UK Trends in Prescribing Preferences for Antidiabetic Medications Among Type 2 Diabetes Patients With and Without Chronic Kidney Disease, 2006-2020

Background: Over the past two decades alone, more than 20 new medications have been approved for treatment of T2DM, while in more recent years, sodium glucose cotransporter inhibitors (SGLT2i), and to a lesser extent, glucagon-like peptide 1 receptor agonists (GLP-1RA) have shown to reduce the risk of deleterious kidney outcomes among patients co-diagnosed with T2DM and CKD. However, there is paucity of data comparing drug prescribing patterns among T2DM patients with and without CKD.

Objectives: To evaluate trends in antidiabetic medication initiation patterns among type-2 diabetes mellitus (T2DM) patients with and without chronic kidney disease (CKD).

Methods: Retrospective cohort study using Clinical Practice Research Datalink (2006-2020) was conducted to evaluate the overall, first- and second line (after metformin) medication initiation patterns among CKD (N=38,622) and non-CKD (N=230,963) patients with T2DM. New treatment initiation was defined as no prior use of study medication 365 days prior to date of initiation. Cohort membership was restricted to patients with a recorded serum creatinine (SCr) value, documented T2DM, and no evidence of type 1 or gestational diabetes, cancer, polycystic ovary syndrome, acute kidney injury, or HIV. The most recent SCr value prior to the index date was used to estimate the glomerular filtration rate (eGFR) via the chronic kidney disease epidemiology collaboration equations (CKD-EPI), and an eGFR threshold of < 60 ml/min was used to designate patients as having CKD.

Results: Relative to other glucose-lowering therapies, metformin initiations declined overall, but remained the treatment of choice as first-line therapy for both CKD and non-CKD patients. Sodium-glucose co-transporter-2 (SGLT2i) use increased modestly among CKD patients, but this increase was more pronounced among non-CKD patients; by 2020, non-CKD compared to CKD patients were three (28.5% vs 9.4%) and six (46.3% vs 7.9%) times more likely to initiate SGLT2i overall and as second-line therapy, respectively. Glucagon like peptide 1 receptor agonist (GLP-1RA) use was minimal regardless of CKD status ( <5%), while both dipeptidyl peptidase-4 inhibitor (DPP4i) and sulfonylurea use remained high among CKD patients. For instance, by 2020 and among CKD patients, DPP4i and sulfonylureas comprised of 28.3% and 20.6% of all initiations, and 57.4% and 30.3% of second-line initiations, respectively.

Conclusions: SGLT2i use increased among T2DM patients, but this increase was largely driven by non-CKD patients. Future work identifying barriers associated with the uptake of therapies with proven cardiorenal benefits (e.g., SGLT2i, GLP-1RA) among CKD patients is needed.