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  • Lundkvist, PerUppsala universitet,Klinisk diabetologi och metabolism (author)

Glucagon Levels During Short-Term SGLT2 Inhibition Are Largely Regulated by Glucose Changes in Patients With Type 2 Diabetes.

  • Article/chapterEnglish2019

Publisher, publication year, extent ...

  • 2018-08-17
  • The Endocrine Society,2019
  • printrdacarrier

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  • LIBRIS-ID:oai:DiVA.org:uu-373521
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-373521URI
  • https://doi.org/10.1210/jc.2018-00969DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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 β-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.

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Added entries (persons, corporate bodies, meetings, titles ...)

  • Pereira, Maria J.,1981-Uppsala universitet,Klinisk diabetologi och metabolism(Swepub:uu)marpe927 (author)
  • Kamble, Prasad G.Uppsala universitet,Klinisk diabetologi och metabolism(Swepub:uu)kampr247 (author)
  • Katsogiannos, PetrosUppsala universitet,Klinisk diabetologi och metabolism(Swepub:uu)petka500 (author)
  • Langkilde, Anna MariaAstraZeneca Res & Dev, S-43150 Molndal, Sweden (author)
  • Esterline, RussellAstraZeneca Res & Dev, S-43150 Molndal, Sweden (author)
  • Johnsson, EvaAstraZeneca Res & Dev, S-43150 Molndal, Sweden (author)
  • Eriksson, Jan W.Uppsala universitet,Klinisk diabetologi och metabolism(Swepub:uu)janer909 (author)
  • Uppsala universitetKlinisk diabetologi och metabolism (creator_code:org_t)

Related titles

  • In:Journal of Clinical Endocrinology and Metabolism: The Endocrine Society104:1, s. 193-2010021-972X1945-7197

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