Research
Print page Print page
Switch language
Rigshospitalet - a part of Copenhagen University Hospital
Published

The Role of Glucagon in the Acute Therapeutic Effects of SGLT2 Inhibition

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. Genetic Studies of Leptin Concentrations Implicate Leptin in the Regulation of Early Adiposity

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Glucagon Resistance at the Level of Amino Acid Turnover in Obese Subjects with Hepatic Steatosis

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Cardiac Autonomic Function is Associated With Myocardial Flow Reserve in Type 1 Diabetes

    Research output: Contribution to journalJournal articleResearchpeer-review

  • Sofie Hædersdal
  • Asger Lund
  • Elisabeth Nielsen-Hannerup
  • Henrik Maagensen
  • Gerrit van Hall
  • Jens J Holst
  • Filip K Knop
  • Tina Vilsbøll
View graph of relations

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) effectively lower plasma glucose (PG) concentration in patients with type 2 diabetes, but studies have suggested that circulating glucagon concentrations and endogenous glucose production (EGP) are increased by SGLT2i, possibly compromising their glucose-lowering ability. To tease out whether and how glucagon may influence the glucose-lowering effect of SGLT2 inhibition, we subjected 12 patients with type 2 diabetes to a randomized, placebo-controlled, double-blinded, crossover, double-dummy study comprising, on 4 separate days, a liquid mixed-meal test preceded by single-dose administration of either 1) placebo, 2) the SGLT2i empagliflozin (25 mg), 3) the glucagon receptor antagonist LY2409021 (300 mg), or 4) the combination empagliflozin + LY2409021. Empagliflozin and LY2409021 individually lowered fasting PG compared with placebo, and the combination further decreased fasting PG. Previous findings of increased glucagon concentrations and EGP during acute administration of SGLT2i were not replicated in this study. Empagliflozin reduced postprandial PG through increased urinary glucose excretion. LY2409021 reduced EGP significantly but gave rise to a paradoxical increase in postprandial PG excursion, which was annulled by empagliflozin during their combination (empagliflozin + LY2409021). In conclusion, our findings do not support that an SGLT2i-induced glucagonotropic effect is of importance for the glucose-lowering property of SGLT2 inhibition.

Original languageEnglish
JournalDiabetes
Volume69
Issue number12
Pages (from-to)2619-2629
Number of pages11
ISSN0012-1797
DOIs
Publication statusPublished - Dec 2020

ID: 61025696