What is the lowest effective dose of semaglutide (GLP-1 receptor agonist) for weight loss?

Lowest Effective Semaglutide Dose for Weight Loss

The lowest effective semaglutide dose for weight loss is 0.5 mg weekly, which produces clinically meaningful weight loss of approximately 8.6% at 52 weeks, though the FDA-approved maintenance dose of 2.4 mg weekly provides superior results with 14.9% weight loss. 1, 2, 3

Evidence-Based Dose-Response Data

The dose-ranging phase 2 trial provides the most direct evidence for determining the lowest effective dose:

• Semaglutide 0.05 mg weekly produced 6.0% weight loss at 52 weeks, which exceeded placebo (2.3%) but falls below the clinically significant 5% threshold for most patients 2

• Semaglutide 0.1 mg weekly achieved 8.6% weight loss, representing the first dose to consistently produce clinically meaningful results across the study population 2

• Doses of 0.2 mg and above (0.2 mg, 0.3 mg, 0.4 mg) produced progressively greater weight loss (11.2-13.8%), with 37-65% of patients achieving ≥10% weight loss 2

FDA-Approved Dosing vs. Lower Doses

The FDA-approved maintenance dose is 2.4 mg weekly, which demonstrated 14.9% mean weight loss in the pivotal STEP 1 trial with 86.4% of patients achieving ≥5% weight loss 1, 3. However, real-world evidence suggests lower doses may be effective:

• Real-world data shows 1 mg weekly produces 13.6% weight loss at 6 months, comparable to 2 mg weekly (12.8% weight loss), suggesting some patients respond well to sub-maximal doses 4

• At 3 months, patients on various doses (median not specified but including 1 mg) achieved 7.4 kg (6.6%) weight loss, with 70% achieving ≥5% weight loss 4

• Low-dose semaglutide (0.25-1 mg weekly) produced 5.91 kg (6.15%) weight loss at 12 weeks in non-diabetic patients, demonstrating efficacy even at doses well below the FDA-approved maintenance dose 5

Practical Dosing Algorithm

Start with the FDA-approved titration schedule but consider stopping at lower maintenance doses for responders:

• Weeks 0-4: 0.25 mg weekly (initial dose to minimize gastrointestinal side effects) 6

• Weeks 5-8: 0.5 mg weekly (first potentially effective maintenance dose based on phase 2 data) 6, 2

• Weeks 9-12: 1.0 mg weekly (assess response at 12-16 weeks) 6

• Weeks 13-16: 1.7 mg weekly (if additional weight loss needed) 6

• Week 17+: 2.4 mg weekly (FDA-approved maintenance dose for maximal effect) 1, 6

When to Stop Titration at Lower Doses

Consider maintaining at 0.5-1.0 mg weekly if:

• Patient achieves ≥5% weight loss after 3 months at current dose (early responder criteria) 1

• Patient experiences significant gastrointestinal side effects that would worsen with dose escalation 1, 4

• Patient reaches their weight loss goal before reaching 2.4 mg weekly 4

However, the American Gastroenterological Association recommends prioritizing semaglutide 2.4 mg over other anti-obesity medications due to its superior magnitude of benefit, suggesting maximal dosing should be the goal when tolerated 6

Critical Caveats

Weight loss is dose-dependent, with higher doses consistently producing greater results in clinical trials 2. The phase 2 trial showed:

• 0.1 mg: 8.6% weight loss
• 0.2 mg: 11.6% weight loss
• 0.4 mg: 13.8% weight loss 2

Gastrointestinal side effects are dose-related but typically mild-to-moderate and transient, occurring in approximately 65% of patients but leading to discontinuation in only 2.5% 4. Slow titration every 4 weeks is essential to minimize these effects 1, 6

Long-term use is necessary for sustained weight loss, as significant weight regain (11.6% of lost weight) occurs after cessation 6. Therefore, finding the lowest effective dose that produces sustained results may improve long-term adherence.

Monitoring Requirements

Assess efficacy at 12-16 weeks on any given dose:

• If <5% weight loss achieved, escalate to next dose level 1
• If ≥5% weight loss achieved, continue current dose or escalate based on weight loss goals 1
• Monitor monthly for first 3 months, then quarterly 1