Safety and Efficacy Study of Canagliflozin in Older Patients
Introduction: This phase 3 study evaluated the safety and efficacy of canagliflozin in older patients with type 2 diabetes who were inadequately controlled on previous diabetes medications.
Methods: A total of 716 patients aged 55 to 80 years with hemoglobin A1C levels ≥7.0% to 10.0% were randomized to receive either canagliflozin 100 mg or 300 mg, or placebo for 26 weeks.
Results: Both the 100-mg and 300-mg dosage of canagliflozin were associated with significant reductions in A1C levels at week 26 compared with placebo (-0.60%, -0.73%, -0.03%, respectively; P<0.001). Both doses were also linked to a greater likelihood for achieving an A1C <7.0%, as well as reduced body weight, fasting plasma glucose level, and systolic blood pressure and increased high-density lipoprotein cholesterol level compared with placebo (P<0.001).
The incidence of adverse events was high in all three groups—72.2% and 78.0% for low and high-dose canagliflozin groups, and 73.4% for placebo. The rate of serious adverse events and treatment-related discontinuation was low in all groups with no significant between-group differences.
Both canagliflozin doses were linked to higher rates of genital mycotic infections in both men and women compared with placebo—with rates ranging from a high of 15.4% among women receiving 100 mg canagliflozin to a low of 3.2% among men receiving the same dose. These infections were generally mild to moderate in intensity and responded to standard treatments. Canagliflozin also was linked to slightly higher rates of urinary tract infections (5.8% and 8.1% with the 100-mg and 300-mg doses vs. 5.1% with placebo), pollakiuria (2.5% and 5.1% vs 2.1%), polyuria (1.7% for both doses vs 0 with placebo).
Among patients taking diabetes medications associated with hypoglycemia (n=529), the rate of reported hypoglycemia was higher in the canagliflozin groups (43.1% and 47.4%) compared with placebo (37.7%).
Conclusion: Canagliflozin had beneficial effects on glycemic control, body weight, and systolic blood pressure compared with placebo in a cohort of older patients whose diabetes was inadequately controlled on previous therapy. This agent was generally tolerated in this population.
In 2010 the Centers for Disease Control and Prevention estimated that 27% of Americans over the age of 65 had type 2 diabetes mellitus. The progression of diabetes over time mandates an escalation of therapy to achieve treatment goals. It also makes it so that older individuals frequently need multiple medications to keep their diabetes under control. With the introduction of multiple medications for type 2 diabetes into the U.S. market, there are many different combinations of medications that elderly patients may use for glycemic control.
In this study by Dr. Bode and colleagues, one of two canagliflozin doses or placebo was added to the current regimen of diabetes medications of elderly patients whose diabetes was not well controlled. Both doses of canagliflozin improved glycemic control, helped achieve reductions in body weight, and led to improvements in blood pressure and lipids. The incidence of hypoglycemia with the addition of canagliflozin in this trial is likely due to concomitant hypoglycemic medication use.
Elderly patients with metabolic disorders universally require polypharmacy to treat glycemia, lipids, and blood pressure. Therefore, the selection of medications must be based on comorbidities, the potential for drug-drug interactions, affordability, and a goal to simplify the medication regimen. Canagliflozin offers the unique benefit of helping across all metabolic derangements.
It is worth noting that this trial was conducted over a 26-week observation period. People with renal disease or established cardiovascular disease were excluded. The population studied was a relatively healthy older population. Thus, the addition of canagliflozin to the diabetes regimen must be done with caution in elderly people. Care should be given to adjust the doses of hypoglycemic agents to prevent hypoglycemia. In addition, patients should be forewarned and monitored, given the risk of complications from osmotic diuresis.