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In this article, we will explore liraglutide and semaglutide and their roles in weight loss. The article will focus on understanding the mechanism of action, their effect on weight loss, and human studies examining their efficacy and safety.

Introduction

Losing and sustaining weight presents a formidable challenge for many people. Consequently, some individuals may require medications to assist in their weight loss efforts and prevent regaining lost weight.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a type of medication class that is utilized in the treatment of type 2 diabetes and obesity (Collins L and Costello 2023). 

The Food Drug Association (FDA) approved liraglutide (Saxenda) as a treatment for type 2 diabetes in 2010 (Victoza 2010 and Jackson, et al. 2010) and as a treatment for obesity (3 mg/day) in 2014 (Nuffer and Trujillo 2015) and for patients aged 12 and older in 2021 (FDA 2021). The semaglutide injection has emerged as a notable option in the treatment of type 2 diabetes, demonstrating efficacy in improving glycemic control. Semaglutide (Ozempic) was approved by the FDA in 2017 at doses up to 1 mg for the treatment of type 2 diabetes in adults (FDA 2020). Ozempic, however, is not approved by the FDA for weight loss but has shown a promising bodyweight reduction of 6.9% in the STEP-2 clinical trial (Davis, et al. 2021). The FDA has granted approval for Wegovy (semaglutide) injection at a dosage of 2.4 mg administered once weekly. This approval is for the purpose of managing chronic weight-related issues in adults dealing with obesity or overweight conditions, provided they have at least one associated weight-related condition, such as high blood pressure, type 2 diabetes, or high cholesterol. This medication is intended for use in conjunction with a calorie-restricted diet and increased physical activity (FDA 2014).

Many individuals have explored the potential benefits of using liraglutide for weight loss under the guidance of healthcare professionals. Liraglutide for weight loss can be taken alongside a reduced-calorie diet and increased physical activity. It’s meant for patients aged 12 and older who are obese (with a high body mass index [BMI] of 30 or more) or overweight (with a BMI of 27 or more) and have a health condition related to their weight, like high blood pressure, type 2 diabetes, or high cholesterol (FDA 2014 and Victoza 2010).

How do GLP-1RAs (Saxenda and Ozempic) help with weight loss?

GLP-1RAs function by decreasing appetite and sensations of hunger, delaying the emptying of the stomach, and enhancing the feeling of fullness following a meal.

These drugs mimic the GLP-1 hormone released from the L cells in the gut and imitate the actions of the endogenous hormone GLP-1 by activating the Glucagon-Like Peptide-1 receptor (located in the hypothalamus of the brain). This stimulation tells the brain that there has been enough food consumed, which decreases hunger and increases feelings of fullness. Longer satiety is also facilitated by GLP-1 RAs, which slow down gastric emptying and increase the amount of time nutrients stay in the stomach and small intestine. Additionally, by lowering blood sugar spikes and falls, which can trigger cravings for high-calorie foods, these drugs help control blood sugar levels. When combined, these effects help people lose weight when they follow a well-thought-out weight-management plan that is monitored by medical professionals (Ard, et al 2021 and Holst 2007).

Clinical insight into the efficacy of Saxenda and Ozempic

Liraglutide (Saxenda)

After liraglutide was initially approved to treat diabetes, a number of studies were carried out to assess its potential as an obesity treatment. A few important ones are discussed below.

The SCALE diabetes clinical trial randomized 846 participants and treated them with 3.0, 1.8 mg, or placebo as subcutaneous injections of liraglutide. The result showed that a total of 50% of individuals on 3.0 mg, 36% of individuals on the 1.8 mg dose, and 14% on the placebo liraglutide showed ≥5.0% of body weight reduction, respectively. A total of 23%, 14%, and 4% in the 3.0 mg, 1.8 mg, and placebo groups, respectively, showed ≥10% of body weight reduction (Davis, et al. 2015). 

The SCALE Obesity and Prediabetes Study was a 56-week study comprising 3731 patients who did not have type 2 diabetes and who had a BMI of at least 30 or a BMI of at least 27 if they had treated or untreated dyslipidemia or hypertension. They studied the once-daily injection of 3.0 mg liraglutide for weight management. The result showed that liraglutide, as an adjunct to diet and exercise, was associated with reduced body weight and improved metabolic control (Pi-Sunyer, et al. 2015).

The SCALE maintenance randomized study was a 56-week study comprising 422 patients with a BMI of at least 30 who lost ≥5% of their initial weight during a low-calorie diet run and were randomly assigned to liraglutide 3.0 mg per day or placebo. The study showed that liraglutide, with diet and exercise, maintained weight loss achieved by a low-calorie diet and induced further weight loss over 56 weeks (Wadden, et al. 2013).

An early study conducted on 564 individuals for 20 weeks showed that liraglutide was well tolerated and induced weight loss (Astrup 2009).

Semaglutide (Ozempic)

Semaglutide weight loss is a topic of interest, with ongoing research exploring its efficacy and safety as a medication to aid in weight management. The Ozempic injection has gained popularity as a once-weekly treatment option for individuals with type 2 diabetes, offering improved blood sugar management and potential weight-loss benefits. Clinical trials are currently evaluating the effectiveness of semaglutide for weight loss in non-diabetics, shedding light on its potential as a pharmacological intervention for managing body weight in individuals without diabetes. Some individuals using Ozempic for weight loss have reported positive outcomes, emphasizing the medication's dual benefits in diabetes management and weight control.

Semaglutide for weight loss has shown promising results in clinical trials, prompting interest in its potential as a therapeutic option for managing obesity. Semaglutide Treatment Effect in People with Obesity (STEP)-1 was a 68-week trial to evaluate the efficacy and safety of semaglutide at a subcutaneous dose of 2.4 mg once weekly in 1961 overweight or obese patients, with or without weight-related complications. The study showed a sustained and clinically relevant reduction in body weight. The mean change in body weight from baseline to week 68 was −14.9% in the semaglutide group as compared with −2.4% with placebo (Wilding, et al. 2021). 

The STEP 2 was a 68-week trial to evaluate the efficacy and safety of once-a-week subcutaneous semaglutide 2·4 mg versus semaglutide 1·0 mg and placebo for weight management in adults with overweight or obesity and type 2 diabetes. The results showed an average bodyweight reduction of 9.6%, 6.9%, and 3.4% with semaglutide 2.4 mg, 1.0 mg, and placebo, respectively (Davis, et al. 2021).

The STEP 3 trial was a 68-week trial including 611 adults with obesity or overweight with comorbidities (but not diabetes) to receive semaglutide 2.4 mg or placebo in conjunction with behavioral therapy to support them in adopting a healthier lifestyle. The result showed an average weight reduction of 16.0% with semaglutide versus 5.7% with placebo (Wadden, et al. 2021).

The STEP 4 trial included 902 participants who were administered semaglutide 2.4 mg for the first 20 weeks, and then for the next 48 weeks, they were randomized to receive either semaglutide or placebo. The findings demonstrated that individuals who continued taking semaglutide after randomization lost an additional 7.9% of their bodyweight on average, resulting in a total weight loss of 17.4% during the trial. In contrast, individuals who switched to a placebo regained an average of 6.9% of their bodyweight, resulting in a weight loss of 5.0% overall (Rubino D, et al 2021).

Other trials under the STEP program (STEP 5 and 6) had similar results of sustained weight loss with semaglutide (Garvey WT, et al 2022 and Kadowaki, et al. 2022). 

The STEP-8 trial compared the efficacy and safety of once-weekly subcutaneous semaglutide, 2.4 mg, vs. once-daily subcutaneous liraglutide, 3.0 mg, in obese patients. The administration was in conjunction with diet and physical activity. The result showed a significantly greater average bodyweight reduction of 15.8% with semaglutide compared with 6.4% with liraglutide (Rubino D, et al 2022). Discussions with healthcare professionals can provide valuable insights into the potential benefits and considerations of semaglutide weight loss as part of an individuals overall health strategy.

Clinical insight into the safety of Saxenda and Ozempic Liraglutide

(Saxenda)

The safety data from liraglutide studies indicates that the administration was generally well received. The most frequently reported treatment-related side effects were related to the gastrointestinal system (nausea, constipation, vomiting, and diarrhea), but these were generally well-tolerated (Davis, et al. 2015, Pi-Sunyer, et al. 2015, Wadden, et al. 2013, Astrup 2009).

The prescribing information for liraglutide warns about the risk of thyroid c-cell tumors. This warning was based on an animal study done using doses that were 8 times higher than human doses. However, no significant elevated risk of thyroid cancer has been reported among liraglutide users (Funch, et al. 2021 and Hu, et al. 2022). 

A clinical trial also studied liraglutide and its effect in mental health (depression and suicidal thoughts). Overall, the study didn’t show any major concerns about the drug’s impact on mental health (O'Neil, et al. 2017).

Semaglutide (Ozempic)

The safety results for semaglutide were similar to those for liraglutide. The most common adverse event reported in all of the STEP clinical trial programs was gastrointestinal disorders, which were mostly mild to moderate (Wilding, et al. 2021; Davis, et al. 2021; Wadden, et al. 2021; Rubino D, et al 2021; Garvey WT, et al 2022; Kadowaki, et al. 2022; Rubino D, et al 2022). 

Conclusion

A promising approach to the management of weight loss is provided by the clinical efficacy and safety of liraglutide and semaglutide. Both of these drugs have proven to be effective at lowering blood sugar levels, assisting in weight loss, and enhancing cardiovascular health. Additionally, they have a generally favorable safety profile, with the majority of side effects being mild or moderate. Recent studies have indicated that the use of semaglutide for weight loss treatment can be a promising and effective strategy when incorporated into a comprehensive health and wellness plan. Many healthcare professionals consider prescribing Ozempic for weight loss in conjunction with lifestyle changes, offering a comprehensive approach to managing obesity. When compared to liraglutide, semaglutide appeared to be more effective for controlling blood sugar and weight loss, especially at its higher dose for weight management. The decision between the two should be made in consultation with a healthcare professional, considering specific health objectives and any potential negative side effects.