Clinical evidence on dapagliflozin's safety in older adults
Numerous large-scale, placebo-controlled trials have provided robust evidence on the safety and efficacy of dapagliflozin across different age groups. The findings from these studies generally indicate that dapagliflozin is well-tolerated in older patients when used appropriately, although certain age-related risks must be managed carefully.
Key clinical trials and findings:
- DECLARE-TIMI 58: A significant cardiovascular outcomes trial that included a large cohort of elderly and very elderly patients (up to age 94). This study confirmed consistent cardiovascular and renal benefits of dapagliflozin across age subgroups, with no significant increase in major adverse cardiovascular events (MACE). Safety outcomes, including fractures, volume depletion, and urinary tract infections, were balanced between dapagliflozin and placebo groups regardless of age.
- DAPA-HF: This trial focused on patients with heart failure with reduced ejection fraction (HFrEF), with 21% of participants being over 75 years of age. The results showed that dapagliflozin reduced the risk of death and worsening heart failure and improved symptoms consistently across the broad age spectrum studied. Tolerability and safety were comparable in older and younger patients, refuting concerns that frail elderly patients cannot tolerate or benefit from this treatment.
- DELIVER: This study extended the findings to patients with heart failure with preserved or mildly reduced ejection fraction (HFpEF/HFmrEF), with a mean patient age of 71.7 years and over 40% aged 75 or older. Dapagliflozin consistently reduced the risk of cardiovascular death or worsening heart failure events across all age categories, with a safety profile comparable to younger patients.
- Pooled analyses and real-world studies: A pooled analysis of multiple phase III studies found that while overall adverse events and discontinuations were more common in older patients (as is typical), serious adverse event frequency was similar between treatment groups across all ages. A recent study focusing specifically on elderly chronic kidney disease (CKD) patients found that dapagliflozin was safe and effective, improving renal and liver function without negatively affecting muscle mass or strength.
Potential side effects and specific considerations for older adults
While generally well-tolerated, older adults using dapagliflozin require specific monitoring due to physiological changes and the potential for exacerbated side effects.
Common side effects and risks:
- Genitourinary infections: The mechanism of dapagliflozin increases glucose excretion in the urine, which can lead to a higher risk of genital fungal infections and, less commonly, urinary tract infections (UTIs). In older adults, especially females, this risk is a concern and may require closer monitoring or treatment.
- Volume depletion and hypotension: The diuretic effect of dapagliflozin can cause loss of body water and salt, leading to dehydration and low blood pressure (hypotension). This risk is heightened in older patients, particularly those with pre-existing kidney problems or those also taking loop diuretics. Dizziness or lightheadedness upon standing may occur and necessitate careful monitoring of volume status and renal function.
- Renal function changes: Initial, transient increases in serum creatinine are common with dapagliflozin and can be more frequent in older patients. However, this typically stabilizes and does not negate the long-term renal protective benefits of the drug. Continuous monitoring of renal function is advisable.
- Hypoglycemia: When used alone, dapagliflozin has a low intrinsic risk of causing low blood sugar. However, this risk increases significantly when combined with insulin or sulfonylureas, which is a common scenario in older patients. Dose adjustments of concomitant diabetes medications may be needed.
- Diabetic ketoacidosis (DKA): A rare but serious side effect, DKA can occur even with normal blood sugar levels (euglycemic DKA) in patients taking SGLT2 inhibitors. Elderly and frail patients with poor fluid intake are at higher risk. Signs include fruity-smelling breath, stomach pain, nausea, and vomiting.
Comparison of Dapagliflozin vs. Placebo in Older Adults (Pooled Trial Data)
| Side Effect / Event | Dapagliflozin (≥65 years) | Placebo (≥65 years) | Notes | References |
|---|---|---|---|---|
| Overall Adverse Events | 77.4% | 73.1% | More common in older vs. younger patients, but serious AE frequency was similar between groups. | |
| Discontinuation due to AEs | 14.4% | 12.2% | Discontinuations increased with age but were not significantly imbalanced vs. placebo in trials. | |
| Genital Infections | 6.6% | 0.9% | More common with dapagliflozin, but not increased in older vs. younger patients. | |
| Hypoglycemia | 20.2% | 17.7% | Rates were similar across age groups and higher with dapagliflozin vs. placebo when combined with insulin/sulfonylureas. | |
| Urinary Tract Infections | 8.1% | 7.6% | No significant difference observed in older patients vs. placebo in some studies. | |
| Renal AEs | 14.0% | 7.9% | More frequent with dapagliflozin; majority were non-serious, transient creatinine changes. | |
| Volume Depletion AEs | 2.3% | 1.7% | Uncommonly reported; slightly higher frequency with dapagliflozin vs. placebo. | |
| Cardiovascular Outcomes | Consistent benefit across age groups. | N/A | Benefits regarding HF hospitalization and CV death consistent in older patients. |
Practical considerations for managing dapagliflozin in older patients
Given the increased potential for side effects in older adults, a cautious and individualized approach to treatment is recommended.
- Initial assessment: A thorough evaluation of renal function and volume status should be conducted before starting dapagliflozin. For frail elderly patients, close monitoring is particularly important.
- Hydration: Maintaining adequate fluid intake is crucial to minimize the risk of dehydration, especially in those with limited fluid intake or who are on diuretics.
- Individualized dosing: Treatment plans should be tailored to each patient's overall health, existing comorbidities, and other medications to minimize risks and maximize benefits.
- Drug interactions: Older patients often take multiple medications (polypharmacy), increasing the risk of drug interactions. A comprehensive review of all medications is essential.
- Patient education: Educating patients and their caregivers on the signs and symptoms of dehydration, genitourinary infections, and ketoacidosis is vital for early detection and intervention.
- Monitoring: Regular follow-up visits are essential to monitor for adverse effects and assess the treatment's efficacy and safety over time.
Conclusion
Is dapagliflozin safe for older adults? Yes, based on extensive clinical trial data, dapagliflozin has demonstrated consistent efficacy and a generally manageable safety profile in older adults with conditions like heart failure, chronic kidney disease, and type 2 diabetes. However, its use requires a cautious and individualized approach, with particular attention to potential age-related risks such as dehydration, hypotension, and genitourinary infections. Close monitoring, proactive patient education, and careful management of comorbidities and polypharmacy are essential to ensure the safe and effective use of dapagliflozin in this population.
Key takeaways
- Consistent Efficacy and Safety: Clinical trials like DAPA-HF and DELIVER have shown that dapagliflozin's benefits are consistent across age groups, including older adults.
- Increased Risk of Specific Side Effects: Older adults have a higher risk of certain side effects, such as volume depletion, hypotension, and genitourinary infections.
- Renal Function Monitoring is Crucial: While beneficial for renal outcomes, dapagliflozin can cause transient changes in serum creatinine, necessitating regular monitoring.
- Low Hypoglycemia Risk (Alone): Dapagliflozin has a low inherent risk of hypoglycemia, but this risk increases when used with insulin or sulfonylureas.
- Individualized Care is Key: A personalized approach, considering comorbidities and polypharmacy, is essential for maximizing benefits and minimizing risks in older patients.
- Education and Hydration are Vital: Patient education on potential side effects and the importance of adequate fluid intake is critical for safe management.
