What is the new Lilly drug for weight loss?: Zepbound, Orforglipron, and Retatrutide

October 11, 2025 •

4 min read

With nearly 42% of US adults considered obese, the search for effective treatments is more urgent than ever. Pharmaceutical giant Eli Lilly has emerged as a leader in this space, with its FDA-approved injectable, Zepbound, and several promising new medications in its pipeline, addressing the common question: what is the new Lilly drug for weight loss?.

Quick Summary

Eli Lilly's FDA-approved Zepbound (tirzepatide) treats obesity by targeting two hunger hormones. The company also has an oral pill, orforglipron, and a triple-hormone injectable, retatrutide, in development, offering multiple future options for weight management.

Key Points

FDA-Approved Zepbound: Zepbound (tirzepatide) is Eli Lilly's current FDA-approved weekly injectable for chronic weight management, targeting GIP and GLP-1 hormones.
Pipeline Oral Option: Orforglipron is Eli Lilly's investigational once-daily oral pill, expected to enter the market around 2026 pending regulatory approval.
Triple-Agonist Injectable: Retatrutide is an investigational weekly injectable in Phase 3 trials that targets three hormone receptors (GIP, GLP-1, and glucagon) and may offer greater weight loss.
Mechanism Differences: While Zepbound is a dual-agonist and orforglipron is a GLP-1 agonist, retatrutide's triple-agonist action could set a new standard for weight loss efficacy.
Convenience vs. Potency: The choice between Lilly's drugs may come down to patient preference between the convenience of an oral pill (orforglipron) and the potential higher potency of an injectable (Zepbound or retatrutide).
Not a Quick Fix: All of these medications require long-term use alongside diet and exercise for sustained results, and weight regain is common if the medication is stopped.
Requires Prescription: Like other potent GLP-1 drugs, all of Lilly's weight loss medications are available by prescription only and are not intended for cosmetic use.

Eli Lilly has a robust and expanding pipeline of weight-loss medications designed to address the significant and growing public health challenge of obesity. While Zepbound is its most prominent and currently approved offering for weight management, two other investigational drugs, orforglipron and retatrutide, are generating significant buzz in the medical community. These newer treatments aim to offer different delivery methods and potentially higher efficacy for patients.

Zepbound (Tirzepatide): The Current FDA-Approved Option

Zepbound is the brand name for tirzepatide when prescribed for chronic weight management in adults. It received FDA approval for this indication in November 2023. Before that, the same active ingredient was approved as Mounjaro for type 2 diabetes management.

How Zepbound Works

Zepbound is a dual-agonist drug, meaning it activates two key hormone receptors in the body. These are:

Glucose-dependent insulinotropic polypeptide (GIP): This hormone plays a role in insulin secretion and fat metabolism.
Glucagon-like peptide-1 (GLP-1): This hormone helps regulate blood sugar, slows gastric emptying, and suppresses appetite.

By mimicking the effects of these two natural incretin hormones, tirzepatide slows the movement of food through the stomach, making a person feel full sooner and for a longer period. It also helps regulate blood sugar levels, though this is a secondary effect when used for weight loss.

Clinical Efficacy

In clinical trials, Zepbound has shown significant weight loss results when used in combination with diet and exercise.

Participants without diabetes on the highest dose (15mg weekly) achieved an average weight loss of 23.6 kg (52.0 lbs) over 72 weeks.
Higher doses generally produced greater weight loss.

Orforglipron: The Anticipated Oral Pill

For patients who prefer not to use injections, Eli Lilly has an oral option in its pipeline: orforglipron. This investigational drug is a once-daily pill currently completing Phase 3 trials. Lilly is on track to seek regulatory approval by the end of 2025, with potential market availability in 2026 if all goes well.

How Orforglipron Works

Orforglipron is a GLP-1 receptor agonist, similar to the active ingredient in Novo Nordisk's Ozempic and Wegovy. However, unlike Novo Nordisk's oral GLP-1 (Rybelsus), orforglipron is a non-peptide small molecule. This key difference means it is absorbed more easily by the body and does not require strict dietary restrictions for absorption.

Clinical Efficacy and Benefits

In a late-stage trial, the highest dose of orforglipron helped patients lose nearly 12% of their body weight over 72 weeks.
This weight loss is lower than what is typically seen with the injectable dual-agonist Zepbound, but it still represents a significant advancement for an oral medication.
The convenience of a daily pill could increase patient adherence and address some of the supply chain challenges that have plagued injectable treatments.

Retatrutide: The 'King Kong' Triple-Agonist

Retatrutide is another investigational drug in Eli Lilly's pipeline and is often dubbed the "triple G" drug. It is a weekly injectable that acts on three different hormone receptors, potentially offering even greater weight loss efficacy than currently approved treatments. Retatrutide is currently in Phase 3 clinical trials, with potential FDA approval in the 2027 timeframe.

How Retatrutide Works

Retatrutide is a triple-hormone-receptor agonist that mimics the actions of:

GIP (Glucose-dependent insulinotropic polypeptide)
GLP-1 (Glucagon-like peptide-1)
Glucagon (GCG): This hormone increases the body's energy expenditure and fat burning.

Clinical Efficacy and Potential

In Phase 2 trials, participants on the highest dose of retatrutide experienced an average weight reduction of 24.2% over 48 weeks, surpassing the efficacy demonstrated by Zepbound in earlier trials.
For some patients, these results rival the weight loss seen with bariatric surgery, positioning retatrutide as a potential game-changer.

Comparative Overview of Lilly's Weight Loss Drugs


Feature	Zepbound (Tirzepatide)	Orforglipron	Retatrutide
Approval Status	FDA-Approved (Nov 2023)	Investigational (Phase 3)	Investigational (Phase 3)
Route of Administration	Once-weekly subcutaneous injection	Once-daily oral pill	Once-weekly subcutaneous injection
Mechanism of Action	Dual GIP and GLP-1 agonist	GLP-1 receptor agonist	Triple GIP, GLP-1, and GCG agonist
Weight Loss Efficacy	Up to ~21% average weight loss in trials	Up to ~12% average weight loss in trials	Up to ~24% average weight loss in trials
Expected Availability	Available now	Possibly 2026	Possibly 2027

What This Means for the Future of Weight Management

Eli Lilly's multi-pronged approach to weight loss offers a glimpse into the future of obesity treatment. By providing a menu of options, including an already-approved injectable (Zepbound), a pipeline oral pill (orforglipron), and a highly-potent investigational injectable (retatrutide), the company is catering to different patient preferences and needs. The oral option addresses the aversion to needles for some patients, while the next-generation injectable may offer the highest efficacy for those with significant weight loss goals.

While this is an exciting time for medical weight management, these medications are not a quick fix. They require long-term use and should be combined with a reduced-calorie diet and increased physical activity for best results. They also carry side effects and risks that must be considered and discussed with a healthcare provider. The development of multiple options suggests a future where treatment can be better tailored to individual patient needs, potentially expanding access and improving long-term health outcomes for those with obesity.

Conclusion

In answer to the question, "What is the new Lilly drug for weight loss?" the immediate answer is Zepbound, a dual-agonist injectable that was FDA-approved in late 2023. However, the company's pipeline contains even more options that may soon come to market. The once-daily oral pill, orforglipron, offers a convenient alternative for patients who prefer not to self-inject, while the investigational triple-agonist injectable, retatrutide, promises even greater weight loss potential. The availability of these different treatment mechanisms and delivery formats will fundamentally change the landscape of chronic weight management, providing more tailored and effective solutions for millions of people.

Authoritative Sources

Frequently Asked Questions

Eli Lilly has a few notable weight-loss drugs. The newest FDA-approved option is Zepbound (tirzepatide), a once-weekly injectable. The company also has two investigational drugs in its pipeline: orforglipron, an oral pill, and retatrutide, a triple-agonist injectable currently in Phase 3 trials.

Eli Lilly is developing both. The FDA-approved option for weight management is Zepbound, a once-weekly injectable. However, the company's daily oral pill, orforglipron, is in late-stage trials and could be available in 2026.

Zepbound works by activating the body's natural GIP and GLP-1 hormone receptors. This dual action suppresses appetite, increases feelings of fullness, and slows digestion, leading to reduced calorie intake and significant weight loss.

Zepbound is a dual-agonist injectable that is already approved. Orforglipron is a daily oral GLP-1 agonist pill still in development. Retatrutide is a highly potent investigational triple-agonist injectable targeting GLP-1, GIP, and glucagon receptors.

Clinical trial data suggests Eli Lilly's injectable Zepbound (tirzepatide) leads to greater average weight loss (up to ~21%) than the experimental pill orforglipron (up to ~12%). However, the pill offers an important needle-free option.

Eli Lilly expects to submit orforglipron for regulatory approval by the end of 2025. If the process goes smoothly, the oral pill could be approved and available as early as 2026.

Yes, Eli Lilly's pipeline includes the investigational injectable drug retatrutide, a triple-agonist that has shown potential for even greater weight loss than Zepbound in early clinical trials. It is not yet FDA-approved.

Common side effects for both approved and investigational Lilly drugs typically include gastrointestinal issues like nausea, vomiting, diarrhea, and constipation. Most of these effects are mild to moderate.

Insurance coverage varies depending on the specific plan and medication. While Zepbound is now approved, coverage often depends on medical necessity criteria and individual plan formularies. Investigational drugs like orforglipron and retatrutide are not yet covered.

Yes, Zepbound is specifically FDA-approved for chronic weight management in adults with obesity (BMI ≥ 30) or those overweight (BMI ≥ 27) with at least one weight-related medical problem, regardless of diabetes status.