Effects of SGLT2 Inhibitors and DPP-4 Inhibitors on Advanced Glycation End Products

Abstract

Clinical trials have revealed that sodium glucose cotransporter 2 (SGLT2) inhibitors suppress the onset of heart failure and cardiovascular death in diabetic patients. On the other hand, few reports have been published concerning such effects of dipeptidyl peptidase-4 (DPP-4) inhibitors. We undertook the present study to evaluate the effects of SGLT2 inhibitors and DPP-4 inhibitors on the advanced glycation end products (AGEs), well known as a risk factor for the development of cardiovascular disorders.

Type 2 diabetes mellitus were divided into two groups and treated with either SGLT2 inhibitors or DPP-4 inhibitors for 3 months. Before and after the 3-month treatment period with each drug, the AGEs and diabetes-related parameters were measured. Methylglyoxal-derived hydroimidazolone-1 (MG-H1) was measured as one of the AGEs.

In the SGLT2 inhibitor group, both the blood HbA1c and MG-H1 levels decreased significantly after the 3-month treatment period. In the DPP-4 inhibitor group, only the blood HbA1c level decreased significantly, with no significant change of the blood MG-H1 level.

SGLT2 inhibitor reduced both the blood levels of HbA1c and AGEs (MG-H1). Considering that the blood levels of AGEs are associated with the risk of heart failure and cardiovascular disorders, the results of the present study suggest that the effect of SGLT2 inhibitors in suppressing cardiovascular death might be mediated by the reduction in the blood levels of AGEs induced by this class of drugs. DPP-4 inhibitors showed no significant effects on the blood levels of AGEs.

Key words

SGLT2 inhibitor - DPP-4 inhibitor - advanced glycation end products - MG-H1 - type 2 diabetes mellitus

Publikationsverlauf

Eingereicht: 18. Oktober 2023

Angenommen: 20. Dezember 2023

Artikel online veröffentlicht:
29. Januar 2024

• References

• 1 Wright EM. Glucose transport families SLC5 and SLC50. Mol Aspects Med 2013; 34: 183-196
• 2 Wright EM, Loo DD, Hirayama BA. Biology of human sodium glucose transporters. Physiol Rev 2011; 91: 733-794
• 3 DeFronzo RA, Davidson JA, Del Prato S. The role of the kidneys in glucose homeostasis: a new path towards normalizing glycaemia. Diabetes, Obesity and Metabolism 2012; 14: 5-14
• 4 Seino Y, Sasaki T, Fukatsu A. et al. Efficacy and safety of luseogliflozin as monotherapy in Japanese patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled, Phase 3 study. Current Medical Research & Opinion 2014; 30: 1245-1255
• 5 Wanner C, Inzucchi SE, Lachin JM. et al. EMPA-REG OUTCOME Investigators: Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes. N Engl J Med 2016; 375: 323-334
• 6 Braunwald E. Gliflozins in the management of cardiovascular disease. N Engl J Med 2022; 386: 2042-2034
• 7 Uribarri J, Cai W, Ramdas M. et al. Restriction of advanced glycation end products improves insulin resistance in human type 2 diabetes: potential role AGER 1, and SIRT 1. Diabetes Care 2011; 34: 1610-1616
• 8 Ueda S, Yamagishi S, Matsui T. et al. Serum levels of advanced glycation end products (AGEs) are inversely associated with the number and migratory activity of circulating endothelial progenitor cells in apparently healthy subjects. Cardiovasc Ther 2012; 30: 249-254
• 9 Kim YG, Hahn S, Oh TJ. et al. Differences in the glucose-lowering efficacy of dipeptidyl peptidase-4 inhibitors between Asians and non-Asians: a systematic review and meta-analysis. Diabetologia 2013; 56: 696-708
• 10 Esposito K, Cozzolino D, Bellastella G. et al. Dipeptidyl peptidase-4 inhibitors and HbA1c target of <7% in type 2 diabetes: meta-analysis of randomized controlled trials. Diabetes Obes Metab 2011; 13: 594-603
• 11 Yamanaka M, Matsumura T, Ohno R. et al. Non-invasive measurement of skin autofluorescence to evaluate diabetic complications. J Clin Biochem Nutr 2016; 58: 135-140
• 12 Ueda S, Yamagishi S, Mataui T. et al. Serum levels of advanced glycation end products (AGEs) are inversely associated with the number and migratory activity of circulating endothelial progenitor cells in apparently healthy subjects. Cardiovasc Ther 2012; 30: 249-254
• 13 Yamagishi S, Fujimori H, Yonekura H. et al. Advanced glycation endproducts accelerate calcification in microvascular pericytes. Biophy Res Commun 1999; 258: 353-357
• 14 Tomosugi N, Yamamoto S, Takeuchi M. et al. Effect of Collagen Tripeptide on Atherosclerosis in Healthy Humans. J Atheroscler Thromb 2017; 24: 530-538
• 15 Sharma C, Kaur A, Thind SS. et al. Advanced glycation End-products (AGEs): an emerging concern for processed food industries. J Food Sci Technol 2015; 52: 7561-7576