In an adult with type 2 diabetes on 133 units of insulin glargine (Lantus) daily and a carbohydrate‑to‑insulin ratio of 1 unit per 2 g carbs, how should I initiate semaglutide (Ozempic) and safely reduce the basal insulin dose?

Initiating Semaglutide (Ozempic) in a Patient on High-Dose Insulin

Start semaglutide at 0.25 mg subcutaneously once weekly and immediately reduce the basal insulin (Lantus) dose by 20% (from 133 units to approximately 106 units) to prevent hypoglycemia. 1

Immediate Insulin Dose Reduction

• Reduce Lantus from 133 units to 106 units (20% reduction) on the day you start semaglutide to mitigate hypoglycemia risk, as GLP-1 receptor agonists enhance insulin sensitivity and reduce insulin requirements by 20–30%. 2
• This patient's current basal insulin dose of 133 units represents approximately 0.7 units/kg/day (assuming ~190 kg body weight based on the carb ratio), which already exceeds the 0.5 units/kg/day threshold where adding adjunctive therapy is more appropriate than further basal escalation. 2, 3
• Reduce prandial insulin (carb ratio coverage) by 10–20% initially when starting semaglutide, as GLP-1 RAs directly address postprandial hyperglycemia through delayed gastric emptying and glucose-dependent insulin secretion. 2

Semaglutide Titration Schedule

• Week 0–4: Semaglutide 0.25 mg once weekly (this is a dose-escalation phase, not therapeutic). 1
• Week 5–8: Increase to 0.5 mg once weekly. 1
• Week 9–12: If additional glycemic control is needed after at least 4 weeks at 0.5 mg, increase to 1 mg once weekly. 1
• Week 13+: The maintenance dose is typically 0.5 mg or 1 mg once weekly; 1 mg provides superior HbA1c reduction but with slightly higher gastrointestinal side effects. 1, 4

Insulin Titration During Semaglutide Escalation

Basal Insulin (Lantus) Adjustments

• Monitor fasting glucose daily during the first 8–12 weeks of semaglutide initiation. 2, 3
• If fasting glucose falls below 100 mg/dL on two consecutive days, reduce Lantus by an additional 10–15% (approximately 10–15 units). 2, 3
• If fasting glucose remains 140–179 mg/dL, increase Lantus by only 2 units every 3 days (slower titration than usual because semaglutide's glucose-lowering effect continues to build over 4–5 weeks). 2, 3
• Target fasting glucose: 80–130 mg/dL. 2, 3

Prandial Insulin Adjustments

• The carb ratio of 1:2 (1 unit per 2 grams carbohydrate) indicates severe insulin resistance and will likely improve significantly with semaglutide. 2, 3
• After 4 weeks at semaglutide 0.5 mg, reassess the carb ratio by checking 2-hour postprandial glucose after meals where you use the 1:2 ratio. 2, 3
• If 2-hour postprandial glucose is consistently <140 mg/dL, liberalize the carb ratio to 1:3 or 1:4 (meaning 1 unit covers 3–4 grams of carbohydrate instead of 2). 2, 3
• Expect to reduce total daily prandial insulin by 30–50% over 8–12 weeks as semaglutide reaches steady state and improves postprandial control. 2, 4, 5

Monitoring Requirements

• Check fasting glucose daily for the first 4 weeks, then at least 3 times weekly. 2, 3
• Check pre-meal glucose before each meal and 2-hour postprandial glucose after the largest meal to guide prandial insulin adjustments. 2, 3
• Reassess HbA1c at 12–16 weeks (after semaglutide reaches maintenance dose) to determine if further titration to 1 mg is needed. 2, 1
• Monitor for hypoglycemia closely during weeks 4–8 when semaglutide is increased to 0.5 mg, as this is when glucose-lowering effects become clinically significant. 2

Hypoglycemia Management

• Treat any glucose <70 mg/dL immediately with 15 grams of fast-acting carbohydrate. 2, 3
• If hypoglycemia occurs without an obvious cause, reduce the implicated insulin dose (basal or prandial) by 10–20% immediately. 2, 3
• Caution is advised when using GLP-1 RAs in combination with insulin or insulin secretagogues (e.g., sulfonylureas); doses should be adjusted as clinically indicated and patients should be counseled and monitored for hypoglycemia. 2

Expected Clinical Outcomes

• Combination of basal insulin plus semaglutide provides superior HbA1c reduction compared to basal-bolus insulin regimens (mean HbA1c reduction of 1.3–1.8% with semaglutide added to basal insulin). 1, 5
• Expect 3–6 kg weight loss over 30 weeks with semaglutide 0.5–1 mg, compared to weight gain typically seen with insulin intensification alone. 1, 4, 5
• Total daily insulin dose typically decreases by 20–30% over 12–16 weeks as semaglutide's glucose-lowering effect builds. 2, 1, 5
• Severe or blood glucose-confirmed hypoglycemia rates are lower with semaglutide plus basal insulin (17–25 events per 100 patient-years) compared to basal-bolus insulin regimens. 5

Gastrointestinal Side Effect Management

• Nausea occurs in approximately 20–22% of patients starting semaglutide, typically during dose escalation (weeks 0–8). 2, 4
• Gradual dose titration (0.25 mg → 0.5 mg → 1 mg over 8+ weeks) minimizes gastrointestinal adverse effects. 2, 1
• If nausea is intolerable at 0.5 mg, remain at 0.25 mg for an additional 4 weeks before attempting escalation. 2
• Most gastrointestinal side effects are transient and resolve within 4–8 weeks as the body adapts to semaglutide. 2, 6

Administration Instructions

• Inject semaglutide subcutaneously in the abdomen, thigh, or upper arm once weekly, on the same day each week, at any time of day, with or without meals. 1
• If a dose is missed, administer within 5 days of the missed dose; if more than 5 days have passed, skip the missed dose and resume the regular schedule. 1
• Do not mix semaglutide with insulin in the same syringe; administer as separate injections. 2

Critical Thresholds and Safety Considerations

• When basal insulin approaches 0.5–1.0 units/kg/day (approximately 95–190 units for this patient), adding semaglutide is more appropriate than further basal insulin escalation to avoid "overbasalization" with increased hypoglycemia risk. 2, 3
• GLP-1 RAs should not be used with other GLP-1 RAs or with DPP-4 inhibitors. 2
• Semaglutide is contraindicated in patients with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2. 2, 7
• GLP-1 RAs have been associated with thyroid C-cell tumors in rodents in a dose- and treatment duration-dependent fashion. 2

Common Pitfalls to Avoid

• Do not delay insulin dose reduction when starting semaglutide—failure to reduce insulin by 20% upfront is the most common cause of hypoglycemia in the first 4–8 weeks. 2, 1
• Do not continue escalating basal insulin beyond 0.5–1.0 units/kg/day without addressing postprandial hyperglycemia with adjunctive therapy (semaglutide is ideal for this). 2, 3
• Do not discontinue metformin when adding semaglutide unless contraindicated—metformin should remain the foundation of therapy and provides complementary glucose-lowering effects. 2, 8
• Do not expect immediate glucose-lowering effects from semaglutide—the full therapeutic effect builds over 4–5 weeks at each dose level. 2, 1