Best GLP-1 for Weight Loss: Complete Comparison Guide

Choosing between semaglutide and tirzepatide for weight loss? Both GLP-1 medications are highly effective, but they have key differences. After trying both, here's my comprehensive comparison to help you choose the best GLP-1 for your weight loss journey.

Semaglutide vs Tirzepatide: Effectiveness

Both medications are highly effective for weight loss. Clinical studies show: Semaglutide: 15-20% total body weight loss on average. Tirzepatide: 20-25% total body weight loss on average. Tirzepatide tends to produce slightly better results, but semaglutide is very effective and often more affordable.

Cost Comparison

Pricing varies significantly by provider: Compounded semaglutide: $99-$299/month. Compounded tirzepatide: $99-$399/month. Brand-name Wegovy (semaglutide): $1000-1400/month. Brand-name Mounjaro/Zepbound (tirzepatide): $1000-1200/month. Compounded versions offer the same active ingredients at fraction of the cost.

Which Should You Choose?

Consider tirzepatide if: you want maximum weight loss results, you can afford the slightly higher cost, you want dual GLP-1/GIP action. Consider semaglutide if: you want excellent results at lower cost, you prefer a well-established medication, budget is a primary concern.

Clinical Trial Results Compared

Both semaglutide and tirzepatide have undergone extensive Phase 3 clinical trials demonstrating their effectiveness for weight loss. The data provides clear guidance on what to expect from each medication.

Semaglutide (STEP trials with over 4500 participants): Average weight loss of 15-20% total body weight over 68 weeks. In the landmark STEP 1 trial, participants lost an average of 14.9% body weight (33 pounds for a 220-pound person) over 68 weeks. 50% of participants lost at least 15% of body weight. 32% lost 20% or more. Results were sustained with continued treatment. Common starting weight 105kg (231 lbs), average weight lost 15.3kg (33.7 lbs).

Tirzepatide (SURMOUNT trials with over 5000 participants across multiple studies): Average weight loss of 20-25% total body weight over 72 weeks. In SURMOUNT-1, the highest dose (15mg) produced average weight loss of 22.5% (49 pounds for a 220-pound person). 63% of participants lost at least 20% body weight. 40% lost 25% or more. Results showed continued improvement beyond 72 weeks. Common starting weight 104kg (229 lbs), average weight lost 23.6kg (52 lbs) on 15mg dose.

Head-to-head: Tirzepatide shows 20-30% greater weight loss than semaglutide at comparable timeframes. Both medications demonstrate sustained weight loss with continued treatment. Both show improvements in blood pressure, cholesterol, and blood sugar. The gap narrows at lower doses—people on semaglutide 2.4mg often achieve similar results to tirzepatide 7.5-10mg.

Mechanism of Action Differences

Understanding how each medication works helps explain their different effectiveness profiles and side effect patterns.

Semaglutide is a GLP-1 receptor agonist, meaning it activates only GLP-1 (glucagon-like peptide-1) receptors. This single-target approach provides powerful appetite suppression, significant slowing of stomach emptying (gastric emptying delayed 3-4 hours), improved insulin secretion and reduced glucagon, enhanced satiety signals to the brain, and reduced food cravings and reward-seeking behavior. The GLP-1 pathway is well-studied with over 15 years of clinical use data.

Tirzepatide is a dual GIP/GLP-1 receptor agonist, activating both GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 receptors simultaneously. This dual mechanism provides all the benefits of GLP-1 activation plus additional effects from GIP stimulation: enhanced insulin secretion with better glucose control, improved fat metabolism and energy expenditure, potential neuroprotective effects on brain reward pathways, synergistic appetite suppression beyond GLP-1 alone, and possibly improved lean muscle preservation during weight loss. The dual mechanism explains tirzepatide's superior weight loss results in clinical trials.

Side Effect Comparison

Both medications share similar side effect profiles since they both activate GLP-1 receptors, but there are some notable differences in frequency and severity.

Semaglutide side effects: Nausea affects 20-40% of users (most common side effect), diarrhea 10-15%, constipation 10-20%, vomiting 5-10%, fatigue/tiredness 10-15%, and heartburn/acid reflux 5-10%. Side effects are typically worst during dose increases and first 4-8 weeks. Most users report side effects become manageable or resolve completely by month 2-3.

Tirzepatide side effects: Nausea affects 20-30% (slightly lower than semaglutide), diarrhea 15-20% (somewhat higher), constipation 10-15%, vomiting 5-10%, fatigue 10-15%, and injection site reactions 5-10%. Some users report tirzepatide causes less severe nausea but more GI motility changes. The dual mechanism may actually reduce some side effects compared to higher-dose GLP-1 agonists.

Overall tolerability: Both medications have similar discontinuation rates due to side effects (4-7% in clinical trials). Neither is definitively "easier" to tolerate—individual response varies significantly. Starting at low doses and increasing gradually minimizes side effects for both. Most people who try both report similar overall tolerability with personal preferences varying.

Cost Considerations

Price is a crucial factor since weight loss is typically a 12+ month commitment requiring sustained treatment.

Brand-name costs: Wegovy (semaglutide) $1000-1400/month without insurance. Zepbound (tirzepatide) $1000-1200/month without insurance. Both are similarly expensive, making them unaffordable for most people without insurance coverage (which most plans don't provide for weight loss).

Compounded medication costs through telehealth: Semaglutide ranges $99-299/month (average $200/month). Tirzepatide ranges $99-399/month (average $280/month). CoreAge Rx offers both at the same $99/month price point. Premium providers typically charge $299-399/month for both medications. The cost difference between semaglutide and tirzepatide at the compounded level is minimal with most providers.

Annual cost comparison: Compounded semaglutide: $1188-3588/year (average $2400). Compounded tirzepatide: $1188-4788/year (average $3360). The $50-80/month difference ($600-960/year) for potentially 20-30% better results makes tirzepatide attractive for many people. However, semaglutide at $99-199/month represents excellent value for those prioritizing affordability.

Who Should Choose Each Medication

Both medications are excellent choices, but individual circumstances may make one more suitable than the other.

Choose semaglutide if: Budget is your primary concern and you want the lowest possible monthly cost. You have private insurance that covers Wegovy but not Zepbound. You prefer the medication with the longest track record (15+ years of GLP-1 clinical use). You achieve your weight loss goals with semaglutide and don't need the additional effectiveness. You want a medication with the most published research and real-world data. You're starting weight loss medication for the first time and want to see how you respond before committing to higher doses.

Choose tirzepatide if: You want maximum weight loss results and can afford the modest price difference. You have significant weight to lose (50+ pounds) and want the most effective option. You didn't achieve satisfactory results with semaglutide and want something stronger. You're interested in the latest medication technology with dual-receptor activation. Your insurance covers Zepbound (rare but occasionally happens). You can afford $299-399/month and want the best possible outcomes.

Many people start with semaglutide to see how they respond to GLP-1 medications, then switch to tirzepatide if they want additional weight loss after reaching a plateau. Some providers allow switching between medications based on your response and goals.

My Recommendation

After extensive testing, CoreAge Rx consistently delivers the best combination of affordability, quality, and service. At $99/month for both semaglutide and tirzepatide, they offer unmatched value without compromising on medical support or medication quality.

For those seeking premium service and willing to invest more, Super Healthy Rx provides exceptional care at $249/month with comprehensive support and high-touch service.

Bottom Line

Whether you choose budget-friendly CoreAge Rx, premium Super Healthy Rx, or another top-rated provider, online telehealth makes GLP-1 medications accessible and affordable. Use the comparison table above to find the best fit for your needs and budget.