In an elderly patient, should I prescribe Jardiance (empagliflozin) or a GLP-1 (glucagon-like peptide-1) receptor agonist for glycemic control?

GLP-1 Receptor Agonists Should Be Preferred Over Jardiance (Empagliflozin) in Most Elderly Patients with Type 2 Diabetes

For elderly patients with type 2 diabetes, GLP-1 receptor agonists (particularly liraglutide or semaglutide) should be the preferred choice over Jardiance (empagliflozin) when cardiovascular disease is present or when major adverse cardiovascular events (MACE) represent the primary threat, as GLP-1 RAs demonstrate superior reduction in cardiovascular death, myocardial infarction, and stroke. 1

Primary Decision Framework

The choice between these agents depends on three critical factors that you must assess:

1. Cardiovascular Disease Profile

• If established atherosclerotic cardiovascular disease (ASCVD) is present: GLP-1 receptor agonists are recommended as the preferred agent because they provide the strongest evidence for MACE reduction (cardiovascular death, myocardial infarction, stroke) 1
• If heart failure or chronic kidney disease predominates: SGLT2 inhibitors like Jardiance become more favorable due to their specific benefits in reducing heart failure hospitalizations and slowing CKD progression 1

The European Heart Journal guidelines explicitly state that both empagliflozin and GLP-1 RAs (liraglutide or semaglutide) are Class I, Level A recommendations for patients with diabetes and CVD, but position GLP-1 RAs as superior for MACE prevention 1

2. Functional Status and Frailty Assessment

Healthy elderly patients (few comorbidities, intact cognition, independent in activities of daily living):

• Either agent is appropriate
• GLP-1 RAs provide equal cardiovascular benefits in patients above and below 65 years of age 1, 2
• Target HbA1c <7.0-7.5% 1

Complex/intermediate health status (multiple chronic illnesses, mild-moderate cognitive impairment, 2+ ADL impairments):

• GLP-1 RAs may be preferred if the patient can manage weekly injections (most are once-weekly) 1, 2
• SGLT2 inhibitors offer the advantage of oral administration 1
• Target HbA1c <8.0% 1

Very frail or end-of-life patients:

• Neither agent may be appropriate; simpler regimens are preferred 1, 2

3. Specific Patient Characteristics That Favor Each Agent

Choose GLP-1 RA when:

• Established ASCVD with high MACE risk is the primary concern 1
• Patient needs weight loss (GLP-1 RAs cause greater weight reduction) 3, 4
• Patient has adequate visual, motor, and cognitive skills for weekly subcutaneous injections, or has reliable caregiver support 1, 2
• Patient maintains stable body weight and adequate oral intake 1

Choose Jardiance (SGLT2 inhibitor) when:

• Heart failure with reduced ejection fraction is present 1
• CKD with eGFR 30-60 mL/min/1.73m² requires renoprotection 1
• Patient cannot manage injections or has cognitive/motor limitations 1
• Oral administration is strongly preferred 1

Critical Safety Considerations in the Elderly

GLP-1 RA-Specific Concerns:

• Gastrointestinal side effects (nausea, vomiting, diarrhea) are common and may be particularly problematic 1, 2
• Avoid in patients with unexplained weight loss, undernutrition, or cachexia as GLP-1 RAs cause further weight reduction 1, 2
• Start at the lowest dose and titrate slowly to minimize GI effects 2
• Requires injection technique capability or caregiver assistance 1, 2

Jardiance (SGLT2 Inhibitor)-Specific Concerns:

• Volume depletion risk is higher in elderly patients, particularly those on diuretics 1
• Urinary tract infections and genital mycotic infections occur more frequently 1
• Worsening urinary incontinence may be problematic in elderly women 1
• Risk of euglycemic diabetic ketoacidosis, though rare, requires awareness 1
• Contraindicated with eGFR <30 mL/min/1.73m² 1

Practical Implementation Algorithm

Step 1: Assess cardiovascular phenotype

• ASCVD predominant → GLP-1 RA preferred
• Heart failure/CKD predominant → Jardiance preferred

Step 2: Evaluate functional status and injection capability

• Can manage weekly injections → GLP-1 RA remains option
• Cannot manage injections/severe cognitive impairment → Jardiance preferred

Step 3: Screen for contraindications

• Unexplained weight loss/poor oral intake → Avoid GLP-1 RA, choose Jardiance
• Recurrent UTIs/severe urinary incontinence → Avoid Jardiance, choose GLP-1 RA
• eGFR <30 → Avoid Jardiance

Step 4: Consider combination therapy

• In patients with both ASCVD and heart failure/CKD, combining both agents provides additive benefits for glycemic control, cardiovascular protection, and renal outcomes 4
• The combination demonstrates superior efficacy without increased hypoglycemia risk 4

Common Pitfalls to Avoid

• Do not use sliding-scale insulin calculations or complex regimens in elderly patients with cognitive impairment 1
• Do not ignore geriatric syndromes (falls, urinary incontinence) when selecting agents, as SGLT2 inhibitors may worsen incontinence 1, 5
• Do not prescribe GLP-1 RAs to patients with unexplained weight loss without first investigating and addressing the underlying cause 1, 2
• Do not continue Jardiance if recurrent volume depletion or hypotension occurs, particularly in patients on loop diuretics 1
• Do not overlook the need for dose adjustments of renally excreted drugs in elderly patients with declining kidney function 1

Age-Specific Considerations for Very Elderly (≥85 Years)

For patients ≥85 years, treatment decisions require even greater caution 2:

• Less stringent HbA1c targets (8.0-8.5%) are appropriate with limited life expectancy 2
• Frailty status becomes the dominant consideration over chronological age 2
• Once-weekly GLP-1 RA injections may reduce treatment burden compared to daily medications 2
• If moderate-to-severe frailty with predicted lifespan <3 years, simpler regimens with less stringent targets are more appropriate 2