2018
DOI: 10.1007/s13300-018-0449-6
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Abstract: IntroductionThe sodium-glucose cotransporter 2 inhibitor dapagliflozin and the glucagon-like peptide-1 (GLP-1) receptor agonist exenatide reduce bodyweight via differing and complementary mechanisms. This post hoc analysis investigated the metabolic effects and baseline associations with bodyweight loss on coadministration of dapagliflozin and exenatide once weekly (QW) among adults with obesity and without diabetes.MethodsIn the primary trial, adults with obesity and without diabetes [n = 50; 18–70 years; bod… Show more

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Cited by 24 publications
(18 citation statements)
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“…However, this finding could be in accordance with the controversial results of another study in a transgenic model of low-grade chronic hyperglycemia, SGLT2 inhibitor treatment was associated with improved muscle and fat insulin resistance but not with improved insulin secretory function [22]; nonetheless, findings not well established in clinical intervention studies. The euglycemic hyperinsulinemic clamp is considered the gold standard for the measurement of insulin sensitivity, and Matsuda index used in this study has a good correlation of 0.73 (p < 0.0001) with the clamp technique [12]; although in our study the urine glucose excretion was not directly measured, the Matsuda index was corrected as it is recommended in the literature for non-diabetic patients with or without SGLT2 inhibitor treatment [13][14][15]. A decrease in glucotoxicity and lipotoxicity could be a hypothetical mechanism that would explain the improvement in insulin sensitivity, because lowering plasma glucose concentration and the effect of hyperglycemia with the administration of dapagliflozin in T2DM patients has shown an improvement in β-cell function [23]; however, experimental studies evaluating glucotoxicity and lipotoxicity in prediabetes with dapagliflozin, are not available to confirm these findings.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…However, this finding could be in accordance with the controversial results of another study in a transgenic model of low-grade chronic hyperglycemia, SGLT2 inhibitor treatment was associated with improved muscle and fat insulin resistance but not with improved insulin secretory function [22]; nonetheless, findings not well established in clinical intervention studies. The euglycemic hyperinsulinemic clamp is considered the gold standard for the measurement of insulin sensitivity, and Matsuda index used in this study has a good correlation of 0.73 (p < 0.0001) with the clamp technique [12]; although in our study the urine glucose excretion was not directly measured, the Matsuda index was corrected as it is recommended in the literature for non-diabetic patients with or without SGLT2 inhibitor treatment [13][14][15]. A decrease in glucotoxicity and lipotoxicity could be a hypothetical mechanism that would explain the improvement in insulin sensitivity, because lowering plasma glucose concentration and the effect of hyperglycemia with the administration of dapagliflozin in T2DM patients has shown an improvement in β-cell function [23]; however, experimental studies evaluating glucotoxicity and lipotoxicity in prediabetes with dapagliflozin, are not available to confirm these findings.…”
Section: Discussionmentioning
confidence: 99%
“…The first phase of insulin secretion was evaluated using the Stumvoll [12]. The Matsuda index was corrected by urine glucose excretion in non-diabetic patients with or without SGLT2 inhibitors, using a web calculator [13], based on reported values in the literature of the glucose excretion decreasing in the calculation 5.9 g to the 75-g oral dextrose load of the OGTT in patients of the dapagliflozin group [14,15].…”
Section: Methodsmentioning
confidence: 99%
“…Precision medicine approaches may also provide an opportunity to select patients who are receptive to the greater efficacy of this combination therapy. In our previous work on combination treatment with an SGLT2 inhibitor and GLP1-RA, we found some baseline characteristics that might identify responders, and relatively low BMI and low insulin secretion were associated with greater bodyweight loss [73]. In addition, the occurrence of the A allele of the SNP10010131, which is related to GLP-1-induced insulin secretion [74], was found to be associated with relatively greater bodyweight loss [73].…”
Section: Future Perspectivesmentioning
confidence: 99%
“…In our previous work on combination treatment with an SGLT2 inhibitor and GLP1-RA, we found some baseline characteristics that might identify responders, and relatively low BMI and low insulin secretion were associated with greater bodyweight loss [73]. In addition, the occurrence of the A allele of the SNP10010131, which is related to GLP-1-induced insulin secretion [74], was found to be associated with relatively greater bodyweight loss [73]. One study has found an association between a genetic variation in the SGLT2 gene (the rs9934336 G-allele) and increased plasma glucose and insulin concentrations during an oral glucose tolerance test [75].…”
Section: Future Perspectivesmentioning
confidence: 99%
“…As GLP1RA may be considered as a potential therapy for wolfram syndrome treatment, analysis of association between WFS1 gene polymorphism and GLP1RA efficacy becomes reasonable. Thus, Pereira and colleagues demonstrated higher body weight loss in allele A carriers of rs10010131 [ 119 ].…”
Section: Genes Associated With Dpp4-inhibitors and Glp1 Receptor Amentioning
confidence: 99%