Dapagliflozin increases the lean-to total mass ratio in type 2 diabetes mellitus

Abstract

We compared the effect of dapagliflozin versus glibenclamide on the ratio of lean-to total mass in patients with type 2 diabetes mellitus, carotid subclinical atherosclerosis, HbA1c 7.0–9.0% and 40–70 years-old. Ninety-eight patients (61% male; mean age 57 ± 7 years) were randomized into dapagliflozin 10 mg/day or glibenclamide 5 mg/day on top of metformin. Body composition was measured by Dual Energy X-Ray at randomization and after 12 weeks of treatment. Glycemic control was equivalent in both groups. Dapagliflozin decreased total body mass (−2741 g [95% CI: −3360 to 1945]; p < 0.001) and lean mass (−347 g [95% CI: −761 to −106]; p < 0.001), while glibenclamide increased total body mass (1060 g [95% CI: 140 to 1836]; p < 0.001) and lean mass (929 g [95% CI: 575 to 1283]; p < 0.001) for the differences between arms. The lean-to-total mass ratio increased by 1.2% in the dapagliflozin group and 0,018% in the glibenclamide group (p < 0.001). Dapagliflozin reduced the risk of a negative balance in the lean-to total mass ratio [OR: 0.16 (95% CI: 0.05 to 0.45); p < 0.001] even after adjustment for baseline lean-to total mass ratio, waist circumference, HOMAIR, HbA1c, mean of the two hands handgrip strength and gait speed [OR: 0.13 (95% CI: 0.03–0.57); p < 0.007]. In conclusion, under equivalent glycemic control, dapagliflozin reduced total body mass but increased the ratio of lean-to-total mass when compared with glibenclamide.

Effect of SGLT-2 inhibitors on body composition in patients with type 2 diabetes mellitus: A meta-analysis of randomized controlled trials

“…The characteristics of the 18 included studies published between 2013 and 2022 are shown in Table 1 [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]. The articles involved 1430 participants (726 SGLT-2 inhibitors participants…”

Ertugliflozin, renoprotection and potential confounding by muscle wasting. Reply to Groothof D, Post A, Gans ROB et al [letter]

“…Acknowledgements The authors would like to thank the participants, their families and all investigators involved in the VERTIS CV study; the list of investigators can be found with the primary publication [11]. Medical writing and/or editorial assistance was provided by M. Hammad and I. Norton, both of Scion (London, UK).…”

“…Beyond this chronological dissociation, existing data have not shown a consistent change in muscle mass in response to SGLT2 inhibition in either direction. In fact, in four [ 4 – 7 ] of the six trials [ 4 – 9 ] with dapagliflozin (which is pharmacologically similar to ertugliflozin) quoted by the authors, there was no effect on measures of lean mass [ 10 ], whilst a recent active comparator (glibenclamide) trial showed an increase in lean:total body mass ratio with dapagliflozin use [ 11 ]. In addition to the inconsistent directional effects on measures of lean body mass, we also wish to emphasise that, even if changes in lean body mass did occur, this variable is composed of several factors, including muscle and water content.…”

Effects of dapagliflozin compared with glimepiride on body composition in Asian patients with type 2 diabetes inadequately controlled with metformin: The BEYOND study

“…40 In a study performed to evaluate the effect of dapagliflozin versus glibenclamide on the ratio of lean-to-total mass in patients with T2D, it was found that dapagliflozin reduced total body mass but increased the ratio of lean-to-total mass that was because of a more intensive reduction in fat mass than in lean mass implying that dapagliflozin causes improvement of skeletal muscle metabolism (skeletal muscle mass index, SMI). 41 Similarly, in the study conducted by Sasaki et al, the SMI decreased over the course of the treatment, but the degree of the change was small. In our study, the lean-to-body mass between the two arms was maintained at end of therapy.…”

“…Another study evaluating the effects of tofogliflozin on body composition revealed that the reduction in BF mass, visceral fat area and skeletal muscle mass was because of the loss of total body water and intracellular and extracellular water, which may have been related with the reduction of body weight 40 . In a study performed to evaluate the effect of dapagliflozin versus glibenclamide on the ratio of lean‐to‐total mass in patients with T2D, it was found that dapagliflozin reduced total body mass but increased the ratio of lean‐to‐total mass that was because of a more intensive reduction in fat mass than in lean mass implying that dapagliflozin causes improvement of skeletal muscle metabolism (skeletal muscle mass index, SMI) 41 . Similarly, in the study conducted by Sasaki et al, the SMI decreased over the course of the treatment, but the degree of the change was small.…”