When can a patient on Ozempic (semaglutide) and Jardiance (empagliflozin) discontinue one of their other diabetes medications?

When to Discontinue a Diabetes Medication in Patients on Ozempic and Jardiance

If a patient on Ozempic (semaglutide) and Jardiance (empagliflozin) needs to discontinue one of their other diabetes medications, discontinue sulfonylureas or insulin first when HbA1c is substantially below target (<6.5%) or when hypoglycemia occurs, while maintaining both Ozempic and Jardiance for their cardiovascular and renal protective benefits. 1, 2

Primary Decision Algorithm

Step 1: Assess Current Glycemic Control

• If HbA1c is <6.5% or substantially below individualized target: Consider medication reduction to prevent hypoglycemia and reduce treatment burden 1
• If HbA1c is 6.5-7.5%: Evaluate for hypoglycemia risk before making changes 1
• If HbA1c is >7.5%: Do not discontinue medications; consider intensification instead 1

Step 2: Prioritize Which Medication to Discontinue

Discontinue FIRST (in order of priority):

1. Sulfonylureas (e.g., glipizide, glyburide): These should be the first medications discontinued because they directly stimulate insulin secretion regardless of glucose levels, causing the highest hypoglycemia risk with minimal cardiovascular or renal benefits 2, 1

2. Insulin: If the patient is on insulin and has achieved excellent control with Ozempic and Jardiance, consider reducing insulin dose by 20-25% initially, then potentially discontinuing if type 2 diabetes is confirmed 1, 2, 3

3. DPP-4 inhibitors (e.g., sitagliptin, linagliptin): These provide modest glucose lowering without cardiovascular benefits and have overlapping mechanisms with GLP-1 RAs like Ozempic 1

NEVER discontinue first:

• Metformin: Continue metformin as it has the lowest hypoglycemia risk, provides cardiovascular benefits, and is considered first-line therapy 1, 2
• Ozempic (semaglutide): Provides significant cardiovascular benefits (reduced CV death, MI, stroke), substantial weight loss, and excellent glucose lowering 1, 2
• Jardiance (empagliflozin): Provides cardiovascular benefits (reduced CV death), heart failure benefits (reduced HF hospitalization), and renal protection 1, 4

Specific Clinical Scenarios

Scenario 1: Patient with Hypoglycemia

• Immediately discontinue sulfonylureas or reduce insulin dose by 25-50% 2, 3
• Continue Ozempic and Jardiance for organ protection 1
• Monitor glucose closely for 3-4 weeks after changes 2

Scenario 2: Patient with HbA1c <6.5% on Multiple Medications

• Discontinue medications with hypoglycemia risk first (sulfonylureas, then insulin) 1, 5
• The ACCORD trial demonstrated increased mortality when targeting HbA1c <6.5%, making deintensification appropriate 5
• Maintain Ozempic and Jardiance for cardiovascular and renal benefits even if glucose lowering is not needed 1

Scenario 3: Patient with Renal Impairment

• If eGFR 30-45 mL/min/1.73 m²: Reduce metformin dose but continue Jardiance for renal protection 4
• If eGFR <30 mL/min/1.73 m²: Discontinue metformin and Jardiance per FDA labeling 4
• Continue Ozempic as no dose adjustment is required for renal function 1

Implementation Strategy

Gradual Deintensification Approach

1. Week 0: Discontinue or reduce the highest-risk medication (sulfonylurea or insulin) 2, 3
2. Weeks 1-4: Monitor fasting and postprandial glucose 2-3 times daily 2
3. Week 4-6: Check HbA1c to assess response 5
4. Week 12: Reassess need for further medication adjustments 1

Monitoring Parameters

• Glucose monitoring: Increase frequency during deintensification period 5, 3
• HbA1c: Recheck in 3 months after medication changes 5
• Weight and blood pressure: Monitor as Ozempic and Jardiance affect both 1, 4
• Renal function: Monitor eGFR every 3-6 months on Jardiance 4

Critical Pitfalls to Avoid

Common Errors

• Discontinuing metformin first: This removes a safe, effective medication with cardiovascular benefits 2, 5
• Stopping Ozempic or Jardiance to "simplify" regimen: This eliminates proven cardiovascular and renal protection that extends beyond glucose lowering 1
• Reducing all medications simultaneously: This makes it impossible to identify which medication was causing problems and risks rebound hyperglycemia 2
• Failing to monitor after changes: Missing opportunities to optimize therapy or detect hyperglycemia 5

Special Populations

Elderly patients (≥75 years):

• Prioritize hypoglycemia prevention over tight glycemic targets 6, 7
• Target HbA1c of 7.5-8.0% is appropriate 1
• Discontinue sulfonylureas and insulin more aggressively 6, 7
• Maintain Ozempic for cardiovascular protection despite age 1

Patients with established cardiovascular disease:

• Never discontinue Ozempic or Jardiance as both provide mortality benefits in this population 1
• These medications should be continued even if glucose lowering is not needed 1

Evidence Strength Considerations

The recommendation to maintain both Ozempic and Jardiance while discontinuing other agents is based on:

• Strong cardiovascular outcomes trial data: EMPA-REG OUTCOME showed 38% reduction in CV death with empagliflozin; SUSTAIN-6 and LEADER showed significant MACE reduction with GLP-1 RAs 1
• Complementary mechanisms: SGLT2 inhibitors and GLP-1 RAs work through different pathways and provide additive benefits 1
• Guideline consensus: Both 2025 ADA Standards of Care and 2020 ACC Expert Consensus prioritize these medication classes for patients with or at risk for cardiovascular disease 1

The evidence for deintensification when HbA1c is low comes from real-world studies showing that 13-42% of patients with tight control have medications discontinued safely, though this remains underutilized in practice 6, 8, 9, 7