bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Parameters, Fuel Oxidation, and Glucose Kinetics in T2D Patients Treated with Dapagliflozin plus Saxagliptin Combination
Authors: QIN YUEJUAN , ADAMS JOHN M. , MARTINEZ ROBERT A. , PINO ANTONINO DI , JOBORI HUSSEIN AL , ALI ALI M. , TRIPLITT CURTIS L. , DEFRONZO RALPH A. , CERSOSIMO EUGENIO 
Published: June 2018

To investigate mechanisms responsible for the clinical and metabolic benefits observed with SGLT2i plus DPP-4i therapy, we randomized 30 T2D patients (A1c=8.6±0.2%, BMI=33.1±1.9) to receive dapagliflozin 10 mg [DAPA], dapagliflozin/saxagliptin 10/5 mg [DAPA/SAXA] or placebo [PCB]. Baseline OGTT, glucose kinetics (3-3H-glucose), indirect calorimetry, HbA1c, FPG, FFA, insulin, and glucagon were repeated after 16 weeks of therapy.
Results: Insulin secretion (δI/δG)0-120 min during OGTT increased (p&lt;0.05) in DAPA (+0.6±0.1) and DAPA/SAXA (+0.6±0.1), but not in PCB (-0.4±0.20). The Matsuda Index improved (p&lt;0.01) in DAPA (+0.6±0.20) and DAPA/SAXA (+0.7±0.1), but not in PCB (-0.1±0.2). The Disposition Index [IS/IR] increased (p&lt;0.05) in DAPA (δ0.23±0.03) and DAPA/SAXA (δ 0.2±0.02), but not in PCB (δ0.03±0.04). The increase in fasting plasma glucagon in PCB (+37±4) and DAPA (+20±2) was blunted (p&lt;0.05) in combo (-7±4 pg/ml). There were no significant changes in fasting plasma FFA.
Conclusion: DAPA/SAXA combination therapy was associated with improved glycemic control vs. DAPA due to the attenuation of the rise in EGP. Further, the increase in glucose Ox in combination with inhibition of lipid Ox and glucagon secretion inhibit ketone production which may reduce the risk of DKA. Addition of SAXA improves insulin secretion and prevents the glucagon elevation induced by DAPA.
CharacteristicsPCBDAPADAPA/SAXAp-valueδ BMI (Kg/m2)+0.16±0.27-0.58±0.42-0.77±0.01*&lt;0.05δ HbA1c (%)+0.6±0.2-1.4±0.1-1.7±0.2*&lt;0.01δ FPG (mg/dl)+35±3-59±6-68±8*&lt;0.001Mean OGTT Glu (mg/dl)+41±6-73±8-86±7*&lt;0.001δ Basal EGP (mg/kg.min)+0.26±0.04+0.19±0.04-0.06±0.05**&lt;0.01δ Lipid Ox (%)-8±6+16±3+10±2*&lt;0.001 & ***&lt;0.05δ Glucose Ox (%)+5±4-31±3-17±2*&lt;0.001 &***&lt;0.001*= DAPA & DAPA/SAXA vs. PCB; **=DAPA/SAXA vs. DAPA & PCB; ***=DAPA vs. DAPA/SAXA EGP=Endogenous Glucose Production; Ox: Oxidation

Disclosure
Y. Qin: None. J.M. Adams: None. R.A. Martinez: None. A. Di Pino: None. H. Al Jobori: None. A.M. Ali: None. C.L. Triplitt: Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Eli Lilly and Company. Consultant; Self; Sanofi, Novo Nordisk Inc. R.A. DeFronzo: Speaker's Bureau; Self; AstraZeneca, Novo Nordisk Inc.. Advisory Panel; Self; AstraZeneca, Novo Nordisk Inc., Janssen Pharmaceuticals, Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Elcelyx Therapeutics, Inc., Intarcia Therapeutics, Inc.. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Takeda Pharmaceuticals U.S.A., Inc. E. Cersosimo: Research Support; Self; AstraZeneca, VeroScience, LLC.. Speaker's Bureau; Self; AstraZeneca, Sanofi, Janssen Pharmaceuticals, Inc., Eli Lilly and Company.
Euglycemic DKA as an Initial Presentation of Immunotherapy-Induced Insulin-Dependent Diabetes
Authors: IYER PRIYANKA , THOSANI SONALI N. 
Published: June 2018

New onset insulin dependent diabetes (DM) has been reported in cancer patients (pts) receiving immunotherapy (IO). Typically, pts have Grade 3 hyperglycemia (CTCAE) and sometimes DKA. Euglycemic DKA has been reported in pts on empagliflozin (Empa). We present a unique case of euglycemic DKA as initial presentation for immunotherapy induced insulin dependent DM. Pt is a 68 year old man without preexisting DM started on nivolumab for metastatic prostate cancer. Following 2 doses of nivolumab, he developed fatigue, weight loss and Grade 2 hyperglycemia for which he was started on metformin, glipizide, and Empa by his outside physician. His BG levels ranged from 130-200 mg/dL on these therapies. Nivolumab treatment was stopped due to significant adverse effects. On return visit to our clinic, approximately 3 months after initial hyperglycemia, pt complained of persistent fatigue, weight loss and a new fruity odor in his breath. Labs revealed BG of 134mg/dl, bicarb of 19 mEq/L (23-30mEq/L), anion gap (AG) of 17mEq/L (4-14mEq/L). Urine ketones were positive and c-peptide level was 0.3ng/ml (0.8- 3.85ng/ml). Pt was advised to immediately stop Empa and follow-up with local ER. When he presented to local ER, approximately 4 days later, he was hyperglycemic with glucose 316 mg/dL, and labwork consistent with classic DKA. Pt was initiated on basal bolus insulin regimen and had resolution of DKA.IO mediated DM results from immune mediated islet cell destruction leading to rapidly progressive insulin deficiency. When suspected, these pts should be evaluated for beta cell dysfunction and insulin should be used for glycemic control. This case highlights that SGLT2 therapy should be used with caution in patients with hyperglycemia on immunotherapy as it could mask the diagnosis of DKA. In addition, this case shows that patients taken off of immunotherapy may develop delayed glycemic complications and may need long term monitoring.

Disclosure
P. Iyer: None. S.N. Thosani: Consultant; Spouse/Partner; Boston Scientific Corporation, Medtronic. Speaker's Bureau; Spouse/Partner; AbbVie Inc..
Placental DNA Methylation of miR-548 and WWTR1 Genes Influence Insulin Sensitivity during Pregnancy
Authors: HIVERT MARIE-FRANCE , BRIGGS CATHERINE M. , CARDENAS ANDRES , PERRON PATRICE , BOUCHARD LUIGI 
Published: June 2018

Insulin sensitivity decrease in pregnancy is a physiologic adaptation to derive nutrients for the growing fetus. The placenta has a major role in this phenomenon, but exact mechanisms remain unknown. A better understanding of the placental role in maternal insulin sensitivity regulation could help us reveal pathophysiologic pathways of gestational diabetes. We tested associations between insulin sensitivity and DNA methylation (DNAm) across the genome in 439 placenta samples from our prospective cohort Gen3G using Illumina EPIC arrays. Women were recruited at 1st trimester of pregnancy and performed a 2-hour 75g oral glucose tolerance test (OGTT) at 24-28 weeks: we measured glucose and insulin levels at each OGTT point to calculate Matsuda insulin sensitivity index. We applied standard quality control procedures for DNAm arrays analyses and adjusted for technical batch effects. We tested 720,077 individual CpGs using robust linear regression on M-values (adjusted for maternal age, BMI, smoking, parity, gestational age at birth, and child sex) and used Bonferroni to account for multiple testing. We found that maternal insulin sensitivity was associated with DNAm in placenta at 318 CpGs across the genome (P&lt;6.94 x10-8). Among these, we found differentially methylated CpGs at loci well known for their role in diabetes (TCF7L2, SPRY2), brown adipose tissue regulation (PRDM16), and near the Prolactin Receptor. Mendelian Randomization (MR) analyses supported that placental DNAm causally influence maternal insulin sensitivity at 28 CpGs (P&lt;0.05). Among these, our two strongest MR associations (FDR adjusted P&lt;0.05) pointed at CpGs near miR-548 (P=5.6x10-5) and WWTR1 (P=9.8x10-5), a gene implicated in PPARalpha regulation and previously associated with preeclampsia. Our findings highlight the role of placenta epigenetic regulation in insulin sensitivity during pregnancy and reveal novel potential biologic targets implicated in gestational metabolic disorders.

Disclosure
M. Hivert: None. C.M. Briggs: None. A. Cardenas: None. P. Perron: Research Support; Self; Merck & Co., Inc., Pfizer Inc., Novo Nordisk Inc.. Speaker's Bureau; Self; Sanofi. Research Support; Self; AstraZeneca. L. Bouchard: None.
HD-6277, a Selective GPR40 Agonist, Can Improve Beta-Cell Signaling and Insulin Secretion
Authors: KANG SEUNG JUN , KIM CHUN HWA , CHOI HYO SUN , YANG GOEUN , LEE SUN HEE , LIM KWAN SOO , PARK MIN AH , KIM DOO YOUNG , YANG JIN , RHEE JAE KEOL , KIM DAEHOON 
Published: June 2018

The free fatty acid receptor 1 (FFAR1/GPR40) mediates fatty acid-dependent augmentation of glucose-induced insulin secretion (GIIS) in pancreatic β-cells. The objective of the studies described here was to examine the pharmacological properties of HD-6277 in cell based assay and preclinical models of T2D. Insulin secretion was evaluated in INS-1 cells, HD-6277 (0.1∼10 μM) treated group enhanced more insulin secretion than sulfonylurea added condition. HD-6277 (100 mg/kg) did not induced hypoglycemia even combinational treatment with Metformin (50 mg/kg) in Sprague-Dawley rats. Goto-Kakizaki (GK) rats have known as type 2 diabetic model with secondary failure and apoptosis of pancreatic beta-cell. HD-6277 and glimepiride were administered to GK rats of 8 (young) and 26 (old) weeks old, respectively. Glucose tolerance tests (GTT) were performed at the starting and the ending point of the chronic administration. Administration of HD-6277 and glimepiride improved glycemic control and insulin secretion, compared to vehicle control groups in young GK rats, however, chronic administration of glimepiride cause loss of glycemic control efficacy, whereas HD-6277 did not. At the end of chronic administration, glimepiride-treated group demonstrated poor glycemic control and insulin secretion during GTT than HD-6277-treated group. In administration of HD-6277 and glimepiride to old GK rats, HD-6277-treated group has showed ameliorate in glycemic control than vehicle group, however glimepiride-treated group did not.
Thus, repeated administration of HD-6277 can preserves pancreatic islets, improves beta cell function and attenuates diabetes.

Disclosure
S. Kang: Employee; Self; Hyundai Pharm. corp. C. Kim: Employee; Self; Hyundai Pharm. corp.. H. Choi: None. G. Yang: Employee; Self; Hyundai Pharm. CORP. S. Lee: Employee; Self; Hyundai Pharm. CORP. K. Lim: Employee; Self; Hyundai Pharm. corp. M. Park: Employee; Self; Hyundai Pharm.corp. D. Kim: Employee; Self; Hyundai Pharm. CORP. J. Yang: Employee; Self; Hyundai Pharm. corp. J. Rhee: Employee; Self; Hyundai Pharm. corp. D. Kim: Employee; Self; Hyundai Pharm. Corp..
Pharmacodynamics Post-Hoc Analysis of Glucose Kinase Activator Dorzagliatin (HMS5552)—Twelve Weeks Treatment in T2D Patients in China
Authors: ZHU DALONG , ZHAO YU , TANG CUI , TIANXIN HU , LI YONG-GUO , ZHAO GUIYU , HOU XINGHUA , ZHANG YI , CHEN LI ,   HMM0201 STUDY GROUP
Published: June 2018

In a phase II study, dorzagliatin, a novel glucokinase activator (GKA), demonstrated significant HbA1c reduction and safety profile in Chinese T2D patients. Two hundred fifty eight (258) T2D patients were randomly assigned to 5 groups (50mg BID, 75mg BID, 75mg QD, 100mg QD and placebo) for a 12 weeks treatment. Compared with placebo group, HbA1c changes from baseline was significantly lower in the 100mgQD (0.69%, P&lt;0.05), 50mgBID (0.79%, P&lt;0.01) and 75mgBID (1.12%, P&lt;0.001) groups. Post-hoc analyses of the phase II results were conducted to investigate the effects of dorzagliatin on the composite response rate (defined as reaching HbA1c&lt;7.0%, no weight gain and no hypoglycemia), efficacy response β cell functions (HOMA-IR and Disposition Index), and efficacy response in stratified subgroups. Post-hoc analysis showed that the composite response rate was 28.3% (P &lt; 0·05) and 35.4% (P &lt; 0·001), respectively for 50mgBID and 75mgBID groups. It was significantly higher than the placebo group. HOMA-IR and Disposition Index was improved at Week 12 for the 75 mg BID group compared with placebo. Improvement of HOMA-IR was maintained at Week 13, one week after treatment discontinuation. Subjects were stratified into subgroups according to their medical history, disease history, gender, age and BMI. In drug naïve subjects, HbA1c change from baseline was -0.85% in 75mgQD (P&lt;0.05), -0.95% in 100mgQD (P&lt;0.01), -1.04% in 50mgBID (P&lt;0.01), -1.21% in 75mgBID (P&lt;0.001), and -0.17% in placebo group. Significant HbA1c reduction was also observed in 75mgBID (-0.97%, P&lt;0.05) in the subjects who were previously treated with other antidiabetic drugs. No significant trends were observed on HbA1c in subgroups stratified by disease history, gender, age and BMI. The post-hoc analysis demonstrated dorzagliatin provided a comprehensive disease management in T2D patients with benefits of β cell function and insulin resistance improvement in the early stage T2D patients.

Disclosure
D. Zhu: None. Y. Zhao: None. C. Tang: None. H. Tianxin: None. Y. Li: None. G. Zhao: None. X. Hou: None. Y. Zhang: None. L. Chen: None.
Effects of Teneligliptin (Teneli) on Glycemic Indices in Type 2 Diabetes (T2DM) Subjects Uncontrolled with Metformin (Met) and Glimepiride (Glim) Combination
Authors: MAHAPATRA HARIBALLAV , MISHRA SUSANT , KHUNTIA MONALISA , JENA BISWARANJAN , DAS SREEYA , JENA APURBA R. , PADHI RAJESH K. , SAHOO ABHAY K. , MAHAPATRA RAMABALLAV , MAHAPATRA LAXMINARAYAN 
Published: June 2018

Objective: People with diabetes gradually require increasing dose of medications to achieve good control. We studied the glycemic response of adding Teneligliptin (Teneli) in T2DM subjects with high HbA1c despite being on stable doses of Met and Glim dose.
Methods: In this retrospective study T2DM subjects, who were on fixed doses of Met 1000 to 2000mg and Glim 1 to 6mg daily for 3 months were considered. Subjects with an HbA1c between 8-11% and who were prescribed Teneli 20mg OD for at least 6 months, were shortlisted. Those taking insulin or antidiabetic drugs other than Glim+Met or those whose dose was up-titrated during the study period were excluded. We compared HbA1c, fasting (FPG), postprandrial (PPG) plasma glucose, total cholesterol (TC), triglyceride (TG), HDL, LDL, systolic (SBP) and diastolic (DBP) blood pressure at baseline and after 6months of Teneli initiation.
Results: Data of 562 subjects (229, 41% females), who met the inclusion criteria were extracted for analysis from the hospital records. Mean age of the sample was 52.6 (95% CI: 51.7-53.4) years and duration of diabetes was 7.8 (6.6-8.3) years. Addition of Teneli resulted in a drop in HbA1c from 9.6% (8.2-10.6) to 8.8% (7.1-9.4) (p&lt;0.05). FPG decreased from 158.8 (154.3-163.2) to 127.8 (124.5-131.1) and PPG from 236.4 (230.7-242.0) to 191.0 (186.0-196.0) respectively (p &lt;0.05). Teneli also improved lipid parameters significantly, particularly TC and TG. With Tenali, SBP declined from 136.8 (134.8-137.9) to 129.5 (128.1-130.9) and DBP from 83.1 (82.2-83.9) to 81.0 (80.2-81.9). There was no incidence of severe hypoglycemia, though 18 (3.2%) cases of suspected hypoglycemia were managed at home.
Conclusion: Adding Teneli to Met and Glim combination showed promising role in improving glycemic parameters, lipid components and blood pressure. Low hypoglycemia risk makes the drug a suitable add-on option for those with high HbA1c values.

Disclosure
H. Mahapatra: None. S. Mishra: None. M. Khuntia: None. B. Jena: None. S. Das: None. A.R. Jena: None. R.K. Padhi: None. A.K. Sahoo: None. R. Mahapatra: None. L. Mahapatra: None.
Real-Life Investigation of Effectiveness and Tolerability of Hydroxychloroquine in Type 2 Diabetes Mellitus Patients in India
Authors: CHAWLA MANOJ S. , CHAWLA PURVI M. , GUPTA PAYAL 
Published: June 2018

Aim: With the increasing incidence of type 2 diabetes mellitus (T2DM) in India (approximately 72 million affected), there is a growing concern and a need for newer, durable and cheaper therapies. Hydroxychloroquine (HCQ), a common anti-malarial also prescribed in rheumatic disease is associated with increased insulin sensitivity and improved glucose tolerance in these patients, with/without diabetes. As a speciality care provider, we initiated an enquiry into the effectiveness and tolerability of HCQ in T2DM patients, uncontrolled on metformin and sulfonylurea (SU) by undertaking this open-label, prospective study at our center.
Methods: A total of 15 T2DM patients, aged between 43-59 years and unresponsive to metformin and SU were included and prescribed an add-on therapy of HCQ at 400 mg once daily for 24 weeks. Change in glycemic and lipid parameters was evaluated at 0, 12 and 24 weeks.
Results: At the end of 24 weeks, there were clinically relevant decreases of 18% and 0.88% in mean fasting plasma glucose and HbA1c, respectively. The total cholesterol, triglycerides, low-density lipoprotein cholesterol and very low-density lipoprotein cholesterol decreased by 13.24%, 19.7%, 13.31% and 26.94% respectively, considered clinically meaningful with no patients discontinuing due to any adverse effects.
Discussion: Patients of T2DM, uncontrolled on metformin and SU, often require a third drug/insulin for further treatment management. These results clearly demonstrate the benefits and tolerability of HCQ in Indian T2DM patients over 24 weeks with glycemic and lipid advantages. Although the sample size of the study was small, the encouraging results pave way for larger and longer duration, studies with HCQ.
Conclusion: Based on this investigator-initiated prospective study, HCQ offers a safe, efficacious and cheaper alternative to T2DM patients, when uncontrolled on metformin and SU, particularly in limited resource countries, including India.

Disclosure
M.S. Chawla: Speaker's Bureau; Self; IPCA Laboratories, Eli Lilly and Company, Novo Nordisk A/S, MSD Pharmaceutical Pvt. Ltd., Boehringer Ingelheim Pharmaceuticals, Inc., AstraZeneca. Speaker's Bureau; Spouse/Partner; Sanofi. P.M. Chawla: Speaker's Bureau; Self; Sanofi. Speaker's Bureau; Spouse/Partner; Eli Lilly and Company, IPCA LABORATORIES, Novo Nordisk A/S, MSD PHARMACEUTICALS PVT. LTD., Boehringer Ingelheim Pharmaceuticals, Inc., AstraZeneca. P. Gupta: None.
Improvements in Blood Pressure (BP) and Markers of Arterial Stiffness with Canagliflozin (CANA) in the CANagliflozin CardioVascular Assessment Study (CANVAS) Program
Authors: TOWNSEND RAYMOND , DHARMALINGAM MALA , GENOVESE STEFANO , STEELE ANDREW , ARENAS JOSE L. , SLEE APRIL , FABBRINI ELISA , MAHAFFEY KENNETH W. 
Published: June 2018

The CANVAS Program demonstrated a reduced risk of cardiovascular (CV) and renal outcomes with the SGLT2 inhibitor CANA vs. placebo (PBO) in adults with T2DM and established CV disease or ≥2 CV risk factors (N = 10,142; mean age, 63.3 y; systolic BP [SBP], 136.6 mmHg; diastolic BP [DBP], 77.7 mmHg). This analysis assessed the effects of CANA on BP, pulse, and markers of arterial stiffness including pulse pressure (PP = SBP-DBP) and double product (DP = pulse × SBP). CANA lowered SBP and DBP compared with PBO over the CANVAS Program (mean differences of -3.93 mmHg [95% CI: -4.30, -3.56]) and -1.39 mmHg [95% CI: -1.61, -1.17]; both P &lt;0.001). There were no meaningful differences in pulse over 104 weeks; a ∼0.5 bpm reduction in pulse was seen with CANA at Week 26, which remained stable over time, while pulse with PBO was similar to baseline over 104 weeks. CANA provided reductions in PP and DP compared with PBO (Figure). There was an initial reduction in PP that increased over time with CANA, but remained lower compared with PBO. CANA also provided an initial reduction in DP that was sustained over time. Thus we observed favorable effects of CANA on BP, pulse, and markers of arterial stiffness in patients with T2DM with CV risk factors or established CV disease, which may contribute to the beneficial effects of CANA on CV outcomes.

Disclosure
R. Townsend: None. M. Dharmalingam: None. S. Genovese: Speaker's Bureau; Self; Abbott Diabetes Care, AstraZeneca, Boehringer Ingelheim, Bruno Farmaceutici, Bristol-Myers Squibb, Eli Lilly, Janssen, Lifescan, Merck Sharp & Dohme, Novartis, Novo Nordisk, Sanofi, Takeda. Consultant; Self; Abbott Diabetes Care, AstraZeneca, Boehringer Ingelheim, Bruno Farmaceutici, Bristol-Myers Squibb, Eli Lilly, Janssen, Lifescan, Merck Sharp & Dohme, Novartis, Novo Nordisk, Sanofi, Takeda. Research Support; Self; Novartis AG. A. Steele: Speaker's Bureau; Self; Amgen, AZ, Bayer, BI, Lilly, Jansen, Merck, Pfizer, Otsuka, Valeant. Advisory Panel; Self; Amgen, BI/Lilly, Jansen, Otsuka, Shire. J.L. Arenas: None. A. Slee: Other Relationship; Self; Janssen Scientific Affairs, LLC. E. Fabbrini: Employee; Self; Janssen Research & Development. K.W. Mahaffey: Research Support; Self; Afferent, Amgen, AstraZeneca, Daiichi, Ferring, Google (Verily), Janssen, Medtronic, Merck, Novartis, Sanofi, and St. Jude. Consultant; Self; Ablynx, AstraZeneca, BAROnova, Bio2 Medical, Boehringer Ingelheim, Bristol-Myers Squibb, Cardiometabolic Health Congress, Cubist, Eli Lilly, Elsevier, Epson, GlaxoSmithKline, Janssen, Merck, Mt. Sinai, Radiometer, Springer Publishing, The Medicines Company, Theravance, Vindico, and WebMD. Stock/Shareholder; Self; BioPrint Fitness.
The Effect of Saxagliptin on Adipose Tissue Inflammation in Overweight and Obese Nondiabetic Subjects
Authors: KOSKA JURAJ , OSREDKAR TRACY , KAREN D'SOUZA , SINHA SANDEEP , MEYER CHRISTIAN , REAVEN PETER 
Published: June 2018

Inflammation plays a crucial role in early stages of both insulin resistance and atherosclerosis development. Preclinical evidence suggests an important role for DPP-4 in the regulation of adipose tissue (AT) inflammation. The present study tests the hypothesis that DPP-4 inhibition by saxagliptin reduces adipose tissue inflammation independent of changes in glucose metabolism. Forty-four overweight or obese individuals without diabetes were randomized to receive once daily saxagliptin (5 mg) or matching placebo (2:1 randomization) for 6 weeks. Adipose tissue biopsies, 4 hour fat-enriched meal challenge tests, and endothelial function measurement were performed at baseline and at the end of each treatment. Forty-two participants completed the study (27 saxagliptin/15 placebo). There were no group differences in the AT expression of inflammation-related genes (MCP-1, CD36, CD68, IL-6, IL-8, TxNIP and adiponectin) and protein pathway activation (ERK, JNK and NFκB). Secretion of IL-8 from adipose tissue explants was reduced after saxagliptin compared to placebo (median fold-baseline 0.8 saxagliptin vs. 2.3 placebo, p=0.01) and there was also a trend for reduced IL-6 release (0.7 vs. 1.5, p=0.06). After the high-fat meal, plasma glucose was slightly lower after saxagliptin (4 hour AUC, 0.96 vs. 1.0, p=0.04) while insulin and triglycerides were similar between the two groups. There were no treatment differences in endothelial function.
In conclusion, reduced AT secretion of IL-8 and IL-6 (trend) in obese nondiabetic subjects suggests saxagliptin may directly reduce AT inflammation. However, this effect was relatively modest, with many other indicators of tissue inflammation remaining unchanged. The reduction in AT inflammation did not appear sufficiently potent to influence postprandial metabolism or endothelial function.

Disclosure
J. Koska: None. T. Osredkar: None. K. D'Souza: None. S. Sinha: None. C. Meyer: Employee; Self; Merck & Co., Inc. P. Reaven: Research Support; Self; AstraZeneca, Amgen Inc., Bristol-Myers Squibb Company.