What are the changes in HbA1c, and renal function associated with SGLT2 inhibitors among patients with varying stages (3-5) of CKD and Type 2 Diabetes?

Problem

Sodium Glucose Cotransporter 2 inhibitors (SGLT2is) lower blood sugar and reduce the risk of renal failure and cardiac failure in patients with diabetes and chronic kidney disease (CKD). The NICE guidelines currently recommend the use of SGLT2i to accompany other treatment options, such as Angiotensin Converting Enzyme inhibitors (ACEis) or Angiotensin receptor blockers (ARBs), after maximum dosage has been reached. However, the NICE guidelines do not discuss whether the use of SGLT2is by CKD stage affects outcome. We aimed to assess how SLGT2i use by differing CKD stage affects renal and glycaemic control outcomes.

Approach

A systematic review +/- random effects meta-analysis of renal and glycaemic RCT outcomes in adult diabetic patients ≥ 18 years by CKD 3-5 stage will be undertaken. PubMed, PRISMA, Medline, Google Scholar databases and Cochrane systematic reviews will be searched from 2010-2022. Risk of bias and finding certainty will be assessed with Risk of Bias 2 (RoB 2) and GRADEpro tools. Population: Adult patients ≥18 years who have both Type 2 Diabetes and CKD stage 3-5 (eGFR<60mL/min/1.73m2 or UACR >300 mg/g). Intervention: All types of SGLT2i will be included in this study.Comparators: SGLT2i vs. non SGLT2i useOutcomes: Renal function- eGFR, albumin: creatinine ratio (ACR) and glycaemic control (HbA1c). Where data is available, outcomes will be compared across individual CKD stages 3, 4 and 5.

Findings

Relevant extracted adjusted data will be summarised and displayed in tables or charts, with narrative synthesis undertaken. Provided there are sufficient data for meta- analysis, this data will be presented on a forest plot. Statistical heterogeneity will be measured using the I2 statistic and the Tau2 will be reported as a measure of between study variance.

Consequences

The results of this study can help assess SGLT2i effects on glycaemic control and renal function by CKD stage, adding to the evidence base. Our findings may help further inform prescribing evidence for patients with CKD and diabetes to prevent avoidable morbidity and health costs.