Canagliflozin Reduces Hospitalizations

Canagliflozin, an SGLT2 inhibitor, and its impact in reducing hospitalizations and health care costs in people with type 2 diabetes.  

The rise in hospitalizations related to type 2 diabetes places a significant burden on patients and providers. A previous study found that preventable hospitalizations related to diabetes did not significantly differ between 2005 and 2014, resulting from increasing short-term complications. While large randomized controlled trials have shown the impact SGLT2 inhibitors have on reducing cardiovascular events and heart failure hospitalizations, these medications have significant adverse events, such as hypotensive events, resulting in more hospitalizations. A different analysis found that multiple hospitalizations were common in groups of people covered under Medicare or Medicaid and those living in lower-income communities. In addition, 90% of adults had cardiovascular disease, and more than 60% of children had acute complications, contributing to increased hospital utilization and costs. For this reason, reducing hospitalizations in patients with type 2 diabetes is a high priority for clinicians in the health care field.  

The CANVAS program consisted of two randomized controlled trials (CANVAS and CANVAS-R) and evaluated canagliflozin, an SGLT2 inhibitor, for cardiovascular, kidney, and safety outcomes. In this current study, the researchers aimed to explore the reasons for hospitalizations in patients taking canagliflozin or placebo with or without cardiovascular disease. Patients aged 50 years or older were included in the primary prevention cohort if they had two or more risk factors for cardiovascular events with no prior cardiovascular event. Patients aged 30 years and older were included in the secondary prevention cohort if they had type 2 diabetes (HbA1c between 7 and 10.5%) and a documented cardiovascular event such as stroke or myocardial infarction. In CANVAS, patients were randomized in a 1:1:1 ratio to receive canagliflozin 100mg daily, canagliflozin 300mg daily, or a placebo. In CANVAS-R, patients were randomized in a 1:1 ratio to receive either canagliflozin 100mg daily or placebo and had an increased dose of 300mg at week 13. This study included patients taking canagliflozin regardless of dose without equal randomization. The primary outcome was the rate of total hospitalizations obtained from adverse event reporting. Categorical variables were analyzed as well as continuous variables using the intention-to-treat analysis. Negative binomial models were utilized to analyze the rate of total hospitalizations.  

Of the 10,142 participants enrolled in the CANVAS program, many hospitalized patients were older, male, had microvascular complications, had a longer duration of diabetes or cardiovascular disease, and used insulin. Cardiac disorders (23.7%) made up most hospitalizations, followed by infections (15%). Patients in the canagliflozin group had lower hospitalizations than the placebo group due to cardiac disorders ([HR 0.82; 95% CI 0.72, 0.94]).  

This secondary analysis of the CANVAS program showed that compared with placebo, canagliflozin was shown to reduce the rate of hospitalizations due to cardiac disorders significantly. The rate of hospitalizations due to infections were not significantly reduced. While the time to first hospitalizations was not significant between canagliflozin and placebo groups, the total rate of hospitalizations was reduced by canagliflozin. This study showed consistent results with previous studies, showing that 34% of patients were hospitalized primarily due to diabetes. In addition, 75% of participants took a statin medication, recommended in patients with diabetes and a history of cardiovascular events. While this study is the first to assess the hospitalization in patients taking an SGLT2 inhibitor such as canagliflozin, this trial was not powered to show differences in hospitalizations for specific reasons. The duration of hospital stay was not shown, so the severity of hospitalizations between the canagliflozin and placebo groups was unknown. It is necessary to reduce diabetes-related complications to decrease the number of total hospitalizations. Mitigating total hospitalizations in those with diabetes is a priority to reduce rising costs for the patient and healthcare system. This study showed that canagliflozin reduced hospitalizations in patients with type 2 diabetes; however, further studies should analyze the mechanism canagliflozin has on reducing hospitalizations. 

Practice Pearls:  

• The rate of hospitalizations among patients with type 2 diabetes has not improved over the last ten years due to short-term complications of diabetes.  
• A secondary analysis performed on the CANVAS program in patients with type 2 diabetes found that cardiac disorders were the most common reason for hospitalizations. 
• This analysis also found that canagliflozin, an SGLT2 inhibitor, reduced hospitalizations, which can significantly impact the healthcare field in reducing costs and mortality rates.    

Rubens, Muni et al. “Trends in Diabetes-Related Preventable Hospitalizations in the U.S., 2005-2014.” Diabetes Care. 

Scheen, André J. “SGLT2 Inhibitors: Benefit/Risk Balance.” Current diabetes reports. 

Jiang, H Joanna et al. “Multiple hospitalizations for patients with diabetes.” Diabetes Care. 

Feng, Kent Y et al. “Reasons for hospitalizations in patients with type 2 diabetes in the CANVAS program: A secondary analysis.” Diabetes, obesity & metabolism.   

Dalia Elabed, PharmD Candidate 2022, University of South Florida Taneja College of Pharmacy