What's Next for Semaglutide? Beyond Diabetes and Weight Loss

By Dr. Priyom Bose, Ph.D.Reviewed by Danielle Ellis, B.Sc.

How does semaglutide work?
Emerging trends in semaglutide research
Brain health
Cardiovascular benefits
Kidney health
Commercial availability and challenges
References
Further reading

Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist that was originally approved by the Food and Drug Administration (FDA) for the treatment of type 2 diabetes (T2D). Current research findings and clinical trials have highlighted the efficacy of semaglutide beyond diabetes management and cautioned physicians on certain side effects of this medicine.

How does semaglutide work?

The active ingredient of semaglutide is a GLP-1 receptor agonist, which mimics the action of the GLP-1 hormone in regulating blood sugar levels.¹ It binds to GLP-1 receptors on pancreatic cells and subsequently increases insulin secretion in response to meals. A reduction in glucagon release occurs along with deceleration in the gastric emptying process, which promotes weight loss.²

How Does Semaglutide Work to Lose Weight? Find Out More

Emerging trends in semaglutide research

Existing research has indicated the effectiveness of semaglutide in improving brain health and reducing the risk of cardiovascular events in the diabetic population. Some of the prominent benefits and limitations of semaglutide use are listed below:

Brain health

Researchers from the University of Oxford have recently indicated that semaglutide has no added risks of adverse neurological or psychiatric outcomes (e.g., dementia, anxiety, and depression) compared to other antidiabetic drugs.⁴ These observations were based on 100 million patient records in the US, among which 20,000 patients were using semaglutide.

On validating these findings via large-scale clinical trials, semaglutide use could have significant implications for public health with respect to preventing cognitive decline and reducing smoking rates in diabetic patients. More research is required in the future to elucidate how semaglutide may be having these effects.

Dr. Max Taquet, Clinical Lecturer at the University of Oxford, stated that if these results are confirmed, then semaglutide could not only be highly beneficial for diabetic patients with obesity but also those diagnosed with psychiatric disorders.

Another study conducted by researchers from the Perelman School of Medicine at the University of Pennsylvania indicated that semaglutide use does not increase the risk of depressive symptoms or provoke any suicidal thoughts in persons without significant mental health issues.⁵ This observation was based on the analysis of data from over 3,500 participants across four major clinical trials.

Image Credit: Caroline Ruda/Shutterstock.com

In comparison to insulin treatment, semaglutide was found to significantly reduce the risk of first-time Alzheimer's disease (AD) diagnosis.⁶ Therefore, semaglutide could also play a significant role in delaying or preventing AD in the diabetic population.

Cardiovascular benefits

The 'Semaglutide and cardiovascular outcomes in obesity without diabetes' (SELECT) trial, funded by Novo Nordisk, is considered to be the largest and longest clinical trial to evaluate the effects of semaglutide on weight.⁷ This trial, run by an international team, included more than 17,000 overweight adults or those with obesity.

The SELECT trial findings revealed that non-diabetic, overweight, and obese adults taking semaglutide (2.4 mg) for more than three years are at 20% less risk of stroke, heart attack, or death due to cardiovascular events.

According to the preliminary reports of research led by scientists at UCL Institute of Cardiovascular Disease, semaglutide facilitates cardiovascular benefits irrespective of starting weight and amount of weight loss.⁸

Based on the SELECT trial findings, Tricia Tan, consultant at the Imperial College London and NHS Trust, voiced a contradiction to the current National Institute for Health and Care Excellence (NICE) guidance for semaglutide treatment. This guidance recommends stopping medication in patients who have not lost more than 5% of weight after six months of treatment.

Considering the SELECT trial report, the experts indicated the beneficial effects of continuing semaglutide treatment, particularly in patients with cardiovascular disease, even if they do not undergo the recommended weight loss.

Kidney health

The potential anti-inflammatory properties of GLP-1s could help combat kidney disease.  The SELECT trial findings indicated that a dose of 2.4mg of semaglutide could help prevent a decline in renal functions in non-diabetic, obese patients with cardiovascular disease. Patients taking semaglutide were found to be at a 22% lower risk of renal disorders. For instance, this treatment prevented macroalbuminuria onset, which is indicative of kidney disease.⁹

Semaglutide protects kidney functions by reducing the urinary albumin-to-creatinine ratio (UACR). The FLOW trial also indicated the positive effect of semaglutide in reducing the risk of clinically important kidney outcomes and death from cardiovascular causes in patients with T2D and chronic kidney disease (CKD).¹⁰

Commercial availability and challenges

Semaglutide is commercially available under three separate brand names- Ozempic, Wegovy, and Rybelsus.³ The dosage recommendation and efficacy of each brand varies. For instance, the Rybelsus tablet demonstrates efficacy in improving the glycemic index of patients with T2D. Ozempic injection offers not only glycemic control but also reduces the risk of cardiovascular events in patients with and without T2D.

Despite the numerous benefits, clinicians must be careful while prescribing semaglutide because each brand has different preparations and variable dosage schemes linked to different benefits and side effects. Therefore, physicians must be aware of the safety and efficacy of each semaglutide brand.

A recent analysis indicated that many non-diabetic but overweight or obese semaglutide users discontinue their treatment after approximately two years. This decline in patient adherence to medication over time has been attributed to the high cost of treatment, side effects (e.g., gastrointestinal problems), and availability issues. The significant reduction in long-term use could impede semaglutide's future growth.

A collaboration between scientists and healthcare teams, including physicians, dietitians, pharmacists, and nurses, is essential for optimal T2D management and enabling weight loss with semaglutide treatment. Since the benefits of semaglutide are inherently associated with lifestyle modifications, a proper diet tailored by dietitians could play an important role in better management of blood glucose levels, maintaining proper cardiovascular health, and promoting weight reduction.

References

1. Mahapatra MK, et al. Semaglutide, a glucagon like peptide-1 receptor agonist with cardiovascular benefits for management of type 2 diabetes. Rev Endocr Metab Disord. 2022;23(3):521-539. doi: 10.1007/s11154-021-09699-1.
2. Zheng Z. et al. Glucagon-like peptide-1 receptor: mechanisms and advances in therapy. Sig Transduct Target Ther. 2024; 9, 234. doi.org/10.1038/s41392-024-01931-z
3. Kommu S, Whitfield P. Semaglutide. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025. Available from: https://www.ncbi.nlm.nih.gov/books/NBK603723/
4. De Giorgi R, et al. 12-month neurological and psychiatric outcomes of semaglutide use for type 2 diabetes: a propensity-score matched cohort study. eClinicalMedicine. 74, 102726. DOI: 10.1016/j.eclinm.2024.102726
5. Agarwal SM, Hahn M. Semaglutide in Psychiatry—Opportunities and Challenges. JAMA Psychiat. 2024; 81(10):955-956. doi:10.1001/jamapsychiatry.2024.2412
6. Wang W, et al. Associations of semaglutide with first-time diagnosis of Alzheimer's disease in patients with type 2 diabetes: Target trial emulation using nationwide real-world data in the US. Alzheimers Dement. 2024;20(12):8661-8672. doi: 10.1002/alz.14313.
7. Lincoff AM, Brown-Frandsen K, Colhoun HM, Deanfield J, Emerson SS, Esbjerg S, Hardt-Lindberg S, Hovingh GK, Kahn SE, Kushner RF, Lingvay I, Oral TK, Michelsen MM, Plutzky J, Tornøe CW, Ryan DH; SELECT Trial Investigators. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. N Engl J Med. 2023;389(24):2221-2232. doi: 10.1056/NEJMoa2307563.
8. Ryan DH, et al. Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial. Nat Med. 2024; 30, 2049–2057. doi.org/10.1038/s41591-024-02996-7
9. Lakkis J, Weir MR. Diabetes Mellitus and the Cardiovascular Metabolic Syndrome: Reducing Cardiovascular and Renal Events. Hypertension (Second Edition). 2005; 543-556. doi.org/10.1016/B978-0-7216-0258-5.50142-3.
10. Perkovic V, Tuttle KR, Rossing P, Mahaffey KW, Mann JFE, Bakris G, Baeres FMM, Idorn T, Bosch-Traberg H, Lausvig NL, Pratley R; FLOW Trial Committees and Investigators. Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes. N Engl J Med. 2024;391(2):109-121. doi: 10.1056/NEJMoa2403347.

Further Reading

• All Semaglutide Content
• Semaglutide and Type 2 Diabetes: Efficacy, Safety, and Outcomes