Bariatric Surgery vs Semaglutide vs Tirzepatide for Obesity
Recruiting in Palo Alto (17 mi)
Overseen ByAli Aminian
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: Ali Aminian
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?The recent introduction of the new generation of anti-obesity medications (AOMs) will change the future of obesity treatment. These highly effective medications, such as high-dose semaglutide and tirzepatide, are hormone analogues that augment the incretin function and exert multiple physiological effects by activating glucagon-like peptide-1 (GLP-1) and/or glucose-dependent insulinotropic polypeptide (GIP) distributed in various organs. These medications provide an average of 15-22% weight reduction in one-year trials, which had not been seen in the past with medical therapy. While the literature suggests that bariatric surgery is superior to these new highly effective medications, there is no head-to-head comparison between the most common bariatric operations (Roux-en-Y gastric bypass \[RYGB\] and sleeve gastrectomy \[SG\]) with semaglutide (once weekly) and tirzepatide (once weekly). The goal of this Randomized Clinical Trial (RCT) is to compare these effective therapies in patients with severe obesity to provide the best evidence to inform clinical decisions in treating patients with obesity.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but you cannot be on semaglutide, tirzepatide, or other anti-obesity medications within 60 days before screening. If you have type 2 diabetes, you should be on a stable dose of your anti-diabetic medication for at least 3 months before joining.
What data supports the effectiveness of the drugs semaglutide and tirzepatide for obesity?
Research shows that both semaglutide and tirzepatide are effective for weight loss, with tirzepatide often resulting in more weight loss than semaglutide. These drugs have been shown to help people lose a significant amount of weight, making them promising options for treating obesity.
12345Is bariatric surgery, semaglutide, or tirzepatide safe for treating obesity?
Tirzepatide and semaglutide have been studied for safety in treating type 2 diabetes and obesity, showing mild to moderate gastrointestinal side effects like nausea and diarrhea. Bariatric surgery is a well-established procedure for obesity, but it carries surgical risks and requires careful consideration and medical advice.
25678How does the treatment of obesity with tirzepatide differ from other treatments?
Tirzepatide is unique because it acts on two different receptors in the body, GLP-1 and GIP, which help control blood sugar and reduce appetite, making it potentially more effective for weight loss compared to other treatments like semaglutide or bariatric surgery.
137910Eligibility Criteria
This trial is for individuals with severe obesity who are looking to reduce their weight. Participants should be adults eligible for bariatric surgery and willing to take new anti-obesity medications. Specific criteria will determine eligibility, but details are not provided here.Inclusion Criteria
I have not lost more than 20 lbs in the last 3 months.
I am fit for general anesthesia.
My BMI is between 35 and 65.
I am between 18 and 70 years old.
I meet the criteria for weight loss surgery according to 2022 guidelines.
Exclusion Criteria
I regularly use steroids for a long-term condition.
My thyroid condition is not under control.
I need a heart or artery procedure within the next year.
I do not have severe heart or lung disease.
My heart condition severely limits my physical activity.
I have had weight loss surgery in the past.
I have had a solid organ transplant.
I have type 1 or autoimmune diabetes.
I have severe kidney problems or am on dialysis.
I am on blood thinners for treatment.
I have severe anemia.
My liver tests are not normal.
I have an active cancer other than non-melanoma skin cancer.
I have obesity caused by a brain condition.
I have had pancreatitis recently or in the past.
I have a history of Crohn's disease.
I have a history of medullary thyroid cancer or multiple endocrine neoplasia type 2.
My liver is severely damaged and cannot function properly.
I am unable to understand and agree to the study's details on my own.
I understand the risks and requirements of the study.
Participant Groups
The study compares the effectiveness of two new hormone analogue medications, Semaglutide and Tirzepatide (taken weekly), against common bariatric surgeries like RYGB and SG in reducing weight among severely obese patients.
3Treatment groups
Active Control
Group I: Bariatric SurgeryActive Control1 Intervention
Roux-en-Y Gastric Bypass (RYGB) and Sleeve Gastrectomy (SG)
Group II: TirzepatideActive Control1 Intervention
Tirzepatide, which is an incretin-based medication that has been approved for the treatment of obesity, will be used for this arm.
Group III: SemaglutideActive Control1 Intervention
Semaglutide, which is an incretin-based medication that has been approved for the treatment of obesity, will be used for this arm.
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
The Cleveland ClinicCleveland, OH
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Who is running the clinical trial?
Ali AminianLead Sponsor
Ethicon, Inc.Industry Sponsor
References
Efficacy of tirzepatide 5, 10 and 15 mg versus semaglutide 2 mg in patients with type 2 diabetes: An adjusted indirect treatment comparison. [2022]To conduct an adjusted indirect treatment comparison (aITC) of the efficacy of tirzepatide 5/10/15 mg versus semaglutide 2 mg in patients with type 2 diabetes.
The Upcoming Weekly Tides (Semaglutide vs. Tirzepatide) against Obesity: STEP or SURPASS? [2022]The rapidly increasing prevalence of obesity and obesity-associated morbidity is causing an ever-increasing global burden. Beyond lifestyle modifications, pharmacological approaches to losing body weight to achieve a decrease in cardiometabolic complications are in the spotlight. Pre-existing anti-obesity medications (AOMs) approved for long-term prescription use showed a weight reduction of around 5% more than placebo. In contrast to the modest efficacy of pre-existing AOMs, two newly developed, weekly-administered injectable drugs, semaglutide and tirzepatide, exhibited outstanding weight-loss effects in a series of multinational randomized phase III trials. Considering that these two peptides are the most promising candidates for the upcoming battle in the anti-obesity market, comparison of their efficacy and safety is essential. This review summarizes the body weight reduction efficacy, glycemic control, and safety of semaglutide up to a 2.4-mg dose and tirzepatide up to a 15-mg dose, focusing on the Semaglutide Treatment Effect in People with Obesity (STEP) 2, SURPASS-1, and SURPASS-2 trials, the subjects of which were all patients with type 2 diabetes mellitus.
The catcher in the gut: Tirzepatide, a dual incretin analog for the treatment of type 2 diabetes mellitus and obesity. [2022]The ever-increasing burden of obesity, type 2 diabetes mellitus (T2DM) and related comorbidities is demanding a better pathophysiological understanding as well as new treatment options. Incretin based therapies are already available while the recent Food and Drug Administration (FDA) approval of the dual glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist tirzepatide appears to revolutionize the treatment of T2DM and obesity. GLP-1 and GIP exert pleiotropic physiological actions, including enhancement of insulin secretion, glycemic and appetite control, cardioprotection, and adipose tissue improved function among others. Evidence from recent clinical trials has shown that tirzepatide is at least or more effective compared to classic metabolic therapeutic agents, including insulin, when it comes to glycemic control in T2DM. Of importance, it also exerts remarkable weight-lowering actions, emerging as an alternative to bariatric surgery for obesity treatment. Overall, current data show that tirzepatide is a highly effective therapeutic option for T2DM. Numerous ongoing randomized controlled clinical trials are further examining its potential as a treatment for obesity.
In type 2 diabetes, tirzepatide reduced HbA1c vs. semaglutide. [2022]Label="SOURCE CITATION">Frias JP, Davies MJ, Rosenstock J, et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N Engl J Med. 2021;385:503-15. 34170647.
Comparative effectiveness of glucagon-like peptide-1 receptor agonists for the management of obesity in adults without diabetes: A network meta-analysis of randomized clinical trials. [2023]Tirzepatide is a new glucagon-like peptide-1 receptor agonist (GLP-1RA) that has shown promising results for weight loss. A Bayesian network meta-analysis was conducted to compare the efficacy and safety of GLP-1RAs for obesity management. Embase and MEDLINE were searched looking for randomized clinical trials (RCTs) that evaluated the efficacy of GLP-1RAs for weight loss in patients without diabetes. The main efficacy outcomes evaluated were the mean change in actual and percentage weight loss and the proportion of patients with weight loss of ≥5%-20%. Main safety outcomes evaluated include nausea, vomiting, diarrhea, constipation, loss of appetite, pancreatitis, gallbladder-related disorders, and withdrawal due to adverse events. Seven RCTs with more than 12,300 patients were analyzed, including patients with body mass index (BMI) ≥ 30 kg/m2 , or BMI ≥ 27 kg/m2 with comorbidities. Weekly tirzepatide 10 and 15 mg resulted in more weight loss than weekly semaglutide 2.4 mg, daily semaglutide 0.4 mg, or liraglutide 3 mg. Tirzepatide and weekly semaglutide demonstrated comparable results but with significantly higher odds of achieving ≥5%-20% weight loss compared with liraglutide. GLP-1RAs triggered more gastrointestinal adverse events than placebo, with no in-between difference. Although all GLP-1RAs lead to significant weight reduction, tirzepatide was associated with better efficacy outcomes while having a comparable safety profile.
Evaluation and comparison of efficacy and safety of tirzepatide and semaglutide in patients with type 2 diabetes mellitus: A Bayesian network meta-analysis. [2023]As new antidiabetic drugs, tirzepatide (Tir) and semaglutide (Sem) are progressively applied in clinical practice. However, their efficacy and safety profiles have not been comprehensively assessed. Therefore, a Bayesian network meta-analysis was used to evaluate and compare the efficacy and safety of Tir and Sem in treating type 2 diabetes mellitus (T2DM).
Tirzepatide Once Weekly for the Treatment of Obesity. [2023]Obesity is a chronic disease that results in substantial global morbidity and mortality. The efficacy and safety of tirzepatide, a novel glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, in people with obesity are not known.
Efficacy and Safety of Tirzepatide in Adults With Type 2 Diabetes: A Perspective for Primary Care Providers. [2023]This article reviews the efficacy and safety data of tirzepatide, a once-weekly, novel glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 (GLP-1) receptor agonist approved in the United States, the European Union, and other regions for the treatment of type 2 diabetes. All doses of tirzepatide demonstrated superiority in reducing A1C and body weight from baseline versus placebo or active comparators. The safety profile of tirzepatide was consistent with that of the GLP-1 receptor agonist class, with mild to moderate and transient gastrointestinal side effects being the most common adverse events. With clinically and statistically significant reductions in A1C and body weight without increased risk of hypoglycemia in various populations, tirzepatide has demonstrated potential as a first-in-class treatment option for many people with type 2 diabetes.
Tirzepatide versus semaglutide for weight loss in patients with type 2 diabetes mellitus: A value for money analysis. [2023]Higher doses of the glucagon-like peptide-1 agonist semaglutide and, more recently, tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 agonist showed a significant reduction in body weight in patients with type 2 diabetes mellitus. However, their comparative value for money for this indication is unclear. Therefore, we aimed to establish which provides better value for money.
Beyond glycemia: Comparing tirzepatide to GLP-1 analogues. [2023]Glucagon-like peptide-1 receptor analogs (GLP-1 RAs) have been an innovative and instrumental drug class in the management of both type 2 diabetes and obesity. Tirzepatide is a novel agent that acts as an agonist for both GLP-1 receptors and gastric inhibitory polypeptide (GIP) receptors, another incretin that lowers glucose and appetite. Although previous studies showed a lack of therapeutic benefit for GIP agonists, current studies show that the glucose lowering and weight loss effects of tirzepatide are at least as effective as GLP-1 RAs with a similar adverse effect profile. Some studies, though not conclusive, predict that tirzepatide may in fact be more potent than GLP-1 RAs at reducing weight. A thorough review of the studies that led to tirzepatide's approval allows for comparisons between tirzepatide and GLP-1 RAs; it also allows for predictions of tirzepatide's eventual place in therapy - an agent used preferentially over GLP-1 RAs in patients with or without diabetes desiring to lose weight.