Which of the following is a concern when using SGLT2 inhibitors in an elderly patient?

As the use of SGLT2 inhibitors expands to older patients for their significant cardiorenal benefits, it's crucial to address potential side effects. Knowing which of the following is a concern when using SGLT2 inhibitors in an elderly patient helps clinicians balance benefits against risks and implement proper monitoring strategies.

Quick Summary

The main concerns for older patients on SGLT2 inhibitors include an increased risk of dehydration, genitourinary infections, and potentially serious euglycemic diabetic ketoacidosis, particularly with comorbid conditions.

Key Points

• Dehydration and Volume Depletion: The osmotic diuretic effect of SGLT2 inhibitors can cause dehydration, especially in older adults, those with heart failure, or patients taking concomitant diuretics, increasing the risk of falls and orthostatic hypotension.

• Genitourinary Infections: Increased glucose excretion can lead to a higher incidence of genital mycotic infections, a class effect of SGLT2 inhibitors, and potentially a higher risk of UTIs in some older patients, especially women.

• Euglycemic Diabetic Ketoacidosis (DKA): A rare but serious concern, where ketoacidosis occurs with near-normal blood glucose levels. Older adults, especially those who are frail or on insulin, should be educated on the symptoms and 'sick day' management.

• Hypoglycemia Risk: While low with monotherapy, the risk of hypoglycemia increases when SGLT2 inhibitors are combined with insulin or sulfonylureas, requiring careful dose adjustments.

• Monitoring is Key: Individualized patient assessment, baseline renal function checks, and ongoing monitoring for side effects, including volume status, are crucial for safe SGLT2 inhibitor use in the elderly.

• Fracture Risk Debate: The link between SGLT2 inhibitors and fracture risk is debated, with most recent data suggesting no increased class risk, but volume depletion leading to falls remains a concern.

• Polypharmacy Interactions: Elderly patients on multiple medications, particularly diuretics or RAAS inhibitors, are at higher risk for adverse effects like volume depletion, requiring careful management.

Understanding SGLT2 Inhibitors and the Elderly

SGLT2 inhibitors are a class of medications that work by blocking the reabsorption of glucose in the kidneys, leading to its excretion in the urine. This action not only lowers blood glucose levels but also provides important cardiovascular and renal protective benefits, which are especially valuable in an aging population often affected by heart failure and chronic kidney disease. However, the same mechanism of action can create specific risks that require careful consideration in elderly and frail patients.

Major Concerns When Prescribing SGLT2 Inhibitors

Volume Depletion and Dehydration

One of the most significant concerns for older patients is the increased risk of volume depletion, which can lead to dehydration. The osmotic diuresis caused by SGLT2 inhibitors means more fluid is excreted, which can be problematic for elderly individuals who may have a diminished sense of thirst, reduced fluid intake, or are already volume-depleted due to comorbidities like heart failure. This effect is magnified in patients also taking diuretics or those with reduced renal function.

Potential Consequences of Dehydration:

• Orthostatic Hypotension: The drop in blood volume can cause dizziness or lightheadedness upon standing, increasing the risk of falls.
• Falls and Fractures: Falls are a major risk in the elderly, and the combination of dehydration and hypotension can exacerbate this danger.
• Acute Kidney Injury (AKI): While SGLT2 inhibitors often have a long-term renoprotective effect, the initial volume contraction can cause a transient dip in kidney function. In the presence of dehydration, this can theoretically increase the risk of AKI, though overall data suggests a net protective effect.

Increased Risk of Genitourinary Infections

The increased urinary glucose excretion creates a nutrient-rich environment for bacteria and fungi, raising the risk of infections. This is particularly relevant for older patients, especially women, who are already at a higher baseline risk for these types of infections.

Types of Infections:

• Genital Mycotic Infections: Fungal infections, such as vulvovaginal candidiasis in women or balanitis in men, are a well-documented class effect of SGLT2 inhibitors.
• Urinary Tract Infections (UTIs): The association with UTIs is less clear. While some early reports raised concerns, large clinical trials and meta-analyses have found no significantly increased risk of serious UTIs with the class as a whole, although an increased risk with specific agents like dapagliflozin has been noted. However, UTIs in the elderly can present with atypical symptoms like delirium and should not be underestimated.
• Fournier's Gangrene: A rare but life-threatening necrotizing fasciitis of the perineum has been reported with SGLT2 inhibitor use, emphasizing the need for vigilance.

Euglycemic Diabetic Ketoacidosis (DKA)

Euglycemic DKA is a rare but serious complication where patients develop ketoacidosis with relatively normal or only mildly elevated blood glucose levels. It is more commonly reported in Type 1 diabetes but can occur in older adults with Type 2 diabetes who are on SGLT2 inhibitors, especially in the context of precipitating factors like acute illness, surgery, or significant fluid loss. The diagnosis can be challenging because the classic sign of severe hyperglycemia is absent.

Hypoglycemia Risk

When used as a monotherapy, SGLT2 inhibitors carry a low risk of hypoglycemia because their action is not dependent on insulin secretion. However, the risk increases significantly when combined with insulin or other insulin secretagogues like sulfonylureas. Given the prevalence of polypharmacy in the elderly, this combination is not uncommon, and careful dose adjustments are necessary to prevent hypoglycemic episodes.

Comparison of SGLT2 Inhibitor Concerns in Elderly Patients

Concern	Mechanism	Increased Risk Factors in Elderly	Monitoring/Management Strategies
Dehydration/Volume Depletion	Osmotic diuresis increases urinary fluid and sodium excretion.	Reduced thirst sensation, underlying heart failure, chronic kidney disease, concomitant diuretic use, acute illness.	Regular monitoring of volume status (e.g., blood pressure, weight), electrolyte levels, and renal function. Consider diuretic dose reduction. Educate on hydration.
Genitourinary Infections	Glucosuria provides a growth medium for pathogens.	Age, female sex, incontinence, history of UTIs.	Counsel on proper hygiene. Educate on infection symptoms. Manage infections promptly. Discontinue during severe infection.
Euglycemic DKA	State of reduced insulin and increased glucagon/ketogenesis, masked by glucosuria.	Type 1 or insulin-dependent Type 2 diabetes, acute illness, surgery, low-carbohydrate diet, poor fluid intake.	Educate on DKA symptoms. Discontinue temporarily during acute illness ('sick day' rules). Test for ketones if symptoms present.
Hypoglycemia	Minimal risk with monotherapy; increased when combined with insulin or sulfonylureas.	Concomitant use of insulin or sulfonylureas.	Dose adjustment of concomitant medications (insulin, sulfonylureas). Educate on hypoglycemia symptoms.

Managing the Risks and Monitoring for Safety

Effective management of SGLT2 inhibitor therapy in the elderly requires a personalized approach. Key strategies include:

• Thorough Patient Selection: Carefully evaluate comorbidities (heart failure, CKD), frailty status, cognitive function, and current medication list before initiating therapy.
• Initial Baseline Assessment: Establish baseline values for renal function (eGFR), volume status, and blood pressure to track changes.
• Patient and Caregiver Education: Ensure the patient understands the potential side effects, including symptoms of dehydration, infections, and DKA. Provide clear instructions on what to do during acute illness ('sick day' protocols), such as temporarily holding the medication.
• Close Monitoring and Follow-Up: Particularly during the initial weeks of treatment, monitor for adverse effects. For those on combination therapy, pay close attention to blood sugar levels.
• Medication Review: Re-evaluate and potentially adjust the dosages of other medications, especially diuretics, to mitigate the risk of volume depletion.

Conclusion

While SGLT2 inhibitors offer significant and potentially life-extending benefits for older patients, particularly those with type 2 diabetes and cardiorenal conditions, their use requires vigilance. The main concerns, including dehydration, genitourinary infections, and the low but serious risk of euglycemic DKA, must be actively managed. By performing a careful risk-benefit analysis, ensuring appropriate patient selection, providing comprehensive education, and maintaining close monitoring, clinicians can mitigate these risks and safely leverage the substantial benefits of SGLT2 inhibitors for elderly individuals.

Frequently Asked Questions

What is the primary concern regarding SGLT2 inhibitors and dehydration in elderly patients?

The primary concern is that the medication's osmotic diuretic effect can cause significant fluid loss. Elderly patients are more susceptible to dehydration due to a reduced sense of thirst and increased vulnerability, which can lead to orthostatic hypotension and an increased risk of falls.

Do SGLT2 inhibitors increase the risk of urinary tract infections (UTIs) in older adults?

While the overall risk of serious UTIs for the SGLT2 inhibitor class is not consistently increased compared to placebo, some specific agents, such as dapagliflozin, have shown an increased risk. Increased genital mycotic infections are a clearer class effect, and infections in older patients require careful monitoring.

How should an elderly patient taking SGLT2 inhibitors handle an acute illness?

During acute illnesses that cause dehydration, like vomiting or diarrhea, the SGLT2 inhibitor should be temporarily discontinued. This is known as following 'sick day' rules and helps prevent serious complications like diabetic ketoacidosis.

Is hypoglycemia a major risk with SGLT2 inhibitors in older patients?

Hypoglycemia is generally not a major risk when SGLT2 inhibitors are used alone. However, the risk increases significantly when they are combined with insulin or other insulin secretagogues. In such cases, dose adjustments of the other medications are necessary.

What is euglycemic diabetic ketoacidosis (DKA) and why is it a concern?

Euglycemic DKA is a rare but life-threatening complication where ketoacidosis occurs with blood glucose levels that are not severely high. It is a concern because it can be missed due to the absence of classic hyperglycemia, and older patients with pre-existing conditions may be more susceptible.

Do SGLT2 inhibitors increase the risk of falls or fractures in the elderly?

Dehydration and the resulting orthostatic hypotension caused by SGLT2 inhibitors can increase the risk of falls. The overall evidence on fracture risk is conflicting; some early trials showed a potential risk with canagliflozin, but other major trials and meta-analyses have not found an increased risk with the class as a whole.

How should a doctor monitor an elderly patient starting SGLT2 inhibitors?

Monitoring should include an assessment of volume status, blood pressure, renal function (eGFR), and electrolytes. Regular follow-up appointments and clear patient education on signs of adverse effects are critical, especially during the first few weeks of treatment and during illness.