# Effects of different dosages of Sodium-glucose cotransporter 2 inhibitors on glucose level change in patients with type 2 diabetes stratified by HbA1c and renal function: a systematic review and meta-analysis

## TL;DR

This study finds that higher doses of SGLT2 inhibitors provide only small improvements in blood sugar control for people with type 2 diabetes, regardless of their initial blood sugar levels or kidney function.

## Contribution

The study is the first to systematically evaluate how SGLT2 inhibitor dosages affect glycemic control across different HbA1c and renal function levels in T2DM patients.

## Key findings

- High-dose SGLT2 inhibitors reduced HbA1c by an additional 0.08% compared to low-dose.
- Dose escalation had minimal impact on HbA1c levels across varying glycemic and renal strata.
- Higher doses provided limited additional benefit for poorly controlled T2DM patients.

## Abstract

Type 2 diabetes mellitus (T2DM) is a major global health challenge due to high cardiovascular risk. Sodium-glucose cotransporter 2 (SGLT2) inhibitors can offer glycemic and cardiorenal benefits. Most agents are available in low and high doses, with the assumption that higher doses improve glycemic control. However, previous evidence shows only marginal hemoglobin A1c (HbA1c) reduction (≈0.08–0.18%) with high doses, raising uncertainty about their clinical necessity. Patient factors such as baseline HbA1c and renal function influence SGLT2 efficacy, but whether these factors modify dose response remains unclear. This study evaluates dose-dependent effects across HbA1c and renal function strata.

To assess the glycemic impact of high- versus low-dose SGLT2 inhibitors in T2DM, stratified by HbA1c and renal function.

This analysis followed PRISMA guidelines (PROSPERO ID: CRD42024605351). PubMed, the Cochrane Library, and EMBASE were systematically searched for randomized controlled trials involving SGLT2 inhibitors in adults with T2DM through November 24, 2024. The primary outcome was change in glycated hemoglobin, stratified by hemoglobin A1c (HbA1c) and glomerular filtration rate (GFR) levels. Subgroup analyses were performed based on different SGLT2 inhibitors and dosages.

A total of 23 studies were included for the meta-analysis. Seventeen studies (n = 7,021) were stratified by HbA1c, and eight (n = 7,998) by GFR. Overall, high-dose SGLT2 inhibitors showed a slightly better glycemic control than low-dose SGLT2 inhibitors, with an additional 0.08% (95%CI: -0.12, -0.04) reduction in HbA1c levels. High-dose vs. low-dose SGLT2 inhibitors showed a 0.06%-0.16% further HbA1c reduction across varying glycemia levels (with HbA1c under or over 8%, 8.5%, 9%) and a change in HbA1c levels ranging from -0.07% to 0.04% across varying GFR levels (with GFR under or over 45, 60, 90 ml/min/1.73m2).

Dose escalation had minimal effect on HbA1c across glycemic and renal strata; higher doses of SGLT2 inhibitors offer limited additional benefit for glycemic control in poorly controlled T2DM.

https://www.crd.york.ac.uk/prospero/, identifier CRD42024605351.