Highlights
- •Luseogliflozin 2.5 mg was administered once daily for 24 weeks to 30 outpatients with type 2 diabetes.
- •Urinary glucose significantly increased at Week 24.
- •HbA1c and mean blood glucose significantly declined at Week 24.
- •Blood urea nitrogen was significantly increased, and urate significantly decreased.
- •Acyl ghrelin levels remained constant but des-acyl ghrelin increased significantly
Abstract
Aims
We investigated the effects of the SGLT2 inhibitor luseogliflozin on blood and urinary
glucose and body weight.
Methods
Luseogliflozin 2.5 mg was administered once daily for 24 weeks to 30 outpatients with
type 2 diabetes. Urinary glucose concentration, continuous glucose monitoring values,
HbA1c, fasting glucose, and body weight were evaluated. Correlations with urinary
glucose, subcutaneous/visceral fat mass, insulin, EPA/AA ratio, plasma free fatty
acids, ghrelin, blood ketones, plasma 1,5-anhydro-D-glucitol were evaluated.
Results
Urinary glucose significantly increased from 11.1 ± 11.8 g at Week −4 to 84.5 ± 46.8 g
at Week 24. HbA1c significantly declined from 7.88 ± 0.88% to 7.36 ± 1.13% at Week
24. Mean blood glucose significantly decreased from 149.6 ± 41.8 to 131.6 ± 31.1 mg/dL
at Week 24. Subcutaneous and visceral fat mass was also significantly decreased, as
were AST and ALT (P < 0.01). Blood urea nitrogen was significantly increased, and urate significantly
decreased from 5.04 ± 1.07 to 4.53 ± 0.94 mg/dL. The homeostasis model assessment
ratio remained significantly improved throughout the treatment period. Acyl ghrelin
levels remained constant but des-acyl ghrelin increased significantly.
Conclusions
Luseogliflozin monotherapy resulted in an improvement in blood glucose, a decrease
in body weight, and decreased insulin resistance. Luseogliflozin appears to be an
effective therapy for obese diabetics.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Diabetes Research and Clinical PracticeAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
Cho NH, Shaw JE, Karuranga S, et al. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract 2018;138:271-281. PMID:29496507. doi: 10.1016/j.diabres.2018.02.023.
- Introduction: Standards of medical care in diabetes-2019.Diabetes Care. 2019; 42: S1-S2https://doi.org/10.2337/dc19-Sint01
Japan Diabetes Clinical Data Management Study Group. Basic accumulated data 2018. http://jddm.jp/data/index-2018/. Accessed January 27, 2020. (in Japanese)
- Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes.N Engl J Med. 2015; 373: 2117-2128https://doi.org/10.1056/NEJMoa1504720
- Canagliflozin, an SGLT2 inhibitor, attenuates the development of hepatocellular carcinoma in a mouse model of human NASH.Sci Rep. 2018; 8: 2362https://doi.org/10.1038/s41598-018-19658-7
- Canagliflozin and renal outcomes in type 2 diabetes and nephropathy.N Engl J Med. 2019; 380: 2295-2306https://doi.org/10.1056/NEJMoa1811744
- The association between the dosage of SGLT2 inhibitor and weight reduction in type 2 diabetes patients: A meta-analysis.Obesity (Silver Spring). 2018; 26: 70-80https://doi.org/10.1002/oby.22066
- Efficacy and safety of luseogliflozin as monotherapy in Japanese patients with type 2 diabetes mellitus: A randomized, double-blind, placebo-controlled, phase 3 study.Curr Med Res Opin. 2014; 30: 1245-1255https://doi.org/10.1185/03007995.2014.912983
- Ghrelin is a growth-hormone-releasing acylated peptide from stomach.Nature. 1999; 402: 656-660https://doi.org/10.1038/45230
- Ghrelin, a novel growth hormone-releasing acylated peptide, is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats and humans.Endocrinology. 2000; 141: 4255-4261https://doi.org/10.1210/endo.141.11.7757
- Ghrelin is an appetite-stimulatory signal from stomach with structural resemblance to motilin.Gastroenterology. 2001; 120: 337-345https://doi.org/10.1053/gast.2001.22158
- A role for ghrelin in the central regulation of feeding.Nature. 2001; 409: 194-198https://doi.org/10.1038/35051587
- Ghrelin and desacyl ghrelin: two major forms of rat ghrelin peptide in gastrointestinal tissue.Biochem Biophys Res Commun. 2000; 279: 909-913
- Ghrelin and des-acyl ghrelin inhibit cell death in cardiomyocytes and endothelial cells through ERK1/2 and PI 3-kinase/AKT.J Cell Biol. 2002; 159: 1029-1037
- Cardiac effects of ghrelin and its endogenous derivatives des-octanoyl ghrelin and des-Gln14-ghrelin.Eur J Pharmacol. 2003; 476: 87-95
- Identification, characterization, and biological activity of specific receptors for natural (ghrelin) and synthetic growth hormone secretagogues and analogs in human breast carcinomas and cell lines.J Clin Endocrinol Metab. 2001; 86: 1738-1745
- Stomach regulates energy balance via acylated ghrelin and desacyl ghrelin.Gut. 2005; 54: 18-24
- Concurrent use of teneligliptin and canagliflozin improves glycemic control with beneficial effects on plasma glucagon and glucagon-like peptide-1: A single-arm study.Diabetes Ther. 2019; 10: 1835-1846https://doi.org/10.1007/s13300-019-0666-7
- Effects of ipragliflozin on glycemic control, appetite and its related hormones: A prospective, multicenter, open-label study (SOAR-KOBE Study).J Diabetes Investig. 2019; 10: 1254-1261https://doi.org/10.1111/jdi.13015
- Insulin secretion capacity in the development from normal glucose tolerance to type 2 diabetes.Diabetes Res Clin Pract. 2004; 66: S37-S43https://doi.org/10.1016/j.diabres.2003.11.024
- The SGLT2 inhibitor dapagliflozin reduces liver fat but does not affect tissue insulin sensitivity: A randomized, double-blind, placebo-controlled study with 8-week treatment in type 2 diabetes patients.Diabetes Care. 2019; 42: 931-937https://doi.org/10.2337/dc18-1569
- Sodium-glucose cotransporter 2 inhibitor-induced changes in body composition and simultaneous changes in metabolic profile: 52-week prospective LIGHT (Luseogliflozin: the Components of Weight Loss in Japanese Patients with Type 2 Diabetes Mellitus) Study.J Diabetes Investig. 2019; 10: 108-117https://doi.org/10.1111/jdi.12851
- Dapagliflozin significantly reduced liver fat accumulation associated with a decrease in abdominal subcutaneous fat in patients with inadequately controlled type 2 diabetes mellitus.Diabetes Res Clin Pract. 2018; 142: 254-263https://doi.org/10.1016/j.diabres.2018.05.017
- SGLT2-inhibitor and DPP-4 inhibitor improve brain function via attenuating mitochondrial dysfunction, insulin resistance, inflammation, and apoptosis in HFD-induced obese rats.Toxicol Appl Pharmacol. 2017; 333: 43-50https://doi.org/10.1016/j.taap.2017.08.005
- Emerging roles of SGLT2 inhibitors in obesity and insulin resistance: Focus on fat browning and macrophage polarization.Adipocyte. 2018; 7: 121-128https://doi.org/10.1080/21623945.2017
Seino Y, Inagaki N, Heneda M, et al. Efficacy and safety of luseogliflozin added to various oral antidiabetic drugs in Japanese patients with type 2 diabetes mellitus. J Diabetes Investig. 2015 Jul; 6(4): 443-453.30.
- A comparison of effects of DPP-4 inhibitor and SGLT2 inhibitor on lipid profile in patients with type 2 diabetes.Lipids Health Dis. 2017; 16: 58https://doi.org/10.1186/s12944-017-0443-4
- Efficacy and safety of tofogliflozin on 24-h glucose profile based on continuous glucose monitoring: Crossover study of sodium-glucose cotransporter 2 inhibitor.Diabetes Technol Ther. 2019; 21: 385-392https://doi.org/10.1089/dia.2019.0099
- Effects of dapagliflozin on 24-hour glycemic control in patients with type 2 diabetes: A randomized controlled trial.Diabetes Technol Ther. 2018; 20: 715-724https://doi.org/10.1089/dia.2018.0052
Article info
Publication history
Published online: June 10, 2021
Accepted:
June 3,
2021
Received in revised form:
May 26,
2021
Received:
December 13,
2020
Identification
Copyright
© 2021 Elsevier B.V. All rights reserved.
