This study aims to determine if different diabetes treatments have different effects on inflammation; in particular, kidney inflammation. This type of inflammation is common in people with diabetes, and can lead to kidney failure. This study will investigate the effect of different types of diabetes treatment on kidney inflammation. This will help us to decide if certain types of medicine should be preferred in people with evidence of inflammation in their kidneys, as this may help prevent major complications including kidney failure.

In this prospective cohort study, patients who are clinically determined to require escalation of their glycaemic therapy, and prescribed a DPP4 inhibitor, GLP-1 receptor agonist, or insulin, will be invited to participate.

Blood and urine samples will be taken before, 4 to 8 weeks after, and 26 weeks after starting the new therapy. Markers of inflammation, renal function and glycemic control will be measured at each timepoint.

Inclusion Criteria:

• Age over 30 years
• Diagnosis of type 2 diabetes for one year or more
• Diagnosis of DKD as defined by two distinct albumin:creatinine ratio measurements above the gender specific range in the local reference laboratory with an interval of no less than eight week between measurements
• Stable dose of an inhibitor of the renin angiotensin system for a period of 8 weeks

Exclusion Criteria:

• Any cognitive impediment that preclude the participant from giving free and informed consent
• Substance abuse including alcohol excess
• Use of a GLP-1 analogue in the last 6 months
• Pregnancy
• Hypersensitivity to the prescribed treatment

This study will be a prospective cohort study with 120 participants: 40 per group. I have calculated this sample size to achieve a 90% power based on a 50% reduction in urinary chemokines and circulating pro-inflammatory immune cells 1-4. This power calculation anticipates a 10% dropout rate.

Patients with DKD presenting to the diabetes service of St Vincent's University Hospital (SVUH) and Mater Misericordiae University Hospital (MMUH) who are commenced on GLP-1, DPP4i or insulin for the first time will be invited to participate in the study.