Does Wegovy 0.5 mg Eventually Stop Working?
No, Wegovy (semaglutide) 0.5 mg does not "stop working" in the sense of losing its pharmacologic effect, but 0.5 mg is an intermediate titration dose—not the therapeutic maintenance dose—so weight loss will plateau if you remain at this dose instead of escalating to the full 2.4 mg weekly target. 1, 2
Understanding the Titration Schedule
Wegovy 0.5 mg is designed as a 4-week titration step, not a maintenance dose—the FDA-approved escalation protocol starts at 0.25 mg weekly for 4 weeks, then advances to 0.5 mg, 1.0 mg, 1.7 mg (each for 4 weeks), and finally reaches the 2.4 mg maintenance dose after 16 weeks. 2
Remaining at 0.5 mg will produce suboptimal weight loss because clinical trials demonstrating 14.9% mean weight loss at 68 weeks used the full 2.4 mg dose, not intermediate titration doses. 1, 3
Why Weight Loss Plateaus at Subtherapeutic Doses
The dose-response relationship is clear: higher semaglutide doses produce greater weight reduction, with 2.4 mg weekly achieving 15.8% weight loss compared to only 6.4% with liraglutide 3.0 mg daily (a lower-potency GLP-1 agonist), demonstrating that maximal dosing is essential for optimal outcomes. 4
Semaglutide does not show maximal benefit until after 6 months of therapy at the full maintenance dose, with mean weight loss increasing from -13.4% at 6 months to -17.6% at 12 months in real-world data from patients on 2.4 mg weekly. 5, 6
Patients who remain on lower doses will experience a weight-loss plateau because the medication's appetite suppression, delayed gastric emptying, and metabolic effects are dose-dependent—staying at 0.5 mg means you are receiving only about 20% of the therapeutic dose. 1, 7
The Correct Action: Dose Escalation
You should continue titrating upward to 2.4 mg weekly following the standard 4-week escalation schedule (0.5 mg → 1.0 mg → 1.7 mg → 2.4 mg), unless gastrointestinal side effects prevent further dose increases. 2, 5
Gradual dose escalation minimizes gastrointestinal adverse effects (nausea, vomiting, diarrhea), which occur in 30-40% of patients but are typically transient and mild-to-moderate in severity, subsiding with time. 2, 3
If you cannot tolerate 2.4 mg, the maximum tolerated dose (even if 1.7 mg or 1.0 mg) should be maintained for at least 12 months before concluding the treatment is inadequate, as some patients achieve meaningful weight loss at lower doses. 5
What Happens at the Full Maintenance Dose
At 2.4 mg weekly, semaglutide produces sustained weight loss: 86.4% of patients achieve ≥5% weight loss, 69.1% achieve ≥10%, and 50.5% achieve ≥15% weight loss at 68 weeks. 3
Weight loss continues to increase over time: real-world data show mean weight loss of -13.4% at 6 months, -17.6% at 12 months, -20.3% at 18 months, and -20.4% at 24 months in patients maintained on 2.4 mg weekly. 6
The medication requires lifelong use to maintain benefits—after cessation of semaglutide, significant weight regain occurs (11.6% of lost weight regained after 52 weeks), so stopping at 0.5 mg or any dose will result in weight regain. 1, 2
Common Pitfalls to Avoid
Do not remain at 0.5 mg indefinitely—this is a titration dose, not a maintenance dose, and will not produce the weight loss demonstrated in clinical trials. 2
Do not assume the medication "stopped working" if weight loss plateaus at 0.5 mg—the plateau occurs because you are on a subtherapeutic dose, not because of medication resistance or tachyphylaxis. 1, 5
Do not skip the lifestyle intervention component—all clinical trials incorporated a 500-kcal daily deficit diet and 150 minutes per week of physical activity, which are essential for optimal outcomes even at the full 2.4 mg dose. 5, 3
Do not discontinue treatment prematurely—treatment response should be evaluated at 12-16 weeks on the maximum tolerated therapeutic dose (ideally 2.4 mg), not at intermediate titration doses like 0.5 mg. 5
If You Reach 2.4 mg and Still Plateau
Verify you have been on 2.4 mg for at least 12 months, as semaglutide does not show maximal benefit until after 6 months of therapy, and weight loss continues to increase through 24 months. 5, 6
Reassess lifestyle intervention adherence, including the 500-kcal daily deficit and 150 minutes per week of physical activity (including resistance training to preserve lean body mass). 5
If inadequate response persists after 12 months on 2.4 mg with optimized lifestyle interventions, consider switching to tirzepatide, which demonstrates superior weight loss of 20.9% compared to semaglutide's 14.9%. 5
Continue therapy even if weight plateau occurs if you have established cardiovascular disease, as semaglutide 2.4 mg reduces cardiovascular death, nonfatal MI, or nonfatal stroke by 20% (HR 0.80) independent of ongoing weight loss. 5