Home Men Health Combination therapy of dapagliflozin and semaglutide shows superior efficacy in type 2 diabetes management

Combination therapy of dapagliflozin and semaglutide shows superior efficacy in type 2 diabetes management

Combination therapy of dapagliflozin and semaglutide shows superior efficacy in type 2 diabetes management

In a recent study published within the journal Pharmacological Research, researchers investigated the synergistic efficacy of two glycemic control drugs – dapagliflozin and semaglutide. They carried out an observational, real-world methodological approach using a test cohort comprising 1,335 type 2 diabetes (T2D) patients. Their findings revealed that the mix oral therapy of dapagliflozin and semaglutide outperformed the previous alone by reducing glycated hemoglobin by 1.2% (in comparison with 0.5% for dapagliflozin).

The mix therapy further induced significant positive changes in body mass index (BMI), blood pressure, total cholesterol, fasting plasmatic glucose low-density lipoprotein (LDL), and the albumin to creatinine ratio. Notably, the mix intervention was found to attain 55% glycated hemoglobin near-normalization, making it a viable and preferable alternative to traditional dapagliflozin therapy in T2D remission.

Study: Type 2 diabetes mellitus pharmacological remission with dapagliflozin plus oral semaglutide. Image Credit: Dragana Gordic / Shutterstock

What’s T2D, and the way will we combat it?

Type 2 diabetes mellitus (T2D) is a chronic, non-transmissible condition characterised by the body’s inability to provide or utilize insulin typically, leading to abnormal blood glucose concentrations. Symptoms of T2D include frequent thirst and urination, excessive hunger and fatigue, and, in extreme cases, blurred vision. Alarmingly, diabetes prevalence is rapidly growing, with research estimating a greater than four-fold increase between 1980 (108 million patients) and 2014 (422 million).

T2D is influenced by quite a few health behaviors, especially weight loss program and physical activity. Unfortunately, because of the increased consumption of unhealthy diets (e.g., the Western weight loss program) and a shift towards more sedentary lifestyles, the International Diabetes Federation (IDF) Diabetes Atlas (2021) reports that greater than 10% of the world’s adult population suffer from T2D, with almost half unaware of the condition. Extensive research up to now 15 years has resulted in the invention of novel drugs for controlling T2D, most notably the Glucagon-like peptide-1 receptor agonists (GLP-1RA) and the sodium-glucose cotransporter-2 inhibitors (SGLT2i).

Dapagliflozin, a selective inhibitor of the SGLT2i class, and semaglutide, a GLP-1RA class drug, have independently been shown to effectively control T2D via oral administration. Nonetheless, while the synergistic effects of mixing SGLT2i and GLP-1RA drugs have been hypothesized and demonstrated in laboratory settings, the real-world advantages of combination therapy remain unknown. Investigating these advantages may allow for novel therapeutic interventions that perform higher or utilize lower dosages than conventional clinical modalities.

In regards to the study

In the current study, researchers aimed to guage the efficacy of dapagliflozin combined with oral semaglutide in aiding glycemic control in T2D patients. They compared this intervention against dapagliflozin taken alone.

The study cohort was derived from the PRECARE2 study, an observational, real-world study aimed toward evaluating the efficacies of clinical therapeutics on T2D patients. Data for this study was obtained from 11 centers in Lombardia, Italy, and comprised demographic and clinical patient histories. Study inclusion criteria included age (>18 years), clinical diabetes diagnosis (at the very least three months), and current interventions (dapagliflozin [dapa] or dapagliflozin together with oral semaglutide [dapa+sema]). A complete of 1,335 individuals met the inclusion criteria and were enrolled in the current study.

Study interventions comprised the dapa (control) cohort (443) and the dapa+sema (case) cohort (892). Outcomes were measured via follow-up at 3- and 6-months following treatment initiation. Outcomes of interest included weight, body mass index (BMI), estimated glomerular filtration rate, blood pressure, fasting blood sugar, glycated hemoglobin (HbA1c), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and the urinary albumin to creatinine ratio (ACR).

Study findings

At six months following intervention initiation, the dapa+sema cohort presented a mean reduction of 1.2% in baseline HbA1c levels, significantly outperforming dapa alone (-0.5%). The mix therapy was observed to lead to improved renal and cardiovascular advantages across serum creatinine, BMI, weight, fasting plasmatic glucose, and LDL metrics. HDL increased barely in each case and control cohorts, though these findings are statistically insignificant. Interestingly, the control (dapa) group was observed to indicate reductions in triglycerides, which was absent within the case (dapa+sema) group.

A logistical binary regression identified serum HbA1c levels and kidney function because the metrics most strongly corresponding to opposed T2D outcomes, as assessed via the Kidney Disease Improving Global Outcomes (KDIGO) classification system. Because the combination therapy resulted in essentially the most remarkable improvements in each metrics and corresponding KDIGO risk classification, the mix of dapagliflozin and oral semaglutide shows promise as a future clinical intervention in T2D pharmacological remission.


The current study assessed the efficacy of dapagliflozin combined with oral semaglutide versus dapagliflozin alone in a cohort of 1,335 Italians. Findings revealed that the mix therapy improved just about all measured outcomes aside from HDL and triglyceride levels in comparison to dapagliflozin treatments. Notably, the mix therapy was found to diminish baseline HbA1c levels by 1.2% in comparison with dapagliflozin (0.5%), leading to significantly improved KDIGO risk assessments.

“Even when further research is required, we advise that the mix regimen of dapagliflozin plus oral semaglutide may induce type 2 diabetes pharmacological remission in clinical practice in greater than 50% of patients.”

Journal reference:

  • Lunati, M. E., Cimino, V., Bernasconi, D., Gandolfi, A., Morpurgo, P. S., Tinari, C., Lazzaroni, E., Baruffaldi, L., Muratori, M., Montefusco, L., Pastore, I., Rossi, A., Franzetti, I. G., Muratori, F., Manfrini, R., Disoteo, O. E., Terranova, R., Desenzani, P., Girelli, A., . . . Fiorina, P. (2023). Type 2 diabetes mellitus pharmacological remission with dapagliflozin plus oral semaglutide. Pharmacological Research, 199, 107040, DOI – https://doi.org/10.1016/j.phrs.2023.107040, https://www.sciencedirect.com/science/article/pii/S1043661823003961


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