Objective: This study was conducted to describe a 10-year trend of the supplement from 2000 to 2009 and to evaluate age, gender and racial disparities using a national level health data. Design: Cross-sectional observational study. Setting and Participants: Data collected from patient visit records to stand-alone US ambulatory care clinics. Visits made by men and women who were 40 years of age and older were included (n=175,830). Measurements: Overall prevalence of recorded calcium and vitamin D use for osteoporosis prevention and treatment, and annual visit rates were estimated by age, gender, race, insurance types, physician specialties, geographical regions, and metropolitan status using chi square test. Multivariate logistic regression was conducted to determine potential predictive factors for calcium and vitamin D supplements. Results: An increase in yearly trend of calcium and vitamin D supplements was observed. The increase was proportional to patients' age (p<0.05) and female gender was a strong predictor of calcium and vitamin D supplement (p<0.0001). Visits made by blacks were significantly less likely to be associated with the supplement (p<0.05). Visits associated with self-pay and Medicaid was less likely to be recorded with vitamin D (p<0.05) but not calcium supplements. Osteoporosis diagnosis was an independent predictor of calcium and vitamin D records (p<0.0001). Conclusions: In spite of the observed increases in the trend of visits associated with calcium and vitamin D supplements, variability in the access to the medications was observed. More focused strategies targeting elderly, men, or black population are needed to maintain and improve adequate calcium and vitamin D supplements.

In Canada, the most commonly utilized oral third-line agent for patients with T2DM inadequately controlled on metformin (MET) and a sulfonylurea (SU) is sitagliptin (SITA). Canagliflozin (CANA), a novel agent that inhibits sodium glucose co-transporter 2 (SGLT2), has demonstrated HbA1c lowering, as well as improvements in weight and systolic blood pressure (SBP). The objective of this analysis was to evaluate the cost-effectiveness of CANA 100 and 300 mg versus SITA 100 mg in patients inadequately controlled on MET + SU in the Canadian setting. In accordance with the CADTH guidelines for economic evaluations, cost-utility analysis using ECHO-T2DM, a validated economic model, was done to simulate lifetime outcomes and costs of using CANA versus SITA in the third-line setting. Patient characteristics and treatment effects were sourced from a head-to-head study for the comparison of CANA 300 mg to SITA 100 mg. In the absence of a direct comparison of CANA 100 mg versus SITA 100 mg, relative treatment effects for this simulation were obtained from an indirect comparison via Bayesian network meta-analysis (NMA), with baseline patient characteristics sourced from a pooled analysis of two CANA trials (patients on background therapy of MET + SU) that contributed to the NMA. ECHO-T2DM was populated with Canadian costs and utility estimates relevant to the Canadian population. Using CANA 300 and 100 mg resulted in mean quality-adjusted life year (QALY) gains of 0.08 and 0.04, respectively, and lower costs of $2,035 and $981, respectively, compared to SITA over 40 years in patients failing to meet glycemic control on MET + SU. Therefore, CANA “dominated” SITA. CANA used as a third-line agent added on to MET + SU background therapy may result in better quality of life outcomes and lower costs when compared to SITA (the most common third-line agent in Canada).

People aged ≥65 years with T2DM contribute significantly to the increasing rate of health care utilization. CANA, an agent that inhibits sodium glucose co-transporter 2 (SGLT2), and SAXA, a dipeptidyl peptidase-4 inhibitor, have provided meaningful HbA1c reductions when used as monotherapy and as add-on to other antihyperglycemic agents in older patients. This analysis estimates the cost-effectiveness of CANA 100 or 300 mg versus SAXA 5 mg in patients with T2DM aged ≥65 years in the Canadian setting. ECHO-T2DM was used to simulate outcomes associated with using CANA versus SAXA as an add-on therapy in patients with T2DM aged ≥65 years. As head-to-head data were unavailable, an indirect comparison (IC) was performed using published data on SAXA 5 mg and results from a post hoc analysis of CANA data where possible (HbA1c and weight). IC estimates were calculated for those inadequately controlled on a mix of different background therapies (lifestyle intervention alone or combination with metformin, metformin plus sulfonylurea, or metformin plus pioglitazone). For other biomarkers (ie, cholesterol, systolic blood pressure) and adverse event rates, SAXA 5 mg values were assumed to be equal to those of placebo in the post hoc analysis. The post hoc dataset was also the source of the background patient characteristics. Costs and benefits were discounted at 5% and assessed from the Canadian perspective. Sensitivity analyses were performed. Both CANA 100 and 300 mg were dominant compared to SAXA 5 mg (lower net cost and greater quality-adjusted life-years [QALYs]). CANA 100 and 300 mg reduced costs (–$375 and –$771, respectively) and improved QALYs (0.033 and 0.057, respectively) over 40 years. Sensitivity analyses support these findings. These results suggest that using CANA in older individuals is cost-effective versus SAXA in Canada.

To assess the cost-effectiveness of CANA versus SITA in patients with T2DM inadequately controlled with metformin and sulfonylurea from the perspective of the Brazilian private healthcare system. The validated Economics and Health Outcomes Model of T2DM (ECHO-T2DM) was used to estimate the cost-effectiveness of CANA 100 and 300 mg versus SITA 100 mg added to metformin and sulfonylurea over a 20-year horizon. Patient characteristics were obtained from a pooled analysis of two CANA trials as add-on to metformin and sulfonylurea (DIA3002 and DIA3015). Efficacy and adverse event inputs were sourced from DIA3002 for CANA 100 mg and from DIA3002/DIA3015 for CANA 300 mg and SITA. Pharmaceutical costs were sourced from list prices; hospitalizations and resource use were from a medical claims database. Outcomes and costs were discounted at 5%. Sensitivity analyses were conducted that varied parameters relevant to the Brazilian setting, including using data from Latin American patients in CANA trials. CANA 100 and 300 mg were associated with QALY gains of 0.09 and 0.21 and mean cost increases of R$2,403 and R$2,947 relative to SITA. Non-medication cost offsets were seen with CANA 100 and 300 mg versus SITA (0.3% and 2.0%). CANA 100 mg was cost-effective per WHO criteria (<3 times the gross domestic product [GDP] per capita) and CANA 300 mg was very cost-effective (<1 times the GDP per capita) based on GDP per capita (R$26,082), with incremental cost-effectiveness ratios of R$27,755 and R$13,904 per QALY gained, respectively. The cost-effectiveness of CANA versus SITA was robust to different specifications in the sensitivity analyses. These Resultssuggest that adding CANA 100 or 300 mg versus SITA in patients with T2DM inadequately controlled on metformin and sulfonylurea would be a more efficient use of healthcare resources in Brazil.

Differences in the frequency and severity of hypoglycemic episodes associated with alternative treatments often contribute significantly to differences in QALYs (the denominator of the cost-effectiveness ratio). The 2013 T2DM CADTH report examining third-line therapy used disutility values from studies conducted before 2009 based on small samples. A new study with over 1,600 individuals with T2DM (including Canadian respondents) found disutility estimates that were meaningfully greater (e.g. 0.005 versus 0.000004767 per non-severe hypoglycemic event). This analysis examined the impact of these alternative estimates on QALYs in an evaluation of canagliflozin 300mg versus sitagliptin 100mg in patients inadequately controlled on MET+SU. Two 40-year simulations were performed using a validated economic model (ECHO-T2DM), differing only in the hypoglycemia disutility weights: (A) CADTH and (B) new estimates. Disutilities for T2DM-related complications and other adverse events were sourced from the literature. Data for patient characteristics, treatment effects (i.e. A1C, SBP, BMI, and cholesterol), and rates of adverse events were obtained from a previously reported 52-week trial, where canagliflozin 300mg demonstrated statistically superior A1C-lowering, as well as reductions in blood pressure and weight versus sitagliptin 100mg. Hypoglycemic event rates were similar. In the simulations, insulin (which has an excess risk of hypoglycemia) was added and titrated as necessary to maintain A1C < 7.0%. Discounted QALYs for canagliflozin and sitagliptin were (A) 8.4 and 8.32; (B) 7.91 and 7.81. The higher QALYs associated with canagliflozin versus sitagliptin are largely attributable to the delay in the need for insulin for canagliflozin-treated patients. The contribution of hypoglycemic events to these total QALY differences was greater in scenario B (20.8%) than scenario A (2.3%). These results illustrate the need to carefully consider downstream assumptions in economic evaluations. Using the older values yielded 20% fewer net QALYs, implying that the corresponding ICER would be approximately 25% greater.

CANA and DAPA are sodium glucose co-transporter 2 inhibitors indicated for the treatment of adults with T2DM as monotherapy and as add-on combination therapy with other antihyperglycemic agents. The objective of this analysis was to evaluate the cost-effectiveness of using CANA 300mg versus using DAPA 10mg in dual therapy (with MET background) in patients with inadequate A1C control. A validated health economics model, Economic and Health Outcomes (ECHO)–T2DM, was used to estimate 30-year outcomes associated with using each treatment in patients as an add-on to MET monotherapy. Treatment effects for A1C, weight and the probability of hypoglycemia were obtained from a Bayesian Network Meta-Analysis (NMA) of 52 (+/-4) week trials of subjects inadequately controlled on MET monotherapy. For parameters unavailable in the NMA (i.e., SBP, LDL, HDL and rates of AEs), values were obtained from a post-hoc analysis of pooled data from two trials of subjects receiving CANA and MET. In the model, treatment was intensified when A1C exceeded 7.5%, first by adding basal insulin and subsequently by adding prandial insulin. Utility decrements and U.S. costs associated with key macrovascular and microvascular heath states and AEs were sourced from the literature. All costs and benefits were discounted at 3%. CANA dominated DAPA; CANA was associated with both cost savings ($3,204) and more Quality Adjusted Life Years (0.22). The reductions in the relative risks of microvascular (up to 4.4%) and macrovascular events (up to 1.7%) as well as a delay in the use of insulin are the key drivers. This simulation suggests that CANA will not only produce cost-savings, but also result in QALY gains versus DAPA in the treatment of patients inadequately controlled on MET in the US.

Canagliflozin (CANA) is a novel inhibitor of the sodium glucose co-transporter 2 in development for treating patients with type 2 diabetes mellitus (T2DM). In a previously reported randomized, double-blind, 4 arm parallel group (placebo, CANA 100mg, CANA 300mg and sitagliptin 100mg [SITA]) study of 1284 subjects inadequately controlled on MET monotherapy, CANA 100mg and 300mg significantly decreased HbA1c versus placebo after 26 weeks of therapy by 0.62% and 0.77%, respectively; SITA decreased HbA1cversus placebo by 0.65%. In this trial, both CANA doses and SITA significantly reduced systolic blood pressure (CANA 100mg: 5.36 mmHg; CANA 300mg: 6.58 mmHg; SITA 3.34 mmHg), however, only CANA significantly reduced body weight (CANA 100mg: 2.5%; CANA 300mg: 2.9%) versus placebo. The objective of this study was to simulate the health outcomes and associated costs attributable to using CANA versus SITA in Mexico. Forty-year outcomes associated with adding CANA 100mg or CANA 300mg versus SITA to MET were simulated using ECHO (Economic and Health Outcomes)-T2DM, a validated micro-simulation model. Treatment effects and patient characteristics were sourced from the trial. Simulated treatment was intensified when HbA1cexceeded 7.5% by adding basal insulin, and subsequently prandial insulin. Disutilities associated with micro- and macro-vascular events were obtained from the literature and costs were adapted to the Mexican setting. Using CANA 300mg versus SITA was projected to reduce relative risks for key events (e.g. myocardial infarction 10.2%; congestive heart failure 6.6%; macroalbuminuria 6.6%; microalbuminuria 6.2%), improve QALYs (0.046), and result in lower costs per patient ($1927MXN). Simulation results of CANA 100mg versus SITA were generally similar, albeit estimates of reductions in relative risks, QALY gains and associated costs differences were smaller. These simulations suggest that using CANA versus SITA as an add-on to MET could result in improved outcomes and reduced costs in Mexico.