glezer: Stock/Shareholder; Self; Sanofi. Stock/Shareholder; Spouse/Partner; Sanofi. Employee; Self; ADOCIA, Novo Nordisk Inc.. Employee; Spouse/Partner; Pfizer Inc., Teva Pharmaceutical Industries Ltd.. Stock/Shareholder; Spouse/Partner; Teva Pharmaceutical Industries Ltd. G. Meiffren: Employee; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA.

The Ultra-rapid Insulin (URI) BioChaperone Lispro (BCLIS) Shows Favorable Pharmacodynamics (PD) and Pharmacokinetics (PK) vs. Faster Aspart (FIA) and Insulin Aspart (ASP) in Insulin Pumps (CSII)

This double-blind randomized crossover trial is the first to compare the PD and PK properties of two URIs (BCLIS and FIA) and of a conventional analog (ASP). Forty-three patients with type 1 diabetes received a bolus of 0.15 U/kg of BCLIS, FIA or ASP with CSII on top of a 0.01 U/kg/h basal rate under euglycemic clamp conditions (ClampArt®). Compared to ASP, BCLIS had significantly faster-on and -off PD with higher AUCs in the first two hours, lower AUCGIR 2-6h and earlier tearly0.5GIRmax and tlate0.5GIRmax (Table, Figure). Compared to FIA, BCLIS showed similar early GIR excursions and a significantly faster-off PD with earlier tlate0.5GIRmax. PK was aligned with PD and showed higher early (0-1h) and lower late (2-6h) exposures of BCLIS vs. FIA.Table: Mean±SD PD and PK parametersParameterDefinitionBCLISASPFIAp-valueBCLIS/ASPp-valueBCLIS/FIAAUCGIR 0-2h[mg/kg]PD effect in first two hours592±275500±244566±2760.00380.3127AUCGIR 2-6h[mg/kg]PD effect 2-6 hours post-dose693±329881±387753±2680.00150.3087tearly0.5GIRmax[min]Time to early half-maximum PD44±2257±1942±13<0.00010.9020tlate0.5GIRmax[min]Time to late half-maximum PD210±68232±52228±610.00200.0017AUCINS 0-1h [h.mU/L]Insulin exposure 0-1 hour post-dose68±2743±2259±21<0.00010.0284AUCINS 2-6h [h.mU/L]Insulin exposure 2-6 hours post-dose81±4395±4193±450.00060.0001tlate0.5INSmax[min]Time to late half-maximum insulin concentrations147±48183±68165±59<0.00010.0028 Disclosure B.W. Bode: Research Support; Self; Abbott. Advisory Panel; Self; ADOCIA. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Janssen Pharmaceuticals, Inc.. Research Support; Self; GlaxoSmithKline plc., Lexicon Pharmaceuticals, Inc., Medtronic MiniMed, Inc., Novo Nordisk Inc., Diasome Pharmaceuticals, Inc., Sanofi US, Eli Lilly and Company, MannKind Corporation, Dexcom, Inc., OmniPod, Senseonics. O. Klein: None. C. Seroussi: Employee; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. A. Ranson: Employee; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. J. Arrubla: None. J. Correia: Employee; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. M. Gaudier: Employee; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. O. Soula: Board Member; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. Employee; Spouse/Partner; ADOCIA. R. Soula: Employee; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. Board Member; Self; Cellnovo. B. Alluis: None. G. Meiffren: Employee; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. S. Glezer: Stock/Shareholder; Self; Sanofi. Stock/Shareholder; Spouse/Partner; Sanofi. Employee; Self; ADOCIA, Novo Nordisk Inc.. Employee; Spouse/Partner; Pfizer Inc., Teva Pharmaceutical Industries Ltd.. Stock/Shareholder; Spouse/Partner; Teva Pharmaceutical Industries Ltd. T. Heise: Research Support; Self; ADOCIA, Boehringer Ingelheim GmbH, Dance Biopharm, Eli Lilly and Company, Janssen Research & Development, MedImmune, Merck Sharp & Dohme Corp., Mylan, Nordic Bioscience, Novo Nordisk A/S, Poxel SA, Roche Diagnostics Corporation, Saniona, Sanofi, Senseonics, Zealand Pharma A/S. Advisory Panel; Self; Novo Nordisk A/S, Mylan. Speaker's Bureau; Self; Dexcom, Inc., Eli Lilly and Company, Novo Nordisk A/S, Sanofi.

BioChaperone 222 (BC222), the New Excipient Enabling the Ultra-rapid BioChaperone Lispro (BCLIS) Formulation, Is Completely Absorbed and Rapidly Excreted after Subcutaneous (s.c.) Injection

BC222 is an oligosaccharide grafted with anionic charges and amino acid moieties designed to speed up the absorption of insulin lispro in the BCLIS formulation. Non-clinical data indicated that BC222 is rapidly excreted unchanged by the kidney. This open label clinical trial conducted in 12 healthy volunteers [mean±SD age 31.4±9.5 years; weight 95.3±16.8 kg; BMI 28.6±4.1 kg/m²] investigated the PK properties and safety and tolerability of a single s.c. dose of BC222 (equal to the BC222 content in 1.0 U/kg BCLIS) using validated liquid chromatography mass spectrometry assays for BC222 in plasma and urine samples. BC222 was rapidly absorbed, with a median plasma Tmax of 1.2 h (Figure). BC222 was rapidly cleared from the blood with a mean terminal half-life of 2.07 (±0.52) h reaching baseline levels 10-12 h after administration. Urinary BC222 concentrations reached 95.4±4.5% of the injected dose within 12 h post-dosing and was as high as 9 % ± 5% of the total dose after 48h indicating that BC222 was completely absorbed from the s.c. tissue into the blood and quickly cleared via the urine. BC222 was well tolerated and safe with only two mild adverse events occurring in the whole study. In conclusion, BC222 is completely absorbed after s.c. injection and rapidly excreted by the kidneys. Disclosure G. Meiffren: Employee; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. L. Plum-Moerschel: None. A. Ranson: Employee; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. E. Anastassiadis: None. C. Seroussi: Employee; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. J. Correia: Employee; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. G. Andersen: None. M. Gaudier: Employee; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. O. Soula: Board Member; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. Employee; Spouse/Partner; ADOCIA. S. Glezer: Stock/Shareholder; Self; Sanofi. Stock/Shareholder; Spouse/Partner; Sanofi. Employee; Self; ADOCIA, Novo Nordisk Inc.. Employee; Spouse/Partner; Pfizer Inc., Teva Pharmaceutical Industries Ltd.. Stock/Shareholder; Spouse/Partner; Teva Pharmaceutical Industries Ltd.. B. Alluis: None.

A1C Target Attainment in Patients with T2D Receiving iGlarLixi Who Reach PPG and FPG Targets in the Lixilan-L Trial

Treatments that reduce A1C levels often do not reflect improvements in both fasting and postprandial hyperglycemia. Data from 731 patients (pts) with T2D uncontrolled on basal insulin ± OADs in the LixiLan-L trial (NCT02058160) were used to investigate the association between achieving FPG/PPG targets and A1C target attainment after 30 weeks of treatment with iGlarLixi (n=366) or iGlar (n=365). Outcomes were A1C target attainment, A1C change from baseline, and mean A1C at Week 30 in pts achieving both FPG and PPG target, FPG target only, PPG target only, or neither, using ADA glycemic targets. The proportion of pts reaching PPG only, or both FPG and PPG target, was numerically higher for iGlarLixi, while the proportion reaching FPG target only was numerically higher for iGlar (Figure. 1A). iGlarLixi-treated pts reaching both FPG and PPG targets, or FPG target only, showed statistically significant greater A1C changes from baseline, lower end-of-trial A1C, and a higher proportion reaching A1C target than iGlar-treated pts (Figure. 1B-D). Despite a numerically higher proportion of pts reaching FPG target only in the iGlar arm, A1C outcomes were in favor of pts receiving iGlarLixi. In conclusion, the complementary actions of iGlarLixi on both fasting and postprandial hyperglycemia were associated with better A1C target attainment compared with iGlar alone, which mainly targets fasting hyperglycemia. Disclosure L.A. Leiter: Advisory Panel; Self; AstraZeneca. Research Support; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca. Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Advisory Panel; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company. Research Support; Self; GlaxoSmithKline plc.. Advisory Panel; Self; Janssen Pharmaceuticals, Inc.. Research Support; Self; Janssen Pharmaceuticals, Inc.. Speaker's Bureau; Self; Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Merck & Co., Inc.. Speaker's Bureau; Self; Merck & Co., Inc.. Research Support; Self; Merck & Co., Inc.. Advisory Panel; Self; Novo Nordisk Inc.. Research Support; Self; Novo Nordisk Inc.. Speaker's Bureau; Self; Novo Nordisk Inc.. Advisory Panel; Self; Sanofi. Research Support; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Advisory Panel; Self; Servier. Speaker's Bureau; Self; Servier. Research Support; Self; Servier. Advisory Panel; Self; Amgen Inc.. Speaker's Bureau; Self; Amgen Inc.. Research Support; Self; Amgen Inc., Esperion Therapeutics, Kowa Pharmaceuticals America, Inc., The Medicines Company. Advisory Panel; Self; Akcea Therapeutics, Novartis Pharmaceuticals Corporation. J. Chao: None. A. Saremi: Employee; Self; Sanofi US. T.A. Dex: Employee; Self; Sanofi US. Stock/Shareholder; Self; Pfizer Inc., Merck Sharp & Dohme Corp., Teva Pharmaceutical Industries Ltd. J.A. Davidson: Other Relationship; Self; American Association of Clinical Endocrinologists. Consultant; Self; Aspire Bariatrics. Advisory Panel; Self; AstraZeneca. Consultant; Self; Boston Therapeutics, Inc.. Advisory Panel; Self; GlaxoSmithKline plc., Intarcia Therapeutics, Inc., Merck & Co., Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk A/S, Sanofi.

Visiting the Dentist May Help Diagnose Prediabetes

Diabetes is a well known risk factor for periodontal and dental diseases. Despite increasing diabetes awareness, up to a third of diabetes cases remain undiagnosed. We assumed that a visit at the dentist’s is an opportunity to assess one’s glucose tolerance. We conducted a nationwide cross-sectional study evaluating whether a dentist can help diagnose diabetes in at-risk subjects. The study was performed between March and June 2017. Thirty dental surgeries across the country participated in the study. Each surgery was given 20 laboratory referral notes for free fasting plasma glucose (FPG) measurement to be handed over to 20 consecutive eligible individuals who gave their consent to take part in the study. The referred patients were asked to perform FPG test during the following 4 weeks. The study inclusion criteria were: age ≥18 years, any degree of any dental or periodontal disease, presence of at least one diabetes risk factor (i.e., BMI ≥25 kg/m2, family history of diabetes, sedentary lifestyle, past gestational diabetes, hypertension, dyslipidemia, cardiovascular disease, policystic ovary syndrome) and negative history of any glucose intolerance. Out of 600 referred patients, 469 (78.2%, 330 [70.4%] women, mean [±SD] age 53.7±15.4 years) had FPG assessed. Mean FPG in all subjects was 97.2±20.9 mg/dl (range 63-377 mg/dl). In 140 subjects (29.9% of those tested and 23.3% of those referred) impaired fasting glucose (IFG; i.e., FPG ≥100 and <126 mg/dl) was diagnosed. 19 subjects had FPG ≥126 mg/dl. IFG subjects were older than those with normal FPG: 60.1±12.6 vs. 50.9±15.7 years (p<0.001), and were more often men (40% vs. 27%; p<0.01). Odds ratio for IFG in subjects aged ≥60 vs. those <60 years was 3.413 (95% CI 2.215-5.264). In conclusion, approx. every fourth patient with at least one diabetes risk factor visiting the dentist’s presents with IFG. Dentists should be concerned about prediabetes particularly in their male patients aged ≥60. Increasing diabetes awareness among the dentists may help diagnose prediabetes and thus further prevent diabetes. Disclosure L. Czupryniak: Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company. Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company. Speaker's Bureau; Self; Novo Nordisk A/S. Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Merck Sharp & Dohme Corp., Merck & Co., Inc., Polpharma, Servier. E. Szymanska-Garbacz: Speaker's Bureau; Self; Sanofi, Eli Lilly and Company, Novo Nordisk A/S, Boehringer Ingelheim Pharmaceuticals, Inc., Medtronic MiniMed, Inc., Merck & Co., Inc. P. Bijos: Employee; Self; Teva Pharmaceutical Industries Ltd..

Co-occurrence of 2+ Early Complications in Type 1 Diabetes—SEARCH for Diabetes in Youth

SEARCH reported a high burden of early complications in type 1 diabetes (T1DM). We examined co-occurrence of complications and related risk factors among 1327 SEARCH T1DM participants aged 10-30 years. Risk factors were assessed at baseline (mean diabetes duration and age = 0.8 and 10.9 years, respectively) and follow-up (7.8 and 18.0 years, respectively). Retinopathy (RET), diabetic kidney disease (DKD), peripheral neuropathy, cardiovascular autonomic neuropathy (CAN), and arterial stiffness (AS) were assessed at follow-up. We examined co-occurrence of ≥2 complications overall, by type, and within four demographic/metabolic risk factor clusters identified using cluster analysis. Clusters were characterized by worsening risk profiles (Table). Co-occurrence of ≥2 complications was observed in 5.9% of participants, more frequently than expected by chance (4.4%, p=0.02). Specifically, RET+DKD (0.83% vs. 0.23%), RET+AS (0.98% vs. 0.34%), and AS+CAN (1.81% vs. 1.04%) all co-occurred more frequently (all p<0.05). Prevalence of ≥2 complications increased across risk clusters from 2.3% to 20.8%. Selected characteristics and prevalence of 2+ complications at follow-up by risk factor clustersCluster 1 (n=261)Cluster 2 (n=509)Cluster 3 (n=348)Cluster 4 (n=24)p-valueNHW (n, %)217 (83.1)395 (77.6)257 (73.9)15 (62.5)0.002Private insurance (n, %)211 (80.8)386 (76.1)222 (64.2)9 (37.5)<0.001A1c (%)8.5 ± 1.59.0 ± 1.79.7 ± 1.911.8 ± 2.0<0.001Non-HDLc (mg/dl)79.0 ± 12.9105.7 ± 12.2147.9 ± 21.5245.5 ± 33.5<0.001Waist to height ratio0.44 ± 0.050.46 ± 0.060.49 ± 0.070.50 ± 0.05<0.001Mean arterial pressure (mmHg)80.0 ± 8.082.6 ± 8.682.4 ± 8.484.4 ± 10.1<0.001≥2 complications (n, %)6 (2.3)32 (6.3)28 (8.0)5 (20.8)<0.001 In conclusion, early T1DM complications co-occur more frequently than expected, at a young age and short diabetes duration. A cluster of risk factors including minority race/ethnicity, lack of private insurance, and poor metabolic profiles identifies groups to target with interventions to reduce complications. Disclosure K.A. Sauder: None. J.M. Stafford: None. E.J. Mayer-Davis: None. E.T. Jensen: None. S. Saydah: None. A.K. Mottl: None. L.M. Dolan: None. R.F. Hamman: None. J.M. Lawrence: None. C. Pihoker: None. S.M. Marcovina: None. R. Dagostino: Consultant; Self; Teva Pharmaceutical Industries Ltd., Acelity, RedHill Biopharma, Edwards Lifesciences. D. Dabelea: None.

Use of a Machine Learning Algorithm Improves Prediction of Progression to Diabetes

Identification a-priori of subjects at high risk of progression from prediabetes to diabetes may enable targeted delivery of interventional programs, while avoiding the burden of prevention and treatment in those at low risk. This study relies on the NHS THIN database cohort of 2,761,222 persons with at least 2 glucose measurements during an average follow-up of 6 years. Prediabetes was diagnosed in 470,107 persons, with 4.8% of them progressing annually to diabetes. We constructed a non-linear model identifying those at high risk of annual progression based on all available patient data and history. The major variables contributing to the model were glucose, HbA1c, BMI, age and gender. Using the clinically acceptable cutoffs of HbA1c≥6.0% and/or glucose≥110mg/dl identified 76.5% of those who actually progressed to diabetes (sensitivity), while labelling 33.2% of the population as high risk (positivity rate). Setting our model at the same sensitivity yielded a lower positivity rate of 22.0%, thereby identifying the same number of progressors while labelling a significantly smaller population as high risk. The predictive ability of our model was superior to simple logistic regression based on glucose, HbA1c, BMI, age and gender as well (Table). In conclusion, our algorithm enables judicious selection of the target population for a clinical intervention, with a higher positive predictive value, thus leading to cost saving. Disclosure A. Cahn: Advisory Panel; Self; AstraZeneca, Novo Nordisk Inc.. Research Support; Self; AstraZeneca. Consultant; Self; GlucoMe. Stock/Shareholder; Self; GlucoMe. Advisory Panel; Self; Eli Lilly and Company. Speaker's Bureau; Self; Novo Nordisk Inc., Eli Lilly and Company, AstraZeneca. Advisory Panel; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp.. Consultant; Self; medial early sign. A. Shoshan: Employee; Self; Medial Research. T. Sagiv: Employee; Self; Medial EarlySign. R. Yesharim: None. I. Raz: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca. Advisory Panel; Self; Boehringer Ingelheim GmbH. Speaker's Bureau; Self; Boehringer Ingelheim GmbH. Advisory Panel; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company. Stock/Shareholder; Self; DarioHealth. Advisory Panel; Self; Merck Sharp & Dohme Corp., Novo Nordisk Inc.. Speaker's Bureau; Self; Novo Nordisk Inc.. Advisory Panel; Self; Orgenesis Inc., Pfizer Inc., Sanofi R&D, SmartZyme Biopharma. Consultant; Self; Bristol-Myers Squibb Company. Speaker's Bureau; Self; Bristol-Myers Squibb Company, Johnson & Johnson Diabetes Institute, LLC., Merck Sharp & Dohme Corp., Novartis Pharma K.K., Sanofi-Aventis. Consultant; Self; FuturRx Ltd, Insuline Medical,Camereyes Ltd, Exscopia, Medial EarlySign Ltd. Stock/Shareholder; Self; Glucome Ltd, InsuLine Medical Ltd.. Consultant; Self; Dermal Biomics Inc. Stock/Shareholder; Self; Orgenesis Inc.. Speaker's Bureau; Self; Teva Pharmaceutical Industries Ltd.. Advisory Panel; Self; Concenter BioPharma/Silkim Ltd, Camereyes Ltd. Stock/Shareholder; Self; CameraEyes Ltd. Advisory Panel; Self; Breath of Life PharmaLtd, Panaxia. R. Goshen: Consultant; Self; Medial EarlySign Ltd..

Relationship of Ethnicity to Clinical Outcomes in iGlarLixi-Treated Patients with Type 2 Diabetes

Pharmacogenetic studies have shown significant differences among racial and ethnic groups. This post-hoc analysis of 2 30-week phase 3 trials of patients with type 2 diabetes uncontrolled on metformin ± oral antidiabetes drugs (OADs) (LixiLan-O: NCT02058147) or basal insulin ± OADs (LixiLan-L: NCT02058160) determined the safety of iGlarLixi vs. insulin glargine (iGlar) among Hispanic and non-Hispanic patients. Analysis of variance/covariance was used for continuous variables and χ2/Cochran-Mantel-Haenszel for categorical variables. A generalized linear model using negative binomial distributions with factors of treatment arm and ethnicity, covariates of age and baseline weight or BMI, and log exposure as offset, was used for symptomatic hypoglycemia (plasma glucose ≤70mg/dL) rates. Adjusted hypoglycemia rates used the same model with mean values of age and baseline weight or BMI. Across studies 20% (353/1730) of all patients were Hispanic. At baseline, Hispanic patients had significantly lower body weight, BMI, and fasting plasma glucose vs. non-Hispanic patients (all, P<0.001). Overall, clinical outcomes were similar for Hispanic and Non-Hispanic patients, regardless of drug type (Figure). However, iGlarLixi demonstrates better glycemic control in both Hispanic and non-Hispanic patients, with similar safety outcomes to iGlar. Disclosure P. Mora: Advisory Panel; Self; Novo Nordisk Inc.. Consultant; Self; Sanofi US. Speaker's Bureau; Self; Novo Nordisk Inc.. Advisory Panel; Self; Sanofi US. J. Chao: None. A. Saremi: Employee; Self; Sanofi US. T.A. Dex: Employee; Self; Sanofi US. Stock/Shareholder; Self; Pfizer Inc., Merck Sharp & Dohme Corp., Teva Pharmaceutical Industries Ltd.. M. Roberts: None. G.E. Umpierrez: Research Support; Self; Sanofi US, Merck & Co., Inc., Novo Nordisk Inc., AstraZeneca. Advisory Panel; Self; Sanofi, Intarcia Therapeutics, Inc..

Glycemic Target Attainment in Insulin-Naïve Patients with T2D Receiving iGlarLixi

This study assessed the relationship between FPG, PPG and glycated hemoglobin (A1C) target attainment using ADA glycemic targets in patients (pts) with T2D. A post-hoc analysis of the phase 3 LixiLan-O (NCT02058147) trial assessed the efficacy and safety of iGlarLixi (n=468) vs. insulin glargine U100 (iGlar) (n=466) and lixisenatide (Lixi) (n=233) in pts uncontrolled on metformin ± a second OAD, continuing only on metformin, over a 30-week period. The proportion of pts reaching both FPG and PPG target was highest for iGlarLixi, while the proportions of those reaching FPG or PPG targets only were highest for iGlar (targeting FPG) and Lixi (targeting PPG), respectively (Figure 1A). There was a stepwise trend in A1C change, end-of-study A1C, and proportion of pts reaching A1C goals in favor of iGlarLixi, followed by iGlar and Lixi (Figure 1B-D). Pts reaching both FPG and PPG targets had the greatest A1C drop and lowest A1C values, and represented the largest proportion of pts acheiving A1C target. No differences were observed in hypoglycemia rates in all treatment arms, and a greater proportion of pts experienced weight loss with iGlarLixi vs. iGlar (55.3% vs. 39.9%). By simultaneously targeting fasting and postprandial hyperglycemia, iGlarLixi treatment results in greater A1C reduction and better A1C target attainment than iGlar or Lixi alone. Disclosure C. Desouza: Consultant; Self; Novo Nordisk A/S, Sanofi. Research Support; Self; Merck & Co., Inc.. Advisory Panel; Self; Medscape. V. Fonseca: Consultant; Self; Abbott. Board Member; Self; American Association of Clinical Endocrinologists. Consultant; Self; Eli Lilly and Company. Stock/Shareholder; Self; Amgen Inc.. Consultant; Self; Asahi Kasei Corporation, AstraZeneca, Novo Nordisk Inc., ADOCIA, Intarcia Therapeutics, Inc., Sanofi-Aventis. J.P. Frias: Research Support; Self; AbbVie Inc., Allergan, Amgen Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company. Consultant; Self; CeQur Corporation. Research Support; Self; Cirius Therapeutics, AstraZeneca, Calibra Medical, Elcelyx Therapeutics, Inc.. Consultant; Self; Elcelyx Therapeutics, Inc.. Research Support; Self; Eli Lilly and Company, Genentech, Inc., Ionis Pharmaceuticals, Inc., ICON plc., Janssen Pharmaceuticals, Inc.. Consultant; Self; Johnson & Johnson Diabetes Institute, LLC.. Research Support; Self; Lexicon Pharmaceuticals, Inc., Ligand Pharmaceuticals, Inc.. Consultant; Self; Ligand Pharmaceuticals, Inc.. Research Support; Self; Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Pfizer Inc., Sanofi. Consultant; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Research Support; Self; Theracos, Inc. L. Van Gaal: Advisory Panel; Self; Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen J & J, Merck MSD, Novo Nordisk, Sanofi and Servier/Intarcia. Speaker's Bureau; Self; Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen J & J, Merck MSD, Novo Nordisk, Sanofi and Servier/Intarcia. Research Support; Self; EU (Hepadip & Resolve consortium) and National Research Funds. F. Giorgino: Consultant; Self; Abbott, AstraZeneca, Boehringer Ingelheim GmbH. Research Support; Self; Eli Lilly and Company, Johnson & Johnson Services, Inc.. Consultant; Self; MedImmune, Merck Sharp & Dohme Corp., Roche Diabetes Care Health and Digital Solutions, Sanofi. Research Support; Self; Takeda Development Centre Europe Ltd.. J. Chao: None. T.A. Dex: Employee; Self; Sanofi US. Stock/Shareholder; Self; Pfizer Inc., Merck Sharp & Dohme Corp., Teva Pharmaceutical Industries Ltd.. M. Roberts: None. A. Saremi: Employee; Self; Sanofi US. L.A. Leiter: Advisory Panel; Self; AstraZeneca. Research Support; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca. Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Advisory Panel; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company. Research Support; Self; GlaxoSmithKline plc.. Advisory Panel; Self; Janssen Pharmaceuticals, Inc.. Research Support; Self; Janssen Pharmaceuticals, Inc.. Speaker's Bureau; Self; Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Merck & Co., Inc.. Speaker's Bureau; Self; Merck & Co., Inc.. Research Support; Self; Merck & Co., Inc.. Advisory Panel; Self; Novo Nordisk Inc.. Research Support; Self; Novo Nordisk Inc.. Speaker's Bureau; Self; Novo Nordisk Inc.. Advisory Panel; Self; Sanofi. Research Support; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Advisory Panel; Self; Servier. Speaker's Bureau; Self; Servier. Research Support; Self; Servier. Advisory Panel; Self; Amgen Inc.. Speaker's Bureau; Self; Amgen Inc.. Research Support; Self; Amgen Inc., Esperion Therapeutics, Kowa Pharmaceuticals America, Inc., The Medicines Company. Advisory Panel; Self; Akcea Therapeutics, Novartis Pharmaceuticals Corporation.

Feasibility of Creating a Diagnosis-Based Diabetic Foot Registry in a Large Health Care Provider

We aimed to assess the validity of diagnostic codes relating to diabetic foot ulcer (DFU) in real-world data seeking to create a national DFU registry. Data were obtained from the diabetes registry of Maccabi Healthcare Service (MHS), a 2.1 million member sick fund in Israel, which included 122,500 patients in 2015. We randomly selected and reviewed ∼400 patient files from each of the following categories: 1) had a diagnostic code of DFU in 2015; 2) had a diagnostic code suggestive of DFU in 2015 including: leg ulcer, amputation, DFU in proximate years or abnormality reported by nurse; 3) high risk patients (peripheral arterial disease (PAD), neuropathy, etc.). The patients' charts were reviewed by study physicians and DFU was validated or refuted. Relying upon diagnostic codes entered by physicians, the positive predictive value was 73.1% (95% CI 67.6-78.2) and the sensitivity was 48.2% (95% CI 45.8-50.7%). We therefore conclude that the diagnostic codes alone cannot be reliably used to create a DFU registry, and a prospective registry is considered. The estimated annual prevalence of DFU in the diabetes registry of MHS in 2015 was 1.3% (95% CI 1.0-1.6%). Clinical features and outcomes of patients with validated diagnostic codes of DFU are shown (Table). In multivariate analysis: age, diabetes duration, socioeconomic status, previous amputation and PAD were independently associated with risk of amputation or death. Disclosure A. Cahn: Advisory Panel; Self; AstraZeneca, Novo Nordisk Inc.. Research Support; Self; AstraZeneca. Consultant; Self; GlucoMe. Stock/Shareholder; Self; GlucoMe. Advisory Panel; Self; Eli Lilly and Company. Speaker's Bureau; Self; Novo Nordisk Inc., Eli Lilly and Company, AstraZeneca. Advisory Panel; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp.. Consultant; Self; medial early sign. T. Altaras: None. T. Agami: None. O. Liran: None. C.E. Touaty: None. R. Pollack: None. I. Raz: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca. Advisory Panel; Self; Boehringer Ingelheim GmbH. Speaker's Bureau; Self; Boehringer Ingelheim GmbH. Advisory Panel; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company. Stock/Shareholder; Self; DarioHealth. Advisory Panel; Self; Merck Sharp & Dohme Corp., Novo Nordisk Inc.. Speaker's Bureau; Self; Novo Nordisk Inc.. Advisory Panel; Self; Orgenesis Inc., Pfizer Inc., Sanofi R&D, SmartZyme Biopharma. Consultant; Self; Bristol-Myers Squibb Company. Speaker's Bureau; Self; Bristol-Myers Squibb Company, Johnson & Johnson Diabetes Institute, LLC., Merck Sharp & Dohme Corp., Novartis Pharma K.K., Sanofi-Aventis. Consultant; Self; FuturRx Ltd, Insuline Medical,Camereyes Ltd, Exscopia, Medial EarlySign Ltd. Stock/Shareholder; Self; Glucome Ltd, InsuLine Medical Ltd.. Consultant; Self; Dermal Biomics Inc. Stock/Shareholder; Self; Orgenesis Inc.. Speaker's Bureau; Self; Teva Pharmaceutical Industries Ltd.. Advisory Panel; Self; Concenter BioPharma/Silkim Ltd, Camereyes Ltd. Stock/Shareholder; Self; CameraEyes Ltd. Advisory Panel; Self; Breath of Life PharmaLtd, Panaxia. G. Chodick: None. I. Zucker: None.

Urinary NGAL and KIM-1 Are Significantly Elevated in Young Adults (YA) with Type 1 (T1D) and Type 2 (T2D) Diabetes

Urinary (U) neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) are markers of renal tubular injury. Whether NGAL and KIM-1 are elevated in early diabetic kidney disease (DKD) is not known. We performed a pilot study to compare the U concentrations (C) of NGAL and KIM-1 in YA with T1D or T2D from the SEARCH registry and healthy controls (n 45 in each group). The YA with diabetes were selected based on age at dx > 10 years and duration >8 years and were randomly selected across the quartiles of eGFR with similar age, gender and ethnicity. T1D (age 21 ± 2 years; duration 9.6 ± 1.0 years; HbA1c 9.3 ± 2.1% eGFR 126 ± 19 mL/min/1.73m2, UACR 11 ± 16 µg/mg), T2D (age 24 ± 3 years, duration 9.8 ± 1.2 years, HbA1c 8.5 ± 3.0%, eGFR 128 ± 21 mL/min/1.73m2, UACR 38 ± 71 µg/mg), controls (age 23 ± 3 years). In each group 50% were female, 41% white, 43% AA, and 16% Hisp. NGAL and KIM-1 were significantly elevated in T1D and T2D compared with controls (p < 0.001, p< 0.007). Although there was a trend for a greater UC of NGAL in T2D than T1D and a greater UC of KIM-1 in T1D than T2D, these differences were not statistically significant. Elevated UC of NGAL and KIM-1 are present in YA with T1D and T2D suggesting the presence of tubular damage early in the course of diabetes. Further investigation will determine if these markers can be used to assess the natural history of tubular injury or monitor therapeutic intervention in DKD. Disclosure N.M. Sheanon: None. A.K. Mottl: None. R. Dagostino: Consultant; Self; Teva Pharmaceutical Industries Ltd., Acelity, RedHill Biopharma, Edwards Lifesciences. C. Suerken: None. M. Afkarian: None. D. Dabelea: None. G. Imperatore: None. S.M. Marcovina: None. D.J. Pettitt: None. S. Saydah: None. L.M. Dolan: None.