Exploring the beneficial impact of Linagliptin on de novo chronic kidney disease (CKD) clusters in the CARMELINA trial

Chronic kidney disease (CKD) is a long-term condition where the kidneys do not work as well as they should. It affects about 10% of people worldwide and can lead to serious health problems, such as heart disease, kidney failure, and even death. People with CKD are often also affected by other health conditions, such as type 2 diabetes, high blood pressure, or inflammation, which can further increase their risks of adverse events.

Medications currently used to treat CKD include drugs that lower blood pressure, particularly those that block the renin–angiotensin–aldosterone system (RAAS inhibitors), and newer drugs, such as sodium-glucose co-transporter 2 inhibitors (SGLT2 inhibitors). These medicines can help to slow kidney damage. Another type of medication called DPP-4 inhibitors (dipeptidyl peptidase-4 inhibitors)—like Linagliptin—is often used in people with diabetes. DPP-4 inhibitors are a class of medications used to manage type 2 diabetes by blocking the DPP-4 enzyme, which then increases the body's incretin hormones (GLP-1 and GIP). These hormones stimulate insulin production and lower the amount of glucose produced by the liver, which helps lower blood sugar levels. Linagliptin has shown benefits in controlling blood sugar and reducing kidney damage markers, but its full impact on kidney and heart outcomes in CKD patients remains unclear.

We believe that CKD in patients with type 2 diabetes is not one single disease but a mix of different subtypes, with patients showing different combinations of symptoms and risks. Our goal is to identify specific groups (or “clusters”) of patients with CKD who might respond differently to treatments like Linagliptin. Understanding these differences could lead to more targeted, personalized care and better outcomes.

To do this, we will analyze data from the CARMELINA clinical trial, which studied the effects of Linagliptin in people with type 2 diabetes and high risk of kidney or heart problems. We will group patients based on common, easy-to-measure clinical features such as age, blood pressure, blood sugar levels, body weight, and kidney function. Then, we will study whether these patient groups experienced different outcomes, such as kidney disease progression, heart events, changes in blood sugar control, or side effects.

We will also look specifically at how well Linagliptin worked in each group—does it help to slow the progressive kidney function decline? Does it reduce the chance of a heart event or serious side effects in some groups more than others?
Our approach uses statistical techniques to group patients into clusters and then compare their outcomes. We will also conduct additional analyses using data from other clinical studies in Germany to confirm our findings and ensure they apply to a wide range of patients.

This research could help identify which patients benefit most from drugs like Linagliptin and improve how treatments are chosen in the future. It may also provide new insight into how CKD develops and progresses in different people.