Effects of luseogliflozin and voglibose on high-risk lipid profiles and inflammatory markers in diabetes patients with heart failure

Ejiri, Kentaro; Miyoshi, Toru; Nakamura, Kazufumi; Ito, Hiroshi; Kihara, Hajime; Hata, Yutaka; Nagano, Toshihiko; Takaishi, Atsushi; Toda, H.; Namba, Sayaka; Nakamura, Yoichi; Akagi, Satoshi; Sakuragi, Satoru; Minagawa, Tomonori; Kawai, Yusuke; Nishii, Nobuhiro; Sato, Tetsuya; Fuke, Soichiro; Yasukawa, Masaki; Sugiyama, Hiroyasu; Imai, Michio; Gotoh, Naoki; Segawa, Tomio; Noda, Toshiyuki; Koshiji, Masatoshi

doi:10.1038/s41598-022-19371-6

Cited by 12 publications

(12 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Of the 34 trials from which data were used for this analysis, most of the studies were of a parallel design, except for two crossover designs. Except for three multinational trials (Garvey et al, 2018;Oldgren et al, 2021;Docherty et al, 2022), most trials were recruited from ten different countries: 17 from Japan (Kaku et al, 2014;Kashiwagi et al, 2015a;Kashiwagi et al, 2015b;Kashiwagi et al, 2015c;Ishihara et al, 2016;Ito et al, 2017;Shigiyama et al, 2017;Hattori, 2018;Sato et al, 2018;Seino et al, 2018;Aso et al, 2019;Koshizaka et al, 2019;Katakami et al, 2020;Kinoshita et al, 2020;Sakurai et al, 2020;Ejiri et al, 2022;Takahashi et al, 2022); three from Germany (Bosch et al, 2019;Kahl et al, 2020;Thiele et al, 2021); two from Denmark (Eickhoff et al, 2020;Omar et al, 2022); two from the United Kingdom (Bailey et al, 2012;Brown et al, 2020); two from Thailand (Phrommintikul et al, 2019;Phrueksotsai et al, 2021); one from China (Hao et al, 2022); one from Austria (Antlanger et al, 2022); one from Brazil (Sposito et al, 2021); one from Finland (Latva-Rasku et al, 2019); and one from the Netherlands (Dekkers et al, 2018)). The study characteristics are listed in Table 1.…”

Section: Search Results and Description Of The Included Studiesmentioning

confidence: 99%

The effect of sodium-glucose cotransporter 2 inhibitors on biomarkers of inflammation: A systematic review and meta-analysis of randomized controlled trials

et al. 2022

View full text Add to dashboard Cite

Aims: Inflammatory biomarkers may play vital roles in the pathophysiology of diabetes and diabetic cardiorenal complications. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have a potential cardiovascular and renal protective effect in type 2 diabetes. The aim of this meta-analysis was to quantify the effects of SGLT2 inhibitors on biomarkers of inflammation in randomized controlled trials (RCTs).Methods: PubMed, Cochrane Library, EMBASE, and Web of Science were searched for eligible RCTs of adults with type 2 diabetes (T2D) with no time limit (updated to 12 October 2022). The biomarkers selected included C-reactive protein (CRP), interleukin-6, tumor necrosis factor-alpha, leptin, adiponectin, ferritin, plasminogen activator inhibitor (PAI)-1, and vascular cell adhesion molecule-1. Data were analyzed using a random-effect model in Review Manager 5.4.Results: Thirty-four studies with 6,261 patients (68.6% male) were eligible for this meta-analysis. The mean age of the participants was 62.57(±11.13) years old, and the median treatment duration length with follow-up was 24 weeks. Generally, the included trials were of good methodological quality. The meta-analysis revealed that ferritin levels were significantly reduced in SGLT2 inhibitor treatment groups versus placebo or standard diabetes therapies (SMD: 1.21; 95% CI: −1.91, −0.52, p < 0.001). The effects of CRP (SMD: 0.25; 95% CI: −0.47, −0.03, p = 0.02) and leptin (SMD: −0.22; 95% CI: −0.43, −0.01, p = 0.04) were reduced, and the effects of adiponectin were improved (SMD: 0.28; 95% CI: 0.15, 0.41, p < 0.001) in placebo-controlled studies. PAI-1 levels were significantly reduced in studies controlled for diabetes therapies (SMD: −0.38; 95% CI: −0.61, −0.15, p = 0.001).Conclusion: This analysis provides strong evidence supporting anti-inflammatory effects of SGLT2 inhibitors in T2D subjects. The mechanisms and possible targets for the inflammation reducing and cardiorenal protective properties of SGLT2 inhibitors remain to be explored.

show abstract

Section: Search Results and Description Of The Included Studiesmentioning

confidence: 99%

The effect of sodium-glucose cotransporter 2 inhibitors on biomarkers of inflammation: A systematic review and meta-analysis of randomized controlled trials

et al. 2022

View full text Add to dashboard Cite

show abstract

“…No significant changes were observed in LDL-C and ApoB levels. In a study by Ejiri et al [ 34 ] using luseogliflozin in patients with diabetes and heart failure with baseline lipid profiles at normal range, no significant changes were observed in small dense LDL-C, TG, or LDL-C levels. In a retrospective analysis by Kubota et al [ 35 ], 63 patients with T2DM on usual doses of SGLT2-i (Empagliflozin, Canagliflozin, Dapagliflozin, or Tofogliflozin), showed a significant decrease in total cholesterol and non-HDL-C levels, but no changes in TG, HDL, or LDL-C levels.…”

Section: Discussionmentioning

confidence: 99%

Beneficial effects of luseogliflozin on lipid profile and liver function in patients with type 2 diabetes mellitus (BLUE trial): a single-center, single-arm, open-label prospective study

Hajika

Kawaguchi

Hamazaki

et al. 2023

Diabetol Metab Syndr

View full text Add to dashboard Cite

Background Arteriosclerosis and non-alcoholic fatty liver disease are major complications of diabetes mellitus. Hyperglycemia, insulin resistance, obesity, and metabolic syndrome are associated with the progression of these complications. Sodium-glucose transporter 2 inhibitors such as luseogliflozin are oral hypoglycemic agents that reduce glucose levels, induce loss of weight or body fat, and improve liver function. However, the effects of these agents on lipid profiles are unclear. Therefore, this study aimed to investigate these effects and their relationship with arteriosclerosis and non-alcoholic fatty liver disease. Methods This single-center, single-arm, open-labeled prospective study enrolled 25 outpatients with type 2 diabetes mellitus who visited Minami Osaka Hospital. Laboratory tests and body measurements were performed at weeks 0 and 24. Luseogliflozin was started at 2.5 mg/day after breakfast, and data from weeks 0 and 24 were evaluated. There were no changes in the doses of other antidiabetic and dyslipidemia drugs a month prior to or during the study. Results The patients showed significant reductions in the levels of triglycerides, remnant-like particle cholesterol, and triglyceride/high-density lipoprotein cholesterol ratio, along with significant increases in the levels of high-density lipoprotein cholesterol and apolipoprotein A-1. Alanine aminotransferase, γ-glutamyl transpeptidase, and the fatty liver index were significantly reduced. Conclusions Luseogliflozin-induced changes in the lipid profile were related to the suppression or improvement of arteriosclerosis and liver function, respectively. Patients who received this drug also showed improvements in the levels of liver enzymes and reductions in the fatty liver index. Earlier use of luseogliflozin might prevent diabetic complications. Trial registration This study was registered in the University Hospital Medical Information Network Clinical Trial Registry (UMIN 000043595) on April 6th, 2021

show abstract

“…Gürkan et al reported that 6 months of dapagliflozin therapy decreased the serum levels of LDL-cholesterol and TGs in T2DM patients [ 76 ]. Moreover, in another clinical study, 6 months of SGLT2i therapy with luseogliflozin decreased the LDL-cholesterol and increased the HDL-cholesterol levels in T2DM patients [ 77 ].…”

Section: Sglt2 Inhibitors and Lipid Metabolismmentioning

confidence: 99%

“…Bosch et al performed a clinical trial on patients with T2DM and found that empagliflozin had no significant effect on the total cholesterol, HDL-cholesterol, and LDL-cholesterol levels [ 82 ]. Another more recent study also showed that treatment with luseogliflozin and voglibose had no significant effect on the cholesterol profile in T2DM patients [ 77 ]. It showed that luseogliflozin had no significant effect on malondialdehyde, LDL particles, and small dense LDL particle cholesterol [ 77 ].…”

Section: Sglt2 Inhibitors and Lipid Metabolismmentioning

confidence: 99%

“…Another more recent study also showed that treatment with luseogliflozin and voglibose had no significant effect on the cholesterol profile in T2DM patients [ 77 ]. It showed that luseogliflozin had no significant effect on malondialdehyde, LDL particles, and small dense LDL particle cholesterol [ 77 ]. It seems that SGLT2 inhibitors have different effects on cholesterol metabolism and may increase, decrease, or not have any effect on its level, and the mechanisms by which any of these actions are performed are still unknown.…”

Section: Sglt2 Inhibitors and Lipid Metabolismmentioning

confidence: 99%

See 1 more Smart Citation

Mechanistic View on the Effects of SGLT2 Inhibitors on Lipid Metabolism in Diabetic Milieu

Yaribeygi

Maleki

Reiner

et al. 2022

JCM

View full text Add to dashboard Cite

Chronic hyperglycemia induces pathophysiologic pathways with negative effects on the metabolism of most substrates as well as lipids and lipoproteins, and thereby induces dyslipidemia. Thus, the diabetic milieu is commonly accompanied by different levels of atherogenic dyslipidemia, which is per se a major risk factor for subsequent complications such as atherosclerosis, coronary heart disease, acute myocardial infarction, ischemic stroke, and nephropathy. Therefore, readjusting lipid metabolism in the diabetic milieu is a major goal for preventing dyslipidemia-induced complications. Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a class of relatively newly introduced antidiabetes drugs (including empagliflozin, canagliflozin, dapagliflozin, etc.) with potent hypoglycemic effects and can reduce blood glucose by inducing glycosuria. However, recent evidence suggests that they could also provide extra-glycemic benefits in lipid metabolism. It seems that they can increase fat burning and lipolysis, normalizing the lipid metabolism and preventing or improving dyslipidemia. Nevertheless, the exact mechanisms involved in this process are not well-understood. In this review, we tried to explain how these drugs could regulate lipid homeostasis and we presented the possible involved cellular pathways supported by clinical evidence.

show abstract

Effects of luseogliflozin and voglibose on high-risk lipid profiles and inflammatory markers in diabetes patients with heart failure

Cited by 12 publications

References 35 publications

The effect of sodium-glucose cotransporter 2 inhibitors on biomarkers of inflammation: A systematic review and meta-analysis of randomized controlled trials

The effect of sodium-glucose cotransporter 2 inhibitors on biomarkers of inflammation: A systematic review and meta-analysis of randomized controlled trials

Beneficial effects of luseogliflozin on lipid profile and liver function in patients with type 2 diabetes mellitus (BLUE trial): a single-center, single-arm, open-label prospective study

Mechanistic View on the Effects of SGLT2 Inhibitors on Lipid Metabolism in Diabetic Milieu

Contact Info

Product

Resources

About