Clinical Trial Compares Semaglutide and Dulaglutide for Type 2 Diabetes Treatment
Rising Incidence of Type 2 Diabetes
Researchers have recently conducted a clinical trial to evaluate the safety and effectiveness of semaglutide compared to dulaglutide in treating type 2 diabetes. The incidence of this disease has surged dramatically over the past 30 years, affecting approximately 392 million people globally, up from around 30 million in 1985. This increase can be attributed to dietary and lifestyle changes that disrupt the body’s metabolic balance, particularly a rise in the consumption of processed foods and refined sugars, leading to an obesity epidemic.
Type 2 diabetes is characterized by high blood sugar levels and insulin resistance, which can result in long-term complications such as heart disease, strokes, kidney failure, and poor circulation. Maintaining a balanced blood glucose level is crucial, as both hyperglycemia (high blood sugar) and hypoglycemia (low blood sugar) can be life-threatening. Insulin, a hormone produced by the pancreas, plays a vital role in this balance by regulating glucose levels in the bloodstream.
The Need for New Treatments
The rising prevalence and chronic nature of type 2 diabetes have placed a substantial burden on healthcare systems in developed nations. This has spurred research and development of various treatment options to help patients manage their condition effectively. In some cases, direct insulin administration is necessary, although it carries a risk of hypoglycemia. Consequently, alternative treatments are often explored first.
Metformin is the first-line medication for managing type 2 diabetes, functioning by reducing glucose production in the liver. Another category of medications includes glucagon-like peptide-1 receptor agonists (GLP-1R agonists), which stimulate insulin production and can be administered weekly, unlike daily injections.
The SUSTAIN Trials
A recent clinical trial, known as the SUSTAIN trial, evaluated two GLP-1R agonists, semaglutide and dulaglutide. Conducted at 194 sites across 16 countries and published in the Lancet Diabetes & Endocrinology, the trial was sponsored by Novo Nordisk, the patent holder for semaglutide. Participants over the age of 18, diagnosed with type 2 diabetes and already on metformin, were randomly assigned to receive high or low doses of either semaglutide or dulaglutide. The trial involved injections followed by follow-up visits over 40 weeks, measuring primary outcomes through glycated hemoglobin (HbA1c) levels and secondary outcomes including weight change and blood glucose targets.
Results: Semaglutide Outperforms Dulaglutide
The findings indicated that semaglutide was more effective than dulaglutide in reducing HbA1c levels after 40 weeks across both dose levels. Additionally, semaglutide facilitated greater weight loss and a more significant reduction in fasting plasma glucose levels. While the study did not measure insulin sensitivity or beta cell function directly, the authors suggested that weight loss from semaglutide treatment could have improved insulin sensitivity, contributing to lower blood sugar levels.
The study proposed that semaglutide’s lower molecular weight may allow it better access to brain regions that regulate appetite, though further research is needed to substantiate this hypothesis.
Study Limitations
One notable limitation of the study was its open-label design, meaning both patients and clinicians were aware of the drugs administered, and no placebo was included. This design choice was necessary due to the use of a patented device for dulaglutide, which could have introduced variability if a different device was used. Additionally, participants had normal or only mild liver function impairment, which may limit the generalizability of the findings to broader populations.
Overall, the trial suggests that semaglutide may offer a more effective treatment option than dulaglutide for individuals with type 2 diabetes without an increase in adverse effects.
Conclusion
The findings from the SUSTAIN trial underscore the need for effective treatments for type 2 diabetes in light of its rising prevalence and impact on healthcare systems. Ongoing research is essential to further explore the benefits and mechanisms of new diabetes treatments.
Written by Adriano Vissa, PhD
Reference: Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open-label, phase 3b trial. Pratley RE, Aroda VR, Lingvay I, Lüdemann J, Andreassen C, Navarria A, Viljoen A; SUSTAIN 7 investigators. Lancet Diabetes Endocrinology. 2018 Apr;6(4):275-286