| Empagliflozin, a novel potent and selective SGLT-2 inhibitor, improves glycaemic control alone and in combination with insulin in streptozotocin-induced diabetic rats, a model of type 1 diabetes mellitus. | |
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MedLine Citation:
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PMID: 22268612 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Aims - Sodium glucose cotransporter-2 (SGLT-2) is key to reabsorption of glucose in the kidney. SGLT-2 inhibitors are in clinical development for treatment of type 2 diabetes mellitus (T2DM). The mechanism may be of value also in the treatment of type 1 diabetes mellitus (T1DM). This study investigated effects of the SGLT-2 inhibitor empagliflozin, alone and in combination with insulin, on glucose homeostasis in an animal model of T1DM. Materials and Methods - Sprague-Dawley rats were administered a single intraperitoneal injection of streptozotocin (STZ; 60 mg/kg). Acutely, STZ-rats received 2 doses of insulin glargine with or without empagliflozin, and blood glucose was measured. In a subchronic study,STZ-rats received empagliflozin alone, 1 or 2 insulin-releasing implantsor a combination of 1 implant and empagliflozinover 28 days;blood glucose and HbA(1c) were measured. Results - In the acute setting, empagliflozin in combination with 1.5 IU insulin induced a similar glucose lowering effect as 6 IU insulin. Both interventions were more efficacious than monotherapy with 1.5 IU insulin. In the subchronic study, 12-hour blood glucose profile on day 28 in the combination group was lower than with 1 implant, and similar to 2 implants. Plasma HbA(1c) was improved in the combination group and in animals with 2 implants. Conclusions- Empagliflozin reduced blood glucose levels in a T1DM animal model. Empagliflozin combined with low-dose insulin showed comparable glucose lowering efficacy to treatment with high-dose insulin. Our data suggest that empagliflozin is an efficaciousadjunctive-to-insulin therapy with the clinical potential for the treatment of T1DM. |
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Authors:
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Gerd Luippold; Thomas Klein; Michael Mark; Rolf Grempler |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-23 |
Journal Detail:
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Title: Diabetes, obesity & metabolism Volume: - ISSN: 1463-1326 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-24 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100883645 Medline TA: Diabetes Obes Metab Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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© 2012 Blackwell Publishing Ltd. |
Affiliation:
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Department of CardioMetabolic Diseases Research (G.L., T.K., M.M.), and Department of Drug Metabolism and Pharmacokinetics (R.G.), Boehringer Ingelheim Pharma GmbH&Co.KG, 88397 Biberachan der Riss, Germany. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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