Diabetes secondary to disorders of the exocrine pancreas (DEP), also referred to as type 3c diabetes or pancreatogenic diabetes, is a form of diabetes resulting from both structural and functional loss of insulin secretion in the context of exocrine pancreatic dysfunction [1]. The main etiologies of DEP are acute and chronic pancreatitis, pancreatic cancer, and cystic fibrosis [2].

DEP is the second most common cause of adult-onset diabetes after type 2 diabetes (T2D), with a higher incidence than that of type 1 diabetes (T1D) [[3], [4], [5]]. A study conducted in the United Kingdom (UK) found a DEP prevalence of 1.8%, which was significantly higher than the 1.1% prevalence of adult-onset T1D [3]. The incidence of DEP varies according to the healthcare setting and country. In a primary care setting in the UK, the incidence of DEP was estimated to be 2.59 per 100,000 individuals per year, whereas in a tertiary care setting in New Zealand, the incidence was estimated to be 10.00 per 100,000 individuals per year [3,6]. DEP is estimated to account for 1% to 9% of patients with diabetes [7].

The heterogeneous etiologies of DEP, its complex clinical presentation, and limited clinical awareness of it as an entity distinct from T1D and T2D make accurate diagnosis challenging. These factors often lead to the misclassification of DEP as either T1D or T2D. Notably, previous studies report that approximately 45–90% of individuals with DEP are misdiagnosed as having T2D [3,8]. Recent large-scale studies suggest that the risk of hypoglycemia and all-cause mortality is higher in patients with DEP than in those with T2D [[9], [10], [11]]. Furthermore, the incidence of both microvascular and macrovascular complications is higher in patients with DEP than in those with T2D [9].

Recent advancements in T2D treatment, including the development of new drugs and the results of randomized controlled trials (RCTs), have led to a more diverse range of therapeutic options compared with those previously available [12,13]. However, no RCTs have specifically focused on the pharmacological treatment of DEP other than in patients with cystic fibrosis-related diabetes. In addition, major diabetes drug trials, including those evaluating incretin-based therapies, have excluded patients with DEP from study enrollment. As a result, treatment decisions for DEP are largely based on established therapies for T1D and T2D [7,14]. To date, metformin and insulin have been the primary therapies used for managing DEP, in line with recent expert recommendations [7,15,16]. However, a recent nationwide Danish population-based cohort study examining the use of other glucose-lowering treatments in patients with post-pancreatitis diabetes revealed the use of other antidiabetic medications such as incretin-based therapies, sulfonylureas, and sodium-glucose cotransporter-2 (SGLT2) inhibitors, beyond the traditional use of metformin and insulin were used [8]. Incretin-based therapies and sulfonylureas are generally not recommended for patients with DEP [7,16,17]. However, the increasing use of new diabetes medications for T2D, coupled with the misdiagnosis of DEP as T2D in clinical practice, may explain the growing use of these agents in the management of DEP.

Recent advancements have been made in understanding the characteristics and natural course of DEP, but research on pharmacological treatments other than insulin and metformin remains relatively limited. It is important to move away from the traditional focus on insulin deficiency as the sole defining feature of DEP and to consider the diverse clinical profiles of patients with DEP [14]. In this context, exploring the application of newer therapies widely used in the treatment of T2D may be a more feasible approach for DEP management. SGLT2 inhibitors, which have demonstrated not only glucose-lowering effects but also cardiovascular and renal benefits in T2D, warrant investigation for their potential impact on cardiorenal outcomes and safety in patients with DEP [18,19]. Therefore, we investigated the real-word cardiovascular and renal effectiveness and adverse drug reactions associated with SGLT-2 inhibitor in patients with DEP using the Korean National Health Insurance Service (NHIS) database.