Elias Zintzaras1, Michael Miligkos2, Panayiotis Ziakas3, Ethan M Balk4, Despoina Mademtzoglou2, Chrysoula Doxani2, Theodoros Mprotsis2, Raman Gowri4, Paraskevi Xanthopoulou2, Ioanna Mpoulimari2, Chrysoula Kokkali2, Georgia Dimoulou2, Paraskevi Rodopolou2, Ioannis Stefanidis2, David M Kent5, Georgios M Hadjigeorgiou6. 1. Center for Clinical Evidence Synthesis, The Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts; Evidence-Based Medicine Unit, Department of Biomathematics, University of Thessaly School of Medicine, Larissa, Greece. 2. Evidence-Based Medicine Unit, Department of Biomathematics, University of Thessaly School of Medicine, Larissa, Greece. 3. Division of Infectious Diseases, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, Rhode Island. 4. Center for Clinical Evidence Synthesis, The Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts. 5. Predictive Analytics and Comparative Effectiveness Center, The Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts. 6. Evidence-Based Medicine Unit, Department of Biomathematics, University of Thessaly School of Medicine, Larissa, Greece. Electronic address: gmhadji@med.uth.gr.
Abstract
PURPOSE: The relative effectiveness and tolerability of treatments for type 2 diabetes mellitus (T2DM) is not well understood because few randomized, controlled trials (RCTs) have compared these treatments directly. The purpose of the present study was to evaluate the relative effectiveness and tolerability of treatments of T2DM. METHODS: We performed a network meta-analysis of available RCTs with pharmacologic interventions in T2DM and compared antidiabetic drugs and combination regimens with metformin (the reference drug). Glycemic control (proportion achieving HbA1c goal) and tolerability (risk of hypoglycemia) were the primary outcomes of interest. Direct and indirect relative effects (unadjusted) were expressed as odds ratios and 95% CIs. FINDINGS: Eight treatments (glucagon-like peptide-1 [GLP-1] agonists plus metformin, sulfonylureas plus metformin, dipeptidyl peptidase-4 [DPP-4] inhibitors] plus metformin, colesevelan plus metformin, thiazolidinediones plus metformin, meglitinides plus metformin, α-glucosidase inhibitor plus metformin, and rosiglitazone monotherapy) outperformed metformin (direct effects). Triple combinations of GLP-1, thiazolinedione, insulin, metiglinide, or sulfonylureas added to a metformin backbone improved glycemic control (indirect effects). Higher risk of hypoglycemia was noted for sulfonylureas, α-glycosidases, and metiglinides when added to metformin (direct effects). Across indirect effects, only 17% of comparisons yielded less risk of hypoglycemia (70% were worse and 13% were comparable). IMPLICATIONS: Our results point out the relative superiority of 2- and 3-drug combination regimens over metformin and summarize treatment effects and tolerability in a comprehensive manner, which adds to our knowledge regarding T2DM treatment options.
PURPOSE: The relative effectiveness and tolerability of treatments for type 2 diabetes mellitus (T2DM) is not well understood because few randomized, controlled trials (RCTs) have compared these treatments directly. The purpose of the present study was to evaluate the relative effectiveness and tolerability of treatments of T2DM. METHODS: We performed a network meta-analysis of available RCTs with pharmacologic interventions in T2DM and compared antidiabetic drugs and combination regimens with metformin (the reference drug). Glycemic control (proportion achieving HbA1c goal) and tolerability (risk of hypoglycemia) were the primary outcomes of interest. Direct and indirect relative effects (unadjusted) were expressed as odds ratios and 95% CIs. FINDINGS: Eight treatments (glucagon-like peptide-1 [GLP-1] agonists plus metformin, sulfonylureas plus metformin, dipeptidyl peptidase-4 [DPP-4] inhibitors] plus metformin, colesevelan plus metformin, thiazolidinediones plus metformin, meglitinides plus metformin, α-glucosidase inhibitor plus metformin, and rosiglitazone monotherapy) outperformed metformin (direct effects). Triple combinations of GLP-1, thiazolinedione, insulin, metiglinide, or sulfonylureas added to a metformin backbone improved glycemic control (indirect effects). Higher risk of hypoglycemia was noted for sulfonylureas, α-glycosidases, and metiglinides when added to metformin (direct effects). Across indirect effects, only 17% of comparisons yielded less risk of hypoglycemia (70% were worse and 13% were comparable). IMPLICATIONS: Our results point out the relative superiority of 2- and 3-drug combination regimens over metformin and summarize treatment effects and tolerability in a comprehensive manner, which adds to our knowledge regarding T2DM treatment options.