Effectiveness and cost-effectiveness analysis of cardioprotective antidiabetic drugs for type 2
diabetes in a middle-income country
Type 2 diabetes; cardiovascular disease; antidiabetic drugs; cost-effectiveness.
The steady increase in the prevalence of type 2 diabetes (T2DM), particularly in
low- and middle-income countries, represents an unprecedented economic and social disaster.
Cardiovascular disease, in particular coronary disease, the most prevalent macrovascular
complication in diabetics, constitutes the main source of health costs for these patients,
accounting for approximately 76% in hospitalizations alone. Objectives: To analyze the efficacy
and cost-effectiveness of cardioprotective antidiabetic drugs in individuals with T2D in a
middle-income country. Methods: A systematic search was performed for randomized clinical
trials published until April 2021 reporting the incidence of the composite outcome of
cardiovascular death, nonfatal myocardial infarction, and stroke for pioglitazone, GLP1A, or
SGLT2i. Based on the dataset of two large national cohorts of T2D, we developed a multi-state
Markov model to estimate the outcomes for each treatment based on incremental cost-
effectiveness ratio (ICER) and the disease-adjusted life years [DALYs] averted per dollar spent
projected over a lifetime horizon using a 3,5% annual discount rate. Results: A total of 157 RCT
including 267,508 patients and 176 active arms were considered. Compared with
sulfonylureas, SGLT2i, GLP1A and pioglitazone reduced the relative risk of non-fatal MACE with
HR of 0.81 (95% CI 0.69 to 0,96, p=0.011), 0.79 (95% CI 0.67 to 0,94, p=0.0039) and 0.73 (95%
CI 0.59 to 0.91, p=0.0057), respectively. Pioglitazone resulted in incremental effectiveness of
0.2339 DALYs averted per patient, at a mean incremental cost of Int$ 1660 and a Int$ 7,082
(95% CI: 4,521; 10,770) incremental cost per DALY averted, when compared to standard care.
The addition of SGLT2i or GLP1A led to more evident incremental effectiveness (0.261 and
0.259, respectively) but the incremental costs of these therapies headed to higher ICERs [Int$
12,061 (95% CI: 7,227; 18,121) and Int$ 29,119 (95% CI: 23,811; 35,367) per DALY averted,
respectively]. Compared to SGLT2i and GLP1A, pioglitazone had the highest probability of
being cost-effective based on the estimated maximum willingness-to-pay threshold.
Conclusions: The three therapies bear similar effectiveness in reducing cardiovascular events.
In a middle-income country, pioglitazone presents a higher probability of being cost-effective
followed by SGLT2i and then GLP1A.