Second- and third-line pharmacotherapy for type 2 diabetes : update

Since the original CADTH reports were published, interest has emerged in the combined use of incretins and insulin, and some incretins have received regulatory approval for combined use with insulin in Canada and other jurisdictions. Hence, the updated clinical reviews will also address a supplement...

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Corporate Author: Canadian Agency for Drugs and Technologies in Health
Format: eBook
Language:English
Published: Ottawa (ON) Canadian Agency for Drugs and Technologies in Health 2013, July 2013
Series:CADTH optimal use report
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Online Access:
Collection: National Center for Biotechnology Information - Collection details see MPG.ReNa
Summary:Since the original CADTH reports were published, interest has emerged in the combined use of incretins and insulin, and some incretins have received regulatory approval for combined use with insulin in Canada and other jurisdictions. Hence, the updated clinical reviews will also address a supplemental research topic regarding the combination use of incretin agents with insulin
In August 2010, the Canadian Agency for Drugs and Technologies in Health (CADTH) published an Optimal Therapy Report which assessed the clinical and cost-effectiveness of second-line therapies for patients with type 2 diabetes inadequately controlled on metformin. The results from the CADTH review indicated that there were no apparent differences in efficacy across drug classes, and that sulfonylureas were the most cost-effective treatment option. Based on these analyses, the Canadian Optimal Medication Prescribing and Utilization Service (COMPUS) Expert Review Committee (CERC) recommended that most patients requiring a second treatment after metformin should be prescribed a sulfonylurea. CADTH followed this report with a Therapeutic Review which examined the evidence for third-line treatment options for adults with type 2 diabetes inadequately controlled on metformin and a sulfonylurea.
The results demonstrated that insulins (basal, biphasic, bolus), dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) analogues, and thiazolidinediones (TZDs) all produced statistically significant reductions in hemoglobin A1C in combination with metformin and a sulphonylurea. Meglitinides and alpha-glucosidase inhibitors, however, did not. The addition of insulin neutral protamine Hagedorn (NPH) to metformin plus a sulfonylurea was associated with the most favourable cost-effectiveness estimates. CADTH's Therapeutic Review Panel (TRP) recommended that, for most adults with type 2 diabetes inadequately controlled on metformin and a sulfonylurea, insulin NPH should be added as the third-line agent. Long-acting insulin analogues at prices similar to insulin NPH were also considered an option for patients inadequately controlled on metformin and a sulfonylurea.
The original clinical reviews of second- and third-line pharmacotherapy for type 2 diabetes included GLP-1 analogues and DPP-4 inhibitors currently available in Canada; however, the cost-effectiveness analyses and subsequent recommendations could not address the use of GLP-1 analogues, as there were no agents approved for use in Canada at the time of the reviews. Two GLP-1 analogues, exenatide (Byetta) and liraglutide (Victoza), are now approved for use in Canada. As well, sitagliptin and saxagliptin were the only DPP-4 inhibitors considered in the original economic analyses and recommendations, while agents in this class that were not yet approved by Health Canada (e.g., linagliptin) were excluded. Therefore, there is interest in updated optimal therapy recommendations for second- and third-line therapy in diabetes that incorporate the GLP-1 analogues and newer DPP-4 inhibitors.
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