Even low-risk diabetes patients obtain renal, mortality benefits with SGLT2 inhibitors

Sodium-glucose cotransporter-2 (SGLT2) inhibitors help reduce the risk of lung function decline and mortality in a low-risk population of patients with type 2 diabetes (T2D) who have normal or low BMI, as shown in a single-centre retrospective study from Korea.

The primary outcome of estimated glomerular filtration rate (eGFR) increased by 0.3 mL/min/1.73 m²/year over a median follow-up of 3.2 years among users of SGLT2 inhibitors but remained relatively unchanged (0.0 mL/min/1.73 m²/year) over a median follow-up of 5.0 years among nonusers (control group) (p=0.0398). [BMJ Open Diabetes Res Care 2025;13:e004876]

In subgroup analysis, the renoprotective effect observed with SGLT2 inhibitor use vs nonuse was pronounced among patients with baseline urine albumin-to-creatinine ratio of ≥30 mg/gCr (1.0 vs 0.1 mL/min/1.73 m²/year; p=0.041) and among those with baseline eGFR of <90 mL/min/1.73m² (1.0 vs 0.2 mL/min/1.73 m²/year; p=0.021).

Results for the secondary outcomes likewise favoured the SGLT2 inhibitor group. Relative to nonusers, users of SGLT2 inhibitors saw a significantly lower incidence of composite renal outcome (ie, eGFR decline of ≥40 percent from baseline or end-stage kidney disease) (2.57 vs 11.24 per 1,000 person-years; hazard ratio [HR], 0.223, 95 percent confidence interval [CI], 0.052–0.952; p=0.0426) and all-cause mortality (0.21 vs 1.09 per 1,000 person-years; HR, 0.171, 95 percent CI, 0.041–0.718; p=0.0159). No between-group difference was seen for the incidence cardiovascular disease.

As for BMI, the control group showed an initial increase in the first year, followed by a decrease. On the other hand, the SGLT2 inhibitor group showed a lower BMI than the control group at years 1 and 2, with BMI values becoming similar from year 3 onward. These indicated that SGLT2 inhibitors did not cause significant weight loss and may prevent weight gain in T2D patients with normal or low BMI, as the investigators pointed out.

Overall, the findings of the present study “alleviate previous concerns about the SGLT2 inhibitor use in patients with normal or low BMI and support their potential use in a broader population with diabetes,” the investigators said.

“Clinicians may consider prescribing SGLT2 inhibitors for renal protection and mortality reduction, even in patients with normal or low BMI and without overt proteinuria or significant renal dysfunction,” they added.

The investigators called for additional research to establish the long-term benefit of SGLT2 inhibitors and elucidate the mechanisms underlying its effects in low-risk populations.

For the present study, researchers used data from the Clinical Data Warehouse DARWIN-C of Samsung Medical Center. They identified 5,842 adult T2D patients with a BMI of <23 kg/m². None of the patients had pre-existing CKD stage 4 or 5. Underweight was defined as BMI of <18.5 kg/m², while normal weight was defined as BMI of 18.5–22.9 kg/m², according to the WHO guidelines for the Asia-Pacific region.

Of the patients, 216 SGLT2 users and 432 nonusers were propensity-score matched and included in the analysis. In the SGLT2 inhibitor and control groups, the mean ages were 61.8 and 61.5 years, median BMIs were 21.8 and 21.7 kg/m², and mean eGFRs were 84.5 and 84.8 mL/min/1.73 m², respectively. The SGLT2 inhibitor group had higher HbA1c concentrations than the control group (7.5 percent vs 7.3 percent; p=0.0141).