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Second- and Third-Line Pharmacotherapy for Type 2 Diabetes: Update [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2013 Jul. (CADTH Optimal Use Report, No. 3.1.)

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Second- and Third-Line Pharmacotherapy for Type 2 Diabetes: Update [Internet].

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Based on the updated systematic review, there was insufficient evidence to evaluate the comparative efficacy of third-line treatments added to metformin and a sulfonylurea in terms of clinically important long-term complications of diabetes. Compared with continued treatment with metformin and a sulfonylurea, addition of DPP-4 inhibitors, GLP-1 analogues, TZDs, and insulins produced statistically significant reductions in A1C; whereas, meglitinides and alpha-glucosidase inhibitors did not. Insulins and TZDs were all associated with an increase in body weight, DPP-4 inhibitors and alpha-glucosidase inhibitors were not associated with significant weight gain, and GLP-1 analogues were associated with weight loss. The various insulin-containing strategies were typically associated with a greater risk of hypoglycemia relative to other active comparators, although the risk of severe hypoglycemia was low across all drug classes. Further studies of adequate size and duration are required to assess comparative efficacy in terms of durability of antihyperglycemic effect, long-term complications of diabetes, and quality of life.

The results of the updated cost-effectiveness analysis comparing third-line treatments were congruent with those of the original analysis. The addition of insulin NPH to metformin and sulfonylurea combination therapy represented the most cost-effective third-line therapy. GLP-1 analogues, which could not be considered in the original analysis since no agents were approved in Canada at the time, were found to be associated with a high ICUR in the updated analysis. In order to surpass insulin NPH as the most cost-effective third-line therapy, reductions in cost of 40% or more would be required for this class and the DPP-4 inhibitors. Because of the lack of adequate clinical data, there was considerable uncertainty surrounding some of the key drivers in the economic analysis. These included the impact of insulin use and hypoglycemia on quality of life, and the incidence of hypoglycemia across various treatments.

Copyright © CADTH 2013.
Bookshelf ID: NBK169654
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