Cost-effectiveness of second-line antihyperglycemic therapy in patients with type 2 diabetes mellitus inadequately controlled on metformin

Abstract

Background: Metformin is widely accepted as first-line pharmacotherapy for patients with type 2 diabetes mellitus when glycemic control cannot be achieved by lifestyle interventions alone. However, uncertainty exists regarding the optimal second-line therapy for patients whose diabetes is inadequately controlled by metformin monotherapy. Increased use of newer, more costly agents, along with the rising incidence of type 2 diabetes, carries significant budgetary implications for health care systems. We conducted this analysis to determine the relative costs, benefits and cost-effectiveness of options for second-line treatment of type 2 diabetes.

Methods: We used the United Kingdom Prospective Diabetes Study Outcomes Model to forecast diabetes-related complications, quality-adjusted life-years and costs of alternative second-line therapies available in Canada for adults with type 2 diabetes inadequately controlled by metformin. We obtained clinical data from a systematic review and mixed treatment comparison meta-analysis, and we obtained information on costs and utilities from published sources. We performed extensive sensitivity analyses to test the robustness of results to variation in inputs and assumptions.

Results: Sulphonylureas, when added to metformin, were associated with the most favourable cost-effectiveness estimate, with an incremental cost of $12 757 per quality-adjusted life-year gained, relative to continued metformin monotherapy. Treatment with other agents, including thiazolidinediones and dipeptidyl peptidase-4 inhibitors, had unfavourable cost-effectiveness estimates compared with sulphonylureas. These results were robust to extensive sensitivity analyses.

Interpretation: For most patients with type 2 diabetes that is inadequately controlled with metformin monotherapy, the addition of a sulphonylurea represents the most cost-effective second-line therapy.

Figure 1:

Overview of the United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model and submodels, with application to the current economic analysis. COMPUS = Canadian Optimal Medication Prescribing and Utilization Service, DPP-4 = dipeptidyl peptidase-4, TZDs = thiazolidinediones, QALYs = quality-adjusted life-years. Adapted, with permission, from Clarke and associates.

Figure 2:

Cost-effectiveness acceptability curves for reference case analysis. These curves show the probability that second-line therapies are cost-effective across a range of decision-makers’ willingness-to-pay thresholds, using probabilistic sensitivity analysis. For example, at a willingness-to-pay of $25 000 per quality-adjusted life-year (QALY), metformin with a sulphonylurea is more likely to be cost-effective than metformin monotherapy (96% v. 4%). Some strategies (e.g., thiazolidinediones) are not visible, either because they have low probability of being most cost-effective or because they would only be acceptable at very large willingness-to-pay thresholds.