In recent years, drugs such as liraglutide and semaglutide have revolutionised the way we treat obesity, diabetes and appetite control.   

These two drugs belong to the class of GLP-1 (glucagon-like peptide-1) receptor agonists. GLP-1 is a hormone produced in the intestine after meals that helps control blood sugar levels and appetite. It acts on the pancreas, brain and stomach, stimulating the release of insulin, inhibiting glucagon and reducing hunger.  

GLP-1 receptor agonist medicines, such as liraglutide and semaglutide, are medicines that mimic the action of this hormone, thereby helping to reduce blood sugar, control appetite and promote weight loss. (1,2)  

Liraglutide is marketed under the names Victoza and Saxenda, while semaglutide is available as Ozempic, Wegovy, and Rybelsus.  

But what are the differences between them? And what does science say about their long-term effects?   

Liraglutide 

Liraglutide was the first GLP-1 agonist approved for type 2 diabetes and obesity. Administered daily subcutaneously, it has been shown to be effective in promoting moderate weight loss, reducing cardiovascular risk in people with type 2 diabetes, and lowering blood glucose and glycated haemoglobin (HbA1c). Glycated haemoglobin is a marker that reflects average blood sugar levels over the past 3 months and is essential for assessing diabetes control. (3-5)  

In a study of more than 9,000 participants, liraglutide reduced major cardiovascular events by 13% and cardiovascular mortality by 22%. (5) 

Semaglutide   

Semaglutide represents an evolution of liraglutide, with a significantly longer half-life (about 7 days), which allows for weekly administration and even an oral formulation, facilitating treatment adherence and promoting greater stability in blood glucose levels. (6)  

In several clinical studies, the use of semaglutide in obese individuals led to an average reduction of approximately 15% in body weight after just over a year of treatment, while the control groups showed much lower losses. (7)  

Other investigations have shown that semaglutide is capable of reducing glycated haemoglobin (HbA1c) by up to 1.8% and body weight by 4 to 6 kg, with results superior to those observed with liraglutide. HbA1c is a marker that reflects the average blood sugar levels over the last three months and is essential for assessing diabetes control. (8) 

In addition, long-term studies indicate that treatment with semaglutide may be associated with an approximately 25% reduction in the risk of major cardiovascular events, such as myocardial infarction and stroke, reinforcing its potential metabolic and cardioprotective benefits. (9)  

Other drugs used  

In addition to liraglutide and semaglutide, there are other GLP-1 receptor agonists with similar mechanisms, such as exenatide, lixisenatide, and dulaglutide. All act by mimicking the action of natural GLP-1, promoting insulin release and reducing appetite, but differ in the duration of effect and frequency of administration. While liraglutide requires daily injections and semaglutide allows weekly doses, drugs such as dulaglutide and extended-release exenatide also offer weekly regimens, promoting treatment adherence. Although they share similar metabolic benefits, semaglutide continues to stand out for its greater effectiveness in weight loss and glycaemic control.  

Cardiovascular and metabolic benefits 

Both liraglutide and semaglutide have proven cardioprotective effects, reducing inflammation, oxidative stress, and the risk of cardiac events. Both help to reduce systolic blood pressure, improve lipid profile, and protect renal function in patients with type II diabetes. (5,9,10) 

Precautions and contraindications   

Despite their clinical benefits, it is important to consider potential adverse effects and precautions for use. The most common adverse effects are nausea, vomiting, and mild gastrointestinal discomfort, which are usually temporary.  

Both liraglutide and semaglutide can cause transient gastrointestinal effects (nausea, constipation, feeling of fullness) and are contraindicated in people with a history of pancreatitis; medullary thyroid carcinoma; and genetic syndromes such as multiple endocrine neoplasia type 2 (MEN2).   

Conclusion  

Liraglutide and semaglutide represent advances in the management of diabetes and obesity. In order to maximise the benefits of treatment with these drugs, it is essential to adopt a balanced lifestyle.   

Therefore, you should prioritise the consumption of foods rich in lean protein, legumes, and fibre, opting for small, light meals throughout the day. In addition, it is essential to maintain adequate hydration, limiting the intake of alcoholic beverages and ultra-processed foods. Regular physical activity is crucial and contributes to the preservation of lean body mass and better metabolic results.   

In conclusion, when combined with a balanced diet, physical exercise, and professional monitoring, these medications are powerful tools for improving the metabolic health and quality of life of people with these conditions. 

Bibliography: 

1. Nauck MA, Meier JJ. Incretin hormones: their role in health and disease. Diabetes Obes Metab. 2018;20(Suppl 1):5–21.
2. Drucker DJ. Mechanisms of action and therapeutic application of glucagon-like peptide-1. Cell Metab. 2018;27(4):740–756.
3. Jacobsen LV. Liraglutide in Type 2 Diabetes Mellitus: Clinical Evidence and Mechanisms of Action. Curr Diabetes Rev. 2016;12(3):211–223. PMID: 26597252.
4. Pastor R, Tur JA. Liraglutide for the Treatment of Obesity: Analyzing Published Reviews. Curr Pharm Des. 2019;25(15):1625–1633.
5. Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes (LEADER Trial). N Engl J Med. 2016;375(4):311–322.
6. Lau J, Bloch P, Schäffer L, et al. Discovery of the Once-Weekly GLP-1 Analogue Semaglutide. J Med Chem. 2015;58(18):7370–7380.
7. Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). N Engl J Med. 2021;384(11):989–1002.
8. Pratley RE, Aroda VR, Lingvay I, et al. Semaglutide versus Dulaglutide Once Weekly in Patients with Type 2 Diabetes (SUSTAIN 7). Lancet Diabetes Endocrinol. 2018;6(4):275–286.
9. Marso SP, Bain SC, Consoli A, et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes (SUSTAIN-6). N Engl J Med. 2016;375(19):1834–1844.
10. Kristensen SL, Rørth R, Jhund PS, et al. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in type 2 diabetes: a systematic review and meta-analysis. BMJ. 2019;366:l4573. 

Author: Sofia Silva 5784N