Benefits of Semaglutide
Monday, February 26th, 2024

With a rapidly increasing global epidemic of obesity, the concomitant rise in cardiometabolic disorders such as type 2 diabetes mellitus (T2DM) and hypertension has emerged as a pressing public health concern, underscoring the urgent need for innovative therapeutic approaches to address this multifaceted challenge.

The world of medical therapeutics has evolved a lot recently to find the right treatment option for lowering the prevalence of obesity and mitigating the subsequent risk of developing cardiovascular disease. In particular, the introduction of semaglutide for weight loss, a potent glucagon-like peptide-1 (GLP-1) receptor agonist, has proven to be a game-changer in fighting against this metabolic epidemic and aiding in disease control.

Based on thorough scientific research and ground-breaking clinical studies, the profound and wide array of benefits that semaglutide offers owes to the diverse physiological pathway of the incretin system that it targets.

Besides its primary role in regulating blood sugar levels, recent studies have shown its transformative potential in treating obesity, cardiovascular risk mitigation, improved metabolic health parameters, and beyond.

This detailed thread is all you need to know about what semaglutide has to offer to enhance your overall health by reducing the possibility of life-threatening complications.

Benefits of Semaglutide Include:

• Promotes weight loss
• Fights type 2 diabetes and lowers blood sugar levels
• Prevents cognitive decline
• Lowers blood pressure Lowers the risk of cardiovascular disease

Semaglutide for Chronic Weight Management:

Semaglutide follows a multi-approach system to promote weight loss. It delays gastric emptying, which develops the feeling of fullness after meals, and reduces appetite as well as overall calorie intake (3). This effect is particularly beneficial for individuals with obesity or those struggling with weight management alongside diabetes. Furthermore, semaglutide acts on the central nervous system to decrease appetite, leading to reduced food intake and sustained weight loss over time.

Clinical trials have demonstrated significant reductions in body weight among patients treated with semaglutide compared to placebo or other antidiabetic/anti-obesity medications, highlighting its efficacy as a chronic weight management tool in addition to its glucose-lowering effects (4-7).

Perhaps owing to its potency in clinical trials, the FDA approved the use of semaglutide injection (brand name Wegovy) once every week for chronic weight management in people with high body mass index (BMI) if used in conjunction with all lifestyle modifications such as moderate exercise/physical activity as well as a healthy diet (8).

Semaglutide for Enhanced Glycemic Control:

Being a GLP-1 receptor agonist, it initiates a cascade of physiological responses to regulate blood sugar levels. It promotes insulin secretion from pancreatic beta cells in response to elevated glucose levels, helping to lower blood sugar after meals.

Additionally, semaglutide inhibits glucagon secretion, a hormone released from the alpha cells of the pancreas, preventing excessive glucose production by the liver, particularly during fasting periods. These combined effects result in improved glycemic control, as evidenced by reductions in fasting plasma glucose levels and hemoglobin A1c (HbA1c) levels over time (1-3).

Besides, by mimicking the action of GLP-1, semaglutide also slows down gastric emptying, thus helping prevent rapid spikes in blood sugar levels after eating (post-prandial), promoting the feeling of satiety as well as reducing appetite which also leads us to talk about chronic weight management offered by the semaglutide (3).

Semaglutide for Cardiovascular Disease Risk Reduction:

Semaglutide has shown promising cardiovascular benefits in clinical trials, including reductions in major adverse cardiovascular events (MACE) such as cardiovascular death, nonfatal myocardial infarction (heart attack), heart failure, and stroke (9-10). While the exact mechanisms underlying these cardiovascular benefits are not fully understood, several potential pathways have been suggested. These include improvements in endothelial function, reductions in arterial stiffness, and modulation of inflammation and oxidative stress.Perhaps these mechanisms also help individuals with high blood pressure to keep their readings low and have a reduced probability of developing hypertension-related complications which we will talk about in more detail in the next section.

Therefore, this FDA-approved medication semaglutide’s ability to improve cardiovascular outcomes adds an extra layer of therapeutic benefit for individuals with type 2 diabetes, many of whom are at increased risk of cardiovascular disease (11-13).

Benefits of Semaglutide for Blood Pressure Control:

Semaglutide’s effects on blood pressure may be attributed to multiple factors, including weight loss, improved glycemic control, and direct vascular effects. By reducing body weight, semaglutide helps decrease insulin resistance and improve endothelial function, leading to reductions in blood pressure levels over time (14-15).

Additionally, semaglutide’s ability to modulate sympathetic nervous system activity and enhance renal sodium excretion may further contribute to its antihypertensive effects. These combined mechanisms result in improved blood pressure control among individuals treated with semaglutide, reducing their overall cardiovascular risk profile.

Semaglutide for Renal Protection:

Individuals with long-term inadequate blood sugar control are most susceptible to developing kidney failure as high blood sugar levels over time cause diabetic kidney disease (DKD) associated with significant morbidity and mortality.

Preclinical studies have shown that GLP-1 receptor agonists like semaglutide can attenuate renal inflammation, fibrosis, and oxidative stress, thereby slowing the progression of DKD and preserving renal function (16).

Clinical trials investigating semaglutide’s renal effects in individuals with type 2 diabetes and DKD are currently ongoing, with early results showing promising trends toward reducing potential risks associated with renal reduction (17).

Semaglutide for Neuroprotective Effects:

While primarily studied for its metabolic effects, semaglutide has also shown potential neuroprotective benefits in preclinical models of neurodegenerative diseases such as Alzheimer’s disease. GLP-1 receptors are expressed in the brain, where they play a role in neuronal survival, synaptic plasticity, and cognitive function (18).

Semaglutide’s ability to activate these receptors may help mitigate neuroinflammation, oxidative stress, and amyloid-beta accumulation, all of which are implicated in the pathogenesis of Alzheimer’s disease.

Clinical trials investigating semaglutide’s effects on cognitive function and neurodegeneration are ongoing, with preliminary data suggesting potential benefits in preserving cognitive function and slowing disease progression (19).

Semaglutide for Addiction Control:

The role of semaglutide in addiction control is an area of emerging interest and ongoing research. Semaglutide’s effects on appetite regulation and satiety make it a potential candidate for addressing food addiction.

By delaying gastric emptying and increasing the feeling of fullness, it may help individuals with compulsive overeating behaviors and reduce cravings for high reduce cravings for high-calorie, palatable foods.

Clinical trials investigating semaglutide’s effects on food addiction and binge eating disorder are currently underway, with preliminary results showing promising trends toward reduced food intake and improved eating behaviors.

While less extensively studied, there is growing interest in the potential of GLP-1 receptor agonists like semaglutide for addressing substance use disorders, including alcohol dependence and opioid addiction (20-22).

Preclinical research has demonstrated that GLP-1 receptor agonists can modulate reward pathways in the brain implicated in addiction, leading to reduced drug-seeking behavior and attenuated drug cravings. These effects are thought to arise from GLP-1 receptors’ widespread distribution in brain regions involved in reward processing, such as the mesolimbic dopamine system (21).

While clinical trials investigating semaglutide specifically for substance use disorders are limited, early findings from preliminary studies and small-scale human trials are encouraging and warrant further investigation.

Semiglutide Indirect Benefits on Overall Health and Longevity

In addition to the direct benefits of semaglutide on overall health, Semaglutide also has many indirect health benefits throughout the body due to it’s over positive effects on the human body. For example, losing weight will help to also lower cholesterol levels and lower inflammation in the body. This along with optimal blood sugar control will have anti-aging and longevity benefits to help you live a better quality of life for longer.

Semaglutide for Potential Disease Modification:

Semaglutide’s multifaceted mechanisms of action offer the potential for disease modification in type 2 diabetes. By targeting multiple pathophysiological pathways implicated in the development and progression of diabetes and its high-risk complications, semaglutide may exert effects beyond symptomatic relief, altering the natural history of the disease and improving long-term outcomes.

These potential disease-modifying effects underscore the transformative impact of semaglutide on diabetes care and management, offering hope for individuals living with this chronic condition.

Conclusion:

Unlike some other weight loss medications that require daily or multiple weekly injections, semaglutide injection can be administered once weekly which leads to better patient compliance and satisfaction, ultimately improving treatment outcomes and reducing the risk of medication nonadherence.

By addressing various aspects of diabetes management and its associated complications as well as semaglutide’s sophisticated approach beyond glucose control, potential improvements in chronic weight management, mitigating the risk of heart disease, improved renal function, and neuroprotection, it is definitely a valuable addition in the list of all the weight loss medications.

Moreover, as more ongoing research continues to explore the role of semaglutide in treating other health conditions, it will still remain one of the best treatment options for the comprehensive management of type 2 diabetes and its associated comorbidities if used synergistically with lifestyle changes.

References:

1. Andreadis, P., Karagiannis, T., Malandris, K., Avgerinos, I., Liakos, A., Manolopoulos, A., Bekiari, E., Matthews, D. R., &Tsapas, A. (2018). Semaglutide for type 2 diabetes mellitus: A systematic review and meta-analysis. Diabetes, obesity & metabolism, 20(9), 2255–2263.
2. Avgerinos, I., Michailidis, T., Liakos, A., Karagiannis, T., Matthews, D. R., Tsapas, A., &Bekiari, E. (2020). Oral semaglutide for type 2 diabetes: A systematic review and meta-analysis. Diabetes, obesity & metabolism, 22(3), 335–345
3. Gibbons, C., Blundell, J., Tetens Hoff, S., Dahl, K., Bauer, R., & Baekdal, T. (2021). Effects of oral semaglutide on energy intake, food preference, appetite, control of eating and body weight in subjects with type 2 diabetes. Diabetes, obesity & metabolism, 23(2), 581–588.
4. Kushner, R. F., Calanna, S., Davies, M., Dicker, D., Garvey, W. T., Goldman, B., Lingvay, I., Thomsen, M., Wadden, T. A., Wharton, S., Wilding, J., &Rubino, D. (2020). Semaglutide 2.4 mg for the Treatment of Obesity: Key Elements of the STEP Trials 1 to 5. Obesity (Silver Spring, Md.), 28(6), 1050–1061.
5. Christou, G. A., Katsiki, N., Blundell, J., Fruhbeck, G., &Kiortsis, D. N. (2019). Semaglutide as a promising antiobesity drug. Obesity reviews : an official journal of the International Association for the Study of Obesity, 20(6), 805–815.
6. Ard, J., Fitch, A., Fruh, S., & Herman, L. (2021). Weight Loss and Maintenance Related to the Mechanism of Action of Glucagon-Like Peptide 1 Receptor Agonists. Advances in therapy, 38(6), 2821–2839.
7. Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K, Zeuthen N, Kushner RF; STEP 1 Study Group. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Mar 18;384(11):989.
8. Singh G, Krauthamer M, Bjalme-Evans M. Wegovy (semaglutide): a new weight loss drug for chronic weight management. J Investig Med. 2022 Jan;70(1):5-13. doi: 10.1136/jim-2021-001952. Epub 2021 Oct 27. PMID: 34706925; PMCID: PMC8717485.
9. Husain M, Bain SC, Holst AG, Mark T, Rasmussen S, Lingvay I. Effects of semaglutide on risk of cardiovascular events across a continuum of cardiovascular risk: combined post hoc analysis of the SUSTAIN and PIONEER trials. CardiovascDiabetol. 2020;19(1):156. Published 2020 Sep 30.
10. Marso, S. P., Holst, A. G., &Vilsbøll, T. (2017). Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. The New England journal of medicine, 376(9), 891–892.
11. Husain, M., Bain, S. C., Jeppesen, O. K., Lingvay, I., Sørrig, R., Treppendahl, M. B., &Vilsbøll, T. (2020). Semaglutide (SUSTAIN and PIONEER) reduces cardiovascular events in type 2 diabetes across varying cardiovascular risk. Diabetes, obesity & metabolism, 22(3), 442–451.
12. Leiter, L. A., Bain, S. C., Hramiak, I., Jódar, E., Madsbad, S., Gondolf, T., Hansen, T., Holst, I., &Lingvay, I. (2019). Cardiovascular risk reduction with once-weekly semaglutide in subjects with type 2 diabetes: a post hoc analysis of gender, age, and baseline CV risk profile in the SUSTAIN 6 trial. Cardiovascular diabetology, 18(1), 73.
13. Jódar, E., Michelsen, M., Polonsky, W., Réa, R., Sandberg, A., Vilsbøll, T., Warren, M., Harring, S., Ziegler, U., & Bain, S. (2020). Semaglutide improves health-related quality of life versus placebo when added to standard of care in patients with type 2 diabetes at high cardiovascular risk (SUSTAIN 6). Diabetes, obesity & metabolism, 22(8), 1339–1347.
14. Yamamoto, H., Lee, C. E., Marcus, J. N., Williams, T. D., Overton, J. M., Lopez, M. E., Hollenberg, A. N., Baggio, L., Saper, C. B., Drucker, D. J., & Elmquist, J. K. (2002). Glucagon-like peptide-1 receptor stimulation increases blood pressure and heart rate and activates autonomic regulatory neurons. The Journal of clinical investigation, 110(1), 43–52.
15. Røder ME. Clinical potential of treatment with semaglutide in type 2 diabetes patients. Drugs Context. 2019;8:212585. Published 2019 Dec 2. doi:10.7573/dic.212585.
16. Heerspink HJL, Apperloo E, Davies M, et al. Effects of Semaglutide on Albuminuria and Kidney Function in People With Overweight or Obesity With or Without Type 2 Diabetes: Exploratory Analysis From the STEP 1, 2, and 3 Trials. Diabetes Care. 2023;46(4):801-810.
17. Shaman AM, Bain SC, Bakris GL, et al. Effect of the Glucagon-Like Peptide-1 Receptor Agonists Semaglutide and Liraglutide on Kidney Outcomes in Patients With Type 2 Diabetes: Pooled Analysis of SUSTAIN 6 and LEADER. Circulation. 2022;145(8):575-585. doi:10.1161/CIRCULATIONAHA.121.055459
18. Femminella, G. D., Frangou, E., Love, S. B., Busza, G., Holmes, C., Ritchie, C., Lawrence, R., McFarlane, B., Tadros, G., Ridha, B. H., Bannister, C., Walker, Z., Archer, H., Coulthard, E., Underwood, B. R., Prasanna, A., Koranteng, P., Karim, S., Junaid, K., McGuinness, B., … Edison, P. (2019). Evaluating the effects of the novel GLP-1 analogue liraglutide in Alzheimer’s disease: study protocol for a randomised controlled trial (ELAD study). Trials, 20(1), 191.
19. Grieco M, Giorgi A, Gentile MC, et al. Glucagon-Like Peptide-1: A Focus on Neurodegenerative Diseases. Front Neurosci. 2019;13:1112. Published 2019 Oct 18.
20. Richards, J. R., Dorand, M. F., Royal, K., Mnajjed, L., Paszkowiak, M., & Simmons, W. K. (2023). Significant Decrease in Alcohol Use Disorder Symptoms Secondary to Semaglutide Therapy for Weight Loss: A Case Series. The Journal of clinical psychiatry, 85(1), 23m15068.
21. Aranäs, C., Edvardsson, C. E., Shevchouk, O. T., Zhang, Q., Witley, S., Blid Sköldheden, S., Zentveld, L., Vallöf, D., Tufvesson-Alm, M., & Jerlhag, E. (2023). Semaglutide reduces alcohol intake and relapse-like drinking in male and female rats. EBioMedicine, 93, 104642.
22. Marty VN, Farokhnia M, Munier JJ, Mulpuri Y, Leggio L, Spigelman I. Long-Acting Glucagon-Like Peptide-1 Receptor Agonists Suppress Voluntary Alcohol Intake in Male Wistar Rats. Front Neurosci. 2020;14:599646. Published 2020 Dec 23.