Dapagliflozin Treatment in T1D May Reduce Skeletal Muscle Mass

Masahide Hamaguchi, PhD

Credit: Loop (Frontiers)

Dapagliflozin treatment could result in the loss of skeletal muscle mass in people with type 1 diabetes (T1D), particularly in older men and those without obesity, according to the results of a recent posthoc analysis.¹

On the other hand, the data suggest good glycemic control during dapagliflozin treatment might prevent the onset and progression of sarcopenia, the age-related loss of skeletal muscle mass and strength, in patients with T1D.

“We found that ASM / height², but not ASM / weight decreased after starting dapagliflozin medication,” wrote the investigative team, led by Masahide Hamaguchi, PhD, the department of endocrinology and metabolism, graduate school of medical science, Kyoto Prefectural University of Medicine. “The present findings also suggest that the addition of dapagliflozin to individuals with type 1 diabetes, but without obesity, might reduce skeletal muscle mass.”

Sarcopenia is a well-recognized complication of diabetes and individuals with diabetes, notwithstanding disease type, are at high risk for incidence and progression of the complication.² With the increase in global diabetes rates, the investigative team stressed the need for effective measures to prevent functional impairment in this population.¹ However, there is a lack of data examining the effect of good glycemic control on sarcopenia in individuals with T1D.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors, such as dapagliflozin, are a novel treatment for T1D and type 2 diabetes (T2D), as well as an additional therapy to improve glycemic control in diabetes. Evidence has linked muscle mass loss in T2D individuals with SGLT2 inhibitor use, but there is limited data on skeletal muscle mass changes in T1D. The current analysis investigated the change in glycemic control and body composition in individuals with T1D after dapagliflozin, as well as the association between glycemic control and skeletal muscle changes.

Hamaguchi and colleagues conducted a posthoc analysis of a multicenter, open-label, non-randomized, prospective intervention study (RISING-STAR) in T1D individuals. A total of 60 participants with T1D between 20 -80 years old, with a hemoglobin A1c <10.5%, and body mass index (BMI) >18.5 kg/m² were enrolled in the study. Participants received dapagliflozin at 5 mg/day for 4 weeks and were reviewed by investigators before and after treatment.

Both weight- and height-controlled appendicular skeletal muscle mass (ASM) were calculated as indicators of skeletal muscle mass using bioelectrical impedance analysis, according to the investigative team. In the analysis, the changes in skeletal muscle mass with 4 weeks of dapagliflozin treatment were evaluated in 36 participants with T1D (12 men and 24 women).

When stratified by baseline BMI, data showed ASM/height² decreased in individuals with BMI <23 (n = 20) from 6.45 ± 0.87 to 6.33 ± 0.78 kg/m² (P = .005). However, the analysis showed ASM/weight did not change in either group (BMI <23 group: 30.3 ± 4.0 to 30.4 ± 3.8%, P = .52; BMI ≥23 group: 27.3 ± 3.2 to 27.5 ± 3.6%, P = .49).

After stratifying subjects by age, investigators found all men aged ≥60 years showed a decrease in ASM/height², compared with only 4 of 7 men aged <60 years, as well as in ASM/weight. Data showed the change in ASM/weight (%) was negatively correlated with changes in HbA1c (P = .023) and time above range (P = .026). In addition, the change in ASM/height² was also positively correlated with the changes in time within range of 70 – 180 mg/dL (P = .036).

Meanwhile, investigators indicated the key limitations of the study included its posthoc analysis design based on short-term results without a control. They noted the study did not collect data on muscle function or nutritional status, and participants received no exercise or dietary advice during the intervention.

“Future research should consider such variables to further enhance our understanding of dapagliflozin treatment effects on T1D individuals,” investigators wrote.

References

1. Yoshimura Y, Hashimoto Y, Okada H, et al. Changes in glycemic control and skeletal muscle mass indices after dapagliflozin treatment in individuals with type 1 diabetes mellitus [published online ahead of print, 2023 Jul 9]. J Diabetes Investig. 2023;10.1111/jdi.14054. doi:10.1111/jdi.14054
2. Mesinovic J, Zengin A, De Courten B, Ebeling PR, Scott D. Sarcopenia and type 2 diabetes mellitus: a bidirectional relationship. Diabetes Metab Syndr Obes. 2019;12:1057-1072. Published 2019 Jul 8. doi:10.2147/DMSO.S186600