Maria Ida Maiorino1, Paolo Chiodini2, Giuseppe Bellastella3, Annalisa Capuano4, Katherine Esposito1, Dario Giugliano5. 1. Diabetes Unit, Department of Medical, Surgical, Neurological, Metabolic Sciences and Aging, University of Campania "Luigi Vanvitelli," Naples, Italy. 2. Medical Statistics Unit, University of Campania "Luigi Vanvitelli," Naples, Italy. 3. Division of Endocrinology and Metabolic Diseases, Department of Medical, Surgical, Neurological, Metabolic Sciences and Aging, University of Campania "Luigi Vanvitelli," Naples, Italy. 4. Section of Pharmacology, Department of Experimental Medicine, University of Campania "Luigi Vanvitelli," Naples, Italy. 5. Division of Endocrinology and Metabolic Diseases, Department of Medical, Surgical, Neurological, Metabolic Sciences and Aging, University of Campania "Luigi Vanvitelli," Naples, Italy dario.giugliano@unina2.it.
Abstract
OBJECTIVE: 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. RESEARCH DESIGN AND METHODS: 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 ≤7% (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. RESULTS: We identified 26 RCTs, lasting 12-52 weeks, and involving 11,425 patients. When the combination strategy was compared with other injectable treatments (overall data), there were reductions in HbA1c (WMD = -0.47%, 95% CI -0.59 to -0.35), more patients at HbA1c target (RR = 1.65, 95% CI 1.44-1.88), similar hypoglycemic events (RR = 1.14, 95% CI 0.93-1.39) and a reduction in weight (WMD = -2.5 kg, 95% CI -3.3 to -1.7), with high heterogeneity (I2 > 89%, P < 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 0.46-0.93) and reduced weight (WMD = -4.7 kg, 95% CI -6.9 to -2.4). Fixed-ratio combinations yielded results similar to the overall analysis (HbA1c WMD = -0.56%, 95% CI -0.72 to -0.40). CONCLUSIONS: 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.
OBJECTIVE: The combination of basal insulin plus aglucagon-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. RESEARCH DESIGN AND METHODS: 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 ≤7% (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. RESULTS: We identified 26 RCTs, lasting 12-52 weeks, and involving 11,425 patients. When the combination strategy was compared with other injectable treatments (overall data), there were reductions in HbA1c (WMD = -0.47%, 95% CI -0.59 to -0.35), more patients at HbA1c target (RR = 1.65, 95% CI 1.44-1.88), similar hypoglycemic events (RR = 1.14, 95% CI 0.93-1.39) and a reduction in weight (WMD = -2.5 kg, 95% CI -3.3 to -1.7), with high heterogeneity (I2 > 89%, P < 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 0.46-0.93) and reduced weight (WMD = -4.7 kg, 95% CI -6.9 to -2.4). Fixed-ratio combinations yielded results similar to the overall analysis (HbA1c WMD = -0.56%, 95% CI -0.72 to -0.40). CONCLUSIONS: 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.
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