Article Text

Effectiveness, treatment durability, and treatment costs of canagliflozin and glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes in the USA
1. Mukul Singhal1,
2. Hiangkiat Tan1,
3. Craig I Coleman2,
4. Michelle Han3,
5. Chi Nguyen1,
6. Michael Ingham3
1. 1HealthCore, Wilmington, Delaware, USA
2. 2University of Connecticut School of Pharmacy, Storrs, Connecticut, USA
3. 3Janssen Scientific Affairs, LLC, Titusville, New Jersey, USA
1. Correspondence to Mr Michael Ingham; mingham2{at}its.jnj.com

## Abstract

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.

## Discussion

The current study, which used both claims and laboratory results from the HIRD, adds to the existing literature on the real-world effectiveness and costs related to treatment with canagliflozin 300 mg versus GLP-1 receptor agonists at any dose in patients with T2DM. Our findings showed no significant differences in HbA1c levels over time (at 3-month intervals over 12 months) with canagliflozin 300 mg and any dose of GLP-1 receptor agonists, as well as no significant difference in achieving secondary outcome of HbA1c<8.0%, but a lower and higher likelihood of achieving HbA1c<7.0% and HbA1c<9.0%, respectively, greater adherence, less discontinuation, and lower medication costs.

Although the recommended starting dose of canagliflozin is 100 mg,21 approximately one-third of patients in the real world are initiated on canagliflozin 300 mg and approximately two-thirds of patients are on canagliflozin 300 mg within 9 to 12 months, reflecting widespread real-world use of canagliflozin 300 mg.22 23 Findings from our study of claims and laboratory data showed similar patterns of HbA1c over time with canagliflozin 300 mg and any dose of GLP-1 receptor agonists regardless of baseline HbA1c, which is consistent with previous real-world studies.13 24–26 We found that at any time during follow-up, there was no difference in the likelihood of achieving HbA1c<8.0% (HEDIS quality measure) with canagliflozin 300 mg versus any dose of a GLP-1 receptor agonist. Patients were less likely to achieve HbA1c<7.0% and more likely to achieve HbA1c<9.0% with canagliflozin 300 mg. Some differences in HbA1c target attainment with canagliflozin 300 mg and GLP-1 receptor agonists have been observed in a prior study. In that study, an analysis of the IQVIA Real-World Data EMR—US database found that patients initiated on canagliflozin 300 mg versus a GLP-1 receptor agonist were less likely to achieve HbA1c<7.0%, but no differentiation was observed in achievement of HbA1c<8.0% and <9.0%.25 26 Differences in patient characteristics and sample size, the use of additional AHAs in intent-to-treat analyses and follow-up time across studies may explain some of the variation in the achievement of HbA1c<9.0%.

A greater proportion of patients were adherent to treatment with canagliflozin 300 mg versus any dose of a GLP-1 receptor agonist, as measured by the proportion of days covered, and, on average, patients in the canagliflozin 300 mg cohort had more days covered by the index medication than those in the any dose GLP-1 receptor agonist cohort. The rate of discontinuation of index medication was lower with canagliflozin 300 mg versus any dose of GLP-1 receptor agonists, and patients who discontinued index medication were treated longer with canagliflozin 300 mg versus a GLP-1 receptor agonist at any dose before discontinuation. The greater adherence and lower rate of discontinuation seen with canagliflozin 300 mg versus any dose of GLP-1 receptor agonists in this study are consistent with observations from prior real-world studies which showed greater adherence with canagliflozin 100 and 300 mg versus a GLP-1 receptor agonist (medication possession ratio: 0.72–0.92 vs 0.33–0.67; proportion of days covered: 0.71–0.81 vs 0.33–0.58, respectively) and a 30% lower rate of discontinuation with canagliflozin 300 mg versus a GLP-1 receptor agonist.26–28 A possible explanation for the better adherence to treatment with canagliflozin 300 mg versus any dose of a GLP-1 receptor agonist may be its mode of administration (ie, oral vs injection). Medication acquisition costs could also play a role in adherence to treatment.

In the current study, we found that the proportion of patients adding a new AHA was not different between cohorts; however, more patients in the any dose GLP-1 receptor agonist cohort initiated insulin compared with the canagliflozin 300 mg cohort. Furthermore, once patients achieved the glycemic target, those initiating canagliflozin 300 mg versus any dose of a GLP-1 receptor agonist had a similar likelihood of treatment failure, defined as the composite outcome of the prescription of a new non-index AHA or having HbA1c above target. This is in contrast to a previous real-world analysis showing that a lower proportion of patients treated with canagliflozin 300 mg versus a GLP-1 receptor agonist initiated a new AHA or failed treatment.26

Our real-world data suggest that treatment with canagliflozin 300 mg versus any dose of a GLP-1 receptor agonist may be a suitable choice for achieving the triple aim of diabetes care (improving the patient experience of care, improving the health of populations, and reducing the cost of healthcare29). The results of this study highlight the potential impact of the lower adherence and persistence to GLP-1 receptor agonists as used in actual practice, as those on canagliflozin 300 mg remained on treatment longer, with fewer add-on medications, and no differences in HbA1c reductions at 3-month intervals. Furthermore, the real-world glycemic effectiveness of canagliflozin 300 mg versus any dose of a GLP-1 receptor agonist is potentially achieved with lower overall medication costs. This may be helpful to inform clinical decisions regarding the choice of AHA medications.

Our study was strengthened by the use of the HIRD, which contains fully adjudicated claims information on filled prescriptions and laboratory data for about one-third of patients with claims data. The current findings support those of a similar real-world study that showed no difference in HbA1c reductions and lower medication costs with canagliflozin 300 mg versus GLP-1 receptor agonists (IQVIA Real-World Data Electronic Medical Records—US database), but with more accurate adherence and persistence data as adjudicated prescription information was used instead of electronic medical records data, which may overestimate adherence and persistence.13 Our study was also strengthened by the use of the propensity score method, which reduced the potential bias due to dissimilar patient populations by controlling for differences in baseline characteristics.

### Limitations

Due to approval dates and sample sizes, this analysis focused on canagliflozin only and did not include other SGLT2 inhibitors. Another limitation is that patients were required to initiate canagliflozin 300 mg rather than canagliflozin 100 mg, which is not consistent with the prescribing information.21 However, it is known that approximately one-third of patients in the real world are initiated on canagliflozin 300 mg.23 Furthermore, this study compared patients who initiated the highest dose of canagliflozin (300 mg) with those who initiated any dose of a GLP-1 receptor agonist, as the patients may be comparable in terms of disease severity and prior line of therapy. Data from a previous real-world study comparing canagliflozin versus GLP-1 receptor agonists found that most outcomes were generally similar for patients initiated on canagliflozin 100 mg (vs 300 mg).26 Additionally, a prescription claim does not ensure that the medication was taken as prescribed and does not reflect the potential for use of medication samples (ie, the use of canagliflozin 100 mg samples prior to a prescription for canagliflozin 300 mg). Another limitation is that only ~33% of the population in the HIRD had laboratory data, and these patients may not be representative of the overall database. Furthermore, because all patients were commercially insured or had Medicare Advantage insurance, these results may not be generalizable beyond the US managed care population. In addition, interpretation of the novel composite endpoint based on exceeding HbA1c targets and initiation of a new AHA may not fully capture all possible aspects that could be used to define treatment failure. Similar to other retrospective analyses, this study is subject to possible measurement (ie, diagnosis coding) errors and residual confounding for variables that may differentially impact outcomes but are not available for use in the inverse probability of treatment weighting balancing methods. Additionally, this study was designed to assess effectiveness and treatment durability; therefore, safety data, including hypoglycemia, were not available. Lastly, the cost-effectiveness analysis used non-rebate prices, and may not reflect the amount actually paid by patients and health systems.

## Conclusion

This real-world, US-based study demonstrated that initiation of canagliflozin 300 mg versus initiation of any dose of a GLP-1 receptor agonist resulted in no difference in HbA1c values up to 12 months after index at 3-month intervals, with no difference in achievement of HbA1c<8.0%, better achievement of HbA1c<9.0%, and worse achievement of HbA1c<7.0%, but with better adherence, less discontinuation, and lower drug acquisition costs when fully adherent in patients with T2DM.

## Acknowledgments

The authors would like to thank Jennifer Cai, MS, MPH, for her contributions to this study. Medical writing support was provided by Dana Tabor, PhD, of MedErgy, and was funded by Janssen Scientific Affairs, LLC.

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## Footnotes

• Presented at This study was presented, in part, in abstract form at the 78th Scientific Sessions of the American Diabetes Association from 22 to 26 June 2018 in Orlando, Florida.

• Contributors MS, HT, and CN contributed to study design, data analysis and interpretation, and manuscript development. CIC, MH, and MI contributed to study design, data interpretation, and manuscript development. All authors approved the final manuscript for submission.

• Funding This work was supported by Janssen Scientific Affairs, LLC. Canagliflozin has been developed by Janssen Research & Development, LLC, in collaboration with Mitsubishi Tanabe Pharma Corporation.

• Competing interests MS, HT, and CN are employees of HealthCore, which received funding from Janssen Scientific Affairs, LLC, to conduct this study. CIC has received research support from Janssen Pharmaceuticals, Inc., Bayer AG, and Boehringer Ingelheim Pharmaceuticals, Inc. MH and MI are employees of Janssen Scientific Affairs, LLC.

• Patient consent for publication Not required.

• Provenance and peer review Not commissioned; externally peer reviewed.

• Data availability statement No data are available.