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

SGLT2 inhibitors: Clinical benefits by restoration of normal diurnal metabolism?

Research output: Contribution to journalReviewResearchpeer-review

DOI

  1. Risk factors for hyperglycemia in pregnancy in the DALI study differ by period of pregnancy and OGTT time point

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. THERAPY OF ENDOCRINE DISEASE: Growth hormone replacement therapy in adults: 30 years of personal clinical experience

    Research output: Contribution to journalReviewResearchpeer-review

  3. Safety and convenience of once-weekly somapacitan in adult GH deficiency: a 26-week randomized, controlled trial

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Genetic influence on the associations between IGF-I and glucose metabolism in a cohort of elderly twins

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. Targeting either GH or IGF-I during somatostatin analogue treatment in patients with acromegaly: a randomized multicentre study

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Dyslipidemia at diagnosis of childhood acute lymphoblastic leukemia

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Lactation Duration and Long-term Risk for Incident Type 2 Diabetes in Women With a History of Gestational Diabetes Mellitus

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Epigenome- and Transcriptome-wide Changes in Muscle Stem Cells from Low Birth Weight Men

    Research output: Contribution to journalJournal articleResearchpeer-review

  • Russell L. Esterline
  • Allan Vaag
  • Jan Oscarsson
  • Jiten Vora
View graph of relations

Type 2 diabetes (T2D) is associated with inhibition of autophagic and lysosomal housekeeping processes that detrimentally affect key organ functioning; a process likely to be exacerbated by conventional insulin-driven anabolic therapies. We propose that the cardio-renal benefits demonstrated with sodium-glucose cotransporter-2 inhibitor (SGLT2i) treatment in T2D partly may be explained by their ability to drive consistent, overnight periods of increased catabolism brought about by constant glucosuria. Key steps driving this catabolic mechanism include: a raised glucagon/insulin ratio initially depleting glycogen in the liver and ultimately activating gluconeogenesis utilizing circulating amino acids (AAs); a general fuel switch from glucose to free fatty acids (accompanied by a change in mitochondrial morphology from a fission to a sustained fusion state driven by a decrease in AA levels); a decrease in circulating AAs and insulin driving inhibition of mammalian target of rapamycin complex 1 (mTORC1), which enhances autophagy/lysosomal degradation of dysfunctional organelles, eventually causing a change in mitochondrial morphology from a fission to a sustained fusion state. Resumption of eating in the morning restores anabolic biogenesis of new and fully functional organelles and proteins. Restoration of diurnal metabolic rhythms and flexibility by SGLT2is may have therapeutic implications beyond those already demonstrated for the cardio-renal axis and may therefore affect other non-diabetes disease states.

Original languageEnglish
JournalEuropean Journal of Endocrinology
Volume178
Issue number4
Pages (from-to)R113-R125
ISSN0804-4643
DOIs
Publication statusPublished - 1 Apr 2018

ID: 59277576