Substantial Effects of Luseogliflozin Revealed by Analyzing Responses to Postprandial Hyperglycemia: Post Hoc Subanalyses of a Randomized Controlled Study
Introduction In our previous study investigating effects of luseogliflozin, a sodium–glucose cotransporter 2 inhibitor, on 24-h glycemic variability by continuous glucose monitoring (CGM), luseogliflozin elicited parallel downward shifts in fasting and postprandial glucose levels. However, further r...
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| creator | Samukawa, Yoshishige Omiya, Hirohisa Watase, Hirotaka Nozaki, Kazunari Sakai, Soichi Nishimura, Rimei |
| description | Introduction
In our previous study investigating effects of luseogliflozin, a sodium–glucose cotransporter 2 inhibitor, on 24-h glycemic variability by continuous glucose monitoring (CGM), luseogliflozin elicited parallel downward shifts in fasting and postprandial glucose levels. However, further review of individual patients’ data revealed that postprandial hyperglycemia was not reduced in some patients, while preprandial glucose was ameliorated in most patients. Therefore, we divided patients into two groups according to their postprandial glucose responses and conducted a post hoc subanalyses to elucidate which factors contributed to the differential effects of luseogliflozin.
Methods
Thirty-four Japanese type 2 diabetic patients in our previous randomized, double-blind, placebo-controlled, crossover study with 7-day luseogliflozin administration were divided into postprandial glucose responders (PGR,
n
= 23, ameliorated peak glucose) and postprandial glucose non-responders (PGNR;
n
= 11, non-ameliorated peak glucose). Baseline characteristics, variations in CGM-measured 24-h glucose levels, and other pharmacodynamic variabilities were compared.
Results
Baseline characteristics did not differ significantly between groups. Placebo-subtracted peak glucose was significantly lowered in PGR and significantly increased in PGNR (−43.8 and 17.9 mg/dL; both
p
|
| doi_str_mv | 10.1007/s12325-016-0350-5 |
| format | Article |
| fullrecord | <record><control><sourceid>pubmed_cross</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4939154</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>27255763</sourcerecordid><originalsourceid>FETCH-LOGICAL-c508t-c28b05d5b533897069b69a67b912a18a5e122ce081ca64ea94130e63d54e1de93</originalsourceid><addsrcrecordid>eNp9kc1q3DAUhUVIaKZJHyCboBdwqx_LP1kEwpBmCgMt-YHsxLV87TpoLCPZAedR8rSVM21oN10IwT33fEfoEHLG2WfOWP4lcCGFShjPEiYVS9QBWfEiU0k84pCsWJ7yRMji8Zh8DOGJMcFyVXwgxyIXSuWZXJHXu6kKI_RjB5ZeNw2aMVDX0O0U0LW2a6x76Xp6i88IFmtazfSqBzvHYRunYXB9wEBHR3-4MA4e-nohbeYBfWtng7sOLt40unGGxjRY7IsnpgC9jQa3614ieu360Tu7pNyNUz2fkqMGbMBPv-8T8vD1-n69Sbbfb76tr7aJUawYEyOKiqlaVUrKosxZVlZZCVlelVwAL0AhF8IgK7iBLEUoUy4ZZrJWKfIaS3lCLvfcYap2WBuMzwCrB9_twM_aQaf_Vfrup27ds05LWXKVRgDfA4x3IXhs3r2c6aUovS9Kx6L0UpRW0XP-d-i7408zcUHsF0KU-ha9fnKTj38X_kP9BTAdow4</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Substantial Effects of Luseogliflozin Revealed by Analyzing Responses to Postprandial Hyperglycemia: Post Hoc Subanalyses of a Randomized Controlled Study</title><source>MEDLINE</source><source>SpringerNature Journals</source><creator>Samukawa, Yoshishige ; Omiya, Hirohisa ; Watase, Hirotaka ; Nozaki, Kazunari ; Sakai, Soichi ; Nishimura, Rimei</creator><creatorcontrib>Samukawa, Yoshishige ; Omiya, Hirohisa ; Watase, Hirotaka ; Nozaki, Kazunari ; Sakai, Soichi ; Nishimura, Rimei</creatorcontrib><description>Introduction
In our previous study investigating effects of luseogliflozin, a sodium–glucose cotransporter 2 inhibitor, on 24-h glycemic variability by continuous glucose monitoring (CGM), luseogliflozin elicited parallel downward shifts in fasting and postprandial glucose levels. However, further review of individual patients’ data revealed that postprandial hyperglycemia was not reduced in some patients, while preprandial glucose was ameliorated in most patients. Therefore, we divided patients into two groups according to their postprandial glucose responses and conducted a post hoc subanalyses to elucidate which factors contributed to the differential effects of luseogliflozin.
Methods
Thirty-four Japanese type 2 diabetic patients in our previous randomized, double-blind, placebo-controlled, crossover study with 7-day luseogliflozin administration were divided into postprandial glucose responders (PGR,
n
= 23, ameliorated peak glucose) and postprandial glucose non-responders (PGNR;
n
= 11, non-ameliorated peak glucose). Baseline characteristics, variations in CGM-measured 24-h glucose levels, and other pharmacodynamic variabilities were compared.
Results
Baseline characteristics did not differ significantly between groups. Placebo-subtracted peak glucose was significantly lowered in PGR and significantly increased in PGNR (−43.8 and 17.9 mg/dL; both
p
< 0.05). Luseogliflozin significantly lowered “lowest glucose” (defined as the lowest level measured throughout a 24-h period) similarly in PGR and PGNR (−19.2 and −24.0 mg/dL; both
p
< 0.05), significantly reduced the mean amplitude of glucose excursions in PGR (−15.50 mg/dL;
p
< 0.05), and increased the area under the curve for plasma glucagon over 24 h in PGNR (median difference vs. placebo: 240 pg/mL h;
p
< 0.05). Luseogliflozin increased urinary glucose excretion (UGE) and decreased serum insulin by similar magnitudes in both groups.
Conclusions
Luseogliflozin diminished glucose fluctuations in most patients by lowering peak glucose to a greater extent than lowest glucose. Luseogliflozin may also lower lowest glucose in patients whose peak glucose was not ameliorated despite increasing UGE. The glucagon increase in PGNR might explain its hypoglycemic effect on postprandial glucose.
Funding
Taisho Pharmaceutical Co., Ltd, Tokyo, Japan.
Trial Registration
JapicCTI-142548.</description><identifier>ISSN: 0741-238X</identifier><identifier>EISSN: 1865-8652</identifier><identifier>DOI: 10.1007/s12325-016-0350-5</identifier><identifier>PMID: 27255763</identifier><language>eng</language><publisher>Cheshire: Springer Healthcare</publisher><subject>Aged ; Blood Glucose - drug effects ; Cardiology ; Cross-Over Studies ; Diabetes Mellitus, Type 2 - drug therapy ; Double-Blind Method ; Endocrinology ; Female ; Humans ; Hyperglycemia - drug therapy ; Hypoglycemic Agents - therapeutic use ; Internal Medicine ; Japan ; Male ; Medicine ; Medicine & Public Health ; Middle Aged ; Oncology ; Original Research ; Pharmacology/Toxicology ; Postprandial Period - drug effects ; Rheumatology ; Sorbitol - administration & dosage ; Sorbitol - adverse effects ; Sorbitol - analogs & derivatives ; Sorbitol - therapeutic use</subject><ispartof>Advances in therapy, 2016-07, Vol.33 (7), p.1215-1230</ispartof><rights>The Author(s) 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c508t-c28b05d5b533897069b69a67b912a18a5e122ce081ca64ea94130e63d54e1de93</citedby><cites>FETCH-LOGICAL-c508t-c28b05d5b533897069b69a67b912a18a5e122ce081ca64ea94130e63d54e1de93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12325-016-0350-5$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12325-016-0350-5$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,315,781,785,886,27926,27927,41490,42559,51321</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27255763$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Samukawa, Yoshishige</creatorcontrib><creatorcontrib>Omiya, Hirohisa</creatorcontrib><creatorcontrib>Watase, Hirotaka</creatorcontrib><creatorcontrib>Nozaki, Kazunari</creatorcontrib><creatorcontrib>Sakai, Soichi</creatorcontrib><creatorcontrib>Nishimura, Rimei</creatorcontrib><title>Substantial Effects of Luseogliflozin Revealed by Analyzing Responses to Postprandial Hyperglycemia: Post Hoc Subanalyses of a Randomized Controlled Study</title><title>Advances in therapy</title><addtitle>Adv Ther</addtitle><addtitle>Adv Ther</addtitle><description>Introduction
In our previous study investigating effects of luseogliflozin, a sodium–glucose cotransporter 2 inhibitor, on 24-h glycemic variability by continuous glucose monitoring (CGM), luseogliflozin elicited parallel downward shifts in fasting and postprandial glucose levels. However, further review of individual patients’ data revealed that postprandial hyperglycemia was not reduced in some patients, while preprandial glucose was ameliorated in most patients. Therefore, we divided patients into two groups according to their postprandial glucose responses and conducted a post hoc subanalyses to elucidate which factors contributed to the differential effects of luseogliflozin.
Methods
Thirty-four Japanese type 2 diabetic patients in our previous randomized, double-blind, placebo-controlled, crossover study with 7-day luseogliflozin administration were divided into postprandial glucose responders (PGR,
n
= 23, ameliorated peak glucose) and postprandial glucose non-responders (PGNR;
n
= 11, non-ameliorated peak glucose). Baseline characteristics, variations in CGM-measured 24-h glucose levels, and other pharmacodynamic variabilities were compared.
Results
Baseline characteristics did not differ significantly between groups. Placebo-subtracted peak glucose was significantly lowered in PGR and significantly increased in PGNR (−43.8 and 17.9 mg/dL; both
p
< 0.05). Luseogliflozin significantly lowered “lowest glucose” (defined as the lowest level measured throughout a 24-h period) similarly in PGR and PGNR (−19.2 and −24.0 mg/dL; both
p
< 0.05), significantly reduced the mean amplitude of glucose excursions in PGR (−15.50 mg/dL;
p
< 0.05), and increased the area under the curve for plasma glucagon over 24 h in PGNR (median difference vs. placebo: 240 pg/mL h;
p
< 0.05). Luseogliflozin increased urinary glucose excretion (UGE) and decreased serum insulin by similar magnitudes in both groups.
Conclusions
Luseogliflozin diminished glucose fluctuations in most patients by lowering peak glucose to a greater extent than lowest glucose. Luseogliflozin may also lower lowest glucose in patients whose peak glucose was not ameliorated despite increasing UGE. The glucagon increase in PGNR might explain its hypoglycemic effect on postprandial glucose.
Funding
Taisho Pharmaceutical Co., Ltd, Tokyo, Japan.
Trial Registration
JapicCTI-142548.</description><subject>Aged</subject><subject>Blood Glucose - drug effects</subject><subject>Cardiology</subject><subject>Cross-Over Studies</subject><subject>Diabetes Mellitus, Type 2 - drug therapy</subject><subject>Double-Blind Method</subject><subject>Endocrinology</subject><subject>Female</subject><subject>Humans</subject><subject>Hyperglycemia - drug therapy</subject><subject>Hypoglycemic Agents - therapeutic use</subject><subject>Internal Medicine</subject><subject>Japan</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Oncology</subject><subject>Original Research</subject><subject>Pharmacology/Toxicology</subject><subject>Postprandial Period - drug effects</subject><subject>Rheumatology</subject><subject>Sorbitol - administration & dosage</subject><subject>Sorbitol - adverse effects</subject><subject>Sorbitol - analogs & derivatives</subject><subject>Sorbitol - therapeutic use</subject><issn>0741-238X</issn><issn>1865-8652</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><recordid>eNp9kc1q3DAUhUVIaKZJHyCboBdwqx_LP1kEwpBmCgMt-YHsxLV87TpoLCPZAedR8rSVM21oN10IwT33fEfoEHLG2WfOWP4lcCGFShjPEiYVS9QBWfEiU0k84pCsWJ7yRMji8Zh8DOGJMcFyVXwgxyIXSuWZXJHXu6kKI_RjB5ZeNw2aMVDX0O0U0LW2a6x76Xp6i88IFmtazfSqBzvHYRunYXB9wEBHR3-4MA4e-nohbeYBfWtng7sOLt40unGGxjRY7IsnpgC9jQa3614ieu360Tu7pNyNUz2fkqMGbMBPv-8T8vD1-n69Sbbfb76tr7aJUawYEyOKiqlaVUrKosxZVlZZCVlelVwAL0AhF8IgK7iBLEUoUy4ZZrJWKfIaS3lCLvfcYap2WBuMzwCrB9_twM_aQaf_Vfrup27ds05LWXKVRgDfA4x3IXhs3r2c6aUovS9Kx6L0UpRW0XP-d-i7408zcUHsF0KU-ha9fnKTj38X_kP9BTAdow4</recordid><startdate>20160701</startdate><enddate>20160701</enddate><creator>Samukawa, Yoshishige</creator><creator>Omiya, Hirohisa</creator><creator>Watase, Hirotaka</creator><creator>Nozaki, Kazunari</creator><creator>Sakai, Soichi</creator><creator>Nishimura, Rimei</creator><general>Springer Healthcare</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20160701</creationdate><title>Substantial Effects of Luseogliflozin Revealed by Analyzing Responses to Postprandial Hyperglycemia: Post Hoc Subanalyses of a Randomized Controlled Study</title><author>Samukawa, Yoshishige ; Omiya, Hirohisa ; Watase, Hirotaka ; Nozaki, Kazunari ; Sakai, Soichi ; Nishimura, Rimei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c508t-c28b05d5b533897069b69a67b912a18a5e122ce081ca64ea94130e63d54e1de93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Aged</topic><topic>Blood Glucose - drug effects</topic><topic>Cardiology</topic><topic>Cross-Over Studies</topic><topic>Diabetes Mellitus, Type 2 - drug therapy</topic><topic>Double-Blind Method</topic><topic>Endocrinology</topic><topic>Female</topic><topic>Humans</topic><topic>Hyperglycemia - drug therapy</topic><topic>Hypoglycemic Agents - therapeutic use</topic><topic>Internal Medicine</topic><topic>Japan</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Oncology</topic><topic>Original Research</topic><topic>Pharmacology/Toxicology</topic><topic>Postprandial Period - drug effects</topic><topic>Rheumatology</topic><topic>Sorbitol - administration & dosage</topic><topic>Sorbitol - adverse effects</topic><topic>Sorbitol - analogs & derivatives</topic><topic>Sorbitol - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Samukawa, Yoshishige</creatorcontrib><creatorcontrib>Omiya, Hirohisa</creatorcontrib><creatorcontrib>Watase, Hirotaka</creatorcontrib><creatorcontrib>Nozaki, Kazunari</creatorcontrib><creatorcontrib>Sakai, Soichi</creatorcontrib><creatorcontrib>Nishimura, Rimei</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Advances in therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Samukawa, Yoshishige</au><au>Omiya, Hirohisa</au><au>Watase, Hirotaka</au><au>Nozaki, Kazunari</au><au>Sakai, Soichi</au><au>Nishimura, Rimei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Substantial Effects of Luseogliflozin Revealed by Analyzing Responses to Postprandial Hyperglycemia: Post Hoc Subanalyses of a Randomized Controlled Study</atitle><jtitle>Advances in therapy</jtitle><stitle>Adv Ther</stitle><addtitle>Adv Ther</addtitle><date>2016-07-01</date><risdate>2016</risdate><volume>33</volume><issue>7</issue><spage>1215</spage><epage>1230</epage><pages>1215-1230</pages><issn>0741-238X</issn><eissn>1865-8652</eissn><abstract>Introduction
In our previous study investigating effects of luseogliflozin, a sodium–glucose cotransporter 2 inhibitor, on 24-h glycemic variability by continuous glucose monitoring (CGM), luseogliflozin elicited parallel downward shifts in fasting and postprandial glucose levels. However, further review of individual patients’ data revealed that postprandial hyperglycemia was not reduced in some patients, while preprandial glucose was ameliorated in most patients. Therefore, we divided patients into two groups according to their postprandial glucose responses and conducted a post hoc subanalyses to elucidate which factors contributed to the differential effects of luseogliflozin.
Methods
Thirty-four Japanese type 2 diabetic patients in our previous randomized, double-blind, placebo-controlled, crossover study with 7-day luseogliflozin administration were divided into postprandial glucose responders (PGR,
n
= 23, ameliorated peak glucose) and postprandial glucose non-responders (PGNR;
n
= 11, non-ameliorated peak glucose). Baseline characteristics, variations in CGM-measured 24-h glucose levels, and other pharmacodynamic variabilities were compared.
Results
Baseline characteristics did not differ significantly between groups. Placebo-subtracted peak glucose was significantly lowered in PGR and significantly increased in PGNR (−43.8 and 17.9 mg/dL; both
p
< 0.05). Luseogliflozin significantly lowered “lowest glucose” (defined as the lowest level measured throughout a 24-h period) similarly in PGR and PGNR (−19.2 and −24.0 mg/dL; both
p
< 0.05), significantly reduced the mean amplitude of glucose excursions in PGR (−15.50 mg/dL;
p
< 0.05), and increased the area under the curve for plasma glucagon over 24 h in PGNR (median difference vs. placebo: 240 pg/mL h;
p
< 0.05). Luseogliflozin increased urinary glucose excretion (UGE) and decreased serum insulin by similar magnitudes in both groups.
Conclusions
Luseogliflozin diminished glucose fluctuations in most patients by lowering peak glucose to a greater extent than lowest glucose. Luseogliflozin may also lower lowest glucose in patients whose peak glucose was not ameliorated despite increasing UGE. The glucagon increase in PGNR might explain its hypoglycemic effect on postprandial glucose.
Funding
Taisho Pharmaceutical Co., Ltd, Tokyo, Japan.
Trial Registration
JapicCTI-142548.</abstract><cop>Cheshire</cop><pub>Springer Healthcare</pub><pmid>27255763</pmid><doi>10.1007/s12325-016-0350-5</doi><tpages>16</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Advances in therapy, 2016-07, Vol.33 (7), p.1215-1230 |
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| source | MEDLINE; SpringerNature Journals |
| subjects | Aged Blood Glucose - drug effects Cardiology Cross-Over Studies Diabetes Mellitus, Type 2 - drug therapy Double-Blind Method Endocrinology Female Humans Hyperglycemia - drug therapy Hypoglycemic Agents - therapeutic use Internal Medicine Japan Male Medicine Medicine & Public Health Middle Aged Oncology Original Research Pharmacology/Toxicology Postprandial Period - drug effects Rheumatology Sorbitol - administration & dosage Sorbitol - adverse effects Sorbitol - analogs & derivatives Sorbitol - therapeutic use |
| title | Substantial Effects of Luseogliflozin Revealed by Analyzing Responses to Postprandial Hyperglycemia: Post Hoc Subanalyses of a Randomized Controlled Study |
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