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Second-Line Pharmacotherapy for Type 2 Diabetes — Update [Internet]

Second-Line Pharmacotherapy for Type 2 Diabetes — Update [Internet]

CADTH Optimal Use Report - Canadian Agency for Drugs and Technologies in Health

Version: July 2013


In August 2010, the Canadian Agency for Drugs and Technologies in Health (CADTH) published a systematic review and network meta-analysis (NMA) assessing the comparative safety and efficacy of all available classes of antihyperglycemic therapies added to metformin in patients with type 2 diabetes experiencing inadequate glycemic control on metformin monotherapy., At the time, we identified 49 active and non-active randomized controlled trials (RCTs) that compared two or more of the following classes of antihyperglycemic agents (including weight-loss agents with glucose-lowering effects): sulfonylureas, meglitinides, thiazolidinediones (TZDs), dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) analogues, insulins, alpha-glucosidase inhibitors, sibutramine and orlistat. All classes of second-line antihyperglycemic therapies were found to achieve clinically meaningful reductions in glycated hemoglobin (A1C) (0.6% to 1.0%), and no significant differences were found between classes. Insulins and insulin secretagogues were associated with significantly more events of overall hypoglycemia than the other agents, but severe hypoglycemia was rarely observed. An increase in body weight was observed with the majority of second-line therapies (1.8 kg to 3.0 kg) — the exceptions being DPP-4 inhibitors, alpha-glucosidase inhibitors, and GLP-1 analogues (0.6 to –1.8 kg). There were insufficient data available for diabetes complications, mortality, or quality of life.


To update the 2010 CADTH pharmacoeconomic analysis of second-line therapies for type 2 diabetes to incorporate all agents currently approved in Canada, based on the results of the updated systematic review and NMAs.

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