Using Data From Routine Care to Estimate the Effectiveness and Potential Limitations of Outcomes-Based Contracts for Diabetes Medications.

OBJECTIVES: Outcomes-based contracts tie rebates and discounts for expensive drugs to outcomes. The objective was to estimate the utility of outcomes-based contracts for diabetes medications using real-world data and to identify methodologic limitations of this approach. METHODS: A population-based cohort study of adults newly prescribed a medication for diabetes with a publicly announced outcomes-based contract (ie, exenatide microspheres ["exenatide"], dulaglutide, or sitagliptin) was conducted. The comparison group included patients receiving canagliflozin or glipizide. The primary outcome was announced in the outcomes-based contract: the percentage of adults with a follow-up hemoglobin A1C <8% up to 1 year later. Secondary outcomes included the percentage of patients diagnosed with hypoglycemia and the cost of a 1-month supply. RESULTS: Thousands of adults newly filled prescriptions for exenatide (n = 5079), dulaglutide (n = 6966), sitagliptin (n = 40 752), canagliflozin (n = 16 404), or glipizide (n = 59 985). The percentage of adults subsequently achieving a hemoglobin A1C below 8% ranged from 83% (dulaglutide, sitagliptin) to 71% (canagliflozin). The rate of hypoglycemia was 25 per 1000 person-years for exenatide, 37 per 1000 person-years for dulaglutide, 28 per 1000 person-years for sitagliptin, 18 per 1000 person-years for canagliflozin, and 34 per 1000 person-years for glipizide. The cash price for a 1-month supply was $847 for exenatide, $859 for dulaglutide, $550 for sitagliptin, $608 for canagliflozin, and $14 for glipizide. CONCLUSION: Outcomes-based pricing of diabetes medications has the potential to lower the cost of medications, but using outcomes such as hemoglobin A1C may not be clinically meaningful because similar changes in A1C can be achieved with generic medications at a far lower cost.

Effectiveness, treatment durability, and treatment costs of canagliflozin and glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes in the USA.

Introduction: This real-world study compared glycemic effectiveness, treatment durability, and treatment costs with canagliflozin 300 mg versus any dose of glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes mellitus (T2DM) in the USA. Research design and methods: A retrospective cohort study using administrative claims and laboratory data (1 April 2012 to 28 February 2017) from the HealthCore Integrated Research Database were used to assess mean HbA1c at 3-month intervals, achievement of HbA1c thresholds (<7.0%, <8.0%, <9.0%), and treatment durability (ie, adherence, discontinuation, switching, treatment failure (ie, exceeding threshold (7.0%, 8.0%, 9.0%), having a prescription for a new antihyperglycemic agent)) in adults with T2DM who initiated canagliflozin 300 mg or any dose of a GLP-1 receptor agonist. Medication costs were calculated for adherent patients. Results: There were no significant differences in the primary outcome of HbA1c levels at 3-month intervals (≤12 months) in the canagliflozin 300 mg versus any dose GLP-1 receptor agonist cohort. The likelihood of achieving HbA1c<8.0% was not different (p=0.666), the likelihood of achieving HbA1c<7.0% was lower (p=0.016), and the likelihood of achieving HbA1c<9.0% was higher (p=0.020) in the canagliflozin 300 mg versus any dose GLP-1 receptor agonist cohort. The likelihood of treatment failure after reaching any HbA1c target was not different between cohorts. A higher proportion of patients were adherent to treatment (p<0.0001) and a lower proportion discontinued (p<0.0001) or switched medication (p=0.023) in the canagliflozin 300 mg versus any dose GLP-1 receptor agonist cohort. Over 1 year, medication costs were $1421 (p<0.001) lower with canagliflozin 300 mg than any dose of GLP-1 receptor agonists. Conclusions: This real-world, US-based study found that initiation of canagliflozin 300 mg versus any dose of a GLP-1 receptor agonist in patients with T2DM was not associated with significant differences in the primary outcome of HbA1c levels at 3-month intervals for up to 12 months after index, but showed better adherence, less discontinuation, and lower drug acquisition costs compared with initiation of any dose of a GLP-1 receptor agonist.

HBA1C CONTROL AND COST-EFFECTIVENESS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS INITIATED ON CANAGLIFLOZIN OR A GLUCAGON-LIKE PEPTIDE 1 RECEPTOR AGONIST IN A REAL-WORLD SETTING.

OBJECTIVE: To compare glycated hemoglobin (HbA1c) control and medication costs between patients with type 2 diabetes mellitus (T2DM) treated with canagliflozin 300 mg (CANA) or a glucagon-like peptide 1 receptor agonist (GLP-1 RA) in a real-world setting. METHODS: Adults with T2DM newly initiated on CANA or a GLP-1 RA (index date) were identified from IQVIA™ Real-World Data Electronic Medical Records U.S. database (March 29, 2012-April 30, 2016). Inverse probability of treatment weighting accounted for differences in baseline characteristics. HbA1c levels at 3-month intervals were compared using generalized estimating equations. Medication costs used wholesale acquisition costs. RESULTS: For both cohorts (CANA: n = 11,435; GLP-1 RA: n = 11,582), HbA1c levels decreased at 3 months postindex and remained lower through 30 months. Absolute changes in mean HbA1c from index to 3 months postindex for CANA and GLP-1 RA were -1.16% and -1.21% (patients with baseline HbA1c ≥7% [53 mmol/mol]); -1.54% and -1.51% (patients with baseline HbA1c ≥8% [64 mmol/mol]); and -2.13% and -1.99% (patients with baseline HbA1c ≥9% [75 mmol/mol]), respectively. Postindex, CANA patients with baseline HbA1c ≥7% had similar HbA1c levels at each interval versus GLP-1 RA patients, except 9 months (mean HbA1c, 7.75% [61 mmol/mol] vs. 7.86% [62 mmol/mol]; P = .0305). CANA patients with baseline HbA1c ≥8% and ≥9% had consistently lower HbA1c numerically versus GLP-1 RA patients and statistically lower HbA1c at 9 (baseline HbA1c ≥8% or ≥9%), 27, and 30 months (baseline HbA1c ≥9%). Continuous 12-month medication cost $3,326 less for CANA versus GLP-1 RA. CONCLUSION: This retrospective study demonstrated a similar evolution of HbA1c levels among CANA and GLP-1 RA patients in a real-world setting. Lower medication costs suggest CANA is economically dominant over GLP-1 RA (similar effectiveness, lower cost). ABBREVIATIONS: AHA = antihyperglycemic agent BMI = body mass index CANA = canagliflozin 300 mg DCSI = diabetes complications severity index eGFR = estimated glomerular filtration rate EMR = electronic medical record GLP-1 RA = glucagon-like peptide 1 receptor agonist HbA1c = glycated hemoglobin ICD-9-CM = International Classification of Diseases-Ninth Revision-Clinical Modification ICD-10-CM = International Classification of Diseases-Tenth Revision-Clinical Modification IPTW = inverse probability of treatment weighting ITT = intent-to-treat MPR = medication possession ratio PDC = proportion of days covered PS = propensity score PSM = propensity score matching Quan-CCI = Quan-Charlson comorbidity index SGLT2 = sodium-glucose cotransporter 2 T2DM = type 2 diabetes mellitus WAC = wholesale acquisition cost.

Evaluating the costs of glycemic response with canagliflozin versus dapagliflozin and empagliflozin as add-on to metformin in patients with type 2 diabetes mellitus in the United Arab Emirates.

OBJECTIVE: This study evaluates the cost of achieving glycemic control with three sodium glucose co-transporter 2 (SGLT2) inhibitors, canagliflozin, dapagliflozin, and empagliflozin, in patients with type 2 diabetes mellitus (T2DM) from the payer perspective in the United Arab Emirates (UAE). METHODS: A systematic literature review identified randomized controlled trials of antihyperglycemic agents as add-on to metformin in patients with T2DM of 26 ± 4 weeks in duration, published by 10 September 2014. A Bayesian network-meta analysis (NMA) compared HbA1c changes with canagliflozin 100 and 300 mg versus dapagliflozin 10 mg and empagliflozin 10 and 25 mg. The cost associated with a 1% placebo-adjusted HbA1c reduction with each SGLT2 inhibitor as add-on to metformin was calculated based on NMA results and UAE drug costs. RESULTS: In the NMA, canagliflozin 100 and 300 mg were associated with HbA1c reductions (-0.67% and -0.79%) compared with dapagliflozin 10 mg (-0.41%) and empagliflozin 10 and 25 mg (-0.57% and -0.64%). Probabilities of canagliflozin 100 mg performing better were 79%, 60%, and 53% versus dapagliflozin 10 mg and empagliflozin 10 and 25 mg, respectively; probabilities for canagliflozin 300 mg performing better were 88%, 72%, and 65%, respectively. The cost per 1%-point reduction in HbA1c was projected to be lower with canagliflozin 100 and 300 mg ($448 and $422) compared with dapagliflozin 10 mg ($785) and empagliflozin 10 and 25 mg ($527 and $563). CONCLUSIONS: Canagliflozin may provide a greater glycemic response at a lower effective cost than dapagliflozin or empagliflozin for patients with T2DM inadequately controlled with metformin from the payer perspective in the UAE.

Canagliflozin, dapagliflozin and empagliflozin monotherapy for treating type 2 diabetes: systematic review and economic evaluation.

BACKGROUND: Most people with type 2 diabetes are overweight, so initial treatment is aimed at reducing weight and increasing physical activity. Even modest weight loss can improve control of blood glucose. If drug treatment is necessary, the drug of first choice is metformin. However, some people cannot tolerate metformin, which causes diarrhoea in about 10%, and it cannot be used in people with renal impairment. This review appraises three of the newest class of drugs for monotherapy when metformin cannot be used, the sodium-glucose co-transporter 2 (SGLT2) inhibitors. OBJECTIVE: To review the clinical effectiveness and cost-effectiveness of dapagliflozin (Farxiga, Bristol-Myers Squibb, Luton, UK), canagliflozin (Invokana, Janssen, High Wycombe, UK) and empagliflozin (Jardiance, Merck & Co., Darmstadt, Germany), in monotherapy in people who cannot take metformin. SOURCES: MEDLINE (1946 to February 2015) and EMBASE (1974 to February 2015) for randomised controlled trials lasting 24 weeks or more. For adverse events, a wider range of studies was used. Three manufacturers provided submissions. METHODS: Systematic review and economic evaluation. A network meta-analysis was carried out involving the three SGLT2 inhibitors and key comparators. Critical appraisal of submissions from three manufacturers. RESULTS: We included three trials of dapagliflozin and two each for canagliflozin and empagliflozin. The trials were of good quality. The canagliflozin and dapagliflozin trials compared them with placebo, but the two empagliflozin trials included active comparators. All three drugs were shown to be effective in improving glycaemic control, promoting weight loss and lowering blood pressure (BP). LIMITATIONS: There were no head-to-head trials of the different flozins, and no long-term data on cardiovascular outcomes in this group of patients. Most trials were against placebo. The trials were done in patient groups that were not always comparable, for example in baseline glycated haemoglobin or body mass index. Data on elderly patients were lacking. CONCLUSIONS: Dapagliflozin, canagliflozin and empagliflozin are effective in improving glycaemic control, with added benefits of some reductions in BP and weight. Adverse effects are urinary and genital tract infections in a small proportion of users. In monotherapy, the three drugs do not appear cost-effective compared with gliclazide or pioglitazone, but may be competitive against sitagliptin (Januvia, Boehringer Ingelheim, Bracknell, UK). FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Cost-effectiveness of Canagliflozin versus Sitagliptin When Added to Metformin and Sulfonylurea in Type 2 Diabetes in Canada.

BackgroundCanagliflozin, an agent that inhibits sodium glucose co-transporter 2, is approved as add-on to metformin plus sulfonylurea for the treatment of type 2 diabetes in Canada. Canagliflozin offers greater glycemic control, as well as important additional benefits such as weight loss and blood pressure reductions, versus dipeptidyl peptidase-4 inhibitors such as sitagliptin.  ObjectiveThis analysis evaluated the cost-effectiveness of canagliflozin 300 mg and canagliflozin 100 mg versus sitagliptin 100 mg in patients with type 2 diabetes inadequately controlled on metformin plus sulfonylurea from the perspective of the Canadian Agency for Drugs and Technologies in Health. MethodsA 40-year cost-effectiveness analysis was performed using the validated Economic and Health Outcomes Model of Type 2 Diabetes Mellitus (ECHO-T2DM). Patient characteristics, treatment effects, and rates of hypoglycemia and adverse events were sourced from the canagliflozin clinical program. Canada-specific costs and utilities were applied. Sensitivity analyses were conducted using alternative values for key model inputs. ResultsBoth canagliflozin 300 and 100 mg dominated sitagliptin 100 mg over 40 years, providing quality-adjusted life-year gains of 0.31 and 0.28, and cost offsets of $2,217 and $2,560, respectively. Both canagliflozin doses dominated sitagliptin in each of the sensitivity analyses. ConclusionsSimulation results suggested that canagliflozin 300 and 100 mg provided better health outcomes and lower costs than sitagliptin 100 mg as a third-line therapy added-on to metformin and sulfonylurea in patients with type 2 diabetes in Canada.

Demographic and Clinical Profiles of Type 2 Diabetes Mellitus Patients Initiating Canagliflozin Versus DPP-4 Inhibitors in a Large U.S. Managed Care Population.

BACKGROUND: Canagliflozin is the first sodium-glucose co-transporter-2 (SGLT-2) inhibitor-a new class of oral antidiabetic (OAD) medication-approved for type 2 diabetes mellitus (T2DM) treatment in the United States. Approved less than 2 years ago, use of canagliflozin is largely uncharacterized. OBJECTIVE: To investigate and compare baseline demographic, clinical, and economic characteristics of patients initiating canagliflozin and dipeptidyl peptidase-4 (DPP-4) inhibitors in the real-world setting. METHODS: Using administrative claims data from a large, geographically diverse U.S. managed care organization, this retrospective study assessed adult T2DM patients (aged ≥ 18 years) initiating treatment with canagli-flozin or DPP-4 agents. Eligible patients had ≥1 medical claim with a T2DM diagnosis and ≥ 1 outpatient pharmacy claim for canagliflozin or a DPP-4 agent between January 1, 2011, and September 30, 2013. Patients with ≥ 1 canagliflozin fill were selected first and assigned to the canagliflozin cohort following a hierarchical approach; the date of the earliest canagliflozin fill was defined as the index date. Remaining patients with DPP-4 fills were then assigned to the DPP-4 cohort, with the index date as the first DPP-4 fill. Only patients with at least 12 months of pre-index (baseline) enrollment were included. Patients with fills for their cohort-defining drug over 3 months before the index date were excluded in order to focus on new initiators. A subset of patients with ≥ 3 months of continuous enrollment following their index dates was used to examine medication patterns after initiation. Patients with hyperglycemia; type 1, gestational, or nonclinical diabetes; or diabetes with hyperosmolar coma were excluded. Demographic, clinical, and economic characteristics were assessed over baseline and compared using two-sample t-tests or chi-square/Fisher's exact tests. Multivariable logistic regression models were built to assess baseline factors associated with initiation of canagliflozin versus DPP-4. RESULTS: Overall, 1,566 patients initiated canagliflozin, and 26,224 patients initiated DPP-4 treatment. Males constituted slightly more than 60% of each treatment group; mean age was approximately 55 years in each cohort. A significantly smaller proportion of canagliflozin patients (41.3%) initiated treatment with endocrinologists compared with DPP-4 patients (69.2%, P less than 0.001), and canagliflozin patients were more likely (29.4%) to initiate treatment with a primary care physician compared with DPP-4 patients (9.9%, P less than 0.001). Comorbidities were present more frequently in canagliflozin initiators: nephropathy (10.6% vs. 7.0%), retinopathy (10.4% vs. 7.5%), dyslipidemia (82.4% vs. 72.2%), and obesity (24.9% vs. 15.6%), respectively (P less than 0.001 for all comparisons). The mean (SD) Quan-Charlson Comorbidity Index score was greater for canagliflozin, 1.05 (1.7), compared with DPP-4 initiators, 0.92 (1.6), P = 0.002. Among the subset of patients with available hemoglobin A1c (A1c) results, a significantly smaller proportion of canagliflozin initiators (16.5%) versus DPP-4 initiators (26.7%) were at the A1c less than 7% treatment goal at baseline (P less than 0.001). Among patients with 3 months follow-up, 89.2% of canagliflozin and 75.1% of DPP-4 initiators had ≥ 1 fill for their index drugs over this time frame. Canagliflozin initiators had significantly greater baseline utilization of office visits, endocrinologist and outpatient services, and more prescription fills. Total diabetes-related medical costs at baseline ($3,025 vs. $3,477 for canagliflozin and DPP-4 initiators) were not significantly different, while mean diabetes-related pharmacy costs were higher in the canagliflozin group ($4,037 vs. $1,411, P less than 0.001). Regression analysis indicated that baseline insulin and glucagon-like peptide-1 use, as well as comorbid dyslipidemia and obesity, were significantly associated with the initiation of canagliflozin versus DPP-4 agents. CONCLUSIONS: In this sample of commercially insured patients within a large managed care plan, canagliflozin was often initiated as second- or third-line therapy, with a relatively high share of patients receiving concomitant antidiabetic injectables, compared with DPP-4 initiators. Canagliflozin initiators had highly elevated A1c levels and were frequently diagnosed with other metabolic conditions. Baseline pharmacy utilization and costs were higher among canagliflozin patients. Future research is needed to assess real-world clinical outcomes after canagliflozin initiation, while taking these baseline differences into account.

Economic simulation of canagliflozin and sitagliptin treatment outcomes in patients with type 2 diabetes mellitus with inadequate glycemic control.

OBJECTIVES: This study examines the association between changes in diabetes-related quality measures (QMs) (HbA1c, systolic and diastolic blood pressure [BP], low-density lipoprotein cholesterol [LDL-C], and body weight) and healthcare costs in Type 2 diabetes mellitus (T2DM) patients. It also performs an economic simulation that evaluates the cost implications of the changes in QMs and of the incidence rates (IRs) of adverse events (AEs) associated with canagliflozin (CANA) and sitagliptin (SITA) treatments in a real-world setting. METHODS: Health-insurance claims and electronic medical records from the Reliant Medical Group database (2007-2011) were used to identify adult patients with T2DM receiving metformin and sulfonylurea who did not achieve adequate glycemic control. The association between the changes in QMs and healthcare costs was evaluated using multivariate regression and non-parametric bootstrap methods. AE-related costs were taken from the literature. The cost impact of CANA and SITA outcomes was evaluated using the aforementioned costs and the changes in QMs and the IRs of AEs observed in a recent phase 3 trial comparing CANA and SITA as third oral agent (DIA3015). RESULTS: Eight hundred and fifty-six T2DM patients were identified (mean age = 65.8; female 45.4%). The regression analysis found that increases of 1 percentage point in HbA1C and 1% in systolic and diastolic BP, LDL-C, or weight were associated with a per patient per year (PPPY) cost increase of $4476 (p = 0.028) and $566 (p = 0.006), a decrease of $362 (p = 0.070) and $7 (p = 0.817), and an increase of $241 (p = 0.481), respectively. The economic simulation showed that changes in QMs and IRs of AEs equivalent to those reported in DIA3015 would be associated with a reduction in PPPY healthcare costs of $6061 (p = 0.036) for CANA and $2190 (p = 0.098) for SITA. CONCLUSIONS: This study suggests that integrated approaches that manage to control a combination of quality measures are most successful at reducing downstream healthcare costs.

Cost efficiency of canagliflozin versus sitagliptin for type 2 diabetes mellitus.

OBJECTIVES: To compare 1-year clinical outcomes and cost efficiency of treating adults with type 2 diabetes mellitus (T2DM) with canagliflozin (300 mg/day) or sitagliptin (100 mg/day), both added on a background of metformin and sulfonylurea. STUDY DESIGN: An economic model integrated data from an active-controlled, randomized trial, claims database analyses, and published literature. METHODS: The model adopted a US managed care payer perspective and included the clinical and economic impact of achieving specific clinical quality goals. The model was run separately for 2 single clinical quality metrics, glycated hemoglobin (A1C) < 7% (used as base case) or < 8%, and 4 composite metrics (A1C < 7% or < 8% combined with body mass index < 30 kg/m2 and blood pressure < 140/90 mm Hg or low-density lipoprotein cholesterol < 100 mg/dL). Cost savings of achieving versus not achieving metrics were derived from a claims database analysis. Drug and adverse event costs were included. RESULTS: In the base case, compared with sitagliptin 100 mg, treatment with canagliflozin 300 mg resulted in $215 in annual cost savings and 12.3 absolute percentage points more patients achieving goal. Similar findings were found across all other quality metrics (difference in proportion achieving goal ranging from 6.7% to 19.0% and annual savings ranging from $1 to $669). Canagliflozin remained cost saving versus sitagliptin in sensitivity analyses. CONCLUSIONS: Canagliflozin 300 mg may represent a cost-efficient T2DM treatment option versus sitagliptin 100 mg for patients on metformin plus sulfonylurea due to lower overall costs and better achievement of A1C and quality composite goals.