While dapagliflozin was associated with slight muscle mass loss, empagliflozin preserved muscle mass in older adults with type 2 diabetes, with neither drug negatively affecting frailty, cognition, physical performance, or sleep over approximately six months.
Key Findings
Results
Dapagliflozin was associated with significant reductions in skeletal muscle mass index (SMMI) over approximately six months in older adults with type 2 diabetes.
SMMI decreased from 11.68 ± 1.01 to 11.38 ± 0.88 kg/m² in the dapagliflozin group (p = 0.039)
Fat-free mass (FFM) also decreased significantly from 52.75 ± 7.41 to 51.05 ± 6.95 kg (p = 0.020)
BMI decreased from 31.0 ± 4.9 to 27.8 ± 4.7 kg/m² in the dapagliflozin group (p = 0.018)
The dapagliflozin group included 22 adults aged ≥65 years with type 2 diabetes mellitus
Results
Empagliflozin preserved skeletal muscle mass index despite producing significant BMI reduction in older adults with type 2 diabetes.
BMI decreased significantly from 32.8 ± 5.5 to 31.6 ± 4.8 kg/m² in the empagliflozin group (p = 0.013)
SMMI remained stable in the empagliflozin group over the same follow-up period
The empagliflozin group included 20 adults aged ≥65 years with type 2 diabetes mellitus
Results
A significant time × group interaction for SMMI was observed between the dapagliflozin and empagliflozin groups, indicating differential effects of the two drugs on skeletal muscle mass.
The time × group interaction for SMMI was statistically significant (p = 0.023)
This interaction confirms that the two SGLT-2 inhibitors had meaningfully different effects on muscle mass despite both reducing BMI
Total study sample was 42 adults aged ≥65 years assessed at baseline and after approximately six months
Results
Neither dapagliflozin nor empagliflozin produced significant changes in frailty, physical performance, cognitive function, muscle strength, sleep quality, or fall frequency.
No significant changes were detected on the FRAIL scale in either group
Assessments included the Mini-Mental State Examination, Timed Up and Go test, gait speed, Tinetti gait and balance assessment, handgrip strength, and the Pittsburgh Sleep Quality Index
Fall frequency did not change significantly in either treatment group
Comprehensive geriatric assessment (CGA) was used as a core component of the study methodology
Methods
The study used a comprehensive geriatric assessment (CGA) framework to evaluate the longitudinal effects of SGLT-2 inhibitors in older adults with type 2 diabetes.
CGA included the FRAIL scale, Mini-Mental State Examination, Timed Up and Go test, gait speed, Tinetti gait and balance assessment, handgrip strength, and the Pittsburgh Sleep Quality Index
Study design was longitudinal with assessments at baseline and after approximately six months
Sample consisted of 42 adults aged ≥65 years (dapagliflozin n = 22; empagliflozin n = 20)
The authors note that effects of SGLT-2 inhibitors on geriatric syndromes remain incompletely understood
What This Means
This research suggests that two commonly prescribed diabetes medications — dapagliflozin and empagliflozin, both belonging to a class called SGLT-2 inhibitors — have different effects on muscle mass in older adults with type 2 diabetes. Over about six months, patients taking dapagliflozin experienced small but statistically significant losses in skeletal muscle mass and fat-free mass, even as their body weight and BMI went down. In contrast, patients taking empagliflozin also lost body weight, but their skeletal muscle mass remained stable. The difference in muscle mass change between the two drugs was statistically significant.
Despite the muscle mass reduction seen with dapagliflozin, neither drug appeared to negatively affect other important health markers in older adults. Measures of frailty, physical performance (such as walking speed and balance), cognitive function, grip strength, sleep quality, and fall frequency all remained unchanged in both groups. This suggests that while the muscle-related differences are worth noting, neither medication caused broader deterioration in the geriatric health outcomes studied.
This research matters because older adults with diabetes are at increased risk for muscle loss (sarcopenia) and frailty, which can affect independence and quality of life. The findings suggest that clinicians may want to consider these potential differences when choosing between these two medications for older patients, particularly those already at risk for muscle loss. However, the study was small (42 participants total), and larger studies would be needed to confirm these findings and determine their long-term clinical significance.
Check Your Own Numbers
Upload your bloodwork. We'll cross-reference your results against this study and 4,700 others.
Ganidagli S, Akbas E, Ozturk Z. (2026). Differential effects of dapagliflozin and empagliflozin on skeletal muscle mass in older adults with type 2 diabetes.. Endocrine. https://doi.org/10.1007/s12020-026-04670-z