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Glucagon Levels During Short-Term SGLT2 Inhibition Are Largely Regulated by Glucose Changes in Patients With Type 2 Diabetes.
Lundkvist, Per; Pereira, Maria J; Kamble, Prasad G; Katsogiannos, Petros; Langkilde, Anna Maria; Esterline, Russell; Johnsson, Eva; Eriksson, Jan W.
Afiliação
  • Lundkvist P; Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
  • Pereira MJ; Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
  • Kamble PG; Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
  • Katsogiannos P; Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
  • Langkilde AM; AstraZeneca Research and Development, Mölndal, Sweden.
  • Esterline R; AstraZeneca Research and Development, Mölndal, Sweden.
  • Johnsson E; AstraZeneca Research and Development, Mölndal, Sweden.
  • Eriksson JW; Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Glicemia / Glucagon / Diabetes Mellitus Tipo 2 / Inibidores do Transportador 2 de Sódio-Glicose / Hipoglicemiantes Tipo de estudo: Clinical_trials / Prognostic_studies Limite: Adolescent / Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Glicemia / Glucagon / Diabetes Mellitus Tipo 2 / Inibidores do Transportador 2 de Sódio-Glicose / Hipoglicemiantes Tipo de estudo: Clinical_trials / Prognostic_studies Limite: Adolescent / Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2019 Tipo de documento: Article