{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T04:57:12Z","timestamp":1764997032498,"version":"build-2065373602"},"reference-count":38,"publisher":"BMJ","issue":"12","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2014,9,10]]},"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats: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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Setting<\/jats:title>\n                  <jats:p>Studies were multicentre and multinational.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Participants<\/jats:title>\n                  <jats:p>Ten studies including 2967 patients with T2DM.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Interventions<\/jats:title>\n                  <jats:p>Studies that examined DPP-4 inhibitors compared with each other, intermediate-acting insulin, no treatment or placebo in patients with T2DM.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Primary and secondary outcome measures<\/jats:title>\n                  <jats: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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats: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) \u22120.62%, 95% CI \u22120.93% to \u22120.33%) and meta-analysis (MD \u22120.61%, 95% CI \u22120.81% to \u22120.41%), 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).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats: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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Trial registration number<\/jats:title>\n                  <jats:p>PROSPERO # CRD42013003624.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/bmjopen-2014-005752","type":"journal-article","created":{"date-parts":[[2014,12,23]],"date-time":"2014-12-23T22:16:49Z","timestamp":1419373009000},"page":"e005752","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":32,"title":["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"],"prefix":"10.1136","volume":"4","author":[{"given":"Andrea C","family":"Tricco","sequence":"first","affiliation":[{"name":"Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jesmin","family":"Antony","sequence":"additional","affiliation":[{"name":"Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul A","family":"Khan","sequence":"additional","affiliation":[{"name":"Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Ghassemi","sequence":"additional","affiliation":[{"name":"Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jemila S","family":"Hamid","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huda","family":"Ashoor","sequence":"additional","affiliation":[{"name":"Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erik","family":"Blondal","sequence":"additional","affiliation":[{"name":"Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlene","family":"Soobiah","sequence":"additional","affiliation":[{"name":"Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine H","family":"Yu","sequence":"additional","affiliation":[{"name":"Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Hutton","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology Program, Ottawa Hospital Research Institute and the Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brenda R","family":"Hemmelgarn","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Moher","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology Program, Ottawa Hospital Research Institute and the Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sumit R","family":"Majumdar","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alberta, Edmonton, Alberta, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharon E","family":"Straus","sequence":"additional","affiliation":[{"name":"Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada"},{"name":"Department of Geriatric Medicine, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2014,12,23]]},"reference":[{"key":"2025101814575566000_4.12.e005752.1","unstructured":"Canadian Diabetes Association. 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