Differential Effects of Oral Antidiabetic Drugs on Skeletal Muscle Mass and Hemoglobin Levels in Adults with Type 2 Diabetes Mellitus: A Prospective Real-World Cohort Study.

Background/

Objectives

Beyond glycemic control, oral antidiabetic drugs (OADs) may exert class-specific effects on muscle mass and hematologic parameters. However, real-world evidence comparing these effects across OAD classes remains limited. This study aimed to evaluate the differential effects of commonly prescribed OADs on skeletal muscle mass (SMM) and hemoglobin (Hb) levels in adults with type 2 diabetes mellitus (T2DM).

Methods

In this prospective observational cohort study, 60 adults with newly initiated OAD therapy were followed for six months at a tertiary care center in Türkiye. Patients were classified according to the OAD class newly added to their regimen (metformin, sulfonylureas, dipeptidyl peptidase-4 inhibitors, pioglitazone, or sodium-glucose cotransporter-2 inhibitors [SGLT2-i]). Multi-frequency bioelectrical impedance analysis was used to evaluate body composition, and hematologic parameters including Hb were obtained at both time points. To account for potential confounders-including age, sex, BMI, baseline Hb, and eGFR-binary logistic regression analyses were performed.

Results

Patients initiated on pioglitazone (n = 11) demonstrated a borderline within-group increase in SMM in unadjusted analysis (median delta +0.17 kg, IQR -0.55 to +0.50; p = 0.050); however, this association was attenuated and no longer statistically significant after multivariable adjustment (OR 2.16, 95% CI 0.60-7.83; p = 0.240). In contrast, SGLT2-i users (n = 28) showed a significant increase in Hb (median delta +0.10 g/dL, IQR -0.30 to +0.50; p = 0.022), which remained significant after adjustment (OR 4.22, 95% CI 1.32-13.44; p = 0.015). Other OAD classes were not associated with meaningful changes in SMM or Hb.

Conclusions

In this real-world prospective cohort, pioglitazone showed a trend toward increased SMM in unadjusted analysis that did not reach significance after adjustment, suggesting a hypothesis-generating signal warranting further investigation. SGLT2 inhibitors were independently associated with increased Hb levels, though the observed median increment was modest in absolute terms. These findings highlight potentially clinically relevant, non-glycemic effects of OAD classes and may inform individualized treatment selection, particularly in patients at risk of sarcopenia or anemia. Adequately powered, prospective studies are needed to validate and extend these preliminary observations.