What are the considerations for using Empagliflozin (Empagliflozin) in geriatric patients with type 2 diabetes mellitus (T2DM) and potential impaired renal function?

Empagliflozin Use in Geriatric Patients with Type 2 Diabetes

Primary Recommendation

Empagliflozin can be safely used in geriatric patients with type 2 diabetes, but requires careful attention to volume status, renal function monitoring, and dose adjustment based on eGFR thresholds, with particular vigilance for volume depletion and genital infections in this population. 1, 2

Renal Function Considerations and Dosing

eGFR Thresholds for Initiation and Continuation

• Do not initiate empagliflozin if eGFR is below 45 mL/min/1.73 m² for glycemic control, as glucose-lowering efficacy is significantly reduced at lower eGFR levels 1, 3
• Discontinue empagliflozin if eGFR falls persistently below 45 mL/min/1.73 m² during treatment 1
• The recommended starting dose is 10 mg once daily, taken in the morning with or without food, which may be increased to 25 mg once daily if additional glycemic control is needed 1
• Assess renal function before initiating empagliflozin and monitor periodically thereafter, as elderly patients have higher incidence of adverse reactions related to reduced renal function 1, 4

Pharmacokinetic Changes in Renal Impairment

• In patients with mild renal impairment (eGFR 60 to <90 mL/min/1.73 m²), empagliflozin AUC increases by approximately 18% 1
• In moderate renal impairment (eGFR 30 to <60 mL/min/1.73 m²), AUC increases by approximately 20% 1
• In severe renal impairment (eGFR <30 mL/min/1.73 m²), AUC increases by approximately 66%, and the drug is contraindicated at this level 1

Volume Depletion and Hypotension Risk

Assessment and Monitoring Protocol

• Before initiating empagliflozin, assess and correct volume status in elderly patients, those with renal impairment, low systolic blood pressure, or those on diuretics 1
• Geriatric patients have a higher incidence of adverse reactions related to volume depletion and hypotension compared to younger patients 1, 5
• Monitor for signs and symptoms of volume depletion during therapy, including orthostatic hypotension, dizziness, and syncope 1
• Consider temporarily discontinuing empagliflozin in settings of reduced oral intake or fluid losses to prevent acute kidney injury 1

Diuretic Interactions

• Elderly patients on concurrent diuretic therapy are at greater risk for clinically significant volume depletion 2
• Empagliflozin reduces sodium load and lowers blood pressure by approximately 2.9 to 5.2 mm Hg systolic 6, 3
• Consider reducing diuretic doses when initiating empagliflozin in volume-sensitive elderly patients 1

Infection Risk Management

Genital Mycotic Infections

• The most common adverse reactions with empagliflozin (≥5% incidence) are urinary tract infections and female genital mycotic infections 1
• Genital infections occur with higher incidence in women and typically have a non-severe course that is straightforward to manage 5, 3
• Monitor for genital mycotic infections and treat as appropriate; these infections are usually manageable but require patient education 1, 7

Urosepsis and Pyelonephritis

• Evaluate elderly patients for signs and symptoms of urinary tract infections and treat promptly if indicated 1
• Consider temporarily discontinuing empagliflozin if serious urinary tract infection develops 1

Hypoglycemia Risk in Combination Therapy

• Empagliflozin carries a low inherent risk of hypoglycemia due to its insulin-independent mechanism of action 7, 6
• When initiating empagliflozin in elderly patients on insulin or sulfonylureas, consider lowering the dose of these agents to reduce hypoglycemia risk 1, 5
• In combination with sulfonylurea, hypoglycemia may occur and requires dose adjustment of the secretagogue 5

Cardiovascular and Renal Benefits in High-Risk Elderly

Cardiovascular Protection

• Empagliflozin is indicated to reduce the risk of cardiovascular death in adult patients with type 2 diabetes and established cardiovascular disease 1
• In the EMPA-REG OUTCOME trial, empagliflozin reduced cardiovascular death by 38% (HR 0.62; 95% CI 0.49-0.77) and all-cause mortality by 32% (HR 0.68; 95% CI 0.57-0.82) 3, 6
• The drug reduced major adverse cardiovascular events by 14% (HR 0.86; 95% CI 0.74-0.99) 3

Renal Protection

• Empagliflozin demonstrated nephroprotective properties in diabetic patients, reducing renal adverse events 3, 2
• The drug is effective and safe until eGFR 45 mL/min/1.73 m², below which treatment should be discontinued 5

Weight and Blood Pressure Benefits

• Empagliflozin causes glycosuria of 50-100 g glucose/24 hours, resulting in energy expenditure of 200-400 kcal/day 5
• Treatment leads to weight loss of approximately 2 to 3 kg, which may be beneficial in overweight elderly patients 2, 6
• Blood pressure reductions occur without compensatory increase in heart rate 6

Special Precautions for Frail Elderly

• Exercise caution in empagliflozin treatment in elderly and fragile patients due to potential for dehydration and hypotension 5
• The drug does not cause clinically significant dehydration or hypotension in patients under 60 years of age, but vigilance is required in older populations 5
• Consider the patient's overall health status, polypharmacy burden, and ability to maintain adequate hydration before initiating therapy 4

Ketoacidosis Risk and Monitoring

• Assess patients who present with signs and symptoms of metabolic acidosis for ketoacidosis, regardless of blood glucose level 1
• Before initiating empagliflozin, consider risk factors for ketoacidosis in elderly patients 1
• Patients may require monitoring and temporary discontinuation of therapy in clinical situations known to predispose to ketoacidosis, such as acute illness, surgery, or prolonged fasting 1
• If ketoacidosis is suspected, discontinue empagliflozin immediately, evaluate and treat promptly 1

Drug Interactions and Simplicity of Use

• Empagliflozin has clinically non-significant interactions with other drugs, making it suitable for elderly patients on multiple medications 5
• The simple dosage of 1 tablet per day orally enhances adherence in geriatric populations 5
• Empagliflozin pharmacokinetics were similar with and without coadministration of commonly prescribed medications including metformin, glimepiride, sitagliptin, warfarin, verapamil, ramipril, and simvastatin 1

Treatment Efficacy Over Time

• Treatment efficacy does not decrease over time, as it is not dependent on the patient's own insulin production 5
• This characteristic makes empagliflozin particularly valuable in elderly patients with progressive β-cell dysfunction 7