What adjustments should be made to a patient's insulin regimen, currently taking Novolog (insulin aspart) at 2 units and Basaglar (insulin glargine) at 24 units, who has developed hypoglycemia after starting metformin XR (metformin hydrochloride) and Ozempic (semaglutide)?

Immediate Insulin Dose Reductions Required to Prevent Recurrent Hypoglycemia

Reduce Basaglar by 20% to approximately 19 units and discontinue Novolog entirely until hypoglycemia resolves. The combination of GLP-1 receptor agonist (Ozempic) with both basal and bolus insulin is causing dangerous hypoglycemia, particularly given the extremely low bolus insulin dose of 2 units, which suggests minimal insulin requirement 1.

Understanding the Problem

Your hypoglycemia pattern—occurring both postprandially (minutes after eating) and nocturnally (1:00 AM)—indicates that both your mealtime and basal insulin are now excessive after adding Ozempic and metformin XR 1.

• GLP-1 receptor agonists like Ozempic significantly increase hypoglycemia risk when combined with insulin, requiring substantial insulin dose reductions of approximately 20% for basal insulin 1.
• Metformin XR alone carries minimal hypoglycemia risk, but the extended-release formulation can occasionally cause reactive hypoglycemia, particularly when taken without adequate food 2, 3.
• The combination of Ozempic + insulin creates additive glucose-lowering effects that necessitate aggressive insulin downtitration 1.

Specific Medication Adjustments

Basaglar (Basal Insulin)

• Reduce immediately by 20% from 24 units to 19 units at your usual administration time 1, 4.
• This 20% reduction is the standard recommendation when adding GLP-1 receptor agonists to prevent hypoglycemia 1.
• Monitor fasting glucose daily for one week with target range of 80-130 mg/dL 5, 6.
• If more than 50% of fasting values remain above 130 mg/dL after one week, increase by 2 units 5, 6.
• If two or more fasting values per week fall below 80 mg/dL, decrease by an additional 2 units 5, 6.

Novolog (Bolus Insulin)

• Discontinue entirely until hypoglycemia resolves 1.
• At only 2 units per meal, this dose is providing minimal benefit but significant hypoglycemia risk when combined with Ozempic 1.
• Ozempic provides substantial postprandial glucose control, making mealtime insulin potentially unnecessary 7.
• Consider reintroducing only if postprandial glucose consistently exceeds 180 mg/dL after 2-3 weeks, starting at 4 units before the largest meal 5.

Metformin XR

• Continue current dose but ensure taken with or immediately after your evening meal 2, 3.
• Metformin XR reaches peak levels 4-8 hours after administration, so evening dosing with food minimizes nocturnal hypoglycemia risk 3.
• Never take on an empty stomach, as this increases reactive hypoglycemia risk 2, 3.

Ozempic

• Continue current dose unchanged 1.
• SGLT2 inhibitors and GLP-1 receptor agonists have low intrinsic hypoglycemia risk and do not require dose adjustment 1, 6.
• The hypoglycemia is from excessive insulin, not from Ozempic itself 1.

Critical Monitoring Protocol

Immediate (First Week)

• Check fasting glucose every morning upon waking 5, 6.
• Check glucose at 3:00 AM for 3-4 nights to assess nocturnal hypoglycemia patterns 4.
• Check glucose before each meal and 2 hours after meals for the first week 5.
• Treat any glucose <70 mg/dL immediately with 15 grams fast-acting carbohydrate (glucose tablets, 4 oz juice) 8.

Ongoing (Weeks 2-4)

• Continue daily fasting glucose checks 5, 6.
• Check pre-meal glucose if experiencing hypoglycemia symptoms 8.
• Target fasting glucose: 80-130 mg/dL 5, 6.
• Target postprandial glucose: <180 mg/dL 5.

Why This Specific Approach

The 20% Basal Insulin Reduction

• ACC/AHA guidelines explicitly recommend 20% basal insulin reduction when adding GLP-1 receptor agonists to patients on insulin 1.
• This prevents the dangerous synergistic glucose-lowering effect 1.
• Your nocturnal hypoglycemia at 1:00 AM specifically indicates excessive basal insulin coverage 4, 6.

Complete Novolog Discontinuation

• At 2 units per meal, you're already at the absolute minimum effective dose 5.
• Ozempic provides robust postprandial glucose control, often eliminating the need for mealtime insulin 7.
• Postprandial hypoglycemia (minutes after eating) indicates excessive bolus insulin 1.
• The combination of Ozempic + even minimal bolus insulin creates unacceptable hypoglycemia risk 1.

Metformin XR Timing Optimization

• Extended-release metformin peaks 4-8 hours after administration 3, 9.
• Taking with evening meal prevents peak levels during sleep, reducing nocturnal hypoglycemia 3.
• Food intake with metformin XR reduces reactive hypoglycemia risk 2, 3.

Alternative Considerations if Hypoglycemia Persists

If Hypoglycemia Continues After One Week

• Consider switching Basaglar administration from evening to morning to reduce nocturnal hypoglycemia while maintaining 24-hour coverage 6.
• Consider switching to insulin degludec (Tresiba) or insulin glargine U-300, which have lower nocturnal hypoglycemia rates than standard insulin glargine 6.

If Fasting Glucose Becomes Elevated (>180 mg/dL)

• Increase Basaglar by 2 units every 3 days until fasting glucose reaches 80-130 mg/dL 5.
• Do not restart Novolog unless postprandial glucose consistently exceeds 180 mg/dL for 2-3 weeks 5.

Common Pitfalls to Avoid

• Never continue escalating insulin when adding GLP-1 receptor agonists—this guarantees hypoglycemia 1.
• Never take metformin XR on an empty stomach—this increases reactive hypoglycemia risk 2, 3.
• Never ignore glucose <70 mg/dL—treat immediately with 15 grams fast-acting carbohydrate 8.
• Never restart bolus insulin at the same dose after discontinuation—if reintroduction is needed, start at 4 units before the largest meal only 5.
• Never adjust insulin doses more frequently than every 3 days unless experiencing hypoglycemia, which requires immediate 10-20% reduction 5, 4.

Expected Outcomes

• Hypoglycemia should resolve within 3-7 days of implementing these dose reductions 4, 6.
• Fasting glucose may temporarily rise to 130-180 mg/dL, which is acceptable during the adjustment period 5.
• HbA1c should remain well-controlled due to the potent glucose-lowering effects of Ozempic + metformin combination 7.
• Weight loss benefits of Ozempic will continue without the weight gain typically associated with insulin intensification 7.

Follow-Up Requirements

• Contact your healthcare provider within 1-2 weeks to review glucose logs and assess response to dose adjustments 4.
• Schedule HbA1c check in 3 months to ensure glycemic targets maintained without hypoglycemia 5.
• Consider adding prandial insulin only if HbA1c >7% after 3-6 months despite optimized basal insulin and Ozempic 5.