RESUMO
BACKGROUND: To compare the first-in-class sodium glucose co-transporter 2 (SGLT2) inhibitor, dapagliflozin, with existing type 2 diabetes mellitus (T2DM) treatment options available within the European Union (EU) for add-on therapy to sulfonylureas (SUs). METHODS: A systematic review was conducted to identify randomised controlled trials (RCTs) in T2DM patients inadequately controlled by SU monotherapy. Direct meta-analysis, Bucher indirect comparisons and Bayesian network meta-analysis (NMA) were conducted on studies meeting predefined inclusion criteria. Sufficient data were available to assess three clinical endpoints at 24 (+/- 6) weeks follow-up: mean change in HbA1c from baseline, mean change in weight from baseline, and the proportion of patients experiencing at least one episode of hypoglycaemia. The effect of confounding baseline factors was explored through covariate analyses. RESULTS: The search identified 1,901 unique citations, with 1,870 excluded based on title/abstract. From reviewing full-texts of the remaining 31 articles, 5 studies were considered eligible for analysis. All studies were comparable in terms of baseline characteristics, including: HbA1c, age and body mass index (BMI). In addition to dapagliflozin, sufficient data for meta-analysis was available for three dipeptidyl peptidase-4 (DPP-4) inhibitors and one glucagon-like peptide-1 (GLP-1) analogue. Based on fixed-effect NMA, all treatment classes resulted in statistically significant decreases in HbA1c at follow-up compared to placebo. Dapagliflozin treatment resulted in significantly decreased weight at follow-up compared to placebo (-1.54 kg; 95% CrI -2.16, -0.92), in contrast to treatment with GLP-1 analogues (-0.65 kg; 95% CrI -1.37, 0.07) and DPP-4 inhibitors (0.57 kg; 95% CrI 0.09, 1.06). The odds of hypoglycaemia were similar to placebo for dapagliflozin and DPP-4 inhibitor add-on treatment, but significantly greater than placebo for GLP-1 analogue add-on treatment (10.89; 95% CrI 4.24, 38.28). Assessment of NMA model heterogeneity was hindered by the small size of the network. CONCLUSIONS: Dapagliflozin, DPP-4 inhibitors and GLP-1 analogues, in combination with SU, all provided better short-term glycaemic control compared to SU monotherapy. Dapagliflozin was the only add-on therapy that had both a favourable weight and hypoglycaemia profile compared to the other classes of treatment evaluated.
RESUMO
BACKGROUND AND OBJECTIVE: Many patients with type 2 diabetes mellitus (T2DM) on insulin therapy have inadequate glycaemic control. In such cases, Dutch guidelines recommend unlimited up-titration of insulin, yet in practice many patients never reach their glycaemic target. Clinical evidence shows that dapagliflozin-a highly selective sodium-glucose cotransporter 2 inhibitor-meets a need for these patients, i.e. by reducing glycated haemoglobin levels and bodyweight. We estimated the cost effectiveness and cost utility of adding dapagliflozin to insulin compared with not adding dapagliflozin in patients with T2DM who have inadequate glycaemic control while on insulin. METHODS: The cost effectiveness of dapagliflozin was estimated using the Cardiff Diabetes Model, using direct comparative efficacy data from a randomized placebo-controlled trial (ClinicalTrials.gov identifier NCT00673231). In this trial, up-titration of insulin was allowed in case of severe glycaemic imbalance. Risk factor progression and the occurrence of future vascular events were estimated using the United Kingdom Prospective Diabetes Study 68 risk equations. Costs and utilities were derived from the literature. The analysis was conducted from the societal perspective, simulating the remaining lifetime of the patients. RESULTS: The overall incidence of macro- and microvascular complications was lower, and life expectancy was greater (19.43 versus 19.35 life-years [LYs]) in patients receiving dapagliflozin than in those not receiving dapagliflozin. Patients in the dapagliflozin arm obtained an incremental benefit of 0.42 quality-adjusted life-years (QALYs). The lifetime incremental cost per patient in the dapagliflozin arm was 2,293, resulting in an incremental cost-effectiveness ratio of 27,779 per LY gained and an incremental cost-utility ratio of 5,502 per QALY gained. Sensitivity and scenario analyses showed that the results were insensitive to variations in modelling assumptions and input variables. CONCLUSION: Dapagliflozin in combination with insulin was estimated to be a cost-effective treatment option for patients with T2DM whose insulin treatment regimen does not provide adequate glycaemic control in a Dutch healthcare setting.