Semaglutide Clinical Trials Revealed: Breakthrough Weight Loss and Surprising Benefits Uncovered!

Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist (RA), has garnered significant attention for its effectiveness in managing blood glucose, facilitating weight loss, and potentially preventing heart disease. Approved by the FDA in both long-acting injectable (Wegovy and Ozempic) and daily oral tablet (Rybelsus) formulations, semaglutide was initially approved in June 2021 for chronic weight management in individuals with obesity or overweight and at least one weight-related condition, such as high blood pressure, type 2 diabetes, or high cholesterol, in addition to diet and increased exercise. In March 2024, Wegovy (semaglutide) received FDA approval for reducing the risk of major adverse cardiovascular events in adults with known heart disease and with obesity or overweight, alongside a reduced-calorie diet and increased physical activity.

Currently, multiple clinical trials are underway to explore the diverse applications of semaglutide, both as a standalone treatment and in combination with other drugs like cagrilintide. These trials aim to evaluate its efficacy in various conditions, including obesity, type 2 diabetes, alcohol use disorder, and even stroke recovery.

Semaglutide and Cagrilintide Combination: CagriSema

Several clinical trials are investigating the impact of CagriSema, a combination of two drugs - semaglutide (brand names Ozempic and Wegovy) and cagrilintide (not yet approved) - on blood sugar, weight, and heart disease in people with obesity, type 2 diabetes, or both conditions. The REDEFINE program is the first group of clinical trials to study semaglutide and cagrilintide alone and in combination. Recent studies have found that participants taking CagriSema reduced their A1C by an average of 2.2 percentage points and lost almost 16% of their body weight. These reductions in A1C and body weight with CagriSema were significantly greater than reductions seen with cagrilintide alone. Full results confirmed these findings over 32 weeks and also showed time in range improvements of 43%. Through clinical trials, researchers hope to understand whether the two drugs used together could have a greater impact on weight loss, blood sugar management, and reducing heart disease than either drug alone. Clinical trial results so far have been promising, with CagriSema showing significant improvements in A1C, weight loss, and time in range, marking it as a potential new treatment for type 2 diabetes and weight management.

Here are some CagriSema trials currently recruiting:

CagriSema for Type 2 Diabetes and Peripheral Neuropathy

Clinical Trials Identifier: NCT06797869
Trial Name: A Research Study to Investigate the Effects of CagriSema Compared to Placebo in People With Type 2 Diabetes and Painful Diabetic Peripheral Neuropathy
Recruiting: Adults with type 2 diabetes and overweight or obesity diagnosed with painful diabetic peripheral neuropathy
Trial Sponsor: Novo Nordisk

This phase 2 trial is recruiting 134 people and is estimated to last until August 2026. The study will look at the effects of CagriSema on painful peripheral neuropathy compared to a "dummy" drug (placebo) by having participants rate their pain intensity each week.

Read also: Transformations with Ozempic

Long-Term Effects of CagriSema in People with Obesity

Clinical Trials Identifier: NCT06780449
Trial Name: A Research Study to Look Into the Long-term Effect on Weight Loss of CagriSema in People With Obesity
Recruiting: Adults with obesity (but not diabetes)
Trial Sponsor: Novo Nordisk

This larger phase 3 trial is enrolling 400 participants and is estimated to be completed in 2028. Researchers will observe how participants lose weight over time on CagriSema compared to a placebo, and track other measures like waist circumference, cholesterol, and blood pressure.

CagriSema and Bone Metabolism

Clinical Trials Identifier: NCT07010432
Trial Name: The Role of the Amylin Analogue Cagrilintide in Bone Metabolism (RAMBO)
Recruiting: Women ages 50-70 with obesity who have been through menopause
Trial Sponsor: Novo Nordisk

Only available to people in Denmark, this early-stage phase 1 study is recruiting 144 participants and is estimated to be completed in 2028. This study will investigate how CagriSema affects bone health in women with obesity after menopause compared to cagrilintide alone, semaglutide alone, or a placebo.

Semaglutide in Alcohol Use Disorder (AUD) Treatment

One study is currently recruiting participants to test if Semaglutide is safe and may reduce alcohol drinking in people with AUD.

Study Overview:

This study seeks to determine if a medication named Semaglutide is safe and may reduce alcohol drinking in people with AUD. Alcohol use disorder (AUD) is a problematic pattern of alcohol use accompanied by clinically significant medical consequences. Medications can help most people reduce their drinking, but the number is limited, and additional treatment options are needed.

Eligibility:

All Adults aged 18 or older with AUD might be eligible to participate in the study. To be eligible for this study, an individual must meet all of the following criteria:

At least 18 years old
Alcohol Use Disorder (minimum 2 symptoms on a validated diagnostic tool, e.g., the Mini-International Neuropsychiatric Interview (MINI) or the Structured Clinical Interview for DSM Disorders (SCID))
Self-reported drinking, according to alcohol Timeline Follow-Back (TLFB), of > 7 drinks per week for females or > 14 drinks per week for males during the 28-day period prior to screening plus at least four days with > 3 drinks for females or > 4 drinks for males during the 28-day period prior to screening
Most recent Clinical Institute Withdrawal Assessment for Alcohol - revised (CIWA-Ar) score < 10
Able to speak, read, write, and understand English as demonstrated by ability to understand and sign the NIDA screening protocol consent
Normal or corrected-to-normal (e.g., wearing glasses or contacts) vision and normal or corrected-to-normal (e.g., with the use of a hearing aid) hearing

Exclusion Criteria:

An individual who meets any of the following criteria will be excluded from enrolling in this study:

BMI < 23 kg/m^2 or BMI >= 50 kg/m^2
Evidence of malnutrition as determined by the Nutrition Risk Screening 2002 (NRS-2002)
Most recent blood tests: creatinine >= 2 mg/dL, eGFR <45 mL/min/1.73 m^2, triglycerides > 500 mg/dl, ALP > 4x the upper limit of normal, clinically abnormal lipase levels per study clinician
Present diagnosis of diabetes mellitus or blood hemoglobin A1c (HbA1c) >= 6.5 %
Current (within the past 30 days) use of the following medications with glucose lowering properties: GLP-1 analogues, sulfonylurea, insulin, metformin, thiazolidinediones, dipeptidyl peptidase-4 (DPP-IV) inhibitors, sodium-glucose cotransporter-2 (SGLT-2) inhibitors
Current or prior use of semaglutide or tirzepatide
Current (within the past 30 days) use of weight-lowering medications
Current (within the past 30 days) use of FDA-approved pharmacotherapy for AUD (oral or intramuscular naltrexone, acamprosate, disulfiram)
Current (within the past 30 days) use of medications with known interaction with semaglutide
Personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
Known ongoing history of alcohol ketoacidosis, gastroparesis, pancreatitis (either acute or chronic), pancreatic carcinoma, gallbladder disease, jaundice, Mallory-Weiss syndrome (esophageal tears secondary to vomiting), esophageal varices, cirrhosis
Known history of gastric bypass surgery
Known history of prior hypersensitivity reaction to semaglutide, any of the product components, or any other GLP-1 analogue
Known history of suicidal attempts (within the past 24 months) or active suicidal ideation
Known history of clinically significant vestibular disorders or motion sickness
Known history of clinically significant noise-induced hearing loss or tinnitus
Contraindication(s) for brain fMRI
Unstable cardiovascular conditions (e.g., arrhythmias, clinically significant ECG abnormalities)
Physical and/or mental health conditions that are clinically unstable, as determined by the study clinicians, including (but not limited to) major depressive disorder or generalized anxiety disorder unstable during the past three months or other psychiatric conditions (e.g., schizophrenia, bipolar disorder) unstable during the past twelve months prior to screening.

Study Procedures:

Participants will visit the National Institute on Drug Abuse (NIDA) in Baltimore once a week for about 20 weeks (5 months). Each visit will last between 2 and 6 hours depending on the tasks scheduled for that visit. Participants will be assigned by chance (like flipping a coin) to receive either Semaglutide or placebo. A placebo looks just like a real drug but contains no medicine. The study medication is given as a shot under the skin each week.

During the study, participants will:

Give blood, urine, and saliva samples.
Engage in self-paced behavioral therapy on a computer.
Answer questions about their mood, diet, alcohol drinking and craving, tobacco use, etc.
Taste several sweet liquids and tell their preferences.
Sit in a bar-like room and be exposed to cues that might make them feel the urge to eat food or drink alcohol.
Wear a virtual reality headset that creates a cafeteria setting. They will walk the virtual cafeteria and choose food and drinks from a buffet.
Have a functional magnetic resonance imaging (fMRI) scan to take pictures of their brain. During the scans, participants will be shown pictures of alcohol-containing drinks, food, and other items.
Perform tasks on a computer screen.

Participants will have a follow-up visit about 7 weeks after their last shot.

Recruitment and Data Collection:

Participants will be recruited without any preference to sex, race, religion, or other social variables, but sociodemographic data will be collected for sample characterization and potential use in the analyses. Since self-reported psychological measures that have been validated in English constitute a major part of the study assessments, participants need to be able to speak, read, write, and understand English to be in the study. The information needed to assess eligibility will be collected under an IRB-approved NIDA IRP screening protocol, led by the Office of the Clinical Director (OCD) at the NIDA IRP to assess potential research participants' eligibility for entering clinical protocols. Additional details can be found in the NIDA screening protocol documents. Furthermore, NIH medical records (from other NIH clinical protocols) and outside medical records may also be used, if available, to determine whether participants fulfill the eligibility criteria.

Read also: Semaglutide Without Diet Changes

Semaglutide for Stroke Recovery: The ASSET Trial

The ASSET trial is a national, multicenter, clinical trial, investigating the safety and efficacy of Semaglutide in non-diabetic patients with acute ischemic stroke. Stroke is a worldwide leading cause of long-term disability and death. This trial aims to determine if semaglutide can help reduce the damage caused by a stroke.

Additional Areas of Semaglutide Research

Semaglutide is also being investigated for its potential benefits in various other conditions:

Opioid Use Disorder (OUD): A pilot study is examining the effects of semaglutide on cue-reactivity among individuals with OUD newly initiating buprenorphine. The is a pilot, 12-week, double-blind, placebo-controlled, randomized trial of individuals with opioid use disorder (OUD) newly initiating buprenorphine to receive either weekly injections of semaglutide (n=23) or matching placebo (n=23). The primary aim is to determine the effects of semaglutide on cue-reactivity among individuals with OUD.
Schizophrenia-Spectrum Disorders (SSD): Given the high rates of obesity in patients with SSDs, research is exploring the potential of semaglutide to address weight management in this population. Rates of obesity in patients with schizophrenia-spectrum disorder (SSD)s have reached epidemic proportions, with established contributing effects of antipsychotic (AP) medications.
Psoriasis: Obesity is a well known to be an important comorbidity of psoriasis. It gives rise to higher risk of psoriatic arthritis, more severe disease and also poorer response to biologics. Weight loss can lead to reduction in psoriasis severity.
Genetic Basis of Semaglutide Response: The study aims to investigate the genetic basis of the response to short-term (3 months) orally administered semaglutide treatment, in terms of improving metabolic parameters, including the hormonal response to a standardized meal, and changes in body composition and liver steatosis.

Semaglutide 7.2 mg: A Promising Higher Dose

Topline findings from the 72-week STEP UP trial (NCT05646706) show that semaglutide at a dose of 7.2 mg produced superior weight loss compared to semaglutide at a dose of 2.4 mg and placebo.1,2 This is the first of two trials evaluating the effectiveness of semaglutide at a dose of 7.2 mg, with the other being the ongoing, 72-week STEP UP T2D trial.

Trial Design:

STEP UP is a randomized, double-blind, parallel-group, placebo-controlled, superiority study comparing the effectiveness of semaglutide 7.2 mg vs. semaglutide 2.4 mg and placebo as an adjunct to lifestyle intervention. Investigators enrolled 1,407 adult patients with a BMI ≥30 kg/m2 and without diabetes. The trial’s primary endpoint was to establish superiority in weight loss of semaglutide 7.2 mg vs. placebo, with key secondary endpoints that included number of patients who achieve 10%, 15%, 20% and 25% weight loss, respectively. Patients enrolled in STEP UP also receive counseling from study staff regarding how to establish a healthy diet and to increase physical activity.

STEP UP T2D is evaluating semaglutide 7.2 mg in 512 adult patients with obesity and type 2 diabetes. That trial’s primary endpoint is to establish the superiority of semaglutide 7.2 mg vs. placebo in weight loss.

Trial Results:

Among patients who were adherent to the trial regimen, from a mean baseline body weight of 113 kg, patients in the semaglutide 7.2 mg cohort experienced weight loss of 20.7% after 72 weeks, compared to 17.5% in the semaglutide 2.4 mg cohort and 2.4% in the placebo cohort. Further, 33.2% of patients in the semaglutide 7.2 mg cohort experienced weight loss of 25% or greater at 72 weeks, compared with 16.7% in the semaglutide 2.4 mg cohort and 0.0% in the placebo cohort. In terms of the treatment policy estimand, patients in the semaglutide 7.2 mg cohort experienced weight loss of 18.7% vs. 15.6% in the semaglutide 2.4 mg cohort and 3.9% in the placebo cohort.

Semaglutide 7.2 mg was reported to have a safe and well-tolerated profile, with the most frequently reported adverse events (AEs) being gastrointestinal in nature and mild to moderate in severity. These AEs lessened over time, which is consistent with the GLP-1 receptor agonist class.

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