What Is the Best GLP-1 for Weight Loss?
There isn't a one-size-fits-all "best" GLP-1 receptor agonist for weight loss, as the optimal choice depends on individual factors like your medical history, tolerance to side effects, cost, insurance coverage, and specific health goals (e.g., diabetes management alongside weight loss). However, based on the latest clinical trials and real-world data as of July 2025, tirzepatide consistently outperforms other GLP-1 medications in terms of average weight loss achieved. It's a dual agonist targeting both GLP-1 and GIP (glucose-dependent insulinotropic polypeptide) receptors, which enhances its effects on appetite suppression, satiety, and metabolism compared to single GLP-1 agonists like semaglutide or liraglutide.
Tirzepatide is more effective than Semaglutide for treatment of obesity mainly because the former combines both GLP-1 and GIP. The physiology of #GIP is described here… Oxford Academic https://t.co/am9ixC1I5B
— Neil Floch MD (@NeilFlochMD) February 15, 2025
Battle of the weight loss giants . . . and other research https://t.co/M0y89QiqDF
— Truthoverdishonesty (@Nigelj08223326) July 24, 2025
Average weight loss with semaglutide after 72 weeks was 13.7% versus 20.2% with tirzepatide@reesprescribe @DrIanWeissman @ParagSinghal09
🏆 Tirzepatide vs. Semaglutide
— Michael Albert, MD (@MichaelAlbertMD) May 13, 2025
The heavyweight bout we’ve all been waiting for—and it’s a TKO.
- - -
A new NEJM study just dropped the first head-to-head trial in people with obesity (no diabetes).
Here’s how it played out over 72 weeks:
🥇 Tirzepatide (Zepbound) vs 🥈… pic.twitter.com/qihQkv82to
Read more from the Pharmacy Times Clinical Forum using the link below.
— Pharmacy Times (@Pharmacy_Times) July 24, 2025
Semaglutide & tirzepatide are transforming diabetes & obesity management. These GLP-1 receptor agonists offer benefits from glycemic control to weight loss and cardiovascular risk reduction, emphasizing their… pic.twitter.com/gGsrv2LjEW
New study result 🚨
— Michael Weintraub, MD (@MWeintraubMD) May 12, 2025
Tirzepatide vs semaglutide SURMOUNT 5 RCT
📉Total body weight loss:
−20.2% with tirzepatide
−13.7% with semaglutide
🤢Discontinuations due to gastrointestinal events: tirzepatide 2.7%, semaglutide 5.6%
🤮vomiting tirzepatide 15.0% vs semaglutide 21.3%… pic.twitter.com/ydJdklmFv7
Tirzepatide is just such an amazing drug!
— Conrad Fischer (@SeeFisch) March 25, 2023
*First ever COMBINE GLP and GIP drug
*2-2.5% decrease in HgA1c
*15-20% weight loss!!!!!!!!!!!!!!!!!!!!!!!!!!!!
🦉 Tirzepatide activates both GIP and GLP-1 receptors. Early data shows superior glucose and weight loss outcomes vs. semaglutide. Triple agonists targeting GLP-1/GIP/glucagon are under development.
— aponia_analytics (@AponiaAnalytics) July 20, 2025
https://t.co/9TOGfOnYyw#Tirzepatide #obesity $NVO $LLY $AZN $SNY $GSK $PFE…
GLP-1 medications work by mimicking the glucagon-like peptide-1 hormone, which regulates appetite, slows gastric emptying, and improves insulin sensitivity. They're FDA-approved for chronic weight management in adults with obesity (BMI ≥30) or overweight (BMI ≥27) with weight-related conditions. All require lifestyle changes (diet, exercise) for best results, and weight regain often occurs upon discontinuation.
Below, I'll compare the top GLP-1 options for weight loss based on 2025 data, focusing on effectiveness, side effects, dosing, and other considerations. Data comes from head-to-head trials like SURMOUNT-5 (tirzepatide vs. semaglutide) and meta-analyses.
Key Comparison of GLP-1 Medications for Weight Loss
Medication | Brand Name (for Weight Loss) | Mechanism | Average Weight Loss (in Trials) | Dosing | Common Side Effects | Cost & Availability (2025) | Best For |
---|---|---|---|---|---|---|---|
Tirzepatide | Zepbound | Dual GLP-1/GIP agonist | 20-25% body weight loss over 72 weeks (e.g., 20.2% in SURMOUNT-5; up to 22.5% in SURMOUNT-1) | Weekly injection (5-15 mg) | Nausea, diarrhea, vomiting (15-20% rate, often mild); lower discontinuation vs. semaglutide | $1,000-1,300/month (20% less than semaglutide); shortages easing but high demand | Those seeking maximum weight loss; superior for obesity without diabetes; better waist reduction (-18.4 cm) |
Semaglutide | Wegovy | GLP-1 agonist | 13-20% body weight loss over 68-72 weeks (e.g., 13.7% in SURMOUNT-5; 14.9% in STEP-1) | Weekly injection (0.25-2.4 mg) | Similar GI issues (nausea 20-25%, vomiting 21%); higher discontinuation in some trials | $1,300-1,500/month; widely available, including oral form (Rybelsus) | Proven long-term data; good for diabetes + weight loss; cardiovascular benefits |
Liraglutide | Saxenda | GLP-1 agonist | 5-10% body weight loss over 56 weeks (e.g., 8% in SCALE trial) | Daily injection (up to 3 mg) | GI side effects (similar but daily dosing may increase nausea); higher dropout rates | $1,000-1,400/month; generic options emerging | Entry-level option; less effective but suitable for milder cases or needle-phobic patients (daily vs. weekly) |
- Why Tirzepatide Is Often Considered the Best: In direct comparisons, tirzepatide leads to 47% greater relative weight reduction than semaglutide, with more patients achieving ≥20% loss (48% vs. 27%). It's particularly effective for non-diabetic obesity, reducing waist circumference more and improving metabolic markers like blood sugar. Real-world X discussions from doctors echo this, noting its dual mechanism makes it "transformational" and "superior."
- Other Considerations:
- Side Effects: All GLP-1s cause gastrointestinal issues (nausea, vomiting, diarrhea), but tirzepatide may have slightly lower rates in some trials (e.g., 2.7% discontinuation vs. 5.6% for semaglutide). Rare risks include pancreatitis or thyroid tumors—discuss with a doctor.
- Muscle Loss: Up to 25-40% of weight loss can be lean mass; pair with resistance training to preserve muscle.
- Cost and Access: High prices limit access; tirzepatide is cheaper but faces shortages. Compounded versions exist but carry risks.
- Alternatives: Newer options like retatrutide (triple agonist) are in trials but not yet approved. Bariatric surgery may outperform GLP-1s long-term (e.g., 5x more weight loss).
Always consult a healthcare provider before starting any GLP-1 medication, as they can cause serious side effects and aren't suitable for everyone (e.g., history of medullary thyroid cancer). If you're considering options, a specialist can help determine the best fit based on your profile.