What is the appropriate starting dose and titration schedule for Ozempic (semaglutide) in an adult with type 2 diabetes, and what are its contraindications and major adverse effects?

Ozempic (Semaglutide) for Type 2 Diabetes: Dosing, Contraindications, and Adverse Effects

For adults with type 2 diabetes, start Ozempic at 0.25 mg subcutaneously once weekly for 4 weeks, then increase to 0.5 mg weekly; if additional glycemic control is needed after ≥4 weeks, titrate to 1.0 mg weekly, and for further intensification move to 2.0 mg weekly after ≥4 weeks at 1.0 mg. 1, 2

Starting Dose and Titration Schedule

The initial dose is 0.25 mg once weekly for the first 4 weeks, which serves as a dose-escalation period to minimize gastrointestinal adverse effects rather than a therapeutic dose. 1, 2

After the initial 4-week period:

• Increase to 0.5 mg once weekly (first maintenance dose) 1, 2
• If HbA1c remains above target after ≥4 weeks on 0.5 mg, escalate to 1.0 mg weekly 1, 2
• For maximum glycemic control, further increase to 2.0 mg weekly after ≥4 weeks on 1.0 mg 1, 2

Administer subcutaneously in the abdomen, thigh, or upper arm once weekly on the same day each week; timing of day is flexible and does not need to coincide with meals. 1

Missed Dose Management

If a dose is missed by ≤5 days, administer as soon as possible and resume the regular weekly schedule; if >5 days have elapsed, skip the missed dose and give the next dose on the originally scheduled day. 1

The weekly injection day may be shifted provided at least 48 hours (2 days) separate consecutive doses. 1

Absolute Contraindications

Ozempic is absolutely contraindicated in patients with:

• Personal or family history of medullary thyroid carcinoma (MTC) 1, 3
• Multiple endocrine neoplasia type 2 (MEN 2) 1, 3
• History of severe hypersensitivity reaction to semaglutide 1

Screen all patients for these contraindications before prescribing; animal studies showed thyroid C-cell tumors with GLP-1 receptor agonists, forming the basis for these prohibitions. 1

Major Adverse Effects

Gastrointestinal Effects (Most Common)

Nausea occurs in 20-24% of patients, diarrhea in 11-13%, and vomiting in 8-16%; these are dose-dependent, typically mild-to-moderate, and usually resolve within 4-8 weeks. 1, 3

The most frequent reason for treatment discontinuation is gastrointestinal adverse events; approximately 12-13% of patients discontinue due to these effects. 3

Slow titration with 4-week intervals between dose increases is essential to minimize gastrointestinal symptoms and improve tolerability. 1

Serious Adverse Effects

Pancreatitis has been reported in clinical trials, though causality has not been definitively established; patients should be instructed to report persistent severe abdominal pain immediately, and Ozempic should be discontinued if pancreatitis is suspected. 1

Gallbladder disease (cholelithiasis and cholecystitis) occurs 38% more frequently than with placebo; Ozempic should be avoided in patients with symptomatic gallstones. 1

Delayed gastric emptying persists even after extended fasting periods, with 24.2% of semaglutide users showing increased residual gastric content versus 5.1% of controls, creating aspiration risk during anesthesia. 1

Hypoglycemia Risk

Ozempic has minimal intrinsic hypoglycemia risk when used as monotherapy due to its glucose-dependent mechanism of action. 1

However, when combined with insulin or sulfonylureas, hypoglycemia risk increases markedly; reduce basal insulin by approximately 20% and decrease sulfonylurea dose by 50% or discontinue entirely before starting Ozempic. 1, 2

Renal Considerations

No dose adjustment is required across all stages of chronic kidney disease, including eGFR <30 mL/min/1.73 m² and end-stage renal disease. 1, 4

Semaglutide reduces albuminuria by 20.6% and slows eGFR decline, providing renal-protective effects in patients with chronic kidney disease. 1, 4

Concomitant Medication Adjustments

Stop all DPP-4 inhibitors (e.g., sitagliptin, linagliptin) before starting Ozempic; concurrent use offers no additional glycemic benefit. 1

Reduce or discontinue diuretic therapy at initiation to prevent intravascular volume contraction and dehydration. 2

Perioperative Management

For elective surgery requiring anesthesia, discontinue Ozempic at least 3 weeks (three half-lives) before the procedure due to delayed gastric emptying and aspiration risk. 1, 2

Retained gastric contents are documented even after extended fasting periods in patients on semaglutide, independent of appetite-suppression effects. 1

Monitoring Requirements

Re-assess HbA1c, fasting glucose, body weight, and blood pressure at weeks 12-16 to determine treatment efficacy. 1

Continue monitoring HbA1c, weight, blood pressure, and cardiovascular risk factors every 3 months until targets are met; thereafter, monitor every 3-6 months. 1

Advise patients to check capillary blood glucose more frequently during the first 4 weeks of therapy to detect early hypoglycemia, especially if on insulin or sulfonylureas. 1

Common Pitfalls to Avoid

Do not start at the maintenance dose (0.5 mg or higher); initiating at 2.4 mg markedly raises gastrointestinal adverse events and discontinuation rates. 1

Do not overlook the need to reduce or stop sulfonylureas when adding Ozempic; their combination significantly raises hypoglycemia risk. 1

Do not assume renal dose adjustment is necessary; Ozempic dosing remains unchanged across all CKD stages. 1

Do not prescribe to patients with personal or family history of MTC or MEN 2—these are absolute contraindications. 1