What is the recommended dosing and monitoring for a patient on Novolog (insulin aspart) 6 units three times a day (TID) and Lantus (insulin glargine) 12 units daily, starting tirzepatide (a glucagon-like peptide-1 (GLP-1) receptor agonist) for weight loss?

Insulin Dose Reduction When Starting Tirzepatide

Reduce basal insulin (Lantus) by 20% and consider reducing or discontinuing prandial insulin (Novolog) entirely when initiating tirzepatide, given the significant hypoglycemia risk from overlapping glucose-lowering mechanisms and the glucose-dependent insulinotropic effects of tirzepatide. 1, 2

Immediate Insulin Adjustments at Tirzepatide Initiation

Basal Insulin (Lantus) Modification

• Reduce Lantus from 12 units to 10 units daily (approximately 20% reduction) when starting tirzepatide 1
• This reduction prevents hypoglycemia while tirzepatide's glucose-lowering effects develop over the first 4-8 weeks 2, 3
• If A1C is <8%, consider a more aggressive reduction of 4 units (reducing to 8 units daily) 1

Prandial Insulin (Novolog) Modification

• Strongly consider discontinuing Novolog entirely at tirzepatide initiation, as the patient is on a very low dose (6 units TID = 18 units total daily) 1, 2
• Tirzepatide's glucose-dependent insulin secretion and glucagon suppression will replace much of the prandial insulin effect 3, 4
• If you choose to continue Novolog initially, reduce each dose by 50% (from 6 units to 3 units TID) and plan to discontinue within 2-4 weeks based on glucose monitoring 1

Tirzepatide Dosing Protocol

Starting Dose and Titration

• Start tirzepatide at 2.5 mg subcutaneously once weekly for the first 4 weeks 5
• Increase to 5 mg weekly after 4 weeks 5
• Continue dose escalation in 2.5 mg increments every 4 weeks as tolerated, up to maximum 15 mg weekly 5, 6
• The 15 mg dose provides maximum efficacy with 20.9% weight loss at 72 weeks 2, 6

Administration Details

• Inject subcutaneously in abdomen, thigh, or upper arm at any time of day, with or without meals 5
• Rotate injection sites with each dose 5

Intensive Glucose Monitoring Schedule

First 2-4 Weeks (Critical Period)

• Check fasting glucose daily before breakfast 1
• Check pre-meal glucose before each meal for the first 2 weeks 1
• Check 2-hour post-meal glucose after largest meal daily 1
• Check bedtime glucose nightly 1
• If any glucose reading <70 mg/dL, immediately reduce insulin further by 10-20% 1

Weeks 4-12 (Stabilization Period)

• Continue daily fasting glucose checks 1
• Check pre-meal and 2-hour post-meal glucose 2-3 times weekly 1
• Assess for hypoglycemia symptoms (shakiness, sweating, confusion) even with normal readings, as tirzepatide's mechanism is glucose-dependent 4

After 12 Weeks (Maintenance Monitoring)

• Assess at least every 3 months for continued weight loss progress and medication adherence 2
• Evaluate efficacy at 12-16 weeks on maximum tolerated therapeutic dose 2

Specific Hypoglycemia Risk Management

Why This Patient Is High-Risk

• Tirzepatide has minimal hypoglycemia risk as monotherapy due to glucose-dependent insulin secretion and glucagon suppression 2, 3, 4
• However, combining tirzepatide with exogenous insulin creates significant hypoglycemia risk that requires aggressive insulin reduction 1, 7
• The patient's total daily insulin dose of 30 units (12 basal + 18 prandial) will likely need to decrease by 50-70% over 12 weeks as tirzepatide reaches therapeutic effect 1, 3

Hypoglycemia Action Plan

• If glucose <70 mg/dL: consume 15g fast-acting carbohydrates, recheck in 15 minutes 7
• If glucose <54 mg/dL or symptomatic: reduce corresponding insulin dose by 20% immediately 1
• If recurrent hypoglycemia (≥2 episodes in 1 week): reduce total insulin by 20-30% and contact provider 1

Expected Metabolic Changes Over 12-16 Weeks

Glucose Control Evolution

• Tirzepatide reduces HbA1c by 1.87-2.24% in patients with type 2 diabetes 2, 3
• 23.0-62.4% of patients achieve HbA1c <5.7% (normal range) 3, 4
• Fasting glucose typically improves within 2-4 weeks, allowing further basal insulin reduction 3
• Post-prandial glucose improves more gradually over 8-12 weeks as weight loss accelerates 3

Weight Loss Timeline

• Expect 5-10% body weight loss by week 12 2, 8
• Maximum weight loss of 20.9% occurs at 72 weeks with 15 mg dose 2, 6, 8
• Weight loss is dose-dependent: 15.0% with 5 mg, 19.5% with 10 mg, 20.9% with 15 mg 6, 8

Insulin Requirement Changes

• Total daily insulin typically decreases by 30-50% within 12 weeks 9
• Many patients can discontinue prandial insulin entirely by week 8-12 1, 9
• Basal insulin may need reduction to 50% of starting dose or lower 9

Gastrointestinal Side Effect Management

Expected Side Effects During Titration

• Nausea occurs in 17-22% of patients, most common during dose escalation 2
• Diarrhea in 13-16%, vomiting in 6-10%, constipation in 12-18% 2, 6
• These effects are typically mild-to-moderate and decrease over time 2, 6

Mitigation Strategies

• Slow titration every 4 weeks minimizes GI symptoms 2, 5
• Reduce meal size and avoid high-fat meals 2
• Limit alcohol and carbonated beverages 2
• If severe nausea/vomiting persists >1 week at any dose, hold at current dose for additional 2-4 weeks before escalating 2

Contraindications and Safety Monitoring

Absolute Contraindications

• Personal or family history of medullary thyroid cancer 2, 5
• Multiple endocrine neoplasia syndrome type 2 2, 5

Required Monitoring

• Monitor for pancreatitis symptoms (persistent severe abdominal pain radiating to back) 2, 6
• Monitor for gallbladder disease (right upper quadrant pain, especially after meals) 2
• Monitor blood pressure as weight loss may require antihypertensive adjustment 2
• Monitor renal function, especially if baseline impairment present 10

Medication Interactions

• If patient uses oral contraceptives, switch to non-oral method or add barrier contraception for 4 weeks after each dose escalation due to delayed gastric emptying affecting oral medication absorption 6
• Monitor warfarin or other narrow therapeutic index medications more closely 10

Algorithm for Ongoing Insulin Adjustment

Weeks 0-4 (Tirzepatide 2.5 mg)

• Lantus: 10 units daily (reduced from 12)
• Novolog: Discontinue or reduce to 3 units TID
• If fasting glucose consistently >180 mg/dL, may increase Lantus by 2 units 1

Weeks 4-8 (Tirzepatide 5 mg)

• Lantus: Likely reduce to 6-8 units daily based on fasting glucose
• Novolog: Should be discontinued by now
• Target fasting glucose 100-130 mg/dL 1

Weeks 8-12 (Tirzepatide 7.5-10 mg)

• Lantus: Likely 4-6 units daily or potentially discontinue if fasting glucose consistently <100 mg/dL
• Continue monitoring for hypoglycemia risk 1

Week 12+ (Tirzepatide 10-15 mg)

• Many patients require minimal or no basal insulin at this stage 9
• If A1C <7% and no hypoglycemia, continue current regimen 1
• If A1C remains elevated, consider increasing tirzepatide to 15 mg rather than increasing insulin 10, 6

Common Pitfalls to Avoid

• Do not continue full insulin doses when starting tirzepatide—this is the most common cause of severe hypoglycemia 1, 7
• Do not escalate tirzepatide doses faster than every 4 weeks—this increases GI side effects and discontinuation rates 2, 5
• Do not use tirzepatide with other GLP-1 receptor agonists or DPP-4 inhibitors—mechanisms overlap and provide no additional benefit 2
• Do not ignore gastroparesis symptoms—tirzepatide delays gastric emptying and may worsen pre-existing gastroparesis 2, 6
• Do not forget perioperative planning—stop tirzepatide 4-7 days before elective surgery due to aspiration risk from delayed gastric emptying 2, 6