How should a patient's diabetes be managed while on Novolog 70/30 (insulin aspart protamine/insulin aspart), Jardiance (empagliflozin), and Ozempic (semaglutide)?

Managing Diabetes on Novolog 70/30, Jardiance, and Ozempic

Critical Assessment: This Regimen Requires Immediate Simplification

This triple-therapy combination of premixed insulin (Novolog 70/30), SGLT2 inhibitor (Jardiance), and GLP-1 receptor agonist (Ozempic) is unnecessarily complex and potentially problematic—the premixed insulin should be transitioned to a basal-bolus regimen or simplified to basal-only insulin with continuation of the non-insulin agents. 1

Why This Combination Is Problematic

Premixed Insulin Limitations

• Premixed insulins like Novolog 70/30 (70% insulin aspart protamine/30% insulin aspart) provide fixed ratios that cannot be independently adjusted for basal versus prandial needs, making precise glycemic management difficult 1
• The fixed 70/30 ratio may not match individual insulin requirements, which typically need a 50:50 split between basal and prandial components in most patients 1, 2
• Premixed insulins have been associated with significantly increased hypoglycemia rates compared to basal-bolus regimens in clinical trials 2

Drug Interaction Concerns

• Ozempic (semaglutide) should not be mixed with insulin in the same injection, though they can be given in the same body area but not adjacent to each other 3
• GLP-1 receptor agonists like Ozempic increase hypoglycemia risk when combined with insulin, requiring careful dose adjustments 1
• SGLT2 inhibitors like Jardiance should be used with caution in combination with insulin due to increased risk of diabetic ketoacidosis, particularly in patients with insulin deficiency 1

Recommended Management Strategy

Option 1: Transition to Basal-Bolus Insulin (Preferred for A1C >9%)

If the patient has poor glycemic control (A1C ≥9%), convert from Novolog 70/30 to a basal-bolus regimen:

• Calculate current total daily insulin dose from Novolog 70/30 2
• Split 50% as basal insulin (insulin glargine or detemir) once daily 2
• Divide remaining 50% as rapid-acting insulin (insulin aspart) before three meals 2
• Continue both Jardiance and Ozempic unless contraindications develop 1
• Continue metformin at maximum tolerated dose (up to 2000-2550 mg daily) unless contraindicated 1

Option 2: Simplify to Basal Insulin Only (Preferred for A1C 7-9%)

If glycemic control is moderate (A1C 7-9%), consider simplifying to basal insulin alone:

• Discontinue Novolog 70/30 and start basal insulin (glargine or detemir) at 10 units once daily or 0.1-0.2 units/kg/day 1, 2, 4
• Continue Ozempic, which provides excellent postprandial glucose control and reduces need for prandial insulin 1
• Continue Jardiance for cardiovascular and renal benefits 1
• Titrate basal insulin by 2-4 units every 3 days until fasting glucose reaches 80-130 mg/dL 1, 2

Option 3: Optimize Current Regimen (Only if Patient Refuses Changes)

If the patient insists on continuing Novolog 70/30:

• Ensure proper injection timing: Novolog 70/30 should be given 5-15 minutes before breakfast and dinner 5, 6
• Monitor for hypoglycemia closely, especially with concurrent Ozempic use 1, 3
• Consider reducing Novolog 70/30 dose by 10-20% to account for glucose-lowering effects of Ozempic and Jardiance 1
• If adding a third injection is needed for lunch coverage, this can be done but increases complexity 5

Critical Monitoring Requirements

Hypoglycemia Prevention

• The combination of insulin with Ozempic significantly increases hypoglycemia risk—patients must be educated on recognition and treatment 1, 3
• Signs include dizziness, blurred vision, sweating, confusion, shakiness, and fast heartbeat 3
• Treat with 15 grams of fast-acting carbohydrate immediately 2
• Consider reducing insulin doses by 10-20% when initiating or intensifying Ozempic 1

Diabetic Ketoacidosis Risk

• Jardiance increases DKA risk, particularly when combined with insulin 1, 7
• Educate patients to check ketones if glucose >250 mg/dL with nausea, vomiting, or abdominal pain 1
• Jardiance should be held during acute illness, dehydration, or severe stress 1

Dehydration and Kidney Function

• SGLT2 inhibitors like Jardiance increase risk of dehydration, acute kidney injury, and orthostatic hypotension 1
• Monitor kidney function regularly and ensure adequate hydration 1
• Use caution when Jardiance is combined with diuretics, ACE inhibitors, or ARBs 1

Medication-Specific Considerations

Ozempic Administration

• Inject subcutaneously once weekly on the same day each week, at any time of day 3
• May be taken with or without food 3
• Rotate injection sites (abdomen, thigh, or upper arm) with each injection 3
• Do not mix with insulin in the same injection 3

Jardiance Precautions

• Hold during periods of severe illness, vomiting, or dehydration 1
• Monitor for genital infections, which occur more frequently with SGLT2 inhibitors 7
• Be aware of increased amputation and fracture risk with canagliflozin (class effect uncertain) 1

Insulin Injection Technique

• Novolog 70/30 should be gently rolled (not shaken) to resuspend before injection 6
• Inject subcutaneously into abdomen, thigh, or upper arm 3
• Rotate injection sites to prevent lipodystrophy 2, 4
• Never inject insulin into muscle or vein 3

Common Pitfalls to Avoid

• Never delay transitioning from premixed insulin to basal-bolus when glycemic control is inadequate—premixed insulins have higher hypoglycemia rates and less flexibility 2
• Never discontinue metformin when using insulin unless contraindicated—the combination provides superior control with less weight gain 1
• Never ignore the need for insulin dose reduction when adding or intensifying Ozempic—hypoglycemia risk increases significantly 1, 3
• Never continue escalating insulin doses without addressing the complexity of the regimen—simplification often improves outcomes 1, 2

When to Reassess and Modify Therapy

• Reassess every 3 months during active titration to check A1C and adjust therapy 2, 4
• Consider adding prandial insulin if basal insulin alone with Ozempic fails to achieve A1C <7% after 3-6 months 1, 2
• Monitor for signs of overbasalization: basal dose >0.5 units/kg/day, bedtime-to-morning glucose differential ≥50 mg/dL, hypoglycemia, and high glucose variability 2