GLP-1 Drugs Ranked by Weight Loss: 2026 Data Comparison

Introduction#

How do the GLP-1 drugs stack up against each other for weight loss? With more than a dozen incretin-based obesity therapies now in clinical trials, comparing their results requires careful attention to trial design, duration, patient population, and dosing.

This article ranks every major GLP-1 and incretin drug by peak clinical weight loss data, with detailed comparison tables and important caveats about cross-trial comparisons.

Important caveat: Cross-trial comparisons are inherently limited. Differences in patient populations, trial duration, baseline BMI, comparator arms, and statistical methodology mean that only head-to-head trials can definitively establish superiority. The rankings below reflect reported clinical data, not head-to-head superiority.

The Complete Rankings#

Overall Weight Loss Rankings (Peak Reported Data)#

*Placebo-adjusted value

Understanding the Rankings#

Why Cross-Trial Comparisons Are Limited#

Several factors make direct comparisons between different trials unreliable:

1. Trial duration varies widely -- Retatrutide's 28.7% is at 68 weeks; amycretin's 24.3% is at 36 weeks. Amycretin's trajectory suggests it could potentially exceed retatrutide's result at comparable duration, but this is speculative.

2. Patient populations differ -- Baseline BMI, race, sex distribution, and comorbidity profiles vary between trials. GLORY-2 enrolled Chinese patients; SURMOUNT-1 enrolled a global population. Ethnicity affects metabolic responses.

3. Dose optimization varies -- Phase 2 doses are often not the final optimized doses. VK2735's 14.7% at only 13 weeks with earlier-phase dosing may underestimate its potential at optimized Phase 3 doses over longer durations.

4. Statistical estimands differ -- Some trials report treatment policy estimand (intention-to-treat), while others report trial product estimand (on-treatment). CagriSema reported both: 20.4% (treatment policy) vs 22.7% (trial product) in REDEFINE 1.

The Only Head-to-Head Data#

Only two large head-to-head trials have been conducted:

• SURMOUNT-5: Tirzepatide 20.2% vs semaglutide 13.7% at 72 weeks (P<0.001)
• DREAMS-3: Mazdutide superior to semaglutide in glycemic control (Chinese T2D population)

All other rankings are based on cross-trial comparisons.

Tier Analysis#

Tier 1: Over 20% Weight Loss (The Frontier)#

Retatrutide (28.7% at 68 wk) stands alone at the top. The triple agonist mechanism (GLP-1 + GIP + glucagon) produces clearly greater weight loss than any dual agonist tested. The TRIUMPH-4 Phase 3 data confirmed the Phase 2 results, with 26.4% at 9 mg and 28.7% at 12 mg. Seven more Phase 3 readouts are expected in 2026.

Amycretin SC (24.3% at 36 wk) achieved this remarkable result in a small Phase 1b/2a trial with only 36 weeks of treatment. The weight loss curve was still declining at study end, suggesting even greater efficacy at longer durations. However, tolerability was concerning: 82% nausea, 53% vomiting, 33% overall discontinuation.

CagriSema (22.7% at 68 wk) demonstrated that combining GLP-1 with amylin signaling produces weight loss exceeding either component alone. CagriSema outperformed both cagrilintide alone (11.5%) and semaglutide alone (14.9%) in REDEFINE 1. NDA filed with FDA.

CT-388 (22.5% at 48 wk) suggests that signal-biased dual GLP-1/GIP agonism may produce weight loss comparable to other approaches with potentially improved tolerability from reduced beta-arrestin recruitment.

Tirzepatide (20.9% at 72 wk) is the only FDA-approved drug in this tier. SURMOUNT-5 confirmed superiority over semaglutide in a head-to-head trial. Tirzepatide remains the gold standard against which all other agents are judged.

MariTide (~20% at 52 wk) and Mazdutide 9 mg (20.1% at 60 wk) round out this tier with different mechanisms: MariTide uses GIPR antagonism (opposite to tirzepatide's agonism) and mazdutide uses glucagon co-agonism.

Tier 2: 15-20% Weight Loss (Competitive Range)#

Survodutide (18.7% at 46 wk) shares mazdutide's GLP-1/glucagon mechanism but with a different peptide backbone. Phase 3 SYNCHRONIZE results pending in 2026.

Pemvidutide (15.6% at 48 wk) is notable for class-leading lean mass preservation: only 21.9% of weight lost was lean mass vs the typical 25-40%. This makes pemvidutide potentially valuable for body composition optimization.

Aleniglipron (15.3% at 36 wk)* is the only oral drug in this tier (placebo-adjusted). The trajectory at 36 weeks suggests potential for higher efficacy at longer durations.

Oral semaglutide 50 mg (15.1% at 68 wk) demonstrated that an oral peptide can match injectable semaglutide. However, this dose is not FDA-approved.

SC semaglutide 2.4 mg (14.9% at 68 wk) remains the benchmark for approved GLP-1 monoagonist therapy.

Tier 3: 10-15% Weight Loss (Early Data / Oral Agents)#

This tier consists primarily of oral formulations with shorter trial durations or lower doses:

• VK2735 SC (14.7% at 13 wk) -- Impressive trajectory for a 13-week trial
• Oral semaglutide 25 mg (13.6% at 64 wk) -- Approved dose, competitive with injectable
• Oral amycretin (13.1% at 12 wk) -- Extraordinary 12-week result for an oral drug
• Oral VK2735 (12.2% at 13 wk) -- Strong oral dual agonist result
• Oral ribupatide (~12% at 26 wk) -- Dual agonist oral formulation
• Orforglipron (11.2% at 72 wk) -- The most mature Phase 3 oral data

Rankings by Mechanism#

GLP-1 Monoagonists#

GLP-1/GIP Dual Agonists#

GLP-1/Glucagon Dual Agonists#

GLP-1/Amylin Combinations#

Triple Agonists#

Antibody Conjugates#

Weight Loss Per Week Comparison#

Since trial durations vary widely, examining the rate of weight loss provides additional context:

Note: This metric favors shorter trials because weight loss rate typically declines over time as patients approach a new steady state. The early rapid weight loss seen with amycretin and VK2735 may not be sustained linearly.

Approved vs Investigational#

FDA-Approved for Obesity#

NDA Filed#

Investigational (Phase 3)#

*Phase 2 data; Phase 3 results pending

Key Takeaways#

1. Triple agonism leads -- Retatrutide's 28.7% weight loss at 68 weeks confirms that targeting three receptors (GLP-1 + GIP + glucagon) produces the most weight loss.

2. Amylin combinations are competitive -- Both amycretin (24.3%) and CagriSema (22.7%) demonstrate that the GLP-1/amylin axis is a powerful combination for weight loss.

3. The 20% threshold is the new standard -- Six drugs have achieved approximately 20% or greater weight loss, establishing this as the benchmark for next-generation therapies.

4. Oral agents are approaching -- Oral semaglutide 50 mg and aleniglipron 240 mg have exceeded 15%, and several oral dual agonists show promising trajectories.

5. Approved options lag investigational leaders -- The highest approved weight loss (tirzepatide at 20.9%) is surpassed by several investigational agents, suggesting that the obesity pharmacotherapy landscape will improve significantly in the next 2-3 years.

6. Body composition matters -- Raw weight loss numbers do not capture differences in lean mass preservation. Pemvidutide and retatrutide may offer advantages in body composition that are not reflected in the rankings.

Conclusion#

The GLP-1 drug landscape for weight loss has never been more competitive. From retatrutide's 28.7% at the top to oral small molecules approaching the teens, the range of options is expanding rapidly. When choosing between agents, clinicians and patients should consider not just peak weight loss but also approval status, route, dosing frequency, tolerability, cardiovascular data, and cost.

The rankings will continue to evolve as Phase 3 results emerge in 2026 and beyond. Head-to-head trials will be essential to definitively establish the relative efficacy of these agents.

This article is for educational and informational purposes only. It does not constitute medical advice. Consult a healthcare provider for treatment decisions.

References#

Related Peptide Profiles#

Learn more about the peptides discussed in this article:

• Retatrutide Overview and Research Guide
• Retatrutide Dosing Protocols
• Retatrutide Side Effects and Safety
• Amycretin Overview and Research Guide
• Amycretin Dosing Protocols
• Amycretin Side Effects and Safety
• CagriSema Overview and Research Guide
• CagriSema Dosing Protocols
• CagriSema Side Effects and Safety
• CT-388 Overview and Research Guide
• CT-388 Dosing Protocols
• CT-388 Side Effects and Safety
• Tirzepatide Overview and Research Guide
• Tirzepatide Dosing Protocols
• Tirzepatide Side Effects and Safety
• MariTide Overview and Research Guide
• MariTide Dosing Protocols
• MariTide Side Effects and Safety
• Mazdutide Overview and Research Guide
• Mazdutide Dosing Protocols
• Mazdutide Side Effects and Safety
• Survodutide Overview and Research Guide
• Survodutide Dosing Protocols
• Survodutide Side Effects and Safety
• Semaglutide Overview and Research Guide
• Semaglutide Dosing Protocols
• Semaglutide Side Effects and Safety
• Orforglipron Overview and Research Guide
• Orforglipron Dosing Protocols
• Orforglipron Side Effects and Safety
• VK2735 Overview and Research Guide
• VK2735 Dosing Protocols
• VK2735 Side Effects and Safety
• Aleniglipron Overview and Research Guide
• Aleniglipron Dosing Protocols
• Aleniglipron Side Effects and Safety