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

Department of Medicine, University of Alberta, Edmonton, Alta.
Canadian Medical Association Journal (Impact Factor: 5.81). 11/2011; 183(16):E1213-20. DOI: 10.1503/cmaj.110178
Source: PubMed

ABSTRACT 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.
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.
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.
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.

Download full-text


Available from: Chris Cameron, Mar 30, 2014
  • Source
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective The present investigation was to evaluate the possible anti-diabetic effect of mangiferin from Salacia chinensis (S. chinensis) on the activities of kidney carbohydrate metabolic enzymes in chemically induced diabetic rats.Methods Diabetes was induced by streptozotocin (STZ) in adult male rats, as a single intraperitoneal injection at a dose of 55 mg/kg body weight. The STZ-induced diabetic rats were treated by mangiferin and glibenclamide (positive control drug) for 30 days. At the end of the experiment, the rats were sacrificed and carbohydrate metabolic enzyme activities were analyzed in the kidney.ResultsDiabetic control rats showed a significant increase in the level of fasting blood glucose and also increase the activities of carbohydrate metabolic enzymes in kidney on successive days of the experiment as compared with their basal values. Daily oral administration of mangiferin showed a significant decrease in the blood glucose when compared to diabetic control. The anti-hyperglycemic effect was obtained with the dose of 40 mg/kg b.wt. In addition, treatment of mangiferin shows alteration in kidney carbohydrate metabolic enzymes including gluconeogenic enzymes like glucose-6-phosphatase and fructose-1,6-disphosphatase. These results were comparable with positive control drug, glibenclamide.Conclusions The results obtained in this study provide evidence of the anti-diabetic potential of mangiferin, mediated through the regulation of carbohydrate key metabolic enzyme activities.
    Asian Pacific Journal of Tropical Biomedicine 01/2012; 2(3):S1583–S1587. DOI:10.1016/S2221-1691(12)60457-2
  • [Show abstract] [Hide abstract]
    ABSTRACT: To assess the efficacy and safety of dipeptidyl peptidase-4 (DPP-4) inhibitors compared with metformin as monotherapy, or with other commonly used hypoglycaemic drugs combined with metformin, in adults with type 2 diabetes mellitus. Systematic review and meta-analysis of randomised controlled trials. Medline, Embase, the Cochrane Library, conference proceedings, trial registers, and drug manufacturers' websites. ELIGIBILITY CRITERIA: Randomised controlled trials of adults with type 2 diabetes mellitus that compared a DPP-4 with metformin as monotherapy or with a sulfonylurea, pioglitazone, a glucagon-like peptide-1 (GLP-1) agonist, or basal insulin combined with metformin on the change from baseline in glycated haemoglobin (HbA(1c)). The primary outcome was the change in HbA(1c). Secondary outcomes included the proportion of patients achieving the goal of HbA(1c) <7%, the change in body weight, discontinuation rate because of any adverse event, occurrence of any serious adverse event, all cause mortality, and incidence of hypoglycaemia, nasopharyngitis, urinary tract infection, upper respiratory infection, nausea, vomiting, and diarrhoea. 27 reports of 19 studies including 7136 patients randomised to a DPP-4 inhibitor and 6745 patients randomised to another hypoglycaemic drug were eligible for the systematic review and meta-analysis. Overall risk of bias for the primary outcome was low in three reports, unclear in nine, and high in 14. Compared with metformin as monotherapy, DPP-4 inhibitors were associated with a smaller decline in HbA(1c) (weighted mean difference 0.20, 95% confidence interval 0.08 to 0.32) and in body weight (1.5, 0.9 to 2.11). As a second line treatment, DPP-4 inhibitors were inferior to GLP-1 agonists (0.49, 0.31 to 0.67) and similar to pioglitazone (0.09, -0.07 to 0.24) in reducing HbA(1c) and had no advantage over sulfonylureas in the attainment of the HbA(1c) goal (risk ratio in favour of sulfonylureas 1.06, 0.98 to 1.14). DPP-4 inhibitors had a favourable weight profile compared with sulfonylureas (weighted mean difference -1.92, -2.34 to -1.49) or pioglitazone (-2.96, -4.13 to -1.78), but not compared with GLP-1 agonists (1.56, 0.94 to 2.18). Only a minimal number of hypoglycaemias were observed in any treatment arm in trials comparing a DPP-4 inhibitor with metformin as monotherapy or with pioglitazone or a GLP-1 agonist as second line treatment. In most trials comparing a DPP-4 inhibitor with sulfonylureas combined with metformin, the risk for hypoglycaemia was higher in the group treated with a sulfonylurea. Incidence of any serious adverse event was lower with DPP-4 inhibitors than with pioglitazone. Incidence of nausea, diarrhoea, and vomiting was higher in patients receiving metformin or a GLP-1 agonist than in those receiving a DPP-4 inhibitor. Risk for nasopharyngitis, upper respiratory tract infection, or urinary tract infection did not differ between DPP-4 inhibitors and any of the active comparators. In patients with type 2 diabetes who do not achieve the glycaemic targets with metformin alone, DPP-4 inhibitors can lower HbA(1c), in a similar way to sulfonylureas or pioglitazone, with neutral effects on body weight. Increased unit cost, which largely exceeds that of the older drugs, and uncertainty about their long term safety, however, should also be considered.
    BMJ (online) 03/2012; 344:e1369. DOI:10.1136/bmj.e1369 · 16.38 Impact Factor