What is the recommended treatment approach for a patient with type 2 diabetes mellitus (T2DM) and established cardiovascular disease or multiple risk factors for cardiovascular disease, considering the use of Jardiance (empagliflozin)?

Jardiance (Empagliflozin) for Type 2 Diabetes with Cardiovascular Disease

Primary Recommendation

Start empagliflozin 10 mg once daily immediately in all patients with type 2 diabetes and established cardiovascular disease or multiple cardiovascular risk factors, as this provides a 38% reduction in cardiovascular death and 32% reduction in all-cause mortality. 1, 2

Evidence-Based Treatment Algorithm

Step 1: Confirm Indication and Check Eligibility

Empagliflozin is indicated for:

• Improving glycemic control in adults with T2DM as adjunct to diet and exercise 1
• Reducing risk of cardiovascular death in adults with T2DM and established cardiovascular disease 1
• Patients with established coronary artery disease, prior myocardial infarction, stroke, or peripheral arterial disease 1, 2

Check eGFR before initiation:

• Can initiate if eGFR ≥25 mL/min/1.73 m² for cardiovascular protection 3
• For glycemic control alone, do not initiate if eGFR <45 mL/min/1.73 m² 1
• Contraindicated on dialysis or severe renal impairment 1

Step 2: Standard Dosing

Empagliflozin 10 mg once daily is the universal dose - no titration required or recommended 1, 3. The 25 mg dose showed similar cardiovascular benefits in EMPA-REG OUTCOME but offers no additional mortality benefit over 10 mg 4, 5.

Step 3: Cardiovascular and Renal Benefits

Cardiovascular outcomes from EMPA-REG OUTCOME trial (7,020 patients, median 3.1 years follow-up):

• 14% reduction in major adverse cardiovascular events (MI, stroke, CV death): HR 0.86 [95% CI 0.74-0.99] 1
• 38% reduction in cardiovascular death: HR 0.62 [95% CI 0.49-0.77] 1, 4
• 32% reduction in all-cause mortality: HR 0.68 [95% CI 0.57-0.82] 1, 4
• 35% reduction in heart failure hospitalizations 3

Renal protection:

• Slows eGFR decline over time 3, 5
• Reduces risk of doubling serum creatinine or 40% decline in eGFR 1
• Benefits maintained even in patients with chronic kidney disease (eGFR 30-60 mL/min/1.73 m²) 5

Step 4: Integration with Existing Therapy

Continue all guideline-directed medical therapy - empagliflozin provides additive benefit on top of: 3, 2

• ACE inhibitors/ARBs (84% of EMPA-REG patients were on these) 5
• Beta-blockers 2
• Statins (target LDL <55 mg/dL in very high CV risk) 2
• Aspirin 75-160 mg daily 2

If patient is on sulfonylurea or insulin:

• Consider reducing sulfonylurea dose or stopping it entirely when starting empagliflozin to prevent hypoglycemia 1
• Consider reducing total daily insulin dose by approximately 20% 1

Step 5: Dose Modifications for Renal Function

eGFR 45-90 mL/min/1.73 m²: No dose adjustment needed - continue 10 mg daily 1

eGFR 25-44 mL/min/1.73 m²: Continue 10 mg daily for cardiovascular/renal protection, but glucose-lowering efficacy will be reduced 3, 4

eGFR <25 mL/min/1.73 m²: Do not initiate, but may continue if already on treatment until dialysis 3

Step 6: Safety Monitoring and Precautions

Withhold empagliflozin at least 3 days before major surgery or prolonged fasting to prevent postoperative ketoacidosis 1, 6

Hold during acute illness (fever, vomiting, diarrhea, reduced oral intake) to prevent euglycemic diabetic ketoacidosis and volume depletion 6

Monitor for:

• Genital mycotic infections (more common in women) - educate on hygiene measures 1, 7
• Urinary tract infections 1
• Volume depletion, especially in elderly or those on diuretics - consider reducing diuretic dose 1, 3
• Euglycemic diabetic ketoacidosis (can occur with normal blood glucose) 1, 6

Contraindications:

• History of serious hypersensitivity reaction 1
• Pregnancy or breastfeeding 1
• On dialysis 1

Key Clinical Advantages Over Other Glucose-Lowering Agents

Empagliflozin is superior to DPP-4 inhibitors (like sitagliptin) because it provides substantial cardiovascular mortality reduction, whereas sitagliptin is cardiovascular neutral with no reduction in heart failure hospitalizations or cardiovascular death 3

The cardiovascular benefits appear independent of glucose-lowering effects - the mortality benefit occurred within months of starting treatment, suggesting a direct cardiovascular mechanism (likely related to diuretic effect and heart failure prevention) rather than long-term glycemic control 3, 8

Common Pitfalls to Avoid

Do not discontinue empagliflozin solely because eGFR falls below 45 mL/min/1.73 m² - cardiovascular and renal protective benefits persist even when glycemic efficacy is lost 3, 6

Do not use empagliflozin primarily for weight loss - while it causes modest weight reduction (~2 kg), the primary indication is cardiovascular protection 7

Do not combine with canagliflozin without considering amputation risk - unlike canagliflozin, empagliflozin has not been associated with increased risk of lower-limb amputation or bone fractures 1, 9