While dulaglutide is primarily known for its role in managing type 2 diabetes, emerging evidence suggests its potential as a weight loss aid, even for individuals without diabetes. This article explores the efficacy, mechanisms, and considerations surrounding dulaglutide use for weight loss in non-diabetic populations.
Understanding Dulaglutide
Dulaglutide, marketed under the brand name Trulicity®, belongs to a class of medications called glucagon-like peptide-1 (GLP-1) receptor agonists. These drugs mimic the action of the natural GLP-1 hormone in the body. GLP-1 plays a crucial role in regulating blood sugar levels and appetite. Dulaglutide shares 90% of the same structure as human GLP-1 but is man-made. In people with type 2 diabetes, this natural incretin effect is diminished or no longer present.
How Dulaglutide Works
Dulaglutide works by mimicking the functions of natural incretin hormones in the body that help keep blood sugar levels under control, especially immediately following a meal. Incretin hormones are gut peptides that are secreted from the stomach when food is eaten. Two incretin hormones are known as GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1). By activating GLP-1 receptors, dulaglutide stimulates insulin release, reduces glucagon secretion, and slows gastric emptying. These actions collectively contribute to improved blood sugar control and a feeling of fullness, potentially leading to reduced calorie intake and weight loss.
Dulaglutide and Weight Loss: What Does the Evidence Say?
Although dulaglutide is FDA-approved primarily for glycemic control in patients with Type 2 DM, it has also garnered attention for its adjunctive role in weight management. A study analyzing the effect of dulaglutide at 26 weeks following initiation of the drug in Award 1-6 clinical trial showed dulaglutide 1.5 mg caused significantly greater reduction in weight and HbA1c as compared to metformin, sitagliptin, exenatide twice daily, and insulin glargine.
Clinical Trial Results
Clinical trials have demonstrated the potential of dulaglutide for weight loss. The AWARD-11 Trial examined the safety and efficacy of Trulicity at various doses. Patients who took a much lower dose of the medication (about a third of the dosage studied in the AWARD-11 trial) lost between 6-7 pounds on average.
Read also: Glycemic Control: Dulaglutide or Semaglutide?
In a 2021 study published in Diabetes Care, patients with type 2 diabetes with an average BMI of 34 who had failed the first-line diabetes drug metformin were given once-weekly dulaglutide (Trulicity) doses of 1.5 mg, 3.0 mg, or 4.5 mg for 52 weeks. The randomized controlled trial of 1,842 patients found that the 4.5 mg dose of dulaglutide was the most effective, and those who received the 4.5 mg dose had an average weight loss of about 10 pounds after 36 weeks.
Case Report: A Challenging Patient Profile
A case report presented a 27‐year‐old ex‐sumo wrestler with bipolar II disorder, morbid obesity, hypertension, Type 2 Diabetes Mellitus (DM), and a Body Mass Index (BMI) of 49.66 kg/m2. He was non‐compliant with lifestyle modifications and resistant to conventional treatments, including metformin, and was also using multiple antipsychotic drugs. After introducing dulaglutide, he achieved a 40 kg (−21%) weight loss and a BMI reduction of 10.3 kg/m2 over 6 months, with no side effects and improved glycemic control, demonstrating dulaglutide's efficacy for weight loss in such challenging presentations. The 40 kg weight loss in the ex‐sumo wrestler with dulaglutide is unprecedented and not previously documented.
Dulaglutide for Weight Loss in Non-Diabetics: Off-Label Use
While Trulicity is primarily approved for people who need to manage their type 2 diabetes, this does not mean that only type 2 diabetics can take this medication. When medications seem to be useful for reasons outside of their main purpose, physicians can still prescribe them “off-label” to help people reach adjacent goals.
Factors Influencing Weight Loss
Several factors can influence the extent of weight loss achieved with dulaglutide. These include:
- Dosage: Higher doses of dulaglutide may lead to greater weight loss.
- Individual biology: Response to dulaglutide can vary significantly among individuals.
- Lifestyle modifications: Combining dulaglutide with a healthy diet and regular exercise can enhance weight loss outcomes.
Potential Benefits Beyond Weight Loss
In patients with Type 2 Diabetes Mellitus (Type 2 DM), even modest amounts of weight loss as low as 5% have shown to be beneficial for glycemic control, control of blood pressure, and lipid level management, thereby reducing cardiovascular risk.
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Comparing Dulaglutide to Other Weight Loss Medications
Several medications are approved for long-term weight loss in the United States, including orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, semaglutide, and liraglutide. Semaglutide and liraglutide, like dulaglutide, are GLP-1 receptor agonists administered via subcutaneous injection.
Dulaglutide vs. Semaglutide
Tirzepatide and dulaglutide are both injectable medications that are used to treat type 2 diabetes, and are safe for use in pre-diabetics and non-diabetics for the prevention of diabetes and weight loss. Both medications work by helping the body to better use the insulin it produces, and can help to lower blood sugar levels. However, there are some key differences between the two medications, and it is important for patients to understand these differences when deciding which medication is right for them.
Dulaglutide is a GLP-1 receptor agonist, while tirzepatide is both a GIP receptor agonist AND a GLP-1 receptor agonist. GLP-1 and GIP are molecules that are both known to help promote insulin release to help lower blood sugar, slow the emptying of the stomach, and decrease the production of glucagon, the hormone that tells your liver to make more blood sugar. Thus, tirzepatide is a combo drug that may pack more of a punch for reducing blood sugar and helping support weight control or weight loss.
In a randomized trial published in the New England Journal of Medicine, 1,879 adult patients with type 2 diabetes were assigned to once-weekly injections of either tirzepatide (at 5 mg, 10 mg, or 15 mg) or semaglutide 1 mg for 40 weeks. They found that patients on tirzepatide at all three doses had a larger improvement in their hemoglobin A1c and a bigger reduction in body weight. For example, the tirzepatide 15 mg group lost 11.2 kg, versus the semaglutide group, who lost 5.7 kg. That is nearly a 2x difference! Even at the lowest dosage, tirzepatide was found to be superior for both outcome measures.
A 2018 review article comparing GLP-1 receptor agonists reported that, in studies, semaglutide 1 mg once weekly resulted in a mean weight loss from 4.53 to 6.5 kg, while dulaglutide at 1.5 mg once weekly resulted in a mean weight loss from 0.87 to 3.03 kg. With the results of these two studies, we can extrapolate that tirzepatide may lead to greater weight loss than dulaglutide.
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Considerations and Potential Side Effects
Before considering dulaglutide for weight loss, it's crucial to be aware of potential side effects and contraindications.
Common Side Effects
The most common side effects of Trulicity are:
- Nausea
- Diarrhea
- Vomiting
- Abdominal pain
- Decreased appetite
Adjusting your eating patterns and food choices may help you manage these side effects. For example, you might try avoiding large meals, eating more slowly and avoiding fatty, fried or spicy foods. Also, limit sugar intake, caffeine, and alcohol consumption.
Serious Side Effects
Some serious side effects can occur when taking dulaglutide. These include:
- Risk of thyroid C-cell tumors
- Pancreatitis
- Hypoglycemia
- Hypersensitivity reactions
- Acute kidney injury
- Severe gastrointestinal disease
- Diabetic retinopathy complications
- Acute gallbladder disease
Contraindications
People with a personal or family history of a specific type of thyroid cancer called medullary thyroid carcinoma (MTC) or with the condition multiple endocrine neoplasia syndrome type 2 (MEN 2) shouldn’t take Trulicity. Lilly also warns Trulicity “is not for use in people with type 1 diabetes and is not recommended for use in people with severe stomach or intestinal problems.” There’s not enough information or data on taking dulaglutide while pregnant or breastfeeding; talk to your doctor or obstetrician before taking Trulicity to see if its benefits outweigh the possible risks to the fetus or infant through breast milk.
Dosage and Administration
Dulaglutide is administered via a once-weekly subcutaneous injection. The recommended starting Trulicity dosage for weight loss is 0.75 mg once weekly. After four weeks, your provider may increase your dose to 1.5 mg. If you tolerate it, your physician may increase doses by 1.5 mg every four weeks until you reach a maximum dose of 4.5 mg weekly. It is injected under the skin once a week into the thigh, stomach area, or upper arm.
Cost and Availability
In the United States, the sticker price for a four-week supply of Trulicity-one pre-filled pen for each weekly injection-is around $1,100.00. Because Trulicity is a type 2 diabetes drug, many insurance companies cover it for that use. Eli Lilly explains that, with insurance, 92% of Trulicity prescriptions cost between $0 and $30 monthly. Of course, how much Trucity costs you will depend on your insurance, area, local pharmacy prices, and availability.
The Importance of Lifestyle Modifications
While dulaglutide can be a valuable tool for weight loss, it is not a magic bullet. Trulicity works best when paired with strategic lifestyle modifications.
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