Ipragliflozin, a sodium–glucose cotransporter 2 inhibitor, reduces bodyweight and fat mass, but not muscle mass, in Japanese type 2 diabetes patients treated with insulin: A randomized clinical trial

Abstract

Aims/Introduction Sodium–glucose cotransporter 2 inhibitors reduce bodyweight (BW) by creating a negative energy balance. Previous reports have suggested that this BW reduction is mainly loss of body fat and that ~20% of the reduction is lean mass. However, the effects of sodium–glucose cotransporter 2 inhibitors on BW and body composition remain unclear. We examined these effects in Japanese patients with type 2 diabetes mellitus treated with insulin. Materials and Methods In this open‐label, randomized controlled trial, 49 overweight patients (body mass index ≥23 kg/m 2 ) with inadequate glycemic control (hemoglobin A1c >7.0%) receiving insulin treatment were randomly assigned to receive add‐on ipragliflozin or no additional treatment (control group). Patients were followed for 24 weeks. The goal for all patients was to achieve glycated hemoglobin <7.0% without hypoglycemia. The primary end‐point was a change in BW from baseline to week 24. Body composition was assessed with dual‐energy X‐ray absorptiometry and bioelectrical impedance analysis. Results BW change was significantly larger in the ipragliflozin group than in the control group (−2.78 vs −0.22 kg, P < 0.0001). Total fat mass was reduced evenly in the arms, lower limbs and trunk in the ipragliflozin group. Total muscle mass and bone mineral content were maintained, but muscle mass in the arms might have been affected by ipragliflozin treatment. Conclusions Ipragliflozin treatment for 24 weeks resulted in reduced BW, mainly from fat mass loss. Muscle mass and bone mineral content were maintained. Further study is necessary to elucidate the long‐term effects of ipragliflozin.

A Review of the Effects of Glucagon-Like Peptide-1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors on Lean Body Mass in Humans

“…Details of all eligible studies identified in our search can be found in Tables 2,3,4 [242526272829303132333435363738394041424344454647484950515253545556575859606162636465666768]. The following paragraphs provide an overview of the findings for each individual therapy within both drug classes.…”

“…Of the seven studies identified for ipragliflozin, six reported that the contribution of LBM/FFM to total weight loss elicited ranged from 22% to 49% [525354555759]. All of these studies were in individuals with T2DM, and included two studies using DXA, reporting 22% and 49% of 2.8 and 3.5 kg of weight loss over 24 weeks, respectively.…”

Effects of intensive exercise combined with dapagliflozin on body composition in patients with type 2 diabetes: a randomized controlled trial

“…Our concern that SGLT2 inhibitors could reduce fatfree mass was based on the findings from recent human studies [16][17][18][19][20]. On the other hand, DAPA and canagliflozin have been reported to reduce fat mass without a significant change in fat-free mass in patients with type 2 diabetes [29][30][31][32]. Although reasons for this discrepancy are unclear, a recent elegant study in a diabetic animal model (Akita mice) revealed that normalization of blood glucose by an SGLT2 inhibitor (empagliflozin) without affecting insulin secretion could prevent the reduction in skeletal muscle mass and muscle fiber area apparent in the control Akita mice, and the increased expression of muscle atrophy-related genes was also attenuated by the drug [33].…”

The Impact of Antidiabetic Agents on Sarcopenia in Type 2 Diabetes: A Literature Review

“…Yasuda et al reported a case of a lean elderly patient diagnosed with sarcopenia after taking dapagliflozin for 1 year to treat T2DM [39]. Another study reported that a 6-month treatment with ipragliflozin significantly reduced arm muscle mass but not total muscle mass [40]. Similarly, Tsurutani et al demonstrated a clinically significant decrease in skeletal muscle mass index in an ipragliflozin group compared with a sitagliptin group [41].…”