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Diabetologia. 2017 Feb;60(2):364-376. doi: 10.1007/s00125-016-4158-2. Epub 2016 Nov 19.

The beneficial effects of empagliflozin, an SGLT2 inhibitor, on atherosclerosis in ApoE -/- mice fed a western diet.

Author information

1
Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam-city, South Korea, 463-070.
2
Department of Pathology, Seoul National University College of Medicine and Seoul National University Bundang Hospital, Seongnam, South Korea.
3
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.
4
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
5
Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam-city, South Korea, 463-070. limsoo@snu.ac.kr.

Abstract

AIMS/HYPOTHESIS:

A recent large clinical study has shown that empagliflozin has a lower rate of cardiovascular and all-cause mortality when compared with placebo in patients with type 2 diabetes. We investigated the effect of empagliflozin (compared with glimepiride) on the progression of atherosclerosis, and its possible mechanisms of action.

METHODS:

Forty-eight 5-week-old male ApoE -/- mice were fed a western diet for 20 weeks and divided into four groups: control (saline, 154 mmol/l NaCl), glimepiride 0.1 mg/kg, empagliflozin 1 mg/kg and empagliflozin 3 mg/kg (n = 12/group). Plaque size and composition in the aortic arch/valve areas and cardiovascular risk variables in the blood and tissues were evaluated. Insulin resistance was estimated by HOMA and adiponectin levels. Body composition was determined using dual-energy x-ray absorptiometry.

RESULTS:

After 8 weeks of treatment, the empagliflozin and glimepiride groups exhibited decreased blood glucose levels. Atherosclerotic plaque areas in the aortic arch/valve were significantly smaller in the empagliflozin groups than in the control or glimepiride groups. Insulin resistance and circulating concentrations of TNF-α, IL-6, monocyte chemoattractant protein-1 (MCP-1), serum amyloid A and urinary microalbumin decreased after empagliflozin treatment, and this significantly correlated with plaque size. Empagliflozin treatment reduced weight and fat mass, lipid droplets in the liver, fat cell size, mRNA expression of Tnf, Il6 and Mcp-1 (also known as Ccl2) and the infiltration of inflammatory cells in plaque and adipose tissue compared with the control or glimepiride group. Empagliflozin treatment increased adiponectin levels.

CONCLUSIONS/INTERPRETATION:

Improvements in inflammation and insulin resistance seem to be mechanisms involved in the mitigation of atherosclerosis by empagliflozin.

KEYWORDS:

Atherosclerosis; Insulin resistance; Sodium glucose cotransporter; Type 2 diabetes

PMID:
27866224
DOI:
10.1007/s00125-016-4158-2
[Indexed for MEDLINE]

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