OBJECTIVE: The long-term cost-effectiveness of using pioglitazone plus metformin 
(Actoplusmet dagger) compared with rosiglitazone plus metformin (Avandamet 
double dagger) in treating type 2 diabetes (T2DM) was assessed from a US 
third-party payer perspective.
RESEARCH DESIGN AND METHODS: Clinical efficacy (change in HbA(1c) and lipids) 
and baseline cohort parameters were extracted from a 12-month, randomized 
clinical trial (Derosa et al., 2006) evaluating the efficacy and tolerability of 
pioglitazone versus rosiglitazone, both in addition to metformin, in adult T2DM 
patients with insufficient glucose control (n = 96). A Markov-based model was 
used to project clinical and economic outcomes over 35 years, discounted at 3% 
per annum. Costs for complications were taken from published sources. Base-case 
assumptions were assessed through several sensitivity analyses.
MAIN OUTCOME MEASURES: Outcomes included incremental life-years, 
quality-adjusted life-years (QALYs), total direct medical costs, cumulative 
incidence of complications and associated costs, and incremental 
cost-effectiveness ratios (ICERs).
RESULTS: Compared to rosiglitazone plus metformin, pioglitazone plus metformin 
was projected to result in a modest improvement in 0.187 quality-adjusted 
life-years. Over patients' lifetimes, total direct medical costs were projected 
to be marginally lower with pioglitazone plus metformin (difference -$526.), 
largely due to reduced CVD complication costs. While costs were higher among 
renal, ulcer/amputation/neuropathy, and eye complications in the pioglitazone 
plus metformin group, the cost savings for CVD complications outweighed their 
economic impact. Pioglitazone plus metformin was found to be a dominant 
long-term treatment strategy in the US compared to rosiglitazone plus metformin. 
Sensitivity analyses showed findings to be robust under almost all scenarios, 
including short-term time horizons, 6% discounting, removal of individual lipid 
parameters, and modifications of patient cohort to more closely represent a US 
T2DM population. Pioglitazone plus metformin was no longer dominant with 0% 
discounting, with 25% reduction in its HbA(1c) effects, or with a 15% increase 
in its acquisition price.
CONCLUSIONS: Under a range of assumptions and study limitations around cohorts, 
clinical effects, and treatment patterns, this long-term analysis showed that 
pioglitazone plus metformin, when compared to rosiglitazone plus metformin, was 
a dominant treatment strategy within the US payer setting. Results were driven 
by the combination of modest differences in QALYs and modest savings in total 
complication costs over 35 years.