The weight loss curve keeps climbing

One of the most important findings across both trials is the trajectory. Retatrutide weight loss does not flatten out the way some other GLP-1 medications do at 6 to 9 months.

Here is how the 12 mg results progressed across time:

Timepoint	Weight Loss
24 weeks	-17.5% (Phase 2)
48 weeks	-24.2% (Phase 2)
68 weeks	-28.7% (Phase 3)

The slope does moderate over time. But it does not plateau. At 68 weeks, participants were still losing weight. This matters because semaglutide results tend to plateau around weeks 60 to 68 in the STEP trials. Retatrutide at the same timepoint is still on an upward trajectory.

The likely explanation is the glucagon receptor agonism. While GLP-1 and GIP reduce appetite, glucagon receptor activation increases energy expenditure and promotes fat oxidation. This dual mechanism (eating less AND burning more) may prevent the metabolic adaptation that slows weight loss with GLP-1-only drugs.

Head-to-head comparison: retatrutide vs semaglutide vs tirzepatide

No direct head-to-head trials have been published. But we can compare the Phase 3 results across each drug's pivotal trials.

Drug	Trial	Dose	Duration	Weight Loss
Semaglutide 2.4 mg	STEP 1	2.4 mg	68 weeks	-14.9%
Tirzepatide 15 mg	SURMOUNT-1	15 mg	72 weeks	-22.5%
Retatrutide 12 mg	TRIUMPH (Phase 3)	12 mg	68 weeks	-28.7%

Retatrutide at 12 mg nearly doubles semaglutide's weight loss and beats tirzepatide by over 6 percentage points. Even retatrutide's 9 mg dose (26.4%) outperforms tirzepatide's highest dose.

Cross-trial comparisons always carry caveats. Patient populations, baseline weights, and study designs differ. But the magnitude of the gap is hard to explain away with methodology differences alone.

For deeper comparisons, see our full analyses: semaglutide vs tirzepatide vs retatrutide, tirzepatide vs retatrutide, and semaglutide vs retatrutide.

Secondary outcomes: knee pain and physical function

The Phase 3 trial specifically studied participants with obesity and knee osteoarthritis. This was a strategic choice by Eli Lilly since regulators are increasingly interested in weight loss drugs that improve obesity-related conditions, not just the number on the scale.

The results on knee outcomes were significant:

• 75.8% reduction in knee pain on the WOMAC pain scale (12 mg group)
• Substantial improvements in physical function scores
• Over 12% of participants became completely pain-free after treatment

These secondary outcomes matter for the regulatory path. They strengthen the case that retatrutide is not just a weight loss drug but a treatment for obesity as a disease with downstream physical consequences.

Body composition: fat mass vs lean mass

A Phase 2 substudy published in The Lancet Diabetes & Endocrinology examined body composition changes using DEXA scans. This is important because losing muscle along with fat is one of the major concerns with weight loss peptides.

The findings showed that the majority of weight lost was fat mass. Lean mass loss did occur, which is consistent with all significant weight loss interventions. But the ratio of fat-to-lean loss with retatrutide was favorable compared to caloric restriction alone.

The glucagon receptor component may play a role here. Glucagon promotes lipolysis (fat breakdown) while having less direct effect on muscle protein. More data from larger Phase 3 substudies will clarify whether this advantage holds up at scale.

Safety and side effects

The safety profile across both Phase 2 and Phase 3 is consistent with other GLP-1 class drugs, with some additions.

Gastrointestinal side effects (Phase 2, 12 mg group):

• Nausea: 38%
• Diarrhea: 34%
• Vomiting: approximately 20%
• Most GI events occurred during dose escalation and decreased over time

Dysesthesia (unusual skin sensations like tingling or numbness):

• 8.8% at 9 mg
• 20.9% at 12 mg
• This side effect is relatively unique to retatrutide and not commonly seen with semaglutide or tirzepatide

Heart rate increase:

• Small mean increases in resting heart rate were observed
• Consistent with other incretin-based therapies
• Clinical significance remains under study

The dose escalation protocol (starting low and titrating up over weeks) reduced the severity and frequency of GI side effects. This is the same approach used with semaglutide and tirzepatide dosing.

For a full breakdown of adverse events, see our retatrutide side effects page.

What is still coming

The TRIUMPH Phase 3 program includes multiple trials across different indications and populations. The February 2026 readout was only one of them.

Eli Lilly has indicated that 7 additional Phase 3 readouts are expected throughout 2026. These include:

• Obesity without osteoarthritis (the core weight loss indication)
• Type 2 diabetes
• Metabolic dysfunction-associated steatohepatitis (MASH, formerly NASH)
• Sleep apnea
• Heart failure with preserved ejection fraction

Each positive readout strengthens the New Drug Application that Lilly will eventually submit to the FDA. The MASH data is particularly anticipated since no other obesity drug has shown the degree of liver fat reduction that retatrutide demonstrated in Phase 2.

For a full breakdown of the regulatory timeline, see our retatrutide FDA approval timeline guide.

Frequently asked questions

How much weight can you lose on retatrutide?

In clinical trials, the 12 mg dose produced 24.2% body weight loss at 48 weeks (Phase 2) and 28.7% at 68 weeks (Phase 3). For someone weighing 250 pounds, that would be roughly 60 to 72 pounds. Results vary by individual, dose, and duration. See our retatrutide overview for full details.

Is retatrutide better than semaglutide for weight loss?

Based on available clinical trial data, retatrutide produces significantly more weight loss than semaglutide. The 12 mg dose (28.7%) nearly doubles semaglutide 2.4 mg (14.9%) at similar timepoints. No direct head-to-head trial exists. Read our semaglutide vs retatrutide comparison.

Is retatrutide better than tirzepatide?

Retatrutide's 12 mg dose (28.7% at 68 weeks) outperforms tirzepatide's highest dose (22.5% at 72 weeks in SURMOUNT-1). The added glucagon receptor agonism is believed to account for the difference. See tirzepatide vs retatrutide for the full comparison.

When will retatrutide be available?

Retatrutide is currently in Phase 3 trials. The earliest realistic FDA approval is late 2027 to 2028. It is not available through prescriptions, pharmacies, or telehealth. Anything sold online as retatrutide is unregulated. Read our full retatrutide FDA approval timeline.

What are the main side effects of retatrutide?

The most common are gastrointestinal: nausea (38%), diarrhea (34%), and vomiting. A side effect somewhat unique to retatrutide is dysesthesia (skin tingling or numbness), reported in up to 20.9% at the 12 mg dose. See our full retatrutide side effects page.

Does retatrutide cause muscle loss?

Some lean mass loss occurs, as it does with all significant weight loss. Phase 2 body composition data showed the majority of weight lost was fat mass. The glucagon receptor component may help preserve the fat-to-lean ratio compared to caloric restriction alone, but larger studies are needed to confirm this.

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This article was last updated on March 6, 2026. We will update it as new Phase 3 results from the TRIUMPH program are published. For more on weight loss peptides, visit our weight loss goal page or read our guide on retatrutide for weight loss.