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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Le document en format XML
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<author><name sortKey="Antony, Jesmin" sort="Antony, Jesmin" uniqKey="Antony J" first="Jesmin" last="Antony">Jesmin Antony</name>
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<author><name sortKey="Ghassemi, Marco" sort="Ghassemi, Marco" uniqKey="Ghassemi M" first="Marco" last="Ghassemi">Marco Ghassemi</name>
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<country xml:lang="fr">Canada</country>
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<author><name sortKey="Hamid, Jemila S" sort="Hamid, Jemila S" uniqKey="Hamid J" first="Jemila S" last="Hamid">Jemila S. Hamid</name>
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<country xml:lang="fr">Canada</country>
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<author><name sortKey="Blondal, Erik" sort="Blondal, Erik" uniqKey="Blondal E" first="Erik" last="Blondal">Erik Blondal</name>
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<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<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>
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<author><name sortKey="Yu, Catherine H" sort="Yu, Catherine H" uniqKey="Yu C" first="Catherine H" last="Yu">Catherine H. Yu</name>
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Hutton, Brian" sort="Hutton, Brian" uniqKey="Hutton B" first="Brian" last="Hutton">Brian Hutton</name>
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,<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>
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<author><name sortKey="Hemmelgarn, Brenda R" sort="Hemmelgarn, Brenda R" uniqKey="Hemmelgarn B" first="Brenda R" last="Hemmelgarn">Brenda R. Hemmelgarn</name>
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,<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>
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<author><name sortKey="Moher, David" sort="Moher, David" uniqKey="Moher D" first="David" last="Moher">David Moher</name>
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,<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>
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<author><name sortKey="Majumdar, Sumit R" sort="Majumdar, Sumit R" uniqKey="Majumdar S" first="Sumit R" last="Majumdar">Sumit R. Majumdar</name>
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,<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>
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<author><name sortKey="Straus, Sharon E" sort="Straus, Sharon E" uniqKey="Straus S" first="Sharon E" last="Straus">Sharon E. Straus</name>
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,<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>
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<country xml:lang="fr">Canada</country>
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<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>
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<affiliations><list><country><li>Canada</li>
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<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>
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<name sortKey="Khan, Paul A" sort="Khan, Paul A" uniqKey="Khan P" first="Paul A" last="Khan">Paul A. Khan</name>
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<name sortKey="Moher, David" sort="Moher, David" uniqKey="Moher D" first="David" last="Moher">David Moher</name>
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