February 2022

In the United States, 36.5% of adults have obesity while another 32.5% of American adults are overweight.1 The estimated annual medical cost of obesity in the US was $147 billion in 2008. This is about $1,429 higher than medical costs for people with healthy weight.1 Obesity-related conditions include heart disease, stroke, type 2 diabetes and certain types of cancer. These are among the leading causes of preventable, premature death.1

Once-weekly subcutaneous semaglutide, 2.4mg, available for weight management with people with obesity, has demonstrated clinically meaningful reductions in body weight in the ongoing global Phase 3 Semaglutide Treatment Effect in People With Obesity (STEP) program.2  No Phase 3 trials have compared semaglutide and liraglutide for weight management. To investigate how well semaglutide works compared to liraglutide in people living with overweight or obesity by comparing the efficacy and adverse event profileps of once-weekly subcutaneous semaglutide, 2.4 mg, versus once-daily subcutaneous liraglutide, 3.0 mg (both with diet and physical activity).

Novo Nordisk performed a randomized, open-label, 68-week, phase 3b trial. Participants randomized (3:1:3:1) to receive once-weekly subcutaneous semaglutide, 2.4mg with 16-week escalation or matching placebo, or once-daily subcutaneous liraglutide, 3.0 mg with 4-week escalation, or matching placebo, plus diet and physical activity. This study included adults with body mass index (BMI) equal to or above 30.0 kg/m2 or equal to or above 27.0 kg/m2 with the presence of at least one of the following weight-related comorbidities (treated or untreated): hypertension, dyslipidemia, obstructive sleep apnea or cardiovascular disease. 

At week 68, the estimated mean change in body weight was -15.8% with semaglutide and -6.4% with liraglutide. Overall, weight loss with semaglutide was significantly greater vs with liraglutide. Treatment with semaglutide showed significantly greater reductions in absolute body weight, waist circumference, total cholesterol level, very low-density lipoprotein cholesterol level, triglyceride level, HbA1c level fasting plasma glucose level, and C-reactive protein level compared to liraglutide. 

A limitation to this study was that the response to poor tolerance of maintenance dose differed; semaglutide was administered at a lower dose, compared to liraglutide being discontinued and had to be escalated if restarted. Dosing differences meant participants knew which active treatment they could potentially receive. 

Based on the study, semaglutide is a better weight management option for adults living with obesity and overweight versus liraglutide. Semaglutide is also a better option when it comes to medication adherence since it only requires a once-weekly subcutaneous dose compared to liraglutide, subcutaneous once a day. However, gastrointestinal disorders were frequent adverse events with semaglutide and liraglutide, reported by 84.1% and 82.7% of participants, respectively. These adverse effects caused many participants to discontinue the treatment. Therefore, necessary studies need to be conducted to investigate and minimize adverse effects.

References:

[1] Centers for Disease Control and Prevention. (2021, September 30). Adult obesity facts. Centers for Disease Control and Prevention. Retrieved February 10, 2022, from https://www.cdc.gov/obesity/data/adult

[2] Rubino DM, Greenway FL, Khalid U, et al. Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial. JAMA. 2022;327(2):138–150. doi:10.1001/jama.2021.23619

[3] Wadden  TA, Bailey  TS, Billings  LK,  et al; STEP 3 Investigators.  Effect of subcutaneous semaglutide vs placebo as an adjunct to intensive behavioral therapy on body weight in adults with overweight or obesity: the STEP 3 randomized clinical trial.   JAMA. 2021;325(14):1403-1413. doi:10.1001/jama.2021.1831

[4] Wilding  JPH, Batterham  RL, Calanna  S,  et al; STEP 1 Study Group.  Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021;384(11):989-1002. doi:10.1056/NEJMoa2032183

Mesenchymal stem cells found in the umbilical cord (UC-MSC) are derived from both the blood and the gelatinous connective tissue that insulates and protects the integrity of the vessels, otherwise known as the Wharton’s jelly. These stromal cells represent a new frontier of stem cell research in their ability to undergo rapid self-renewal and differentiation into germ layers, initiate tissue repair, and monitor immune responses. The properties of MSCs, in addition to the fact that they are easily isolated and cultured, allow them to be favorable candidates for cell therapy, as they can regenerate tissues at various stages of damage [1].     

Cardiovascular disease provokes a number of pathological changes, including myocardial fibrosis, inflammation, and loss of cardiomyocytes. Over the years, clinical studies have proven the role and feasibility of MSCs in cardiovascular disease. MSCs have the ability to migrate to infarcted myocardial tissue and differentiate into cardiomyocyte-like cells, through means of both transplantation and genetic modification, which helps restore cardiac function and prevent cardiac remodeling. MSCs also promote antifibrotic effects by inhibiting fibroblast activation, reducing collagen deposition, and ventricular remodeling, all of which collectively contribute in improving cardiac function. MSCs can control inflammation through activation of innate and adaptive immunity responses and upregulation of anti-inflammatory mechanisms [2]. These mechanisms make MSC therapy appealing for many diseases that have high hospitalization and mortality rates. 

Umbilical cord stem cell research has shown to be a tangible solution for restoring damaged cells and tissues in the human body. MSCs are viable cells for a great deal of therapies due to their intrinsic properties. Although the topic of stem cell-based science is often focused primarily on the ethical and regulatory considerations, the merits and advancements they promise to the future of medicine cannot be downplayed. Future research in umbilical cord stem cells includes garnering a greater understanding of adverse effects of MSCs on the cardiovascular system, proliferation control, and survival rate and retention of cells.

References:

[1] Nagamura-Inoue, T., & He, H. (2014). Umbilical cord-derived mesenchymal stem cells: Their advantages and potential clinical utility. World journal of stem cells, 6(2), 195–202. https://doi.org/10.4252/wjsc.v6.i2.195

[2] Guo, Y., Yu, Y., Hu, S. et al. The therapeutic potential of mesenchymal stem cells for cardiovascular diseases. Cell Death Dis 11, 349 (2020). https://doi.org/10.1038/s41419-020-2542-9