(A-308) Risk of pre-sarcopenia and SGLT2 inhibitors in young adults with type 2 diabetes: A nationwide cohort study

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) may negatively impact skeletal muscle mass by depletion of hepatic glycogen storage. Evidence on the association between SGLT2i and the risk of pre-sarcopenia remains limited in non-elderly type 2 diabetes (T2D) patients with relatively fewer risk factors for muscle loss.

Objectives: To evaluate changes in skeletal muscle mass index (SMI) and risk of falls/fractures among patients with T2D initiating SGLT2i versus dipeptidyl peptidase-4 inhibitors (DPP4i).

Methods: We conducted an active-comparator, new-user cohort study (2013-2022) linking health screening records from a tertiary hospital to nationwide claims of Korea. The study cohort included T2D patients 1) aged < 65 years to minimize aging effects and 2) with at least 2 health screening records. New-users of SGLT2i were 1:1 propensity score (PS)-matched to new-users of DPP4i, with the index date defined as the date of drug initiation. The primary outcome was the difference between the change in SMI over the five-year follow-up and the age-specific cutoff value (male: 7.0 kg/m2; female: 5.7): SMI was estimated using a validated predictive equation incorporating age, sex, body weight, height, and serum creatinine levels. Then, the difference between the SMI and age-specific cutoff values was calculated for each treatment group and compared. Secondary outcomes included changes in soft lean mass and fat mass, as well as the incidence of falls and fractures. Patients were followed from the day after index date until the earliest of outcome occurrence, death or study end date. Muscle and fat mass changes were estimated using generalized linear mixed models, and hazard ratios (HRs) with 95% confidence intervals (CIs) for falls and fractures were estimated using Cox models.

Results: Among 15,054 T2D patients who initiated SGLT2i or DPP4i, 1,388 PS-matched pairs were included, with a mean age of 45.2 years and 46.4 years, respectively. Over five years, SMI declined slightly from 1.84 kg/m2 (95% CI 1.79-1.89) to 1.72 (1.66-1.78) in SGLT2i users and from 1.74 (1.69-1.80) to 1.61 (1.55-1.67) in DPP4i users. However, there was no significant difference in the amount of reduction in SMI between groups (p=0.81). Changes in soft lean mass and fat mass followed similar trends. Furthermore, the use of SGLT2i was not associated with the risk of composite falls and fractures compared to DPP4i (HR 1.04, 95% CI 0.57-1.89)

Conclusions: In this nationwide cohort study, the use of SGLT2i was not associated with accelerated decline in muscle mass and increased risk of falls/fractures compared to DPP4i in non-elderly patients with T2D. Although our findings provide reassurance regarding the use of SGLT2 inhibitors, further studies with a larger population are warranted.