Clinical Parameters, Fuel Oxidation, and Glucose Kinetics in Patients With Type 2 Diabetes Treated With Dapagliflozin Plus Saxagliptin.
Objective: To examine the mechanisms responsible for improved glycemia with combined sodium-glucose cotransporter 2 inhibitor (SGLT2i) plus dipeptidyl peptidase 4 inhibitor therapy in type 2 diabetes.Research Design and Methods: Fifty-six patients (HbA1c 8.9 ± 0.2% [74 ± 2 mmol/mol]) were randomized...
| Published in: | Diabetes Care Vol. 43; no. 10; pp. 2519 - 2528 |
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| Main Authors: | , , , , , |
| Format: | research Journal Article |
| Published: |
American Diabetes Association
Oct2020
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=146006693&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 146006693 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 01495992 1G7 jtl: Diabetes Care issn: 01495992 maglogo: N pubinfo: dt: Oct2020 vid: 43 iid: 10 pid: 1367 pub: American Diabetes Association place: Arlington, Virginia artinfo: ui: 146006693 146006693 NLM32694214 146006693 10.2337/dc19-1993 NLM32694214 146006693 ppf: 2519 ppct: 9 formats: tig: atl: Clinical Parameters, Fuel Oxidation, and Glucose Kinetics in Patients With Type 2 Diabetes Treated With Dapagliflozin Plus Saxagliptin. aug: au: Qin, Yuejuan Adams, John Solis-Herrera, Carolina Triplitt, Curtis DeFronzo, Ralph Cersosimo, Eugenio affil: Texas Diabetes Institute–University Health System and UT Health San Antonio, San Antonio, TX sug: subj: Glucose Metabolism Glycosides Administration and Dosage Benzhydryl Compounds Administration and Dosage Oligopeptides Administration and Dosage Hydrocarbons, Cyclic Diabetes Mellitus, Type 2 Drug Therapy Glycosuria Urine Hydrocarbons, Cyclic Administration and Dosage Benzhydryl Compounds Adverse Effects Double-Blind Studies Adult Blood Glucose Drug Effects Blood Glucose Metabolism Male Hydrocarbons, Cyclic Adverse Effects Hypoglycemic Agents Administration and Dosage Energy Metabolism Drug Effects Human Kinetics Diabetes Mellitus, Type 2 Metabolism Oxidation-Reduction Drug Effects Glycosides Adverse Effects Hypoglycemic Agents Adverse Effects Oligopeptides Adverse Effects Middle Age Female Drug Therapy, Combination Comparative Studies Multicenter Studies Evaluation Research Validation Studies Scales Adult: 19-44 years Middle Aged: 45-64 years Male Female ab: Objective: To examine the mechanisms responsible for improved glycemia with combined sodium-glucose cotransporter 2 inhibitor (SGLT2i) plus dipeptidyl peptidase 4 inhibitor therapy in type 2 diabetes.Research Design and Methods: Fifty-six patients (HbA1c 8.9 ± 0.2% [74 ± 2 mmol/mol]) were randomized to dapagliflozin (DAPA) 10 mg, DAPA/saxagliptin (SAXA) 10/5 mg, or placebo (PCB) for 16 weeks. Basal endogenous glucose production (EGP) (3-3H-glucose), urinary glucose excretion, glucose/lipid oxidation, HbA1c, and substrate/hormone levels were determined before treatment (Pre-Tx) and after treatment (Post-Tx).Results: At week 16, HbA1c decrease was greater (P < 0.05) in DAPA/SAXA (-2.0 ± 0.3%) vs. DAPA (-1.4 ± 0.2%) and greater than PCB (0.2 ± 0.2%). Day 1 of drug administration, EGP (∼2.40 mg/kg/min) decreased by -0.44 ± 0.09 mg/kg/min in PCB (P < 0.05) but only by -0.21 ± 0.02 mg/kg/min in DAPA and DAPA/SAXA (P < 0.05 vs. PCB). At week 16, EGP increased to 2.67 ± 0.09 mg/kg/min (DAPA) and 2.61 ± 0.08 mg/kg/min (DAPA/SAXA), despite reductions in fasting plasma glucose by 47 and 77 mg/dL, respectively, and no changes in PCB. Baseline plasma free fatty acids rose by 40 µmol/L with DAPA but declined by -110 with PCB and -90 µmol/L with DAPA/SAXA (P < 0.05, Pre-Tx vs. Post-Tx). In DAPA, carbohydrate oxidation rates decreased from 1.1 ± 0.1 to 0.7 ± 0.1 mg/kg/min, whereas lipid oxidation rates increased from 0.6 ± 0.1 to 0.8 ± 0.1 mg/kg/min (P < 0.01). In DAPA/SAXA, the shift in carbohydrate (1.1 ± 0.1 to 0.9 ± 0.1 mg/kg/min) and lipid (0.6 ± 0.1 to 0.7 ± 0.1 mg/kg/min) oxidation was attenuated (P < 0.05).Conclusions: The addition of SAXA to DAPA resulted in superior glycemic control compared with DAPA monotherapy partly because of increased glucose utilization and oxidation. Although the decrease in insulin/glucagon ratio was prevented by SAXA, EGP paradoxical elevation persisted, indicating that other factors mediate EGP changes in response to SGLT2i-induced glucosuria. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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