{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T10:09:50Z","timestamp":1788343790156,"version":"build-2803163510"},"reference-count":46,"publisher":"American Diabetes Association","issue":"4","license":[{"start":{"date-parts":[[2017,3,21]],"date-time":"2017-03-21T00:00:00Z","timestamp":1490054400000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/www.diabetesjournals.org\/content\/license"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,4,1]]},"abstract":"<jats:sec>\n                  <jats:title>OBJECTIVE<\/jats:title>\n                  <jats:p>The combination of basal insulin plus a glucagon-like peptide 1 receptor agonist (GLP-1RA) has been proposed as a treatment option to intensify insulin therapy in type 2 diabetes. We performed a meta-analysis of randomized controlled trials (RCTs) comparing this combination strategy to other injectable antidiabetes treatments on metabolic control in adult patients with type 2 diabetes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                  <jats:p>We conducted an electronic search until November 2016 on many electronic databases to identify RCTs assessing changes in HbA1c, proportion of patients at HbA1c target \u22647% (53 mmol\/mol), hypoglycemia, and weight change. We used a random-effect model to calculate the weighted mean difference (WMD) or relative risk (RR) with the 95% CI.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>We identified 26 RCTs, lasting 12\u201352 weeks, and involving 11,425 patients. When the combination strategy was compared with other injectable treatments (overall data), there were reductions in HbA1c (WMD = \u22120.47%, 95% CI \u22120.59 to \u22120.35), more patients at HbA1c target (RR = 1.65, 95% CI 1.44\u20131.88), similar hypoglycemic events (RR = 1.14, 95% CI 0.93\u20131.39) and a reduction in weight (WMD = \u22122.5 kg, 95% CI \u22123.3 to \u22121.7), with high heterogeneity (I2 &amp;gt; 89%, P &amp;lt; 0.001) and a significant publication bias for three outcomes. In preplanned subgroup analyses, the combination treatment was similar to basal-bolus insulin regimens for glycemic control, with less hypoglycemia (RR = 0.66, 95% CI 0.46\u20130.93) and reduced weight (WMD = \u22124.7 kg, 95% CI \u22126.9 to \u22122.4). Fixed-ratio combinations yielded results similar to the overall analysis (HbA1c WMD = \u22120.56%, 95% CI \u22120.72 to \u22120.40).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>GLP-1RAs alone or as titratable fixed-ratio combinations with basal insulin may represent a promising option to advance basal insulin therapy or to initiate injectable therapy in patients with type 2 diabetes inadequately controlled on oral agents. Longer studies are needed to assess durability and tolerability.<\/jats:p>\n               <\/jats:sec>","DOI":"10.2337\/dc16-1957","type":"journal-article","created":{"date-parts":[[2017,3,21]],"date-time":"2017-03-21T20:02:31Z","timestamp":1490126551000},"page":"614-624","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":116,"title":["Insulin and Glucagon-Like Peptide 1 Receptor Agonist Combination Therapy in Type 2 Diabetes: A Systematic Review and Meta-analysis of Randomized Controlled Trials"],"prefix":"10.2337","volume":"40","author":[{"given":"Maria Ida","family":"Maiorino","sequence":"first","affiliation":[{"name":"Diabetes Unit, Department of Medical, Surgical, Neurological, Metabolic Sciences and Aging, University of Campania \u201cLuigi Vanvitelli,\u201d Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Chiodini","sequence":"additional","affiliation":[{"name":"Medical Statistics Unit, University of Campania \u201cLuigi Vanvitelli,\u201d Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Bellastella","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolic Diseases, Department of Medical, Surgical, Neurological, Metabolic Sciences and Aging, University of Campania \u201cLuigi Vanvitelli,\u201d Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Capuano","sequence":"additional","affiliation":[{"name":"Section of Pharmacology, Department of Experimental Medicine, University of Campania \u201cLuigi Vanvitelli,\u201d Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Esposito","sequence":"additional","affiliation":[{"name":"Diabetes Unit, Department of Medical, Surgical, Neurological, Metabolic Sciences and Aging, University of Campania \u201cLuigi Vanvitelli,\u201d Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario","family":"Giugliano","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolic Diseases, Department of Medical, Surgical, Neurological, Metabolic Sciences and Aging, University of Campania \u201cLuigi Vanvitelli,\u201d Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2017,3,10]]},"reference":[{"key":"2022031202172117500_B1","doi-asserted-by":"crossref","first-page":"140","DOI":"10.2337\/dc14-2441","article-title":"Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes","volume":"38","author":"Inzucchi","year":"2015","journal-title":"Diabetes 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