GZR18 vs Tirzepatide for Obesity

Not yet recruiting at 36 trial locations

Overseen By Kimberly Lazaroff

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Gan and Lee Pharmaceuticals, USA

Must not be taking: Antidepressants, Antipsychotics, Mood stabilizers, others

Disqualifiers: Diabetes, Renal impairment, Depression, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 20

Duration: 36 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, GZR18, to determine its safety and effectiveness for managing weight in individuals who are obese or overweight with related health issues, such as high blood pressure or sleep apnea (a sleep disorder where breathing stops and starts). Participants will receive either different doses of GZR18, a placebo, or tirzepatide (a medication already used for weight loss). The trial seeks individuals who have struggled to lose weight through diet and lifestyle changes. Those with a BMI of 30 or higher, or 27 or higher with conditions like high blood pressure, may be suitable for this study. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications. However, certain medications that cause weight gain or are intended for weight loss are not allowed, and some medications must have stable doses for 30 days before screening. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have found GZR18 injections to be safe and generally well-tolerated. The most common side effects included mild stomach issues, similar to those seen with other treatments in this field. Research supports further testing of GZR18 for managing body weight and blood sugar levels.

Research shows that tirzepatide is effective for weight loss and generally safe. However, it can cause stomach-related side effects and, rarely, more serious issues. Doctors have used it off-label for treating obesity, prescribing it based on existing data, even though it may not be officially approved for this purpose.

Both treatments in this trial have demonstrated promising safety in earlier research, but participants should be aware of the potential for mild to serious side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about GZR18 for obesity because it offers a potentially novel approach compared to current treatments. Most obesity treatments focus on appetite suppression or increasing metabolism, but GZR18 may work through a different mechanism, though specifics are still being studied. Another treatment in the trial, Tirzepatide, is already known for its dual-action on insulin regulation and appetite control, making these treatments exciting candidates for addressing obesity from multiple angles.

What evidence suggests that this trial's treatments could be effective for obesity?

This trial will compare GZR18 with Tirzepatide for obesity. Research has shown that GZR18, which participants in this trial may receive, delivers promising results for weight loss. One study found that individuals taking GZR18 lost an average of 17.29% of their body weight after 30 weeks, indicating its potential effectiveness for weight management. Similarly, Tirzepatide, another treatment option in this trial, has demonstrated significant weight loss results. In trials, some individuals lost over 20% of their body weight. Both treatments hold strong potential for addressing obesity and weight-related issues. ^{5 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults who are obese (BMI ≥30) or overweight (BMI ≥27) with weight-related health issues, but not type 2 diabetes. Participants should be seeking treatment for weight management.

Inclusion Criteria

I am willing and able to self-inject the treatment and follow the study's procedures.

History of failing to lose sufficient weight with lifestyle/dietary modification

My BMI is 30 or higher, or it's 27 or higher with certain conditions.

Exclusion Criteria

History of suicide attempt or high PHQ-9 score

I do not have a history of severe depression or psychiatric disorders.

Laboratory values suggestive of diabetes

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Treatment

Participants receive GZR18 or placebo every 2 weeks, or tirzepatide every week, for weight management

36 weeks

Bi-weekly visits (in-person) for GZR18 and placebo, weekly visits for tirzepatide

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• GZR18
• Tirzepatide

Trial Overview The study tests different doses of GZR18 given every two weeks against Tirzepatide given weekly and a placebo to see which is better at managing weight in participants.

How Is the Trial Designed?

Group I: 48 mg GZR18 group Experimental Treatment 1 Intervention

48 mg GZR18 group: 76 participants (57 receiving GZR18 and 19 receiving placebo)

Group II: 36 mg GZR18 group Experimental Treatment 1 Intervention

36 mg GZR18 group: 76 participants (57 receiving GZR18 and 19 receiving placebo)

Group III: 24 mg GZR18 group Experimental Treatment 1 Intervention

24 mg GZR18 group: 76 participants (57 receiving GZR18 and 19 receiving placebo)

Group IV: Tirzepatide group Active Control 1 Intervention

Tirzepatide group: 57 participants receiving 15 mg tirzepatide

Who Is Running the Clinical Trial?

Gan and Lee Pharmaceuticals, USA

Lead Sponsor

Trials

27

Recruited

3,200+

Published Research Related to This Trial

Tirzepatide, a dual GLP-1 and GIP receptor agonist recently approved by the FDA, shows significant effectiveness in controlling blood sugar levels in type 2 diabetes mellitus (T2DM), outperforming traditional treatments like insulin.

In addition to improving glycemic control, tirzepatide also promotes substantial weight loss, positioning it as a promising alternative to bariatric surgery for obesity management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The catcher in the gut: Tirzepatide, a dual incretin analog for the treatment of type 2 diabetes mellitus and obesity. Lempesis, IG., Liu, J., Dalamaga, M.[2022]

In a 72-week phase 3 trial involving 2539 adults with obesity, tirzepatide (5 mg, 10 mg, or 15 mg) resulted in significant weight loss, with mean reductions of -15.0%, -19.5%, and -20.9% respectively, compared to only -3.1% with placebo.

A high percentage of participants (85% to 91%) on tirzepatide achieved at least a 5% weight reduction, and many experienced improvements in cardiometabolic measures, although gastrointestinal side effects were the most common adverse events, mostly mild to moderate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide Once Weekly for the Treatment of Obesity. Jastreboff, AM., Aronne, LJ., Ahmad, NN., et al.[2023]

Tirzepatide demonstrated a dose-dependent ability to lower HbA1c levels in adults with type 2 diabetes, with reductions ranging from -17.71 to -22.35 mmol/mol compared to placebo, and was also more effective in reducing body weight than other treatments.

While tirzepatide did not increase the risk of hypoglycaemia compared to placebo and showed lower rates than basal insulin, it was associated with a higher incidence of gastrointestinal side effects, particularly nausea and vomiting, especially at the 15 mg dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of type 2 diabetes with the dual GIP/GLP-1 receptor agonist tirzepatide: a systematic review and meta-analysis. Karagiannis, T., Avgerinos, I., Liakos, A., et al.[2023]

In a 72-week phase 3 trial involving 938 adults with obesity and type 2 diabetes, tirzepatide (10 mg and 15 mg) led to significant weight loss, with reductions of -12.8% and -14.7% respectively, compared to only -3.2% with placebo.

The safety profile of tirzepatide was generally favorable, with most adverse events being mild to moderate gastrointestinal issues, and serious adverse events were rare, indicating it is a safe option for weight management in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Garvey, WT., Frias, JP., Jastreboff, AM., et al.[2023]

Tirzepatide significantly reduces body weight in patients with type 2 diabetes and obesity, with an average weight loss of -9.81 kg compared to placebo, based on a meta-analysis of 10 studies involving 9,873 patients.

While tirzepatide is effective for weight loss, it has a higher incidence of gastrointestinal side effects compared to placebo, although serious adverse events and hypoglycemia are less common, indicating a need for monitoring these reactions during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weight loss efficiency and safety of tirzepatide: A Systematic review. Lin, F., Yu, B., Ling, B., et al.[2023]

Tirzepatide is a novel medication that acts on both GIP and GLP-1 receptors, enhancing insulin secretion and reducing glucagon levels, which helps improve glycemic control in adults with type 2 diabetes mellitus (T2DM).

It received its first approval in the USA in May 2022 for T2DM treatment and is currently being studied for additional conditions like obesity, heart failure, and non-alcoholic steatohepatitis, indicating its potential for broader therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide: First Approval. Syed, YY.[2022]

Tirzepatide, a once-weekly medication for type 2 diabetes, not only improves blood sugar control but also leads to significant weight loss and positive changes in cardiovascular health, such as reduced blood pressure and improved insulin sensitivity.

The weight loss and metabolic benefits of tirzepatide are linked to its dual action as a GIP and GLP-1 receptor agonist, suggesting that these mechanisms play a crucial role in its effectiveness for managing type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perspectives on weight control in diabetes - Tirzepatide. Várkonyi, TT., Pósa, A., Pávó, N., et al.[2023]

In a systematic review of randomized controlled trials involving 5800 patients, tirzepatide was found to be highly effective for weight loss, with 78.22% achieving at least 5% weight loss and 32.28% achieving at least 15% weight loss.

Tirzepatide demonstrated superior weight loss compared to placebo and semaglutide, with a significant mean weight loss of -12.47 kg at the 5 mg dose, while showing a manageable safety profile with only a slight increase in gastrointestinal adverse events compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tirzepatide for treatment of overweight or obesity. A systematic review and meta-analysis. Tan, B., Pan, XH., Chew, HSJ., et al.[2023]

Tirzepatide, the first dual GIP/GLP-1 receptor co-agonist approved for type 2 diabetes, significantly reduces HbA1c levels (by 1.24 to 2.58%) and body weight (by 5.4-11.7 kg) in clinical trials involving type 2 diabetic patients, outperforming the selective GLP-1 RA semaglutide.

The safety profile of tirzepatide is similar to that of other GLP-1 receptor agonists, with common side effects including nausea and diarrhea, and it shows potential cardiovascular safety, as no significant increase in major adverse cardiovascular events was observed during the trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide, a dual GIP/GLP-1 receptor co-agonist for the treatment of type 2 diabetes with unmatched effectiveness regrading glycaemic control and body weight reduction. Nauck, MA., D'Alessio, DA.[2022]

Tirzepatide, approved in 2022, is a novel treatment for type 2 diabetes that acts on both GLP-1 and GIP pathways, showing significant efficacy in lowering blood sugar levels and promoting weight loss in various patient groups.

Clinical trials, including the SURPASS and SURMOUNT studies, indicate that tirzepatide has a safety profile similar to traditional GLP-1 receptor agonists, with common gastrointestinal side effects, making it a promising option for patients needing better glycemic and weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide: Clinical review of the "twincretin" injectable. Krauss, Z., Hintz, A., Fisk, R.[2023]

Citations

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ObesityWeek®️ 2024 | Gan & Lee Pharmaceuticals Orally ... The study results showed a significant reduction in body weight from baseline at week 30 in participants receiving different doses and dosing ...

2. ganlee.com ganlee.com/detail/751.html

Gan & Lee Pharmaceuticals' Bi-weekly（twice a month） ... ... GZR18 Injection Achieved 17.29% Weight Loss at 30 Weeks in a ... results in a clinical trial for adults with obesity/overweight in China.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06737042

NCT06737042 | Efficacy and Safety of GZR18 Every 2 ... This is a Phase 2 study to evaluate the safety and efficacy of 24, 36, and 48 mg GZR18 (Q2W) compared with placebo and 15 mg tirzepatide (QW).

4. synapse.patsnap.com synapse.patsnap.com/article/bi-weekly-glp-1-agonist-gzr18-achieves-1729-weight-loss-in-30-weeks-in-phase-iib-trial

Bi-weekly GLP-1 Agonist GZR18 Achieves 17.29% Weight ... The results indicated that GZR18 was significantly more effective in reducing body weight than the placebo. Moreover, there was no notable ...

5. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/558789

A Phase III Clinical Study to Evaluate the Efficacy and Safety ... A Phase III Clinical Study to Evaluate the Efficacy and Safety of GZR18 Injection in Adult Obese/Overweight Subjects. First Posted. Dec 11, 2024. Start. Dec 1 ...

6. ganlee.com ganlee.com/detail/763.html

ObesityWeek®️ 2024 GZR18 injections were safe and well tolerated, with the most commonly reported adverse events being gastrointestinal reactions, comparable to ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06737042

NCT06737042 | Efficacy and Safety of GZR18 Every 2 ... This is a Phase 2 study to evaluate the safety and efficacy of 24, 36, and 48 mg GZR18 (Q2W) compared with placebo and 15 mg tirzepatide (QW).

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40028667/

The safety, tolerability, pharmacokinetics and ... The safety, PK and PD profiles of GZR18 support its further clinical evaluation for glycaemic and body weight control.

9. prnewswire.com prnewswire.com/news-releases/obesityweek-2024--gan--lee-pharmaceuticals-orally-presents-phase-2b-clinical-data-for-gzr18-injection-in-chinese-overweight-and-obese-adults-302301106.html

ObesityWeek®️ 2024 | Gan & Lee Pharmaceuticals Orally ... GZR18 injections were safe and well tolerated, with the most commonly reported adverse events being gastrointestinal reactions, comparable to ...