Tirzepatide for Type 2 Diabetes and Obesity

Recruiting in Palo Alto (17 mi)

+65 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Eli Lilly and Company

Must be taking: Metformin

Must not be taking: Weight loss drugs

Disqualifiers: Type 1 diabetes, Renal impairment, Cardiovascular conditions, others

Prior Safety Data

Approved in 6 Jurisdictions

Trial Summary

What is the purpose of this trial?

The main purpose of this study is to learn more about the safety and efficacy of investigational tirzepatide doses in participants with Type 2 diabetes and obesity that are already taking metformin. The study will last for about 89 weeks.

Will I have to stop taking my current medications?

The trial requires participants to continue taking metformin, as it is part of the study's criteria. However, if you are taking other medications, the protocol does not specify whether you need to stop them.

What data supports the effectiveness of the drug Tirzepatide for type 2 diabetes and obesity?

Tirzepatide has been shown to significantly reduce blood sugar levels and body weight in patients with type 2 diabetes, with some losing more than 10% of their initial weight. It was more effective than other treatments like semaglutide and insulin in clinical trials, and it also improved insulin sensitivity and reduced appetite. ^{1 2 3 4 5}

Is tirzepatide safe for humans?

Tirzepatide has been shown to be generally safe in humans, with common side effects including nausea, vomiting, diarrhea, and constipation, especially at higher doses. It has also been associated with a reduction in cardiovascular events, indicating cardiovascular safety. ^{1 2 3 4 6}

How is the drug Tirzepatide different from other treatments for type 2 diabetes and obesity?

Tirzepatide is unique because it is the first drug that acts as a dual agonist for both GIP and GLP-1 receptors, which helps improve blood sugar control and leads to significant weight loss. It is more effective in reducing blood sugar levels and body weight compared to other treatments like semaglutide, and it is administered once a week. ^{1 4 5 7 8}

Eligibility Criteria

This trial is for adults with Type 2 diabetes and obesity, specifically those with a BMI of 35 or higher who have maintained a stable weight and been on metformin treatment for at least 90 days. Participants should not have had significant weight changes recently.

Inclusion Criteria

Are you currently taking Metformin only to manage your diabetes?

Exclusion Criteria

Do you have a recent history of myocardial infarction, stroke, unstable angina, congestive heart failure, or coronary artery revascularization?

Have you recently used products intended for weight loss including prescription drugs, over the counter drugs or herbal preparations?

Have you ever had surgery for obesity, or do you plan to undergo surgery shortly?

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

up to 5 weeks

Treatment

Participants receive tirzepatide or placebo subcutaneously, with primary endpoint at Week 44

44 weeks

Extension

Tirzepatide extension until Week 80

36 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Tirzepatide (GLP-1 Receptor Agonist)

Trial Overview The study tests the safety and effectiveness of different doses of an experimental drug called Tirzepatide in people taking metformin for Type 2 diabetes and obesity over approximately 89 weeks. Some participants will receive Tirzepatide, while others will get a placebo.

Participant Groups

Group I: Tirzepatide High Dose 2 Experimental Treatment 1 Intervention

Participants will receive tirzepatide SC.

Group II: Tirzepatide High Dose 1 Experimental Treatment 1 Intervention

Participants will receive tirzepatide subcutaneously (SC).

Group III: Tirzepatide Active Control 1 Intervention

Participants will receive tirzepatide SC.

Group IV: Placebo Placebo Group 1 Intervention

Participants will receive placebo.

Tirzepatide is already approved in United States, European Union, Canada, Australia, United States, United Kingdom for the following indications:

🇺🇸 Approved in United States as Mounjaro for:

• Type 2 diabetes

🇪🇺 Approved in European Union as Mounjaro for:

• Type 2 diabetes

🇨🇦 Approved in Canada as Mounjaro for:

• Type 2 diabetes

🇦🇺 Approved in Australia as Mounjaro for:

• Type 2 diabetes

🇺🇸 Approved in United States as Zepbound for:

• Weight loss
• Moderate to severe obstructive sleep apnea

🇬🇧 Approved in United Kingdom as Zepbound for:

• Weight loss

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Care Access - Sacramento Sacramento, CA

Care Access - Aurora Aurora, CO

Who Is Running the Clinical Trial?

Eli Lilly and Company Lead Sponsor

References

1. Germany 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. [2023] Tirzepatide is a novel dual glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1 RA) currently under review for marketing approval. Individual trials have assessed the clinical profile of tirzepatide vs different comparators. We conducted a systematic review and meta-analysis to assess the efficacy and safety of tirzepatide for type 2 diabetes.

2. England pubmed.ncbi.nlm.nih.gov

Tirzepatide: Clinical review of the "twincretin" injectable. [2023] To provide an overview of the safety and efficacy, pharmacology, dosing, place in therapy, and clinical trials for tirzepatide, a novel glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) agonist for treatment of type 2 diabetes.

3. United States pubmed.ncbi.nlm.nih.gov

Adverse Events Related to Tirzepatide. [2023] Tirzepatide is a dual glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1 RA) approved by the US Food and Drug Administration in May 2022 for patients with type 2 diabetes mellitus (T2DM).

4. England 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. [2022] Tirzepatide is the first dual GIP/GLP-1 receptor co-agonist approved for the treatment of type 2 diabetes in the USA, Europe, and the UAE. Tirzepatide is an acylated peptide engineered to activate the GIP and GLP-1 receptors, key mediators of insulin secretion that are also expressed in regions of the brain that regulate food intake. Five clinical trials in type 2-diabetic subjects (SURPASS 1-5) have shown that tirzepatide at 5-15 mg per week reduces both HbA1c (1.24 to 2.58%) and body weight (5.4-11.7 kg) by amounts unprecedented for a single agent. A sizable proportion of patients (23.0 to 62.4%) reached an HbA1c of < 5.7% (which is the upper limit of the normal range indicating normoglycaemia), and 20.7 to 68.4% lost more than 10% of their baseline body weight. Tirzepatide was significantly more effective in reducing HbA1c and body weight than the selective GLP-1 RA semaglutide (1.0 mg per week), and titrated basal insulin. Adverse events related to tirzepatide were similar to what has been reported for selective GLP-1RA, mainly nausea, vomiting, diarrhoea, and constipation, that were more common at higher doses. Cardiovascular events have been adjudicated across the whole study program, and MACE-4 (nonfatal myocardial infarction, non-fatal stroke, cardiovascular death and hospital admission for angina) events tended to be reduced over up to a 2 year-period, albeit with low numbers of events. For none of the cardiovascular events analysed (MACE-4, or its components) was a hazard ratio > 1.0 vs. pooled comparators found in a meta-analysis covering the whole clinical trial program, and the upper bounds of the confidence intervals for MACE were < 1.3, fulfilling conventional definitions of cardiovascular safety. Tirzepatide was found to improve insulin sensitivity and insulin secretory responses to a greater extent than semaglutide, and this was associated with lower prandial insulin and glucagon concentrations. Both drugs caused similar reductions in appetite, although tirzepatide caused greater weight loss. While the clinical effects of tirzepatide have been very encouraging, important questions remain as to the mechanism of action. While GIP reduces food intake and body weight in rodents, these effects have not been demonstrated in humans. Moreover, it remains to be shown that GIPR agonism can improve insulin secretion in type 2 diabetic patients who have been noted in previous studies to be unresponsive to GIP. Certainly, the apparent advantage of tirzepatide, a dual incretin agonist, over GLP-1RA will spark renewed interest in the therapeutic potential of GIP in type 2 diabetes, obesity and related co-morbidities.

5. United States pubmed.ncbi.nlm.nih.gov

Weight loss efficiency and safety of tirzepatide: A Systematic review. [2023] Tirzeptide is a novel glucagon-like peptide-1 receptor (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) drug, which shows good efficiency for weight loss. Therefore, we aim to investigate the efficacy and safety of tirzepatide for weight loss in type 2 diabetes mellitus (T2DM) and obesity patients in this meta-analysis study.

6. United States pubmed.ncbi.nlm.nih.gov

Tirzepatide, the Newest Medication for Type 2 Diabetes: A Review of the Literature and Implications for Clinical Practice. [2023] The objective of this article was to review pharmacology, efficacy, safety, and place in therapy of tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist.

7. Ireland pubmed.ncbi.nlm.nih.gov

Perspectives on weight control in diabetes - Tirzepatide. [2023] Tirzepatide, a once-weekly glucose-dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonist (GIP/GLP-1 RA) improves glycemic control. Besides improvement of glycemic control, tirzepatide treatment is associated with significantly more weight loss as compared to potent selective GLP-1 receptor agonists as well as other beneficial changes in cardio-metabolic parameters, such as reduced fat mass, blood pressure, improved insulin sensitivity, lipoprotein concentrations, and circulating metabolic profile in individuals with type 2 diabetes (T2D). Some of these changes are partially associated with weight reduction. We review here the putative mechanisms of GIP receptor agonism contributing to GLP-1 receptor agonism-induced weight loss and respective findings with GIP/GLP-1 RAs, including tirzepatide in T2D preclinical models and clinical studies. Subsequently, we summarize the clinical data on weight loss and related non-glycemic metabolic changes of tirzepatide in T2D. These findings suggest that the robust weight loss and associated changes are important contributors to the clinical profile of tirzepatide for the treatment of T2D diabetes and serve as the basis for further investigations including clinical outcomes.

8. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Tirzepatide: A New Generation Therapeutic for Diabetes Type 2. [2023] Tirzepatide (mounjaro®) is a derivative of the human glucose-dependent insulinotropic polypeptide (GIP) hormone with a position-20 being modified with 1,20- eicosanedioic acid via a chemical linker. It acts as a glucagon-like peptide-1 (GLP-1) receptor and GIP receptor agonist. It has recently been approved by FDA as an adjunct therapy to exercise and diet to improve glycemic control in patients with type II diabetes mellitus (T2DM). It represents a new transforming paradigm in the management of T2DM. This mini-review will shed light on its different pharmacokinetic and pharmacodynamic aspects.