Sodium-glucose cotransporter-2 inhibitors linked to slower kidney disease progression than dipeptidyl peptidase-4 inhibitors in adults with type 2 diabetes in UK clinics
SGLT2 inhibitor initiation was associated with 7.48 events per 1000 patient-years for composite kidney endpoints compared to 11.77 for DPP-4 inhibitors.
SGLT2 inhibitors were linked to a 36% reduction in the risk of the primary composite endpoint.
All-cause mortality risk was reduced by 26% with SGLT2 inhibitors compared to DPP-4 inhibitors.
The risk of was decreased by 63% with SGLT2 inhibitor use.
SGLT2 inhibitors were associated with a 67% lower rate of sustained low estimated glomerular filtration rate.
Diagnoses of end-stage kidney disease in primary care were significantly lower with SGLT2 inhibitors.
Simplified
AIMS: To confirm the reno-protective effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors compared with dipeptidyl peptidase-4 (DPP-4) inhibitors on the onset and progression of (CKD) in routine clinical practice.
MATERIALS AND METHODS: We conducted a retrospective cohort study using the Clinical Practice Research Datalink Aurum database linked to Hospital Episode Statistics. The primary outcome was risk of the composite CKD endpoint based on the recent consensus guidelines for kidney disease: >40% decline in estimated glomerular filtration rate (eGFR), kidney death or (ESKD; a composite of kidney transplantation, maintenance of dialysis, sustained low eGFR <15 ml/min/1.73m² or diagnosis of ESKD). Secondary outcomes were components of the composite CKD endpoint, analysed separately. Patients were propensity-score-matched 1:1 for SGLT2 inhibitor versus DPP-4 inhibitor use.
RESULTS: A total of 131 824 people with type 2 diabetes (T2D) were identified; 79.0% had no known history of CKD. During a median follow-up of 2.1 years, SGLT2 inhibitor initiation was associated with lower risk of progression to composite kidney endpoints than DPP-4 inhibitor initiation (7.48 vs. 11.77 events per 1000 patient-years, respectively). Compared with DPP-4 inhibitor initiation, SGLT2 inhibitor initiation was associated with reductions in the primary composite CKD endpoint (hazard ratio [HR] 0.64, 95% confidence interval [CI] 0.56-0.74), all-cause mortality (HR 0.74, 95% CI 0.64-0.86) and ESKD (HR 0.37, 95% CI 0.25-0.55), reduced the rate of sustained low eGFR (HR 0.33, 95% CI 0.19-0.57), and reduced diagnoses of ESKD in primary care (HR 0.04, 95% CI 0.01-0.18). Results were consistent across subgroup and sensitivity analyses.
CONCLUSIONS: In adults with T2D, initiation of an SGLT2 inhibitor was associated with a significantly reduced risk of CKD progression and death compared with initiation of a DPP-4 inhibitor.
Key numbers
7.48 events per 1000 patient-years
Reduction in Composite Events
SGLT2 inhibitor initiation
0.64
Hazard Ratio for Primary Composite Endpoint
Compared to DPP-4 inhibitors
0.74
All-Cause Mortality Hazard Ratio
Compared to DPP-4 inhibitors
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Kamlesh Khunti has acted as a consultant, speaker or received grants for investigator‐initiated studies for AstraZeneca, Novartis, Novo Nordisk, Sanofi‐Aventis, Lilly, and Merck Sharp & Dohme, Boehringer Ingelheim, Bayer, Berlin‐Chemie AG/Menarini Group, Janssen and Napp. Iskandar Idris has acted as an advisory board member, speaker or received grants for Eli Lilly, Novo Nordisk, Merck Sharp & Dohme, AstraZeneca, Abbot Diabetes Care, Sanofi and Boehringer. Ruiqi Zhang, Jil B. Mamza, Mike Ford and Tamsin Morris are employed by AstraZeneca UK Ltd, a biopharmaceutical company that develops, manufactures, and markets medicines in the cardiovascular, kidney and metabolic disease area. Amitava Banerjee has received research grants from AstraZeneca.
