Glucagon Levels During Short-Term SGLT2 Inhibition Are Largely Regulated by Glucose Changes in Patients With Type 2 Diabetes.
J Clin Endocrinol Metab
; 104(1): 193-201, 2019 01 01.
Article
em En
| MEDLINE
| ID: mdl-30137410
ABSTRACT
Context The mechanism mediating sodium glucose cotransporter-2 (SGLT2) inhibitor-associated increase in glucagon levels is unknown. Objective:
To assess short-term effects on glucagon, other hormones, and energy substrates after SGLT2 inhibition and whether such effects are secondary to glucose lowering. The impact of adding a dipeptidyl peptidase-4 inhibitor was addressed. Design, Setting, and Patients A phase 4, single-center, randomized, three-treatment crossover, open-label study including 15 patients with type 2 diabetes treated with metformin.Interventions:
Patients received a single-dose of dapagliflozin 10 mg accompanied by the following in randomized order isoglycemic clamp (experiment DG); saline infusion (experiment D); or saxagliptin 5 mg plus saline infusion (experiment DS). Directly after 5-hour infusions, a 2-hour oral glucose tolerance test (OGTT) was performed.Results:
Glucose and insulin levels were stable in experiment DG and decreased in experiment D [P for difference (Pdiff) < 0.001]. Glucagon-to-insulin ratio (Pdiff < 0.001), and levels of glucagon (Pdiff < 0.01), nonesterified fatty acids (Pdiff < 0.01), glycerol (Pdiff < 0.01), and ß-OH-butyrate (Pdiff < 0.05) were lower in DG vs D. In multivariate analysis, change in glucose level was the main predictor of change in glucagon level. In DS, glucagon and active GLP-1 levels were higher than in D, but glucose and insulin levels did not differ. During OGTT, glucose levels rose less and glucagon levels fell more in DS vs D.Conclusion:
The degree of glucose lowering markedly contributed to regulation of glucagon and insulin secretion and to lipid mobilization during short-term SGLT2 inhibition.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Glicemia
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Glucagon
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Diabetes Mellitus Tipo 2
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Inibidores do Transportador 2 de Sódio-Glicose
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Hipoglicemiantes
Tipo de estudo:
Clinical_trials
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Prognostic_studies
Limite:
Adolescent
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Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article