What adjustments should be made to insulin (Humalog (insulin lispro) and Lantus (insulin glargine)) when starting Ozempic (semaglutide)?

Insulin Dose Reduction When Starting Ozempic

Reduce your total daily insulin dose by 20% when initiating Ozempic to prevent hypoglycemia. This means decreasing Humalog from 46 units to approximately 37 units daily and Lantus from 20 units to 16 units daily 1.

Immediate Dose Adjustments

Basal Insulin (Lantus)

• Reduce Lantus from 20 units to 16 units (20% reduction) when starting Ozempic 1
• This reduction prevents hypoglycemia as GLP-1 receptor agonists like Ozempic enhance insulin sensitivity and reduce glucose production 1

Prandial Insulin (Humalog)

• Reduce total daily Humalog from 46 units to approximately 37 units (20% reduction), distributed across meals proportionally 1
• If currently taking Humalog in divided doses (e.g., 15-15-16 units), reduce to approximately 12-12-13 units 1

Critical Monitoring Requirements

First 3-4 Weeks

• Monitor blood glucose closely 4-7 times daily during the initial titration period 1
• Check fasting glucose, pre-meal glucose, and 2-hour post-meal glucose to assess both basal and prandial insulin adequacy 1
• If hypoglycemia occurs (glucose <70 mg/dL), reduce the corresponding insulin dose by an additional 10-20% immediately 1, 2

Ongoing Adjustments

• As Ozempic is titrated up (0.25 mg weekly for 4 weeks, then 0.5 mg weekly, potentially to 1 mg or 2 mg), further insulin reductions will likely be needed 3
• Expect to reduce insulin doses by an additional 10-20% with each Ozempic dose escalation if glucose levels trend downward 1

Why This Approach Matters

Hypoglycemia Risk

• Patients on insulin who add GLP-1 receptor agonists face significant hypoglycemia risk without dose reduction 1
• The 20% reduction is a conservative starting point that balances glycemic control with safety 1
• Substantial initial reductions exceeding 20% should be avoided as they may lead to hyperglycemia 1

Mechanism of Action

• Ozempic enhances glucose-dependent insulin secretion, suppresses glucagon, and slows gastric emptying 3, 4
• These effects are additive to exogenous insulin, necessitating dose reduction 1
• The glucose-lowering effect of semaglutide is substantial—in clinical trials, semaglutide 1.0 mg reduced HbA1c by 1.64% compared to 0.83% with insulin glargine 4

Foundation Therapy Considerations

• Continue metformin unless contraindicated, as it remains the foundation of type 2 diabetes therapy even when using insulin and GLP-1 receptor agonists 1, 2
• Metformin provides complementary glucose-lowering effects and may reduce total insulin requirements further 1, 2

Common Pitfalls to Avoid

• Do not delay insulin dose reduction when starting Ozempic—the 20% reduction should occur immediately with the first Ozempic dose 1
• Do not continue escalating insulin doses if glucose levels improve with Ozempic; instead, reduce insulin further 1
• Do not ignore mild hypoglycemia (glucose 54-70 mg/dL)—this signals the need for additional insulin dose reduction 1
• Avoid relying solely on correction insulin rather than adjusting scheduled basal and prandial doses 1

Expected Outcomes

• Weight loss of 3-5 kg is typical with semaglutide, which may further reduce insulin requirements 4
• Hypoglycemia rates should decrease compared to insulin-only therapy 4, 5
• HbA1c improvements are typically greater with the combination of GLP-1 receptor agonist and reduced insulin compared to insulin intensification alone 4, 5

Long-Term Management Strategy

• Reassess insulin requirements every 2-4 weeks during Ozempic titration 1
• Many patients can reduce insulin doses by 30-50% or more once Ozempic reaches maintenance dosing 4, 5
• Some patients may eventually discontinue prandial insulin entirely, maintaining only basal insulin with Ozempic 5