Clinical Study of Metabolic Parameters, Leptin and the SGLT2 Inhibitor Empagliflozin among Patients with Obesity and Type 2 Diabetes

Abstract

Obesity is a major public health problem worldwide, and it is associated with many diseases and abnormalities, most importantly, type 2 diabetes. The visceral adipose tissue produces an immense variety of adipokines. Leptin is the first identified adipokine which plays a crucial role in the regulation of food intake and metabolism. Sodium glucose co-transport 2 inhibitors are potent antihyperglycemic drugs with various beneficial systemic effects. We aimed to investigate the metabolic state and leptin level among patients with obesity and type 2 diabetes mellitus, and the effect of empagliflozin upon these parameters. We recruited 102 patients into our clinical study, then we performed anthropometric, laboratory, and immunoassay tests. Body mass index, body fat, visceral fat, urea nitrogen, creatinine, and leptin levels were significantly lower in the empagliflozin treated group when compared to obese and diabetic patients receiving conventional antidiabetic treatments. Interestingly, leptin was increased not only among obese patients but in type 2 diabetic patients as well. Body mass index, body fat, and visceral fat percentages were lower, and renal function was preserved in patients receiving empagliflozin treatment. In addition to the known beneficial effects of empagliflozin regarding the cardio-metabolic and renal systems, it may also influence leptin resistance.

Assessment of the Role of Leptin and Adiponectinas Biomarkers in Pancreatic Neuroendocrine Neoplasms

“…Metformin inhibits leptin production and stimulates adiponectin production along with the activation of adenosine monophosphate-activated protein kinase (AMPK), which in turn inhibits mTOR [ 39 , 48 , 49 ]. Sitagliptin, pioglitazone, liraglutide, dapagliflozin, and empagliflozin have been found to reduce leptin levels [ 46 , 50 ]. Pioglitazone and dapagliflozin increase adiponectin concentrations [ 50 , 51 ].…”

“…Sitagliptin, pioglitazone, liraglutide, dapagliflozin, and empagliflozin have been found to reduce leptin levels [ 46 , 50 ]. Pioglitazone and dapagliflozin increase adiponectin concentrations [ 50 , 51 ].…”

Improved Glycaemic Control and Nephroprotective Effects of Empagliflozin and Paricalcitol Co-Therapy in Mice with Type 2 Diabetes Mellitus

“…Moreover, DM triggers renal steatosis and lipotoxicity by inhibiting PPARα and PPARγ lipolytic [8,9,33,34], whilst increasing SREBP-1 lipogenic molecules [10,11], which then provoke chronic renal inflammation by augmenting renal TNF-α, IL-1β, and IL-6 levels, and reducing the potent anti-inflammatory cytokine, IL-10 [12,13]. The levels of several renal adipokines are likewise altered in DN, and renal inflammation is aggravated by a substantial decrease in adiponectin [14,35] that coincides with increases in leptin [15,36] and resistin [16,37] levels. Chronic renal oxidative stress and inflammation subsequently trigger apoptosis through TGF-β-mediated activation of Casp-3 [17,18], with glomerulopathy and tubular damage that are manifested by albuminuria and decreased GFR [38,39], and by increasing renal expression of NGAL and KIM-1 [4,40].…”

“…Furthermore, hyperglycaemia and dyslipidaemia exacerbate renal inflammation by increasing the production of pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumour necrosis factor (TNF)-α, while reducing the antiinflammatory cytokine, IL-10 [12,13]. Renal steatosis also reduces adiponectin [14], and elevates leptin [15] and resistin production in renal tissues [16]. Persistent oxidative stress and inflammation then promote cell apoptosis by upregulating transforming growth factor-β (TGF-β) with caspase-3 (Casp-3), thus aggravating glomerular and tubular damage [17,18].…”

Sodium–Glucose Cotransporter Protein 2 Inhibitors: Novel Application for the Treatment of Obesity-Associated Hypertension

“… 68 , 71 , 72 A recent clinical study showed that empagliflozin significantly reduced leptin levels compared with other glucose-lowering drugs used to treat patients with obesity and T2DM, such as biguanides and sulfonylureas. 73 In addition, leptin levels are proportional to adiposity, and SGLT-2 may reduce leptin secretion via its weight-loss effect. 74 As leptin is a major contributor to obesity and elevated blood pressure, leptin may be a potential target for SGLT-2 inhibitors in the treatment of obesity-associated hypertension.…”