Liraglutide Clinical Trials

What Is Liraglutide?

Liraglutide is an FDA-approved medication for the treatment of type 2 diabetes and for chronic weight management in adults. Specifically, liraglutide 3.0 mg (brand name Saxenda®) is approved for chronic weight management in obese adults (BMI of 30 kg/m² or greater) or overweight adults (BMI of 27 kg/m² or greater) with at least one weight-related co-morbid condition, used as an adjunct to a reduced-calorie diet and increased physical activity. It is also approved for type 2 diabetes (brand name Victoza®) to reduce weight and improve insulin resistance while stabilizing blood glucose metabolism without increasing the risk of hypoglycemia.

Liraglutide is a glucagon-like peptide-1 (GLP-1) agonist, meaning it mimics a natural hormone in the body. This action helps to regulate blood sugar levels and can lead to an appetite-suppressive effect. Participants typically receive liraglutide subcutaneously, meaning it is injected under the skin.

Beyond its approved uses, liraglutide is currently being investigated in clinical trials for conditions such as type 1 diabetes, various metabolism and nutrition disorders, and its potential effects on blood pressure, bone mass, and sleep apnea.

Uses and Conditions Under Study

Liraglutide has been extensively studied across a range of conditions, with a focus on metabolic health.

• Type 2 Diabetes: This is a primary approved use for liraglutide. It is studied for its ability to improve blood glucose control and reduce insulin resistance. Over 100 trials (including 111 trials for Diabetes and 108 for Diabetes Mellitus, Type 2) have investigated liraglutide in this population, often as monotherapy or in combination with other antidiabetic drugs.
• Obesity and Overweight: Liraglutide 3.0 mg is approved for chronic weight management. It is investigated for its appetite-suppressive effects and its ability to promote weight loss, particularly in individuals with weight-related co-morbidities. There are 88 trials specifically for obesity and 13 for overweight individuals.
• Type 1 Diabetes: Although primarily used for type 2 diabetes, liraglutide is being explored as an add-on therapy for type 1 diabetes to help manage blood sugar levels and potentially reduce insulin doses. Approximately 26 trials (15 for Type 1 Diabetes, 11 for Diabetes Mellitus, Type 1) are investigating this use.
• Metabolism and Nutrition Disorders: Liraglutide's impact on broader metabolic health is also under investigation, with 18 trials focusing on various metabolism and nutrition disorders. This includes studies on lipid profiles, blood pressure, and other metabolic markers.
• Other Investigational Uses: Clinical trials are also exploring liraglutide's effects on bone mass, sleep apnea, and its potential role in reducing craving in opioid use disorder. Some studies involve healthy volunteers (23 trials) to understand the drug's pharmacokinetics and safety profile.

Dosing

Liraglutide is administered as a solution for subcutaneous injection, often using a pre-filled pen injector. It is typically taken once daily.

For type 2 diabetes, common dosages studied include 0.6 mg, 1.2 mg, and 1.8 mg daily. For chronic weight management, a dose of 3.0 mg daily (marketed as Saxenda®) has been approved. Some trials investigate a maximum tolerable dose per day.

Liraglutide is also studied in various combinations with other medications. These include:

• Fixed-ratio combinations, such as with insulin degludec (e.g., Xultophy®).
• Co-administration with oral antidiabetic drugs like metformin, pioglitazone, or SGLT2 inhibitors.
• Combination with other weight management therapies, such as orlistat.

Investigational studies have explored a wide range of doses, from 0.3 mg up to 30 mg, depending on the specific research question and formulation being tested, such as depot formulations. The exact dosing regimen and strength depend on the condition being treated and the individual's response, as determined by a healthcare provider.

Side Effects

The most common side effect reported by patients taking Liraglutide in clinical trials was nausea. Across 53 trials involving 18,720 patients on Liraglutide, 27.8% experienced nausea, compared to 8.0% of patients on placebo.

Other common side effects that occurred more frequently with Liraglutide than with placebo include:

• Hypoglycaemia (low blood sugar): 15.6% of patients on Liraglutide experienced this, compared to 6.9% on placebo.
• Vomiting: 14.6% of patients on Liraglutide, compared to 4.1% on placebo.
• Diarrhea: 14.0% of patients on Liraglutide, compared to 6.4% on placebo.
• Constipation: 13.5% of patients on Liraglutide, compared to 6.9% on placebo.
• Decreased appetite: 10.1% of patients on Liraglutide, compared to 2.9% on placebo.
• Dyspepsia (indigestion): 8.3% of patients on Liraglutide, compared to 2.8% on placebo.

Some side effects occurred at similar rates in both Liraglutide and placebo groups. For example, nasopharyngitis (common cold symptoms) was reported by 18.0% of Liraglutide patients and 18.7% of placebo patients. Headache occurred in 11.7% of Liraglutide patients and 11.8% of placebo patients.

Clinical Trial Results

Clinical trials have evaluated Liraglutide for its effects on blood sugar control, body weight, and other metabolic markers in patients with type 2 diabetes and in obese individuals without diabetes.

Effect on Type 2 Diabetes (Liraglutide vs. Glimepiride)

In a study (NCT00294723) comparing Liraglutide to glimepiride in patients with type 2 diabetes, Liraglutide demonstrated superior reductions in blood sugar and body weight. After 52 weeks, patients on Liraglutide 1.8 mg experienced a reduction in HbA1c (a measure of average blood sugar) of 1.14 percentage point, compared to a 0.51 percentage point reduction with glimepiride. Body weight also changed significantly: Liraglutide 1.8 mg led to a reduction of 2.45 kg, while glimepiride resulted in a weight gain of 1.12 kg. Liraglutide also led to significantly fewer hypoglycaemic episodes compared to glimepiride.

Effect on Type 2 Diabetes (Liraglutide + Metformin vs. Metformin + Glimepiride or Metformin Alone)

Another study (NCT00318461) investigated Liraglutide in combination with metformin. After 26 weeks, Liraglutide 1.8 mg plus metformin reduced HbA1c by 1.00 percentage point, which was comparable to metformin plus glimepiride (0.98 percentage point reduction) and superior to metformin alone (0.09 percentage point increase). Liraglutide 1.8 mg plus metformin also led to a body weight reduction of 2.79 kg, whereas metformin plus glimepiride resulted in a weight gain of 0.95 kg. Importantly, Liraglutide combinations were associated with significantly fewer hypoglycaemic episodes compared to metformin plus glimepiride.

Effect on Type 2 Diabetes (Liraglutide vs. Glibenclamide)

A trial (NCT00393718) comparing Liraglutide to glibenclamide showed that after 24 weeks, Liraglutide patients had an HbA1c of 6.99%, compared to 7.50% for glibenclamide patients. Fasting plasma glucose was also lower with Liraglutide (137.2 mg/dL) than with glibenclamide (150.1 mg/dL). Liraglutide also resulted in fewer hypoglycaemic events.

Effect on Type 2 Diabetes (Liraglutide + Sulfonylurea vs. Sulfonylurea Monotherapy)

In a study (NCT00395746) evaluating Liraglutide combined with a sulfonylurea, Liraglutide 0.9 mg plus sulfonylurea achieved an HbA1c of 6.75% after 24 weeks, significantly lower than sulfonylurea monotherapy (8.02%). Fasting plasma glucose was also lower in the Liraglutide 0.9 mg plus sulfonylurea group (126.2 mg/dL) compared to sulfonylurea monotherapy (158.8 mg/dL).

Effect on Body Weight in Obese Subjects Without Diabetes

A study (NCT00422058) in obese individuals without diabetes investigated Liraglutide's impact on weight. After 104 weeks, patients receiving Liraglutide 3.0 mg experienced a mean body weight reduction of 8.2 kg. This compared favorably to Orlistat, which resulted in a 3.8 kg reduction. Liraglutide 3.0 mg also led to a reduction in waist circumference of 9.8 cm and a decrease in systolic blood pressure of 5.6 mmHg.

Currently Recruiting Trials

• A Phase 4 study, NCT07244003, sponsored by Hangzhou Zhongmei Huadong Pharmaceutical Co., Ltd., comparing a triple combination therapy including liraglutide for **430** patients with poorly controlled Type 2 diabetes.
• The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School is conducting a Phase 3 study, NCT06361238, with **260** participants, exploring liraglutide's role in preventing postoperative delirium in elderly diabetic patients after cardiac surgery.
• A Phase 1 trial, NCT06449703, sponsored by Tonghua Dongbao Pharmaceutical Co.,Ltd, is recruiting **44** healthy Chinese subjects to investigate the pharmacokinetics of an insulin degludec/liraglutide combination.
• Brigham and Women's Hospital is sponsoring a Phase 4 study, NCT06438146, for **40** people living with HIV and obesity, evaluating liraglutide for weight management.
• Columbia University is conducting a Phase 4 study, NCT05681299, with **40** healthy and growth hormone deficient adults, examining the effects of growth hormone and liraglutide on AgRP.
• A Phase 1/Phase 2 study, NCT05268237, sponsored by Biolingus, is recruiting **15** patients with Type 2 diabetes to assess the safety and efficacy of sublingual liraglutide.
• The University of Virginia is running a Phase 4 trial, NCT04575844, with **80** adults with metabolic syndrome, studying the effects of exercise and liraglutide on muscle microvascular perfusion and insulin action.
• Finally, The First Affiliated Hospital of Xiamen University is sponsoring a Phase 4 study, NCT03087032, for **164** overweight/obese Type 2 diabetes patients, comparing liraglutide-bolus versus glargine-bolus therapy.

Where to Participate

• Cypress, California
• Rochester, Minnesota
• New York, New York
• Cincinnati, Ohio
• Charlottesville, Virginia

Development Timeline