bluuebunny/crossref_metadata_2025 huggingface dataset:
1172-P: GLUT4-Overexpressing Engineered Muscle Tissue Implants as a Potential Novel Therapy for Type 2 Diabetes: Lessons from Diabetic Mice
Authors: BECKERMAN MARGARITA , KARNIELI EDDY , HAREL CHAVA , KLIP AMIRA , BILAN PHILIP J. , GALLAGHER EMILY , LEROITH DEREK , LEVENBERG SHULAMIT
Published: June 2019

In spite of current therapy protocols many T2DM patients fail to achieve blood glucose homeostasis goals. Insulin resistance in T2DM is associated with impaired GLUT4 function and cellular content. Thus, our aim was to improve overall glucose homeostasis by constructing engineered muscle tissue, using genetically modified skeletal muscle cells that over-express the GLUT4 transporter (OEG4). The OEG4 cells were grafted on biodegradable scaffolds and cultured to allow the formation of engineered muscle tissue constructs (EMC). Using an in-vitro 2-deoxyglucos (DOG) uptake assay, the OEG4-EMCs showed a 1.8-fold increase in DOG uptake with insulin stimulation, compared to unmodified controls. For in-vivo efficacy evaluation OEG4-EMCs and empty constructs, not seeded with cells, as control were implanted in the abdominal wall of immunodeficient recombination-activating gene 1 (Rag1)/MKR mice model of T2DM. Following i.p glucose tolerance test mice implanted with OEG4-EMCs had significantly (p<0.05) reduced maximal blood glucose levels (185+/-14.8 mg/dL), compared to diabetic controls group (294+/-23 mg/dL) and similar to nondiabetic mice (188+/-8.1 mg/dL). In addition, glucose levels returned to basal levels faster than in the control group. Since, EMC implants improved diabetic mice overall glucose homeostasis our data support the potential of such implants as novel therapeutic mode for T2DM therapy.

Disclosure

M. Beckerman: None. E. Karnieli: None. C. Harel: None. A. Klip: None. P.J. Bilan: None. E. Gallagher: None. D. LeRoith: Advisory Panel; Self; AstraZeneca, MannKind Corporation. S. Levenberg: None.

Funding

Rina and Avner Schneur Charitable Giving Fund
1175-P: Circulating CD4+/CD8+ PD-1+ T Cells Are Increased during the Partial Remission Phase in Patients with Type 1 Diabetes
Authors: ZHONG TING , LI XIA , ZHOU ZHIGUANG
Published: June 2019

Programmed death-1 (PD-1) critically regulates T cell tolerance, but the role of PD-1/PD-L1 in the pathogenesis of type 1 diabetes (T1D) patients remains unclear. In this study, we investigated circulating PD-1+/PD-L1+ T cells and their changes during the partial remission (PR) phase in T1D. 79 patients with T1D and 21 normal controls were enrolled, and grouped into 4 groups based on remission phase. The percentage of circulating PD-1+/PD-L1+ T cells, Treg, IL-35-Treg and Breg cells was analyzed by flow cytometry. The results showed that the expression of PD-1 in CD4+/CD8+ T cells was significantly decreased at the onset of T1D, and recovered to a high level during the remission phase. The honeymoon phase was accompanied by the increase of PD-1 expression, suggesting that PD-1 may be a new target for diagnosis and intervention.

Disclosure

T. Zhong: None. X. Li: None. Z. Zhou: None.
1180-P: Development of “Smart mRNAs” that Synthesize Corrective Proteins during Abnormal Metabolic States
Authors: JAFFREY SAMIE
Published: June 2019

Diabetes and related disorders are associated with abnormal cellular metabolism, abnormal levels of various intracellular metabolites, and most importantly, impaired cellular responses which would normally correct these abnormalities. As a result, various tissues, such as liver, adipose, and skeletal muscle, exhibit altered cellular signaling and physiologic responses, which ultimately lead to the clinical signs and symptoms of diabetes. A major goal of synthetic biology is to develop new gene therapy approaches in which proteins are expressed in disease-affected tissues to correct these diverse metabolic abnormalities. However, a major challenge is to develop approaches in which the corrective proteins are only expressed when the cells exhibit metabolic derangements. Here we describe the first "smart mRNAs." These are mRNAs that can be expressed using standard gene therapy approaches, but are only translated when specific diabetes-associated metabolites are present. We describe how the 5' untranslated regions in mRNAs can be designed so that they bind diabetes-associated metabolites, and subsequently induce the translation of the encoded protein. We demonstrate the translational control that can be achieved with this new class of mRNA in various cell types, and we show how translation can be regulated by various metabolites and signaling states associated with diabetes. Lastly, we discuss how smart mRNAs can be used therapeutically in animal models in order to develop organs with restored cellular and signaling functions.

Disclosure

S. Jaffrey: Stock/Shareholder; Self; Gotham Therapeutics, Lucerna Biosciences.

Funding

American Diabetes Association/Pathway to Stop Diabetes (1-18-VSN-02)
1181-P: Effect and Feasibility of High Dose Eplerenone in Type 2 Diabetes: A Mirad Substudy
Authors: BRANDT-JACOBS NIELS HØEG , RASMUSSEN JON BJARKE , JOHANSEN MARIE-LOUISE , ROSSIGNOL PATRICK , FABER JENS , SCHOU MORTEN , KISTORP CAROLINE MICHAELA
Published: June 2019

The use of mineralocorticoid receptor antagonists (MRA) as anti-hypertensive therapy has been limited due to concern of potential hyperkalemia among patients with T2D. The aim of this study was to investigate the effect on blood pressure (BP) and feasibility of use of selective MRA eplerenone in T2D. We randomized 140 patients with T2D and established or high risk of cardiovascular disease to either eplerenone or placebo for 26 weeks. Target study medication dose was 200 mg/day or 100mg/day for patients with an eGFR >60 or 40-60 ml/min/1,73m2, respectively. Outcomes of this substudy was change in 24h-ABPM, office-BP from baseline and incident hyperkalemia (s-K ≥ 5.5 mmol/L). A decrease was found in office systolic BP, in the eplerenone group as compared with placebo (-6 mmHg, [-11; -1], P=0.03). Mean 24h-systolic- (SBP) and diastolic BP (DBP) decreased significantly with eplerenone (SBP: -5 mmHg [-8; -2], P <0.001; DBP: -3 mmHg [-4; -1] P <0.001). The difference in 24h ABPM-change between groups at end-of-study being borderline significant (-3 mmHg [-7; 1], P=0.1). Number of patients with incident hyperkalemia did not differ (eplerenone vs. placebo 6 vs. 2, P = 0.27); with no incidences of severe hyperkaliemia (s-K ≥6.0 mmol/L). We conclude eplerenone to be a feasible option in the treatment of T2D patients with hypertension and normal mean eGFR.

Figure: 24-h ABPM change; comparison of baseline and end-of-study.

Disclosure

N. Høeg Brandt-Jacobs: None. J.B. Rasmussen: None. M. Johansen: None. P. Rossignol: None. J. Faber: None. M. Schou: None. C.M. Kistorp: None.
1188-P: Glycemic Efficacy of Sitagliptin in East Asian Populations: A Pooled Analysis
Authors: CONCEICAO JOAO M. , GONZALEZ CLAUDIO D. , ENGEL SAMUEL S. , AHN JONGHO , TOKITA SHIGERU , ZHANG YE , ZHANG RUYA , LAM RAYMOND L. , PONG ANNPEY
Published: June 2019

The efficacy/safety of sitagliptin (SITA) has been studied in global populations. This post hoc pooled analysis of 20 placebo (PBO)-controlled studies reports data collected specifically in East Asian populations (EAP). Results were summarized for overall EAP and subgroups defined by geography. Change from baseline in A1C was analyzed at week 12 using ANCOVA model with treatment, study, and baseline A1C terms. A1C values following initiation of rescue medication were excluded. Missing A1C values were imputed using LOCF method. Baseline characteristics were generally balanced across treatments (mean A1C 8.5%, age 55-56 years, BMI 25 kg/m2, FPG 177-179 mg/dL, duration T2D 7-8 years). After 12 weeks of SITA, all populations showed significant A1C reductions vs. PBO (Table) and the largest PBO-adjusted reduction was seen in the Japan subgroup. PBO treatment was associated with reductions in A1C in China Mainland (CM), but with increases in Japan. The percentages of SITA-treated pts with A1C <7% were 18.9%, 14.2%, 37.4% and 30.4% for overall EAP, CM, Japan and Other East Asian subgroups, respectively (all p<0.001 vs. PBO). The incidences of hypoglycemia (i.e., symptomatic/asymptomatic) were 13/981 [1.3%] and 5/816 [0.6%] for SITA and PBO, respectively. These results are consistent with previous findings in global populations.

Disclosure

J.M. Conceicao: Employee; Self; Merck Sharp & Dohme Corp. Stock/Shareholder; Self; Merck Sharp & Dohme Corp. C.D. Gonzalez: Employee; Self; Merck & Co., Inc. Stock/Shareholder; Self; Merck & Co., Inc. S.S. Engel: Employee; Self; Merck & Co., Inc. Stock/Shareholder; Self; Merck & Co., Inc. J. Ahn: Employee; Self; Merck Sharp & Dohme Corp. Stock/Shareholder; Self; Merck Sharp & Dohme Corp. S. Tokita: Employee; Self; Merck Sharp & Dohme Corp. Stock/Shareholder; Self; Merck Sharp & Dohme Corp. Y. Zhang: Employee; Self; Merck Sharp & Dohme Corp. R. Zhang: Employee; Self; Merck Sharp & Dohme Corp. R.L. Lam: Employee; Self; Merck & Co., Inc. A. Pong: None.

Funding

Merck & Co., Inc.
119-OR: Amplified Glucagon Response to Hypoglycemia following AMP-Activated Protein Kinase (AMPK) Activator R481 Treatment in Healthy Rats
Authors: CRUZ ANA M.L. , MALEKIZADEH YASAMAN , VLACHAKI WALKER JULIA M. , SHAW SIMON J. , ELLACOTT KATE L. , BEALL CRAIG
Published: June 2019

Episodes of insulin-induced hypoglycemia are frequent in type 1 and advanced type 2 diabetes, but pharmaceutical approaches to prevent these are lacking. Cellular stresses such as low blood sugar activate AMPK, which has emerged as a whole body and cellular energy sensor. Direct delivery of AMPK activator to the ventromedial hypothalamus of rodents leads to increased hepatic glucose-production, observed during hyperinsulinemic-hypoglycemic clamp studies, and genetic activation of AMPK in the pancreatic alpha cell increases glucagon release. It may therefore be suitable to target AMPK for hypoglycemia prevention. Here, R481, a novel metformin-like brain permeable AMPK activator, was used to assess the impact of AMPK pathway activation on the counterregulatory response to hypoglycemia.

Hypothalamic glucose sensing GT1-7 cells were treated with R481 and activation of AMPK pathway by phosphorylation assessed using Western Blotting. R481 was administered orally to male Sprague Dawley rats prior to insulin-induced hypoglycemia, following which blood glucose and feeding were measured. A separate cohort of rats underwent a hyperinsulinemic-hypoglycemic clamp study where glucose infusion rates and counterregulatory hormones levels were determined.

Nanomolar concentrations of R481 increased AMPK pathway phosphorylation in GT1-7 neurons. Administration of R481 (5-20 mg/kg) to rats attenuated insulin-mediated drop in blood glucose during acute insulin-induced hypoglycemia, without altering fast-induced refeeding. R481 decreased the glucose infusion rate during hyperinsulinemic-hypoglycemic clamps, by amplifying plasma glucagon secretion, without altering epinephrine.

Peripheral administration of AMPK activator R481 amplified glucagon release to improve counterregulatory response to hypoglycemia in healthy rats.

Disclosure

A.M.L. Cruz: None. Y. Malekizadeh: None. J.M. Vlachaki Walker: None. S.J. Shaw: Employee; Self; Rigel Pharmaceuticals. K.L. Ellacott: None. C. Beall: None.

Funding

JDRF; Diabetes UK
12-LB: Beta Blocker Type and Hypoglycemia in Hospitalized Patients
Authors: LONG CLARINE , BINKLEY PHILIP F. , DUNGAN KATHLEEN M.
Published: June 2019

Background: Although β-blockers (BB) could increase the risk of hypoglycemia, the difference between subtypes on hypoglycemia and mortality have not been studied.

Aim: To determine the relationship between type of BB and incidence of hypoglycemia and mortality in hospitalized patients.

Methods: We retrospectively identified non-critically ill hospitalized patients who were undergoing bedside glucose monitoring over a 2 year period. Admission BB was categorized as carvedilol (C) or selective BB (SBB). Other nonselective BB were excluded. Hypoglycemia was defined as any glucose < 70 mg/dl within 24 hours of admission (Hypo24) or throughout hospitalization (HypoT) and any glucose <40 mg/dl throughout hospitalization (Hypo40).

Results: There were 1022 patients on C, 886 on SBB, and 10,217 on no BB. After controlling for other variables, the odds of Hypo24 HypoT and Hypo40 were higher for BB recipients, and the odds were greater for SBB vs. carvedilol for HypoT (Table). Findings were not observed in heart failure patients. Hypo24, HypoT, and Hypo40 were all associated with increased mortality in adjusted models among non-BB and C recipients, but not among SBB recipients.

Conclusions: BB use is associated with hypoglycemia, except in heart failure. C is associated with lower odds of hypoglycemia compared to SSB. Moreover, hypoglycemia associated mortality was attenuated with C. The findings warrant further study among patients with diabetes.

Disclosure

C. Long: None. P.F. Binkley: None. K.M. Dungan: Advisory Panel; Self; Eli Lilly and Company, Elsevier, Sanofi-Aventis. Research Support; Self; Eli Lilly and Company, GlaxoSmithKline plc., Novo Nordisk Inc., Sanofi-Aventis, Viacyte. Other Relationship; Self; DKBmed, UpToDate.
120-LB: Early Real-World Hypoglycemia Outcomes with Use of the Tandem Basal-IQ Technology System
Authors: PINSKER JORDAN E. , CASTORINO KRISTIN N. , LEAS SCOTT A. ,   STEPHANIE HABIF
Published: June 2019

The Tandem t:slim X2™ insulin pump with Basal-IQ® technology predicts glucose levels 30 minutes ahead based on the last 4 consecutive CGM readings. Insulin delivery is suspended if the predicted sensor glucose (SG) is <80 mg/dL or if the observed SG is <70 mg/dL. Insulin delivery resumes as soon as SG begins to rise. The pivotal trial (PROLOG) showed 3 weeks of Basal-IQ® use reduced SG time <70 mg/dL by 31% compared to sensor-augmented pump.

De-identified data voluntarily uploaded to the t:connect® diabetes management application between August 30, 2018, and February 7, 2019, from individuals with diabetes who have used Basal-IQ® technology for 3, 6, and 9 weeks (N=4082, 2370, and 1307 respectively) were retrospectively analyzed. Real-world Basal-IQ® hypoglycemia outcomes were compared to the PROLOG results.

After 3 weeks of real-world use, median time SG <70 mg/dL was 1.0% overall (1.0% daytime and 0.9% nighttime) vs. 2.6% (2.4% daytime and 2.7% nighttime) in PROLOG. Median time with SG <60 was 0.3% and time <50 mg/dL was 0.1%, vs. 0.9% and 0.2% in PROLOG. After 6 and 9 weeks, median time SG <70 mg/dL was 1.1%. Number of insulin suspensions and suspension duration were similar to PROLOG (Table 1).

Basal-IQ® technology was found to be safe and effective in a real-world setting, with similar PLGS activation metrics as observed in PROLOG. Results showed the Basal-IQ® algorithm performs successfully at preventing hypoglycemia.

Disclosure

J.E. Pinsker: Research Support; Self; Ascensia Diabetes Care, Dexcom, Inc., Insulet Corporation, LifeScan, Inc., Roche Diabetes Care, Tandem Diabetes Care. Speaker’s Bureau; Self; Tandem Diabetes Care. K.N. Castorino: Consultant; Self; Abbott. Research Support; Self; Abbott, Dexcom, Inc., Drawbridge, Novo Nordisk Inc., Sanofi US. S.A. Leas: Employee; Self; Tandem Diabetes Care. S. Habif: Employee; Self; Tandem Diabetes Care.

Funding

Tandem Diabetes Care, Inc.
120-OR: MicroRNA-7a-5p Overexpression in the VMH Restores the Sympathoadrenal Response to Hypoglycemia in Recurrently Hypoglycemic Rats
Authors: AGRAWAL RAHUL , MONTGOMERY MICHAEL G. , VERMA DINESH , DURUPT GRIFFIN T. , DE ABREU ADRIANA VIEIRA , SWAMINATHAN SANKAR , FISHER SIMON
Published: June 2019

We tested the hypothesis that the impaired sympathoadrenal response induced by recurrent hypoglycemia (RH) is mediated by changes in key microRNA expression in the ventromedial hypothalamus (VMH). MicroRNA-sequencing data from the VMH of RH rats indicated a 67% downregulation of microRNA-7a-5p and a 2.3-fold upregulation of microRNA-665. Rescue experiments were conducted consisting of lentiviral-mediated overexpression of microRNA-7a-5p or downregulation of microRNA-665 targeted to the VMH. Rats were randomized to, 1) recurrent saline (RS), 2) RH (25-50 mg/dl x 3 days), 3) RH + Lenti-scrambled microRNA, or 4) RH + Lenti-targeted microRNA. All rats were subsequently subjected to hyperinsulinemic-hypoglycemic (40-50 mg/dl) clamps. As expected, RH induced a blunted sympathoadrenal hormone response to hypoglycemia. Targeted VMH overexpression (∼3.5 fold) of microRNA-7a-5p in RH rats normalized the epinephrine response to hypoglycemia coinciding with a 30% decreased glucose infusion rate. Targeted VMH downregulation of microRNA-665, however, did not improve counterreguatory responses. These findings indicate that microRNA-7a-5p is a potential mediator of impaired VMH glucose sensing/counterregulation and may be an effective therapeutic target to restore impaired sympathoadrenal responses to hypoglycemia.

Disclosure

R. Agrawal: None. M.G. Montgomery: None. D. Verma: None. G.T. Durupt: None. A. Vieira de Abreu: None. S. Swaminathan: None. S. Fisher: None.
1210-P: Pooled Analysis of the Safety and Efficacy of Ertugliflozin in the Elderly
Authors: PRATLEY RICHARD E. , DAGOGO-JACK SAMUEL , CHARBONNEL BERNARD , PATEL SHRITA M. , HICKMAN MARY A. , LIU JIE , TARASENKO LISA , ELLISON MISOO C. , GANTZ IRA , TERRA STEVEN G.
Published: June 2019

Ertugliflozin (ERTU), an SGLT2 inhibitor, improves glycemic control in adult patients (pts) with T2DM. Elderly pts with T2DM are underrepresented in clinical studies, often present with multiple co-morbidities and are more susceptible to adverse events (AEs). Pooled analyses based on 7 phase 3 studies from the VERTIS program evaluated the safety and efficacy of ERTU in subgroups of pts aged <65 and ≥65 years. Pts with T2DM received ERTU (5 or 15 mg ± sitagliptin [SITA] 100 mg) or control (placebo [PBO], glimepiride or SITA). Safety data were evaluated up to 104 weeks. Efficacy was assessed in a subset of 3 PBO-controlled studies at 26 weeks. Baseline (BL) characteristics were similar between pts aged <65 (n=3605) and ≥65 years (n=1254), with the exception of mean BL estimated glomerular filtration rates (90.2 mL/min/1.73 m2 in pts <65 and 71.4 mL/min/1.73 m2 in pts ≥65). The safety profile of ERTU was similar in both age groups, except for a higher incidence of volume depletion AEs with ERTU relative to control (2.4% vs. 1.1%) in pts ≥65. Excluding pts with BL moderate renal impairment, incidence of renal-related AEs was similar across groups in pts ≥65 (ERTU [0.6%] vs. control [0.8%]), suggesting age alone does not increase risk of renal-related AEs. In the 3 PBO-controlled studies, documented hypoglycemia (4.4% vs.6.0%) and severe hypoglycemia rates (0.4% vs. 0.4%) with ERTU were comparable in pts <65 and ≥65. Efficacy of ERTU by age group is shown in the Figure.

Disclosure

R.E. Pratley: Consultant; Self; Sanofi US. Other Relationship; Self; AstraZeneca, Eli Lilly and Company, GlaxoSmithKline plc., Janssen Global Services, LLC., Janssen Research & Development, Lexicon Pharmaceuticals, Inc., Ligand Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Mundipharma, Novo Nordisk Inc., Pfizer Inc., Sanofi, Takeda Development Center Americas, Inc. S. Dagogo-Jack: Board Member; Self; Jana Care Inc. Consultant; Self; Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Sanofi-Aventis. Research Support; Self; AstraZeneca, Novo Nordisk Inc. Stock/Shareholder; Self; Dance Biopharm Holdings Inc. B. Charbonnel: Consultant; Self; AstraZeneca, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Servier. Speaker's Bureau; Self; AstraZeneca, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Takeda Pharmaceutical Company Limited. S.M. Patel: Stock/Shareholder; Spouse/Partner; Janssen Pharmaceuticals, Inc. Stock/Shareholder; Self; Merck & Co., Inc. M.A. Hickman: Employee; Self; Pfizer Inc. J. Liu: Employee; Self; Merck & Co., Inc. L. Tarasenko: Employee; Self; Pfizer Inc. M.C. Ellison: Employee; Self; Merck & Co., Inc. I. Gantz: Employee; Self; Merck & Co., Inc. S.G. Terra: Employee; Self; Pfizer Inc.

Funding

Merck Sharp & Dohme Corp; Pfizer Inc.
122-OR: Impact of Withdrawal of Interventions in the Restoring Insulin Secretion (RISE) Pediatric Medication Study
Authors: HANNON TAMARA S. , EDELSTEIN SHARON , ARSLANIAN SILVA A. , CAPRIO SONIA , ZEITLER PHILIP , BUCHANAN THOMAS A. , EHRMANN DAVID A. , MATHER KIEREN J. , LESCHEK ELLEN , TRIPPUTI MARK , KAHN STEVEN E. , NADEAU KRISTEN J. , CONSORTIUM RISE
Published: June 2019

The RISE Pediatric Medication Study showed, in 91 obese 10-19 yo youth with impaired glucose tolerance (IGT, 60%) or recent-onset type 2 diabetes (T2D, 40%), that 12 mo of intervention with metformin alone (M) or glargine for 3 mo followed by metformin for 9 mo (G+M) resulted in no change in BMI or HbA1c and a decline in β-cell function measured by hyperglycemic clamp. These outcomes worsened 3 mo after withdrawal of the interventions. We expand our findings to mo 21 (M21) post randomization (9 mo after withdrawal of M or G+M) using oral glucose tolerance test (OGTT) measures of β-cell responsiveness (C-peptide index, CPI; insulinogenic index, IGI; incremental C-peptide/glucose area under the curve), BMI and HbA1c. Paired t-tests were used to compare treatment groups on changes from baseline (BL, n=91) to mo 12 (M12, n=86) and M21 (n=82), and from treatment withdrawal at M12 to M21. At M12 vs. BL, no measures differed in either group (Table). At M21 vs. BL, HbA1c increased in both groups, and BMI increased and CPI and IGI declined in the G+M group. At M21 vs. M12, BMI, HbA1c, fasting and 2-h glucose increased in both groups, and CPI declined in the G+M group. Our findings contrast with studies in adults showing durable benefits of metformin and insulin on HbA1c and β-cell responsiveness. Further investigation is needed to find effective treatments that prevent progression of dysglycemia in youth with IGT or recent-onset T2D.

Disclosure

T.S. Hannon: Advisory Panel; Self; Eli Lilly and Company. S. Edelstein: None. S.A. Arslanian: None. S. Caprio: None. P. Zeitler: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Research & Development, Merck & Co., Inc., Novo Nordisk Inc. T.A. Buchanan: Research Support; Self; Allergan, Apollo EndoSurgery. D.A. Ehrmann: None. K.J. Mather: Advisory Panel; Self; Roche Diabetes Care. Research Support; Self; Abbott, Merck & Co., Inc., Novo Nordisk A/S, Sanofi. E. Leschek: None. M. Tripputi: None. S.E. Kahn: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S. Consultant; Self; Neurimmune. Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S. K.J. Nadeau: None. R. Consortium: None.

Funding

American Diabetes Association (1-14-RISE-01 to S.E.K.); National Institute of Diabetes and Digestive and Kidney Diseases
1222-P: Comparative Efficacy of Ertugliflozin (ERTU) vs. Other Sodium-Glucose Cotransporter 2 Inhibitors (SGLT2i): Model-Based Meta-analysis (MBMA) of HbA1c Lowering
Authors: FEDIUK DARYL , MANDEMA JAAP , SWEENEY KEVIN , TERRA STEVEN G. , SAHASRABUDHE VAISHALI
Published: June 2019

Background: ERTU is a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor approved for the treatment of adults with type 2 diabetes mellitus (T2DM). As several SGLT2i are commercially available, MBMA of the HbA1c-lowering effect of these drugs was undertaken to assess their comparative effectiveness.

Methods: MBMA quantified the time course of dose vs. HbA1c response of SGLT2i and evaluated the impact of covariates including baseline HbA1c, estimated glomerular filtration rate (eGFR) and background diabetes treatment on HbA1c efficacy. Of the 496 randomized controlled trials (RCTs) in the database, 94 RCTs representing >31,000 T2DM patients were with SGLT2i, including 5 RCTs for ERTU.

Results: For SGLT2i, there was a 28.7% (95% CI, 24.5 to 33.1%) greater relative HbA1c efficacy for a 1% absolute increase in baseline HbA1c. Additionally, the HbA1c efficacy was 25.0% (17.0 to 34.0%) greater on a diet background alone relative to a background of metformin (or other oral antidiabetic treatment). For every 10 mL/min/1.73m2 decrease in eGFR, there was a 8.80% (5.90 to 11.6%) decrease in HbA1c efficacy.

Conclusion: This MBMA allowed an indirect comparison of SGLT2 inhibitor efficacy across trials (Table). Overall, ERTU doses of 5 and 15 mg were of comparable or numerically greater efficacy to other SGLT2i.

Disclosure

D. Fediuk: Employee; Self; Pfizer Inc. J. Mandema: Consultant; Self; Merck & Co., Inc., Pfizer Inc., Sanofi. K. Sweeney: Employee; Self; Pfizer Inc. S.G. Terra: Employee; Self; Pfizer Inc. V. Sahasrabudhe: Employee; Self; Pfizer Inc.

Funding

Pfizer Inc.; Merck Sharp & Dohme Corp.
1223-P: Empagliflozin vs. Dapagliflozin in Patients with Type 2 Diabetes Inadequately Controlled with Metformin, Glimepiride, and Dipeptidyl Peptide-4 Inhibitors: A 52-Week Prospective Observational Study
Authors: KU EU JEONG , LEE DONG HWA , JEON HYUN JEONG , OH TAEKEUN
Published: June 2019

Objectives: To directly compare the effectiveness of HbA1c reduction between two distinct SGLT2 inhibitors, Empagliflozin (EMPA, 25 mg/day) and Dapagliflozin (DAPA, 10 mg/day), as part of a quadruple OAD drug regimen.

Research Design and Methods: This study was an open-labeled, prospective, observational, 52-week study conducted in a clinical practice. T2D patients (HbA1c, 7.5-12.0%) with three different OADs (metformin, glimepiride, and dipeptidyl peptidase-4 inhibitors) were enrolled to either EMPA or DAPA. The outcome measures included changes in HbA1c, fasting plasma glucose (FPG), and cardiometabolic variables at week 52 and the safety outcomes of treatment-emergent adverse events.

Results: In total, 350 patients were enrolled with EMPA (N=176) and DAPA (N=174), respectively. After 52 weeks, both groups showed significant reductions (P <0.001) in HbA1c and FPG, but the reduction was greater in the EMPA group. In addition, both groups showed decreased blood pressure and body weight with improved liver function, and high-density lipoprotein cholesterol levels were significantly increased in the EMPA (1.9 ± 5.7 mg/dl, P <0.001 and 0.6 ± 4.5 mg/dl, P = 0.157, respectively) (between groups, P = 0.035). Both groups were well tolerated with overall similar safety profiles.

Conclusions: Our present study demonstrated that SGLT2 inhibitors can be safely and effectively used as a fourth OAD in T2D patients who are already being treated with three other OADs to control their hyperglycemia. More specifically, Empagliflozin was more effective in reducing HbA1c and improving other cardiometabolic parameters affecting patient health in T2D. Our findings show that 4 different OADs can be used as a viable therapeutic regimen to treat T2D, especially in patients who are unwilling to use injectable therapies as their alternate method to control blood glucose.

Disclosure

E. Ku: None. D. Lee: None. H. Jeon: None. T. Oh: None.
1226-P: Antifibrotic Effect of Combination Dapagliflozin and Metformin Therapy in Patients with Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease
Authors: LAVRYNENKO OLGA , KRAVCHUN NONNA , ZEMLIANITSYNA OLHA , DUNAEVA INNA , DEFRONZO RALPH A. , CERSOSIMO EUGENIO , KARACHENTSEV IURIY
Published: June 2019

Objective: Evaluation of long-term results of combination therapy with dapagliflozin and metformin on fibrotic changes in the liver of patients with type 2 diabetes (DM) and nonalcoholic fatty liver disease (NAFLD).

Materials and Methods: We recruited 45 DM patients with clinical NAFLD (27M, 18F) and in addition to dietary recommendations all received dapagliflozin 10 mg/daily plus metformin (max 2000 mg/daily); 7 patients required additional therapy with insulin.

Results: As well documented in the literature, the efficacy of the dapagliflozin/metformin combination in the treatment of DM patients with NAFLD was shown in our series. Improvements in glycemic indices (HbA1c- 7.17 ± 0.16vs. 7.05 ± 0.18; FPG - 10.85 ± 0.48vs. 9.39 ± 0.46,р < 0.05), a reduction of BMI (31.04 ± 0.63kg/m2vs. 29.55 ± 0.50kg/m2, р < 0.05) and in liver function (AST/ALT 0.83 ± 0.05vs. 0.74 ± 0.05) observed during the long-term (16 months) administration of these drugs. The NAFLD, FIB-4 and APRI scales were used to determine the risk of liver fibrosis in this group of DM patients. After the start of the combination therapy, all scales showed decreases in the level of non-invasive liver fibrosis indices of these patients. The most sensitive method for the early diagnosis of liver fibrosis was the NAFLD scale, which decreased significantly (-0.941 ± 0.11 vs. -1.61 ± 0.12 points, р < 0,001). Following treatment, the number of patients with mild liver fibrosis increased from 8 (27.6%) to 21 (64.9%) and those in the "gray zone" also decreased from 29 (72.6%) to 13 (35.1%).

Conclusion: In this non-randomized, single treatment arm group of DM patients study, we demonstrated that following combination therapy of dapagliflozin plus metformin for 16 months, better glycemic control is accompanied by simultaneous improvements in liver function tests and superior NAFLD scale values of liver fibrosis.

Disclosure

O. Lavrynenko: None. N. Kravchun: None. O. Zemlianitsyna: None. I. Dunaeva: None. R.A. DeFronzo: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Elcelyx Therapeutics, Inc., Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc. Speaker's Bureau; Self; AstraZeneca, Novo Nordisk Inc. E. Cersosimo: None. I. Karachentsev: None.
1228-P: Sodium-Glucose Cotransporter 2 Inhibitors and Risk of Genital Mycotic and Urinary Tract Infections: A Population-Based Study of Older Women and Men with Diabetes
Authors: LEGA ILIANA C. , BRONSKILL SUSAN , CAMPITELLI MICHAEL A. , GUAN JUN , STALL NATHAN M. , LAM KENNETH , MCCARTHY LISA M. , GRUNEIR ANDREA , ROCHON PAULA A.
Published: June 2019

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are the newest class of oral diabetes medications. There are concerns of an increased risk of genitourinary infections based on trial data, however this risk at a population level is understudied. We conducted a population-based study using linked administrative databases in Ontario of women and men with diabetes over the age of 66 who were incident users of SGLT2i from Jan-Dec 2016. We quantified the association between SGLT2i and each of genital mycotic infection and urinary tract infection within 30 days of drug initiation using a retrospective cohort design. The comparator group were new users of a DPP-4i. We identified 21,444 incident SGLT2i users and 22,463 DPP-4i users. Among SGLT2i users, 41% were women and the mean age at index was 71.8 ± 5 years. After adjusting for propensity score, age, sex, and recent UTI, there was a 2.47 fold increased risk of a genital mycotic infection with SGLT2i (adjusted hazard ratio (HR), 2.47; 95% CI 2.08-2.92, p < 0.001) within 30 days. For UTI, the adjusted HR was 0.89 (95% CI 0.78-1.00, p=0.05) overall. Incident SGLT2i use among older women and men is associated with an increased risk of genital mycotic infections within 30 days; there is no associated increased risk of UTI. These findings from a real-world setting provide evidence of the potential harms of SGLT2i.

Disclosure

I.C. Lega: None. S. Bronskill: None. M.A. Campitelli: None. J. Guan: None. N.M. Stall: None. K. Lam: None. L.M. McCarthy: None. A. Gruneir: None. P.A. Rochon: None.

Funding

Canadian Institutes of Health Research (PJT153060)
123-LB: Continuous Subcutaneous Insulin Infusion from Diagnosis of Type 1 Diabetes Improves Intermediate Glycaemic Variability in Children
Authors: SCOTT EMMA S. , JANUSZEWSKI ANDRZEJ S. , FULCHER GREG , JONES TIMOTHY , DAVIS ELIZABETH A. , JENKINS ALICIA J.
Published: June 2019

Background: Glucose variability (GV) may be reflected by variation in either the short-term glucose levels (assessed by continuous glucose monitoring (CGM)) or the long-term by HbA1c or intermediate by 1,5-anhydroglucitol (1,5-AG). In patients with T1DM management by continuous subcutaneous insulin infusion (CSII) is usually associated with improved glycaemia compared to multiple daily insulin injections (MDI). Serum 1,5-anhydroglucitol (1,5-AG) correlates with GV on CGM in adult and pediatric T1D groups. It is not known whether CSII therapy without CGM improves intermediate GV.

Methods: Blood was obtained from children (mean age 14.1 +/- 1.3 years) within 3-months of T1D diagnosis. Children were treated with CSII (n=12) or MDI (n=15) and followed for a further 1 to 3 time points (median, LQ-UQ 535, 519-563 days follow-up). GV was assessed measuring 1,5-anhydroglucitol (1,5-AG) (GlycoMark, Inc., Winston-Salem, NC). The mean difference, standard deviation (SD) and coefficient of variation (CV) of 1,5-AG and HbA1c was compared between treatment arms.

Results: There was no difference between treatment modalities in baseline HbA1c (median, LQ-UQ 11.8, 10.2-13.5 % (105, 87-124 mmol/mol) vs. 12.6, 10.3-14.0 % (114, 89-130 mmol/mol) CSII vs. MDI) nor baseline 1,5-AG (median, LQ-UQ 2.8, 1.8-4.0 μg/mL vs. 3.6, 2.1-12.1 μg/mL CSII vs. MDI). 1,5-AG improved more (increased) in the CSII vs. MDI group (3.1 +/- 4.1 vs. -2.2 +/- 7.0 μg/ml respectively, P=0.029). This difference persisted following adjustment for the duration of follow-up. There was no significant difference in the HbA1c improvement between the CSII and MDI groups. There was no significant difference in the SD or CV of 1,5-AG or HbA1c between groups.

Conclusions: Early use of CSII post-T1D-diagnosis in a pediatric population is associated with a higher 1,5-AG than with MDI therapy implying reduced glycaemic variability.

Disclosure

E.S. Scott: None. A.S. Januszewski: None. G. Fulcher: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Research & Development, Merck Sharp & Dohme Corp., Novo Nordisk Inc. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Research & Development, Merck Sharp & Dohme Corp., Novo Nordisk Inc. Research Support; Self; Novo Nordisk Inc. T. Jones: Research Support; Self; Dexcom, Inc., Medtronic MiniMed, Inc. Speaker's Bureau; Self; Eli Lilly and Company, Roche Diabetes Care. E.A. Davis: None. A.J. Jenkins: Advisory Panel; Self; Abbott, Australian Diabetes Society, Medtronic. Research Support; Self; Abbott, GlySens Incorporated, Medtronic, Mylan. Speaker’s Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc.
1232-P: Predictors of ß-Cell Function Changes: Pooled Analysis from Phase 3 Ertugliflozin Studies
Authors: GALLO SILVINA , RAJI ANNASWAMY , CALLE ROBERTO A. , ELLISON MISOO C. , MEYER CHRISTIAN
Published: June 2019

Improving glycemic control generally improves β-cell function in T2DM but the predictors for this effect are unclear. SGLT2 inhibitors improve glycemia and have no known direct effects on β-cell function. Therefore, we aimed to identify predictors of β-cell function changes by treatment with the SGLT2 inhibitor ertugliflozin (ERTU). Data of patients (pts) randomized to ERTU (5 or 15 mg) only or placebo (PBO) only from four phase 3 ERTU studies of the VERTIS clinical program were pooled and analyzed. Change from baseline in β-cell function (fasting homeostatic model assessment beta [HOMA-β] and C-peptide Insulinogenic Index [IGI] at 30 min of a mixed meal tolerance test) at Week 26 was assessed, followed by linear regression analyses to examine the relationship between change in β-cell function versus metabolic and demographic characteristics. ERTU compared with PBO improved β-cell function when assessed by the changes from baseline (95% CIs) in HOMA-β (14.7 [12.3,17.1] versus −0.4 [−3.4, 2.5]) but not IGI. Change in HOMA-β correlated negatively and similarly with change in A1C in both groups (ERTU: r=−0.29; PBO: r=−0.36, both P<0.001). In the ERTU group, change in HOMA-β correlated positively with baseline fasting plasma glucose (FPG; r=0.23, P<0.001) and baseline A1C (r=0.14, P<0.001) but negatively with baseline HOMA-β (r=−0.32, P<0.001) in simple linear regression analyses; no significant correlations were found with age, sex, ethnicity, diabetes duration, baseline serum triglycerides, creatinine, weight or systolic blood pressure. Correlations between change in HOMA-β and baseline FPG, A1C and HOMA-β remained significant in multiple regression analyses. ERTU improves fasting HOMA-β but not the postprandial IGI in pts with T2DM. Pts with high baseline FPG and A1C values but low baseline HOMA-β may derive greater benefit than those with low baseline FPG, A1C and high HOMA-β with ertugliflozin treatment in terms of fasting HOMA-β.

Disclosure

S. Gallo: Employee; Self; Pfizer Inc. Stock/Shareholder; Self; Pfizer Inc. A. Raji: Employee; Self; Merck & Co., Inc. Stock/Shareholder; Self; Merck & Co., Inc. R.A. Calle: Employee; Self; Pfizer Inc. Stock/Shareholder; Self; Pfizer Inc. M.C. Ellison: Employee; Self; Merck & Co., Inc. C. Meyer: Employee; Self; Merck & Co., Inc.

Funding

Merck Sharp & Dohme Corp; Pfizer Inc.
1237-P: Factors Associated with Health-Care Avoidance among Medicare Beneficiaries Aged 65 Years and Over with Reported Type 2 Diabetes
Authors: NG BOON PENG , PEACH BRIAN C. , PARK CHANHYUN , TOWNE SAMUEL D. , LAMANNA JACQUELINE B.
Published: June 2019

Healthcare avoidance by Medicare beneficiaries (MBs) with type 2 diabetes (T2D) can result in significant health and financial burdens. Timely detection/treatment of T2D-related complications can mitigate these burdens. There is limited research using the Anderson Model of Healthcare Utilization to examine healthcare avoidance among MBs with T2D. Therefore, we examined factors associated with healthcare avoidance among MBs with reported T2D. We analyzed two healthcare avoidance measures (“do anything to avoid going to the doctor (DATAGTTD)” and “try to keep sickness to themselves (TTKSTT)”) using the nationally representative 2015 Medicare Current Beneficiary Survey (n=12,311) from CMS. MBs were stratified into two groups, those with and without T2D. We performed four survey-weighted logit models, with two healthcare avoidance variables on those with and without T2D, adjusting for covariates. Approximately 22.4% of MBs reported having T2D. Among those with and without T2D, 28.5% and 26.1% respectively reported they would DATAGTTD. Also, 37.8% of MBs with T2D and 39% of MBs without T2D reported they would TTKSTT. Two key factors were positively associated (P<.01) with DATAGTTD for both groups: 1) worrying about health more than others, 2) past experiences with doctors missing health issues. Also, reporting past experiences with doctors missing health issues was a key factor positively associated (P<.01) with TTKSTT for both groups. Other factors such as socio-economic status, physical limitations, depression, and cost were associated (P<.05) with TTKSTT and DATAGTTD. However, factors differed between those with and without T2D. Although over 90% of MBs with T2D have a regular doctor, one-third of them reported TTKSTT and one-fourth of them reported DATAGTTD. There is a need to address and improve doctor-patient communication for MBs with T2D to avoid unnecessary and costly healthcare avoidance for this particular at-risk group.

Disclosure

B. Ng: None. B.C. Peach: None. C. Park: None. S.D. Towne: None. J.B. LaManna: None.
1238-P: Utilization of Comprehensive Pharmacy Services in Diabetes Care Coordination for Hospitalized Patients
Authors: WELCH ANDREW A. , BOESKEN TIMMI ANNE , WOOLF BRITTANY , BERGER KIMBERLY , CORBIN ADELE , BACHMAN NICHOLE E. , SCHAUER DANIEL , FALCIGLIA MERCEDES
Published: June 2019

A major barrier to effective diabetes care is difficulty with affording and knowing how to use medications. At a 750-bed urban hospital, comprehensive pharmacy services (PS) are offered to support patients in accessing and understanding their medications. Specifically, Medication Access Services (MAS) collaborates with providers and patients to utilize available resources that assist patients in obtaining needed medications. We examined use of these services in a cohort of inpatients with poorly controlled diabetes who were enrolled in a diabetes care-coordination program after discharge, Sweet Transitions (ST). Because participation in ST had been associated with significant reductions in HbA1c (12.0 to 9.0%) and 30-day readmissions, both sustained at one year, the role of PS utilization was explored. We hypothesized that there was greater use of PS among ST participants compared to matched controls and that this may have contributed to the improved outcomes observed. We reviewed data from 544 patients; 197 ST participants with poorly controlled diabetes (A1C ≥ 9) and 347 controls matched for poor diabetes control and cardiovascular disease. Utilization of PS and MAS within 90 days after discharge was compared. Cost savings, defined as expenditures for medications covered by sources outside the patient or healthcare system, were calculated. Compared to 49% of controls, 77% of ST patients used PS, p<0.001. Specifically, 2.6% of the controls vs. 9.1% of the ST cohort utilized MAS, p=0.002. The total cost savings in the ST group using MAS was $61,180 or $3399 per patient. Patients enrolled in the ST program utilized comprehensive pharmacy services more often than controls, suggesting that such services may have contributed to the significant and sustained improved outcomes observed. Approaches that assist patients with the affordability, access, and understanding of their diabetes medications may contribute to sustainably improved outcomes and should be examined further.

Disclosure

A.A. Welch: None. T.A. Boesken: None. B. Woolf: None. K. Berger: None. A. Corbin: None. N.E. Bachman: None. D. Schauer: None. M. Falciglia: None.
124-OR: Comparison of OGTT Model-Derived Measures of ß-Cell Function between Youth and Adults
Authors: UTZSCHNEIDER KRISTINA , MARI ANDREA , TRIPPUTI MARK , MATHER KIEREN J. , NADEAU KRISTEN J. , EDELSTEIN SHARON , HANNON TAMARA S. , ARSLANIAN SILVA A. , CREE-GREEN MELANIE , BUCHANAN THOMAS A. , CAPRIO SONIA , KAHN STEVEN E. , CONSORTIUM RISE
Published: June 2019

Results from hyperglycemic clamps in the Restoring Insulin Secretion (RISE) Study found that youth (10-19 y) with impaired glucose tolerance (IGT) or early type 2 diabetes (T2D) are more insulin resistant and secrete more insulin than adults (20-65 y), despite similar BMI. Here we use Mari modeling of RISE 3-h OGTT data to explore differences in β-cell function between youth and adults. The Mari model describes the relationship between insulin secretion rate (ISR) and glucose concentration. The slope of the relationship is β-cell glucose sensitivity (GS); ISR at a fixed glucose is also calculated. Derived terms include the 3-h to baseline potentiation factor ratio (PFR; a relative insulin secretion increase during the OGTT) and rate sensitivity (RS; the dependence of ISR on the glucose rate of change). Analysis of covariance was used to compare youth vs. adults, with secretion measures adjusted for insulin sensitivity (M/I) from hyperglycemic clamps. Adjusted GS was significantly higher in youth vs. adults with IGT but not in those with T2D. Adjusted RS and ISR at plasma glucose of 5 and 7 mmol/L were higher in youth vs. adults for both IGT and T2D. The PFR was lower in youth than adults, suggesting possible differences in either incretin effects or glucose potentiation. Our OGTT findings provide additional evidence that β-cells in youth are more responsive to glucose than adults, with reduced secretion parameters in those with T2D.

Disclosure

K. Utzschneider: Consultant; Self; Novo Nordisk Inc. A. Mari: Consultant; Self; Eli Lilly and Company. Research Support; Self; Boehringer Ingelheim International GmbH. M. Tripputi: None. K.J. Mather: Advisory Panel; Self; Roche Diabetes Care. Research Support; Self; Abbott, Merck & Co., Inc., Novo Nordisk A/S, Sanofi. K.J. Nadeau: None. S. Edelstein: None. T.S. Hannon: Advisory Panel; Self; Eli Lilly and Company. S.A. Arslanian: None. M. Cree-Green: None. T.A. Buchanan: Research Support; Self; Allergan, Apollo EndoSurgery. S. Caprio: None. S.E. Kahn: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S. Consultant; Self; Neurimmune. Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S. R. Consortium: None.

Funding

American Diabetes Association (1-14-RISE-01 to S.E.K.); National Institute of Diabetes and Digestive and Kidney Diseases
1243-P: Novel Use of Natural Language Processing to Identify Reasons for Insulin Discontinuation in Patients with T2DM: A Real-World Evidence Study
Authors: WU JIANMIN , MORRISON FRITHA J. , ZHAO ZHENXIANG , HE XUANYAO , SHUBINA MARIA , MALMASI SHERVIN , GE WENDONG , PENG XIAOMEI , TURCHIN ALEXANDER
Published: June 2019

Insulin is an important part of treatment of type 2 diabetes mellitus (T2DM). Nevertheless, reasons for discontinuation of insulin therapy are poorly understood.

We conducted a real-world-evidence analysis of EMR data at Partners HealthCare to study adults with T2DM who were prescribed insulin between 2010 and 2016. Reasons for insulin discontinuation were identified from a combination of structured EMR data and natural language processing analysis of EMR notes using a validated tool (sensitivity 76.9% and positive predictive value 89.7%).

The mean age of study patients was 60.2 years; 52.7% were male. Among 7,009 study patients, 2,957 (42.2%) discontinued insulin within 12 months after study start. In multivariable logistic regression analysis adjusted for demographics and comorbidities, patients were more likely to discontinue either basal or bolus insulin if they were on a basal-bolus regimen compared to basal only (OR 1.56, 95% CI 1.33 to 1.83; p < 0.001) or if they were being seen by an endocrinologist (OR 2.58; 95% CI 2.22 to 2.99; p < 0.001). Most patients (2,121/71.7%) had one or more reasons for discontinuation documented. The most common reasons were improving blood glucose (BG) control (33.2%), weight loss (likely ultimately also leading to lower BG) (18.5%) and initiation of non-insulin diabetes medications (16.7%). In multivariable analysis, patients were more likely to stop insulin due to achievement of good BG control if they were treated by an endocrinologist (OR 2.52; 95% CI 2.11 to 3.00; p < 0.001) or by a female physician (OR 1.43; 95% CI 1.26 to 1.63; p < 0.001).

This study represents a successful attempt to use natural language processing to understand reasons for insulin discontinuation. Insulin discontinuation is common, and particularly so for patients on a basal-bolus regimen. Achievement of glycemic control, weight loss and initiation of other diabetes medications were the most common reasons for insulin discontinuation.

Disclosure

J. Wu: None. F.J. Morrison: None. Z. Zhao: Employee; Self; Lilly Diabetes. X. He: Employee; Self; Eli Lilly and Company. M. Shubina: None. S. Malmasi: None. W. Ge: None. X. Peng: None. A. Turchin: Advisory Panel; Self; Monarch Medical Technologies. Research Support; Self; Eli Lilly and Company. Stock/Shareholder; Self; Brio Systems.

Funding

Eli Lilly and Company