Improvement of skeletal muscle insulin sensitivity by 1 week of SGLT2 inhibitor use

Abstract

<jats:sec> <jats:title><jats:italic>Background and Aims:</jats:italic></jats:title> <jats:p>It is currently unclear whether sodium–glucose co-transporter 2 (SGLT2) inhibitor administration can improve the insulin sensitivity as well as rapidly reduce plasma glucose concentrations in humans during the early phase of treatment initiation. This study aimed to investigate the effect of SGLT2 inhibitor on insulin sensitivity in the early phase of treatment initiation.</jats:p> </jats:sec> <jats:sec> <jats:title><jats:italic>Methods and Results</jats:italic></jats:title> <jats:p>This single-center, open label, and single-arm prospective study recruited 20 patients (14 men) with type 2 diabetes mellitus (T2DM). We examined the patients’ metabolic parameters before and 1 week after SGLT2 inhibitor (10 mg/day of empagliflozin) administration. The glucose infusion rate (GIR) was evaluated using the euglycemic hyperinsulinemic glucose clamp technique. Changes in laboratory and anthropometric parameters before and after SGLT2 inhibitor administration were analyzed according to the change in the GIR. The BMI, body fat amount, skeletal muscle amount, systolic blood pressure, and triglyceride level significantly decreased along with the treatment, while urinary glucose level and log GIR value significantly increased. Notably, changes in the GIR after SGLT2 inhibitor administration, which indicated improvement in peripheral insulin sensitivity, were negatively correlated with T2DM duration and positively with reduction in fluctuation of daily plasma glucose profiles before and after treatment.</jats:p> </jats:sec> <jats:sec> <jats:title><jats:italic>Conclusion</jats:italic></jats:title> <jats:p>SGLT2 inhibitor improved insulin sensitivity in the skeletal muscle independent of anthropometric changes. Patients with short duration of T2DM and insulin resistance can be good candidates for short-term SGLT2 inhibitor administration to improve insulin sensitivity in the skeletal muscle.</jats:p> </jats:sec>

Rationale and design of the EMPA-ELDERLY trial: a randomised, double-blind, placebo-controlled, 52-week clinical trial of the efficacy and safety of the sodium–glucose cotransporter-2 inhibitor empagliflozin in elderly Japanese patients with type 2 diabetes

“…Furthermore, 1 week of empagliflozin treatment in Japanese patients in a small, open-label, single-arm study was associated with a slight but significant loss of skeletal muscle mass, among other effects. 31 However, 24-week, randomised, open-label clinical trials of dapagliflozin (n=54) or ipragliflozin (n=49) added to existing diabetes medications versus those medications alone did not find loss of skeletal muscle tissue with these SGLT2 inhibitors in Japanese patients. 32 33 Data in elderly patients susceptible to sarcopenia and frailty, however, still remain limited as none of the studies performed so far were dedicated trials in the elderly.…”

Case Report: Metreleptin and SGLT2 Inhibitor Combination Therapy Is Effective for Acquired Incomplete Lipodystrophy

“…Combination therapy with SGLT2 inhibitor and metreleptin increased both subcutaneous and visceral adipose volume in our patient, who had low adiposity. Administration of an SGLT2 inhibitor may demonstrate adipose redistribution through attenuation of insulin resistance and lipolysis in the extra-adipose tissues (11). Additionally, a recent study has described a case of CCS-related acquired partial lipodystrophy with high adiposity wherein adiposity in the fat tissue was decreased after metreleptin administration.…”

“…Furthermore, both visceral and subcutaneous fat volumes were recovered using the combination therapy of metreleptin and SGLT2 inhibitor administration in this case. SGLT2 inhibitor with metreleptin supplementation may improve glucose metabolism impairment, compensating for the brown and white adipose tissue dysfunction and preserving skeletal muscle volume (9)(10)(11) in CCSs with diabetic lipodystrophy.…”

“…Furthermore, several advantages of SGLT2 inhibitor use have been reported, which includes reduction in hyperinsulinemia in patients with T2DM (21). Additionally, improvements in daily glucose fluctuation, which promote cardiovascular events (22), have been studied (11,23). Both amelioration of insulin resistance and daily glucose fluctuation are plausible pathophysiological mechanisms of reducing the risk of a cardiovascular event.…”

“…SGLT2 inhibitor administration reduces hyperglycemia and fat accumulation in adipose tissues by increasing urinary glucose excretion in patients with type 2 diabetes mellitus (T2DM) (10). Additionally, an SGLT2 inhibitor has been suggested to improve glucose impairment through changes in glucose and lipid metabolisms in both adipose and extra-adipose tissues (11,12). However, the precise mechanism of the beneficial effects of the SGLT2 inhibitor on lipodystrophy remains to be clarified.…”