Safety and effectiveness of dipeptidyl peptidase-4 inhibitors versus intermediate-acting insulin or placebo for patients with type 2 diabetes failing two oral antihyperglycaemic agents: a systematic review and network meta-analysis
Identifieur interne : 000215 ( Main/Exploration ); précédent : 000214; suivant : 000216Safety and effectiveness of dipeptidyl peptidase-4 inhibitors versus intermediate-acting insulin or placebo for patients with type 2 diabetes failing two oral antihyperglycaemic agents: a systematic review and network meta-analysis
Auteurs : Andrea C. Tricco [Canada] ; Jesmin Antony [Canada] ; Paul A. Khan [Canada] ; Marco Ghassemi [Canada] ; Jemila S. Hamid [Canada] ; Huda Ashoor [Canada] ; Erik Blondal [Canada] ; Charlene Soobiah [Canada] ; Catherine H. Yu [Canada] ; Brian Hutton [Canada] ; Brenda R. Hemmelgarn [Canada] ; David Moher [Canada] ; Sumit R. Majumdar [Canada] ; Sharon E. Straus [Canada]Source :
- BMJ Open [ 2044-6055 ] ; 2014.
Abstract
To evaluate the effectiveness and safety of dipeptidyl peptidase-4 (DPP-4) inhibitors versus intermediate-acting insulin for adults with type 2 diabetes mellitus (T2DM) and poor glycaemic control despite treatment with two oral agents.
Studies were multicentre and multinational.
Ten studies including 2967 patients with T2DM.
Studies that examined DPP-4 inhibitors compared with each other, intermediate-acting insulin, no treatment or placebo in patients with T2DM.
Primary outcome was glycosylated haemoglobin (HbA1c). Secondary outcomes were healthcare utilisation, body weight, fractures, quality of life, microvascular complications, macrovascular complications, all-cause mortality, harms, cost and cost-effectiveness.
10 randomised clinical trials with 2967 patients were included after screening 5831 titles and abstracts, and 180 full-text articles. DPP-4 inhibitors significantly reduced HbA1c versus placebo in network meta-analysis (NMA; mean difference (MD) −0.62%, 95% CI −0.93% to −0.33%) and meta-analysis (MD −0.61%, 95% CI −0.81% to −0.41%), respectively. Significant differences in HbA1c were not observed for neutral protamine Hagedorn (NPH) insulin versus placebo and DPP-4 inhibitors versus NPH insulin in NMA. In meta-analysis, no significant differences were observed between DPP-4 inhibitors and placebo for severe hypoglycaemia, weight gain, cardiovascular disease, overall harms, treatment-related harms and mortality, although patients receiving DPP-4 inhibitors experienced less infections (relative risk 0.72, 95% CI 0.57 to 0.91).
DPP-4 inhibitors were superior to placebo in reducing HbA1c levels in adults with T2DM taking at least two oral agents. Compared with placebo, no safety signals were detected with DPP-4 inhibitors and there was a reduced risk of infection. There was no significant difference in HbA1c observed between NPH and placebo or NPH and DPP-4 inhibitors.
PROSPERO # CRD42013003624.
Url:
DOI: 10.1136/bmjopen-2014-005752
PubMed: 25537781
PubMed Central: 4275675
Affiliations:
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Yu</name><affiliation wicri:level="1"><nlm:aff id="af1"><institution>Li Ka Shing Knowledge Institute, St. Michael's Hospital</institution>,<addr-line>Toronto, Ontario</addr-line>,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Hutton, Brian" sort="Hutton, Brian" uniqKey="Hutton B" first="Brian" last="Hutton">Brian Hutton</name><affiliation wicri:level="1"><nlm:aff id="af3"><addr-line>Clinical Epidemiology Program</addr-line>,<institution>Ottawa Hospital Research Institute and the Faculty of Medicine, University of Ottawa</institution>,<addr-line>Ottawa, Ontario</addr-line>,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Hemmelgarn, Brenda R" sort="Hemmelgarn, Brenda R" uniqKey="Hemmelgarn B" first="Brenda R" last="Hemmelgarn">Brenda R. 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Tricco</name><affiliation wicri:level="1"><nlm:aff id="af1"><institution>Li Ka Shing Knowledge Institute, St. Michael's Hospital</institution>,<addr-line>Toronto, Ontario</addr-line>,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Antony, Jesmin" sort="Antony, Jesmin" uniqKey="Antony J" first="Jesmin" last="Antony">Jesmin Antony</name><affiliation wicri:level="1"><nlm:aff id="af1"><institution>Li Ka Shing Knowledge Institute, St. Michael's Hospital</institution>,<addr-line>Toronto, Ontario</addr-line>,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Khan, Paul A" sort="Khan, Paul A" uniqKey="Khan P" first="Paul A" last="Khan">Paul A. Khan</name><affiliation wicri:level="1"><nlm:aff id="af1"><institution>Li Ka Shing Knowledge Institute, St. Michael's Hospital</institution>,<addr-line>Toronto, Ontario</addr-line>,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Ghassemi, Marco" sort="Ghassemi, Marco" uniqKey="Ghassemi M" first="Marco" last="Ghassemi">Marco Ghassemi</name><affiliation wicri:level="1"><nlm:aff id="af1"><institution>Li Ka Shing Knowledge Institute, St. Michael's Hospital</institution>,<addr-line>Toronto, Ontario</addr-line>,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Hamid, Jemila S" sort="Hamid, Jemila S" uniqKey="Hamid J" first="Jemila S" last="Hamid">Jemila S. Hamid</name><affiliation wicri:level="1"><nlm:aff id="af2"><addr-line>Clinical Epidemiology and Biostatistics</addr-line>,<institution>McMaster University</institution>,<addr-line>Hamilton, Ontario</addr-line>,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Ashoor, Huda" sort="Ashoor, Huda" uniqKey="Ashoor H" first="Huda" last="Ashoor">Huda Ashoor</name><affiliation wicri:level="1"><nlm:aff id="af1"><institution>Li Ka Shing Knowledge Institute, St. Michael's Hospital</institution>,<addr-line>Toronto, Ontario</addr-line>,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Blondal, Erik" sort="Blondal, Erik" uniqKey="Blondal E" first="Erik" last="Blondal">Erik Blondal</name><affiliation wicri:level="1"><nlm:aff id="af1"><institution>Li Ka Shing Knowledge Institute, St. Michael's Hospital</institution>,<addr-line>Toronto, Ontario</addr-line>,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Soobiah, Charlene" sort="Soobiah, Charlene" uniqKey="Soobiah C" first="Charlene" last="Soobiah">Charlene Soobiah</name><affiliation wicri:level="1"><nlm:aff id="af1"><institution>Li Ka Shing Knowledge Institute, St. Michael's Hospital</institution>,<addr-line>Toronto, Ontario</addr-line>,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Yu, Catherine H" sort="Yu, Catherine H" uniqKey="Yu C" first="Catherine H" last="Yu">Catherine H. Yu</name><affiliation wicri:level="1"><nlm:aff id="af1"><institution>Li Ka Shing Knowledge Institute, St. Michael's Hospital</institution>,<addr-line>Toronto, Ontario</addr-line>,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Hutton, Brian" sort="Hutton, Brian" uniqKey="Hutton B" first="Brian" last="Hutton">Brian Hutton</name><affiliation wicri:level="1"><nlm:aff id="af3"><addr-line>Clinical Epidemiology Program</addr-line>,<institution>Ottawa Hospital Research Institute and the Faculty of Medicine, University of Ottawa</institution>,<addr-line>Ottawa, Ontario</addr-line>,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Hemmelgarn, Brenda R" sort="Hemmelgarn, Brenda R" uniqKey="Hemmelgarn B" first="Brenda R" last="Hemmelgarn">Brenda R. Hemmelgarn</name><affiliation wicri:level="1"><nlm:aff id="af4"><addr-line>Departments of Medicine and Community Health Sciences</addr-line>,<institution>University of Calgary</institution>,<addr-line>Calgary, Alberta</addr-line>,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Moher, David" sort="Moher, David" uniqKey="Moher D" first="David" last="Moher">David Moher</name><affiliation wicri:level="1"><nlm:aff id="af3"><addr-line>Clinical Epidemiology Program</addr-line>,<institution>Ottawa Hospital Research Institute and the Faculty of Medicine, University of Ottawa</institution>,<addr-line>Ottawa, Ontario</addr-line>,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Majumdar, Sumit R" sort="Majumdar, Sumit R" uniqKey="Majumdar S" first="Sumit R" last="Majumdar">Sumit R. Majumdar</name><affiliation wicri:level="1"><nlm:aff id="af5"><addr-line>Department of Medicine</addr-line>,<institution>University of Alberta</institution>,<addr-line>Edmonton, Alberta</addr-line>,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Straus, Sharon E" sort="Straus, Sharon E" uniqKey="Straus S" first="Sharon E" last="Straus">Sharon E. Straus</name><affiliation wicri:level="1"><nlm:aff id="af1"><institution>Li Ka Shing Knowledge Institute, St. Michael's Hospital</institution>,<addr-line>Toronto, Ontario</addr-line>,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af6"><addr-line>Department of Geriatric Medicine</addr-line>,<institution>University of Toronto</institution>,<addr-line>Toronto, Ontario</addr-line>,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">BMJ Open</title><idno type="eISSN">2044-6055</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Objective</title><p>To evaluate the effectiveness and safety of dipeptidyl peptidase-4 (DPP-4) inhibitors versus intermediate-acting insulin for adults with type 2 diabetes mellitus (T2DM) and poor glycaemic control despite treatment with two oral agents.</p></sec><sec><title>Setting</title><p>Studies were multicentre and multinational.</p></sec><sec><title>Participants</title><p>Ten studies including 2967 patients with T2DM.</p></sec><sec><title>Interventions</title><p>Studies that examined DPP-4 inhibitors compared with each other, intermediate-acting insulin, no treatment or placebo in patients with T2DM.</p></sec><sec><title>Primary and secondary outcome measures</title><p>Primary outcome was glycosylated haemoglobin (HbA1c). Secondary outcomes were healthcare utilisation, body weight, fractures, quality of life, microvascular complications, macrovascular complications, all-cause mortality, harms, cost and cost-effectiveness.</p></sec><sec><title>Results</title><p>10 randomised clinical trials with 2967 patients were included after screening 5831 titles and abstracts, and 180 full-text articles. DPP-4 inhibitors significantly reduced HbA1c versus placebo in network meta-analysis (NMA; mean difference (MD) −0.62%, 95% CI −0.93% to −0.33%) and meta-analysis (MD −0.61%, 95% CI −0.81% to −0.41%), respectively. Significant differences in HbA1c were not observed for neutral protamine Hagedorn (NPH) insulin versus placebo and DPP-4 inhibitors versus NPH insulin in NMA. In meta-analysis, no significant differences were observed between DPP-4 inhibitors and placebo for severe hypoglycaemia, weight gain, cardiovascular disease, overall harms, treatment-related harms and mortality, although patients receiving DPP-4 inhibitors experienced less infections (relative risk 0.72, 95% CI 0.57 to 0.91).</p></sec><sec><title>Conclusions</title><p>DPP-4 inhibitors were superior to placebo in reducing HbA1c levels in adults with T2DM taking at least two oral agents. Compared with placebo, no safety signals were detected with DPP-4 inhibitors and there was a reduced risk of infection. There was no significant difference in HbA1c observed between NPH and placebo or NPH and DPP-4 inhibitors.</p></sec><sec><title>Trial registration number</title><p>PROSPERO # CRD42013003624.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Nathan, Dm" uniqKey="Nathan D">DM Nathan</name></author><author><name sortKey="Buse, Jb" uniqKey="Buse J">JB Buse</name></author><author><name sortKey="Davidson, Mb" uniqKey="Davidson M">MB Davidson</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Cook, Mn" uniqKey="Cook M">MN Cook</name></author><author><name sortKey="Girman, Cj" uniqKey="Girman C">CJ Girman</name></author><author><name sortKey="Stein, Pp" uniqKey="Stein P">PP Stein</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Tricco, Ac" uniqKey="Tricco A">AC 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Smith</name></author><author><name sortKey="Schneider, M" uniqKey="Schneider M">M Schneider</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Canada</li></country></list><tree><country name="Canada"><noRegion><name sortKey="Tricco, Andrea C" sort="Tricco, Andrea C" uniqKey="Tricco A" first="Andrea C" last="Tricco">Andrea C. Tricco</name></noRegion><name sortKey="Antony, Jesmin" sort="Antony, Jesmin" uniqKey="Antony J" first="Jesmin" last="Antony">Jesmin Antony</name><name sortKey="Ashoor, Huda" sort="Ashoor, Huda" uniqKey="Ashoor H" first="Huda" last="Ashoor">Huda Ashoor</name><name sortKey="Blondal, Erik" sort="Blondal, Erik" uniqKey="Blondal E" first="Erik" last="Blondal">Erik Blondal</name><name sortKey="Ghassemi, Marco" sort="Ghassemi, Marco" uniqKey="Ghassemi M" first="Marco" last="Ghassemi">Marco Ghassemi</name><name sortKey="Hamid, Jemila S" sort="Hamid, Jemila S" uniqKey="Hamid J" first="Jemila S" last="Hamid">Jemila S. Hamid</name><name sortKey="Hemmelgarn, Brenda R" sort="Hemmelgarn, Brenda R" uniqKey="Hemmelgarn B" first="Brenda R" last="Hemmelgarn">Brenda R. Hemmelgarn</name><name sortKey="Hutton, Brian" sort="Hutton, Brian" uniqKey="Hutton B" first="Brian" last="Hutton">Brian Hutton</name><name sortKey="Khan, Paul A" sort="Khan, Paul A" uniqKey="Khan P" first="Paul A" last="Khan">Paul A. Khan</name><name sortKey="Majumdar, Sumit R" sort="Majumdar, Sumit R" uniqKey="Majumdar S" first="Sumit R" last="Majumdar">Sumit R. Majumdar</name><name sortKey="Moher, David" sort="Moher, David" uniqKey="Moher D" first="David" last="Moher">David Moher</name><name sortKey="Soobiah, Charlene" sort="Soobiah, Charlene" uniqKey="Soobiah C" first="Charlene" last="Soobiah">Charlene Soobiah</name><name sortKey="Straus, Sharon E" sort="Straus, Sharon E" uniqKey="Straus S" first="Sharon E" last="Straus">Sharon E. Straus</name><name sortKey="Straus, Sharon E" sort="Straus, Sharon E" uniqKey="Straus S" first="Sharon E" last="Straus">Sharon E. Straus</name><name sortKey="Yu, Catherine H" sort="Yu, Catherine H" uniqKey="Yu C" first="Catherine H" last="Yu">Catherine H. Yu</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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