What are the management options for a patient with type 2 diabetes experiencing fatigue while taking Jardiance (empagliflozin)?

Management of Fatigue in Patients Taking Jardiance (Empagliflozin)

First, determine if the fatigue is actually caused by Jardiance or is related to the underlying diabetes itself, as fatigue is a common symptom of both hyperglycemia and type 2 diabetes independent of medication. 1

Initial Assessment: Distinguish the Cause

Check for Hyperglycemia-Related Fatigue

• Measure current HbA1c and fasting glucose immediately – marked hyperglycemia itself causes fatigue through frequent urination, thirst, blurred vision, and recurring infections 1
• If HbA1c remains >8% (64 mmol/mol) or fasting glucose >180 mg/dL, the fatigue is likely from inadequate glycemic control rather than the medication 1, 2
• In this case, intensify therapy rather than discontinue Jardiance 1

Assess for Volume Depletion (Most Common Jardiance-Related Cause)

• Check orthostatic vital signs – empagliflozin causes osmotic diuresis which can lead to volume depletion and fatigue 3
• Look for concurrent symptoms: dizziness upon standing, increased thirst, dry mucous membranes 3
• This risk is higher in patients on diuretics, ACE inhibitors, or ARBs 3
• If volume depletion is present, increase fluid intake and consider reducing diuretic doses before discontinuing empagliflozin 3

Rule Out Euglycemic Diabetic Ketoacidosis (Critical)

• Check beta-hydroxybutyrate or urine ketones if fatigue is accompanied by nausea, vomiting, abdominal pain, or dyspnea – even with normal glucose levels 4
• Euglycemic DKA is a recognized complication of SGLT2 inhibitors and requires immediate hospitalization 4
• If ketones are elevated (>0.6 mmol/L) with anion gap, permanently discontinue empagliflozin 4

Management Algorithm Based on Findings

If Fatigue is Due to Poor Glycemic Control

• Continue empagliflozin and add a second agent (GLP-1 receptor agonist, DPP-4 inhibitor, or basal insulin) to achieve HbA1c <7% 1
• Reassess in 3 months – fatigue should improve as glycemic control improves 1

If Fatigue is Due to Volume Depletion

• Counsel patient to increase oral fluid intake to 2-3 liters daily 3
• Review all medications and reduce doses of other agents causing volume loss (diuretics, ACE inhibitors) if blood pressure allows 3
• Continue empagliflozin at current dose – the cardiovascular and renal benefits outweigh this manageable side effect 5, 6
• If symptoms persist despite hydration, consider reducing empagliflozin from 25 mg to 10 mg daily 2

If Fatigue is Multifactorial (Diabetes-Related)

• Address the five major contributing factors systematically 7:
  • Inflammatory factors: Check CRP and optimize glycemic control to reduce systemic inflammation 7
  • Psychological factors: Screen for depression using PHQ-9 – depression is strongly associated with diabetes-related fatigue 7, 8
  • Lifestyle factors: Assess sleep quality, physical activity levels, and dietary patterns 7
  • Clinical disease factors: Check thyroid function (TSH), vitamin B12, iron studies, and renal function 7
  • Sociodemographic factors: Evaluate work stress, social support, and diabetes self-management burden 7

When to Discontinue Empagliflozin

Only discontinue empagliflozin if:

• Euglycemic DKA develops (permanent discontinuation required) 4
• Severe, persistent volume depletion despite adequate hydration and medication adjustment 3
• Recurrent genital mycotic infections causing significant distress (occurs in ~6% of patients) 5

Do NOT discontinue empagliflozin for mild fatigue alone – the medication provides substantial cardiovascular mortality reduction (38% decrease in CV death), heart failure hospitalization reduction (35%), and renal protection that far outweigh minor side effects 5, 6

Critical Pitfalls to Avoid

• Never assume fatigue equals drug side effect – diabetes itself is a major cause of fatigue through hyperglycemia, and discontinuing effective therapy worsens outcomes 1, 8
• Never stop empagliflozin without checking ketones if patient has nausea or abdominal symptoms – missing euglycemic DKA can be fatal 4
• Never ignore cardiovascular benefits – in patients with established CVD or high CV risk, empagliflozin reduces mortality and should be continued unless contraindicated 5, 6
• Never attribute all symptoms to one cause – fatigue in diabetes is multifactorial and requires systematic evaluation of glycemic control, hydration status, psychological factors, and comorbidities 7, 8

Monitoring Plan

• Recheck HbA1c in 3 months to ensure glycemic targets are met 1
• Monitor volume status at each visit, especially in elderly patients or those on multiple antihypertensives 3
• Screen for depression annually using validated tools, as psychological factors significantly contribute to diabetes-related fatigue 7
• Assess renal function every 6-12 months – empagliflozin provides nephroprotection but requires monitoring 5