Dulaglutide vs Semaglutide | A Comprehensive Comparison

Searching for an in-depth analysis on the efficacy of dulaglutide vs. semaglutide for weight loss?

If so, this is the right place.

Our expert team delves into the latest findings on both peptides, directly comparing their benefits and drawbacks.

Both dulaglutide and semaglutide are incretin mimetics and approved medications for type 2 diabetes. They share many similarities in terms of benefits and research potential, such as:

• Weight loss
• Glycemic control
• Cardiovascular health

Continue reading to unveil a thorough comparison of the safety and effectiveness of these two peptides, backed by the most recent research.

Additionally, researchers will discover our top recommended vendor for acquiring research-grade peptides for weight loss.

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What is Dulaglutide?

Dulaglutide (LY2189265) is a synthetic peptide analog of glucagon-like peptide-1 (GLP-1) hormone. It was developed by pharmaceutical firm Eli Lilly and Co. in the 2000s.

It has a unique structure that prolongs its half-life to approximately five days [1]. Here are some of the most notable facts about its structure:

• The peptide consists of two disulfide-linked chains, each with about 90% similarity to GLP-1 [2].
• The two chains are attached to a modified IgG4-Fc fragment via a peptide linker. This IgG4-Fc modification reduces the peptide’s immunologic cytotoxicity by suppressing Fc receptor affinity [2].
• Dulaglutide’s structure enhances its clinical effects by protecting against DPP-4 degradation. The increased size from the IgG4-Fc linkage slows its elimination rate [3].

As a result, dulaglutide activates the GLP-1 receptors in various organs, such as the pancreas. In the latter, it triggers insulin release, helping to regulate blood sugar levels after meals, including in subjects with type 2 diabetes (T2D).

The peptide has been extensively studied in the clinical development program called Assessment of Weekly Administration of LY2189265 [dulaglutide] in Diabetes (AWARD) [4].

Following the program’s favorable results, the United States Food and Drug Administration (FDA) approved once-weekly injectable dulaglutide for the following indications:

• In 2014, the FDA approved dulaglutide in doses of up to 1.5mg/weekly for glycemic control in T2D [5].
• In 2020, the FDA approved the peptide for reducing major adverse cardiovascular events (MACE) in diabetics [6].
• In 2020, the FDA approved two higher doses of the medication, 3.0mg, and 4.5mg, based on results of the AWARD-11 trial demonstrating improved glucose lowering and weight management benefits [7].

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What is Semaglutide?

Semaglutide is another synthetic peptide analog of the GLP-1 hormone. It was developed in the 2010s by Novo Nordisk and exhibits 94% homology with GLP-1. The peptide has several modifications that contribute to its extended half-life of five days [8]:

• an aminoisobutyric acid substitution at position 8
• an arginine exchange at position 34
• the incorporation of octadecanoic (C-18) diacid moiety at position 26

These refinements fortify its resilience against enzymatic degradation and augment its binding to serum proteins, facilitating a prolonged half-life and enabling once-weekly dosing [9].

Once administered, semaglutide interacts with GLP-1 receptors throughout the body, increasing insulin secretion and aiding blood sugar regulation following meals [10, 11].

Semaglutide was extensively tested in several phase 3 trials for its therapeutic potential, including as part of the Semaglutide Treatment Effect in People with Obesity (STEP) and Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes (SUSTAIN) clinical programs.

Based on the available clinical results, the FDA approved semaglutide for the following indications:

• In 2017, the FDA approved injectable semaglutide (brand name Ozempic) at a 1mg/weekly dose for treating type 2 diabetes (T2D) based on the results of the SUSTAIN program [12].
• Semaglutide received approval in 2020 for reducing MACE in diabetics based on the SUSTAIN-6 trial results [13].
• A higher dosage of 2mg/weekly semaglutide (Ozempic) was approved for T2D management in 2022.
• As of 2019, semaglutide is the only GLP-1 receptor agonist to receive FDA approval in an oral formulation. Marketed as Rybelsus by Novo Nordisk, it serves as another treatment option for T2D [14].
• In 2021, a peak dose of 2.4mg/weekly was authorized for adults under the brand name Wegovy, with its approval extending to adolescent weight management in 2023 [12, 15].

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Dulaglutide vs. Semaglutide | Comparing Benefits

While injectable semaglutide is authorized for a more extensive spectrum of indications compared to dulaglutide, both peptides demonstrate similar benefits in subjects with and without T2D, as per the latest phase-3 trials.

Continue reading to delve into the comparative benefits of the two peptides.

Weight Loss | Is Dulaglutide or Semaglutide More Effective?

Injectable semaglutide has received FDA approval for weight loss and sustained weight management in both adolescents and adults, owing to favorable results from phase 3 trials in the STEP program.

Here is what researchers should know about the STEP program and semaglutide's effectiveness for weight loss:

• The STEP program encompasses ten phase 3 trials (STEP 1-10) aimed at evaluating the weight reduction efficacy of 2.4mg semaglutide administered weekly [16].
• The published STEP trials thus far indicate that the peptide facilitates a decrease of 9.6–17.4% from the study volunteers’ initial body weight over a span of 68 weeks [12].
• The biggest trial, STEP-1, included over 1900 overweight and obese individuals without T2D, with two-thirds of these volunteers administered 2.4mg/weekly semaglutide. The peptide caused a 15.0% (32.2lb) reduction from baseline body weight over 68 weeks [17]

On the other hand, dulaglutide is not approved for chronic weight management and weight loss. The peptide is authorized only as a medication for glycemic control and MACE risk reduction in T2D.

Nevertheless, some of the phase 3 trials investigating the glucose-lowering effects of dulaglutide also report significant weight loss:

• The AWARD-11 trial reported 5.2% (11lb) weight loss from baseline at 52 weeks, at the highest dulaglutide dose of 4.5mg/weekly [18].
• The SUSTAIN-7 trial compared the effectiveness of low-dose semaglutide (1mg/weekly) to low-dose dulaglutide (1.5mg/weekly) in study volunteers with T2D. Within 40 weeks, the semaglutide group lost 14.3lb from baseline compared to 6.6lb for dulaglutide [19].

Another trial, which indirectly compared 1mg/weekly semaglutide to 4.5mg/weekly dulaglutide, reported that the former led to significantly higher weight loss. Specifically, semaglutide led to a 4.3lb higher mean weight loss compared to dulaglutide [20].

Type 2 Diabetes Benefits | Is Dulaglutide or Semaglutide Better?

Both dulaglutide and semaglutide are approved for glycemic control in T2D. Yet, based on the available studies, semaglutide appears to be more effective in improving glycemic control, as measured by the reduction in the levels of glycated hemoglobin (HbA1c):

• According to data from the SUSTAIN-FORTE trial, there was a -2.2% reduction in baseline HbA1c with 2mg/weekly semaglutide and 1.9% reduction with 1mg/weekly semaglutide after 40 weeks [21]
• The AWARD-11 trial revealed a -1.77% reduction in baseline HbA1c with 4.5mg/weekly dulaglutide after 36 weeks [18].

As mentioned, one trial also indirectly compared the effectiveness of 1mg/weekly semaglutide and 4.5mg/weekly dulaglutide. The study authors reported a 0.07% difference between the two GLP-1 agonists in favor of 1mg/weekly semaglutide [20].

Other Potential Benefits | Dulaglutide and Semaglutide

Both semaglutide and dulaglutide have shown significant potential in reducing the risk of cardiovascular problems in T2D patients. Currently, both peptides are approved for MACE reduction based on the following data:

• The effectiveness of semaglutide for reducing MACE risk was studied in the SUSTAIN-6 trial, which included a total of 3297 diabetics, the majority of which had cardiovascular risks. The data indicated that 0.5mg and 1mg/weekly semaglutide reduced the risk of experiencing death from cardiovascular causes by 26% and the risk of nonfatal stroke by 39% compared to placebo [22].
• The effectiveness of dulaglutide for MACE risk reduction was assessed in the Researching CV Events with a Weekly Incretin in Diabetes (REWIND) trial, which included 9901 diabetics. The population tested notably had a lower-than-usual risk for cardiovascular outcome trials. During a median follow-up of 5.4 years, the primary composite outcome of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes was 12% lower in the 1.5mg/weekly dulaglutide group compared to placebo [23].

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Dulaglutide and Semaglutide | Dosage Comparison

Dulaglutide and semaglutide are both suitable for once-weekly subcutaneous administration due to their favorable pharmacokinetics and extended half-lives [1, 9].

To minimize the risk of adverse events during research, either peptide should be initiated at a low dose that is gradually increased in specific increments every four weeks.

Here is a breakdown of the peptides have been dosed in clinical settings:

• Semaglutide: Based on the available data from semaglutide weight loss trials, studies on the peptide should initiate at 0.25mg/weekly. The dose can be gradually increased every four weeks up to a maximum of 2.4mg/weekly [16].

  For comparison, the maximum recommended weekly dosage of semaglutide for managing T2D stands at 2mg/week [21].

• Dulaglutide: For the management of T2D, dulaglutide is typically initiated at 0.75mg/weekly, with the dose titrated up to 1.5mg/weekly if additional glycemic control is needed. Then, it can be increased to 3mg/weekly after four weeks, and then up to 4.5mg/weekly after another 4 weeks, as needed [18].

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Dulaglutide and Semaglutide | Side Effects and Safety

Research into both semaglutide and dulaglutide has shown favorable safety profiles and similar side effects for both compounds.

Based on the available data from AWARD-11, 66.4% of study volunteers given 4.5mg/weekly of dulaglutide had at least one side effect. The most common ones included:

• Nausea (17.3% of subjects)
• Diarrhea (11.6%)
• Vomiting (10.1%)
• Nasopharyngitis (6.2%)
• Dyspepsia (2.8%)
• Gallbladder-related events (1.6%)
• Acute pancreatitis (0.5%)

The discontinuation rate at the highest dose was 8.5% [18].

In comparison, the STEP-1 trial reported that 2.4mg/weekly semaglutide led to side effects in 89.7% of the subjects, with the most common complaints being [17]:

• Nausea (44.2% of subjects)
• Diarrhea (31.5%)
• Vomiting (24.8%)
• Constipation (23.4%)
• Dyspepsia (10.3%)
• Abdominal pain (10%
• Gallbladder-related events (2.6%)

The majority of gastrointestinal reactions were of mild to moderate intensity, temporary, and resolved without needing a permanent halt in treatment. Adverse events prompted 7% of the semaglutide group to discontinue treatment [17].

Semaglutide and dulaglutide come with a contraindication for pregnancy and lactation. Further, laboratory animal investigations imply a potential elevation in thyroid cancer risk with both peptides, yet current evidence does not suggest any similar risk in humans.

Still, subjects with a prior history of thyroid cancer or multiple endocrine neoplasia syndrome type 2 (MEN-2) should be excluded from dulaglutide or semaglutide study [25].

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Where to Buy Weight Loss Peptides Online? | 2024 Edition

Semaglutide is available to qualified professionals as a reference material through select sources.

Adept researchers and lab professionals should carefully choose a reliable peptide supplier to bolster the likelihood of a favorable experimental outcome.

Here are a few recommend sources:

Limitless Life

We at Peptides.org wholeheartedly endorse Limitless Life, a vendor of repute among distinguished researchers.

This vendor stocks research-grade semaglutide through its VIP club. Here's why going with them is beneficial:

• Stringent Quality Control: The vendor engages a third-party laboratory to perform high-performance liquid chromatography and mass spectrometry (HPLC-MS) analysis to ascertain the premier quality of its semaglutide and other peptides.
• Fast, Free Shipping: Researchers who place orders of $350+ will receive free shipping, and most orders reach their destinations in 2-3 business days.
• Exceptional Support and Service: With a strong focus on researcher satisfaction, Limitless Life extends superb support to each and every researcher via phone and email.
• Detailed Guidance: Limitless Life provides exhaustive research summaries for every peptide listed they list for sale, alongside useful guidance on the handling of research chemicals.

Click the link below to sign up to the Limitless VIP Club and get member’s only access to semaglutide and other benefits. Sign up is quick and instant:

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Xcel Peptides

The vendor Xcel Peptides also offers high-quality semaglutide, an extensive product selection, superior customer support, secure ordering, and prompt shipping.

Learn more here:

• Lab-Tested Peptides: Xcel Peptides ensures the quality of their peptides by subjecting them to rigorous purity testing, conducted by MZ Biolabs.
• Convenient Payments: The vendor’s checkout process is simple and streamlined, with major credit cards, e-checks, and cryptocurrencies all accepted.
• Excellent Service and Care: Xcel Peptides' knowledgeable and friendly service team is readily available to assist with any inquiries or concerns. They are fully committed to satisfaction.

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Dulaglutide vs. Semaglutide| Verdict

Both dulaglutide and semaglutide are cutting-edge peptides with potent weight loss effects.

They share similar pharmacokinetics and safety profiles, while demonstrating substantial efficacy in glycemic control improvement and other metabolic benefits like reducing cardiovascular risk.

Yet, only semaglutide is approved for chronic weight management, and based on the data, has the upper hand over dulaglutide in facilitating weight in overweight and obese individuals.

Visit our top supplier to source research-grade semaglutide today.

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