Diabetes mellitus (DM) is one of the leading non-communicable diseases and a significant risk factor for other non-communicable conditions such as cardiovascular and chronic kidney diseases. These conditions account for a high proportion of deaths and disability around the world, ¹ and DM incidence is expected to rise, especially in low and middle-income countries. ²

The approach to DM treatment has evolved from a strict glucose control aimed at reducing the risk of micro- and macrovascular complications ^{3– 5} to a more patient-centered strategy. This new paradigm emphasizes reducing the risk of conditions such as cardiovascular disease, heart failure, and kidney disease through medications with a disease-modifying effect, independent of glucose control. ^{3, 4}

Most recent advancements in DM treatment stem from the clinical evidence on two classes of medication: glucagon-like peptide-1 receptor agonists (GLP-1RAs) ^{5– 8} and sodium-glucose cotransporter-2 inhibitors (SGLT2is). Individually, these medications meet the glucose reduction and cardiovascular safety requirements for DM and they modify the risk of cardiovascular events, heart failure hospitalizations, and progression of kidney disease. They also are related to modest weight loss and a low risk of hypoglycemia. ^{9– 12}

While guidelines recommend combining DM treatments as simultaneous or add-on therapies ^{13, 14} —a natural progression in T2D management—most clinical trials are structured to evaluate a single interventions, including those on GLP-1Ras and SGLT2is. Real-world clinical practice often differs significantly from the controlled environment of clinical trials. Following guidelines recommendations, combined therapy with GLP-1RAs and SGLT2is is expected to become one of the most commonly prescribed treatments for DM. Recently, meta-analyses of clinical trials have synthesized the combined effects of these two drug classes. However, observational studies and post hoc analyses on combination therapy and its impact on key outcomes are likely to offer a more extensive body of evidence. This prompted us to design a scoping review to map the clinical research landscape surrounding combined GLP-1Ras and SGLT2is therapy, focusing on its effects on metabolic, cardiovascular, and renal outcomes.

This review synthesizes the evidence on the metabolic, cardiovascular, and renal outcomes of combined GLP-1Ras and SGLT2is therapy in individuals with DM. Evidence suggests potential benefits from this combined therapy in managing cardiovascular disease, ^{17, 18} kidney disease, ¹⁹ synergistic pathways to enhance glucose control, ²⁰ and promoting weight loss. ²¹ Understanding whether these potential benefits translate into clinically meaningful changes for people with DM is essential, which is why this scoping review focuses on clinically significant outcomes. for people with DM. This is why we have centered this scoping review on clinically significant outcomes. Additionally, we plan to investigate whether any differences exist when the combination therapy is used simultaneously or as an add-on approach, as this distinction could guide future research.

CEBM conceived and designed the review, led the development of the search strategy, and offered guidance for protocol design. All authors critically reviewed and contributed to the final version of the manuscript.

Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

We intend to publish the results in a specialized peer-reviewed journal and present them at local, national, and international conferences. They will also be used as educational material in meetings. Ethical approval and consent were not required.