Effects of dapagliflozin on postprandial lipid metabolism in type 2 diabetes mellitus

in European Journal of Endocrinology
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  • 1 Department of Internal Medicine, Center for Endocrinology, Diabetes and Vascular Medicine, Franciscus Gasthuis & Vlietland, Rotterdam, the Netherlands
  • | 2 Department of Clinical Chemistry, Franciscus Gasthuis & Vlietland, Rotterdam, the Netherlands
  • | 3 Departament de Medicina i Cirurgia, Unitat de Recerca Biomèdica, Universitat Rovira i Virgili, Tarragona, Spain
  • | 4 Division of Pharmacology, Vascular and Metabolic Diseases, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands
  • | 5 Department of Statistics and Education, Franciscus Academy, Franciscus Gasthuis & Vlietland, Rotterdam, the Netherlands
  • | 6 Department of Pharmacy, Franciscus Gasthuis & Vlietland, Rotterdam, the Netherlands
  • | 7 Department of Genetics, University Medical Center Groningen, Groningen University, Groningen, the Netherlands
  • | 8 Department of Internal Medicine, Section of Endocrinology, Erasmus Medical Center, Rotterdam, the Netherlands
  • | 9 Division of Endocrinology, Department of Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands

Correspondence should be addressed to B Burggraaf; Email: burggraaf.benjamin@gmail.com
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Objectives

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) modulate lipid metabolism and improve cardiovascular morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). The exact cardioprotective mechanism of SGLT2i is unclear. We evaluated the effects of SGLT2i on postprandial lipids, lipoprotein concentrations, glucose and fatty acids.

Design

A placebo-controlled randomized, proof-of-concept study.

Methods

Fourteen male patients with T2DM on intensive insulin regimen were randomly and double-blind allocated to 12 weeks dapagliflozin (10 mg) or placebo. Postprandial effects were assessed with an 8-h standardized oral fat loading test.

Results

Mean glycated A1c did not change by dapagliflozin, but the mean daily insulin dose was significantly reduced. Although dapagliflozin did not affect fasting or postprandial levels of glucose and insulin, it increased the postprandial levels of glucagon. While fasting levels of free fatty acids and beta-hydroxybutyrate (bHBA) were unchanged, dapagliflozin significantly increased the postprandial bHBA response. This was seen in the context of increased postprandial glucagon levels by dapagliflozin, without influencing postprandial insulin or glucose levels. Dapagliflozin did not affect fasting or postprandial plasma cholesterol and triglycerides nor postprandial inflammatory markers. Fasting apolipoprotein B48 was decreased without affecting the postprandial response. Markers of inflammation and vascular function did not change.

Conclusion

Treatment with dapagliflozin of patients with T2DM led to a reduction of fasting chylomicron remnants and increased postprandial ketone bodies compared to placebo suggesting enhanced hepatic fatty acid oxidation. The latter may have been caused by decreasing the insulin–glucagon ratio. The beneficial clinical effects seen in the trials using dapagliflozin most likely are not due to effects on postprandial inflammation nor postprandial lipemia.

Supplementary Materials

 

     European Society of Endocrinology

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