While semaglutide has gained widespread recognition for its effectiveness in weight loss and diabetes management, emerging research suggests a broader spectrum of potential health benefits that extend far beyond these initial applications. This article explores the diverse clinical applications of semaglutide, examining its impact on cardiovascular health, kidney function, and potential future uses in neurological and other conditions.
Semaglutide: A Brief Overview
Semaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1 RA) that mimics the effects of the body’s natural incretin hormones. These hormones play a crucial role in regulating blood sugar levels by stimulating insulin release and reducing glucagon secretion after meals. Semaglutide also slows down gastric emptying, leading to increased satiety and reduced appetite.
Originally approved for treating type 2 diabetes mellitus (T2DM) under the brand name Ozempic (Novo Nordisk), semaglutide at higher doses (Wegovy; Novo Nordisk) is prescribed for weight management in patients with a BMI of 30 or more, or a BMI of 27 or more with at least one weight-related co-morbidity. Its efficacy in promoting weight loss has led to its widespread use, sometimes inappropriately, fueled by private online prescribing and concerns about access for those who genuinely need it.
Cardiovascular Benefits
Recent studies have highlighted the potential cardiovascular benefits of semaglutide, independent of its weight-loss effects.
SELECT Trial Findings
The ‘Semaglutide and cardiovascular outcomes in obesity without diabetes’ (SELECT) trial, funded by Novo Nordisk, revealed that non-diabetic, overweight adults taking semaglutide for more than three years experienced a 20% lower risk of heart attack, stroke, or death resulting from cardiovascular disease. Preliminary findings from a University College London-led research team, based on the SELECT trial, indicated that these cardiovascular benefits were irrespective of starting weight and amount of weight lost.
Read also: Weight Loss Guide Andalusia, AL
Philip Newland-Jones, consultant pharmacist in diabetes and endocrinology at University Hospital Southampton NHS Foundation Trust, noted that "there are clearly wider cardiovascular effects of the medicine beyond the weight loss and appetite suppressant actions," adding that the magnitude of cardiovascular risk reduction is not equivalent to that achieved through calorie restriction alone.
Implications for NICE Guidance
Tricia Tan, consultant in diabetes, endocrinology and metabolic medicine at Imperial College London and NHS Trust, highlighted the implications of these findings for National Institute for Health and Care Excellence (NICE) guidance. Currently, NICE recommends stopping semaglutide treatment in patients who have not lost more than 5% of their weight after six months. However, Tan suggests that "even people who do not lose [more than] 5% of weight seem to benefit from the treatment," particularly those with cardiovascular disease.
US FDA Approval
In March 2024, the US Food and Drug Administration approved Wegovy to treat adults with cardiovascular disease who also have obesity or are overweight, but without diabetes mellitus. Paul Wright, consultant cardiovascular pharmacist at Barts Heart Centre in London, anticipates potential NICE endorsements for high cardiovascular risk patients, which could significantly expand the eligible population for semaglutide treatment.
Victoria Ruszala, a specialist pharmacist in cardiology and heart failure at North Bristol NHS Trust, emphasized the importance of interdisciplinary collaboration to fully understand the anti-inflammatory properties of GLP-1s and their impact on the cardiovascular-renal-metabolic system.
Kidney Health
Emerging evidence suggests that semaglutide may also offer benefits for kidney health, particularly in individuals with cardiovascular disease and those with type 2 diabetes and chronic kidney disease.
Read also: Beef jerky: A high-protein option for shedding pounds?
SELECT Trial and Kidney Function
Results from the SELECT trial indicated that a 2.4mg dose of semaglutide has the potential to combat kidney function decline among individuals with cardiovascular disease who are overweight or have obesity, but without diabetes. The trial demonstrated that semaglutide reduced adverse kidney-related events by 22% and highlighted its ability to prevent the onset of macroalbuminuria, a key factor in reducing kidney-related complications. The results also suggested semaglutide's potential to protect kidney function in individuals with pre-existing kidney impairment and reduce urinary albumin-to-creatinine ratio (UACR).
FLOW Trial Findings
The ‘FLOW’ trial, also funded by Novo Nordisk, further supported these findings, demonstrating that semaglutide reduced the risk of clinically important kidney outcomes and death from cardiovascular causes in patients with T2DM and chronic kidney disease (CKD). The risk of a primary-outcome event was 24% lower in the semaglutide group compared to placebo.
Clare Morlidge, a consultant renal pharmacist and deputy chair of the UK Renal Pharmacy Group, noted that semaglutide is "another medication in the cupboard" for slowing the progression of CKD, adding that its use alongside ACEi/ARB, SGLT2 inhibitors, and mineralocorticoid antagonists will help form the pillars of treatment for delaying the progression of CKD and reducing cardiovascular mortality.
Need for Further Research
Helen O’Neil, senior medicines optimisation pharmacist in Tees Valley, emphasized the need for larger trials to assess the impact of semaglutide on top of standard therapies, considering the expense of GLP-1s.
Potential Future Uses
Beyond cardiovascular and kidney benefits, research is underway to explore the potential of semaglutide in treating a range of other conditions, including:
Read also: Inspiring Health Transformation
- Polycystic Ovary Syndrome (PCOS): Semaglutide may help manage PCOS symptoms by addressing weight gain, hormone imbalances, and insulin resistance.
- Addiction: Studies are investigating semaglutide's potential in treating addiction by modulating reward-related behaviors and reducing cravings.
- Alzheimer’s and Parkinson’s Diseases: Research suggests that GLP-1 receptor agonists like semaglutide may have neuroprotective effects, potentially reducing the risk of developing Alzheimer's and Parkinson's diseases.
- Sleep Apnea: Semaglutide is being studied for its potential to improve sleep apnea symptoms, possibly through weight loss and reduced inflammation.
- Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Formerly known as nonalcoholic fatty liver disease (NAFLD), MASLD may be improved by semaglutide's effects on weight loss and metabolic function.
Long-Term Effectiveness and Considerations
While the benefits of semaglutide are promising, it's important to consider the long-term effectiveness and potential limitations.
Weight Regain
A study presented at the American Society for Metabolic and Bariatric Surgery 2024 Annual Scientific Meeting showed that patients who stopped GLP-1s regained 50% of the weight lost within one year, whereas weight loss from bariatric surgery was maintained at approximately 25% for up to ten years. This highlights the importance of addressing the underlying social, financial, and environmental factors that contribute to obesity, rather than relying solely on medication.
Prioritization and Access
Ongoing supply issues and the high cost of semaglutide raise concerns about access and prioritization. Paul Wright suggests prioritizing individuals with poorly controlled diabetes who are deriving significant benefit from the medication. Newland-Jones emphasizes the need to balance the significant benefits of semaglutide with budgetary constraints.
Holistic Approach
O’Neil highlights that while GLP-1s can be a helpful "kick-start" for patients needing to change their relationship with food, a healthy life involves more than just medication. Potential tolerance issues and complications, such as pancreatic inflammation, should also be considered.
The Rise of Dual Receptor Agonists
Semaglutide may be paving the way for dual receptor agonists and combination products, such as tirzepatide (Mounjaro; Eli Lilly and Co). Tirzepatide, which acts on both GLP-1 and GIP receptors, has shown promising results in weight loss and may offer additional benefits for cardiovascular and metabolic health.
A large, controlled trial found that tirzepatide led to significant weight loss compared to placebo, with a mean weight loss percentage of -15.0% with 5 mg, -19.5% with 10-mg and -20.9% with 15-mg weekly doses of tirzepatide, and -3.1% with the placebo.
Addressing Food Cravings
Food cravings are strongly associated with increased food intake and weight gain. Naltrexone, an opioid receptor antagonist, has been shown to decrease the subjective delightfulness of particular foods, particularly those high in sugar and fat. The combination of naltrexone and bupropion has demonstrated synergistic effects in reducing food reward aspects and decreasing the frequency and intensity of food cravings.
Liraglutide, another GLP-1 RA, has also been shown to decrease neural activation in brain areas associated with appetite and reward in response to highly palatable foods.