SGLT2 Inhibitors and the Mechanisms Involved in Weight Loss

Feder, David; Gouveia, Marisa Regina de Fatima Veiga; Govato, Tânia Carmen Peñaranda; Nassis, Cristina de Zotti

doi:10.1007/s40495-020-00236-3

Cited by 12 publications

(10 citation statements)

References 90 publications

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“…The weight gain is attributable to several factors: increase in subcutaneous fat mass with either no change or a small decrease in visceral fat mass, fluid retention, and positive calorie balance because of improved glycemic control. Though the increase in subcutaneous fat mass is distressing to patients with T2D who are trying to lose weight, the TZD-mediated changes in fat mass distribution is related to the improvement in insulin resistance and glycemic control 18 .…”

Section: Discussionmentioning

confidence: 99%

The Effect of Thiazolidinediones and SGLT-2 Inhibitors on Minerals,VIT.D3, Blood Glucose and Weight Gain in Wistar Rats Induced with Type 2 Diabetes

Alshmmari¹,

Al-Hadrawy²

2022

PJMHS

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Type 2 diabetes mellitus and osteoporosis are among the most common health problems around the world. Diabetes is usually associated with increase a risk of bone fracture, Recent studies has indicated the harmful effects of some of anti-diabetic drugs on bone metabolism. Therefore, the goal of this study was to investigate the effect of two types of anti-diabetic drugs: Thiazolidinediones (TZDs) (30 mg/kg) and sodium-glucose cotransporter-2 (SGLT-2) inhibitors (10 mg/kg) on Vit.D and bone minerals on serum of laboratory female rats induced with type 2 diabetes mellitus. The study was conducted on animals Faculty of science/ Department of biology/University of kufa. And Central Laboratories/ In Medical City. during the period from 27 october 2021 till the end of 22 February 2022. Thirty-two adults female Albino rats (Rattus norvigicus) were randomly divided to two main groups of sixteen animals, The first group was treated for a period of 2 weeks and the second group was treated for a period of 2 months. Each group of them was divided into secondary four groups of four rats including: a control (Co1 and Co2) were fed regular rats pellet, the second group (HFD 1 and HFD 2) were fed with high fat diet (42% lipid, 32%g sucrose, 14% protein), the third group were fed with high fat diet and treated with TZDs (30 mg/kg) and fourth group were fed with high fat diet and treated with SGLT-2i (10 mg/kg). After the end of the treatment period, which is two weeks and three months, the blood was drawn using a method of cardiac puncture technique for estimation of blood glucose, bone minerals in serum which include (calcium, magnesium, inorganic phosphate) and serum Vit.D3 concentration. Body weight gain was significantly increased (p≤0.05) in animals treated with HFD high-fat diet (uncontrolled diabetic group) and in animals treated with TZDs compared to the control and animals treated with SGLT-2i. Also, the results of this study showing a significant increase (p0.05) on blood glucose in animals fed with HFD compared with other groups and there was a significant decrease (p0.05) in blood glucose in animals group treated with TZDs and SGLT-2i compared with HFD. The diabetic induced group (HFD group) treated for two months showed a significant decrease (p≤0.05) in vitamin D3 concentrations. The results of calcium concentrations in the blood showed a significant decrease (p≤0.05) in calcium concentration in the group induced with diabetes and the group treated with TZDs for two months compared to other groups. With regard to magnesium concentrations, the results showed a significant decrease (p≤0.05) in the group induced with diabetes and the group treated with TZDs for two months compared to other groups. While there was a significant increase (p≤0.05) in the concentrations of magnesium in the group treated with SGLT2i for two months compared to other groups. Also, the results showed a significant increase in the concentrations of serum inorganic phosphate in the groups treated with high-fat diet (diabetic induced group) for two months and the group treated with SGLT2i for two months, compared to the control group and the groups treated with TZDs. In conclusion: Uncontrolled diabetes mellitus has adverse effects on the concentrations of Vit.D3 and bone minerals. Also, Long-term treatment with Thiazolidinedionse (TZDs) and SGLT-2 inhibitors, despite its control of blood sugar has harmful effects on bone minerals and Vit.D3. Keywords: T2DM, Thiazolidinediones, SGLT-2 inhibitor, Calcium, Vit. D3, Magnesium, Inorganic phosphate.

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Section: Discussionmentioning

confidence: 99%

The Effect of Thiazolidinediones and SGLT-2 Inhibitors on Minerals,VIT.D3, Blood Glucose and Weight Gain in Wistar Rats Induced with Type 2 Diabetes

Alshmmari¹,

Al-Hadrawy²

2022

PJMHS

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“…SGLT2 inhibitors also increase natriuresis and osmotic diuresis, which lead to decreased renin production and reduced filtration rate, intraglomerular hydrostatic pressure, and blood pressure [ 55 ]. Other proposed mechanisms of SGLT2 inhibitors include nephron remodeling, relaxation of vascular smooth muscle cells, and weight loss independent of fluid contraction caused by glycosuria [ 56 , 57 ].…”

Section: Cardiovascular Effects Of Sglt2 Inhibitorsmentioning

confidence: 99%

Unlocking the Full Potential of SGLT2 Inhibitors: Expanding Applications beyond Glycemic Control

Youssef

Yahya

Popoviciu

et al. 2023

IJMS

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The number of diabetic patients has risen dramatically in recent decades, owing mostly to the rising incidence of type 2 diabetes mellitus (T2DM). Several oral antidiabetic medications are used for the treatment of T2DM including, α-glucosidases inhibitors, biguanides, sulfonylureas, meglitinides, GLP-1 receptor agonists, PPAR-γ agonists, DDP4 inhibitors, and SGLT2 inhibitors. In this review we focus on the possible effects of SGLT2 inhibitors on different body systems. Beyond the diabetic state, SGLT2 inhibitors have revealed a demonstrable ability to ameliorate cardiac remodeling, enhance myocardial function, and lower heart failure mortality. Additionally, SGLT2 inhibitors can modify adipocytes and their production of cytokines, such as adipokines and adiponectin, which enhances insulin sensitivity and delays diabetes onset. On the other hand, SGLT2 inhibitors have been linked to decreased total hip bone mineral deposition and increased hip bone resorption in T2DM patients. More data are needed to evaluate the role of SGLT2 inhibitors on cancer. Finally, the effects of SGLT2 inhibitors on neuroprotection appear to be both direct and indirect, according to scientific investigations utilizing various experimental models. SGLT2 inhibitors improve vascular tone, elasticity, and contractility by reducing oxidative stress, inflammation, insulin signaling pathways, and endothelial cell proliferation. They also improve brain function, synaptic plasticity, acetylcholinesterase activity, and reduce amyloid plaque formation, as well as regulation of the mTOR pathway in the brain, which reduces brain damage and cognitive decline.

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“…Briefly at a glance: (A) chronic kidney disease (CKD): evidence suggests that SGLT2 inhibitors impede the development of CKD and help minimize the chance of end‐stage renal disease (ESRD) by reducing glomerular hyper‐filtration and albuminuria, lowering blood pressure, and decreasing the likelihood of cardiovascular events, (B) heart failure: SGLT2 inhibitors have been shown to decrease the chance of hospitalization and death from heart failure by reducing volume overload and cardiac fibrosis, (C) cardiovascular disease (CVD): by regulating blood pressure and halting the progression of albuminuria, SGLT2 inhibitors have been proven to lower the risk of significant clinical cardiovascular events, (D) nonalcoholic steatohepatitis (NASH): SGLT2 inhibitors have been confirmed to improve liver histology and markers of fibrosis in cases with NASH 28 …”

Section: Introductionmentioning

confidence: 99%

SGLT2 inhibitors and AMPK: The road to cellular housekeeping?

Safaie,

Masoumi,

Alizadeh

et al. 2024

Cell Biochemistry & Function

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Sodium‐glucose co‐transporter‐2 (SGLT2) inhibitors, known as Gliflozins, are a class of Glucose‐lowering drugs in adults with type 2 diabetes (T2D) that induce glucosuria by blocking SGLT2 co‐transporters in the proximal tubules. Several lines of evidence suggest that SGLT2 inhibitors regulate multiple mechanisms associated with the regulation of varying cellular pathways. The 5′‐adenosine monophosphate‐activated protein kinase (AMPK) pathway plays an important role in metabolic homeostasis by influencing cellular processes. Recently, it has been shown that SGLT2 inhibitors can affect the AMPK pathway in differing physiological and pathological ways, resulting in kidney, intestinal, cardiovascular, and liver protective effects. Additionally, they have therapeutic effects on nonalcoholic fatty liver disease and diabetes mellitus‐associated complications. In this review, we summarize the results of studies of AMPK‐associated therapeutic effects of SGLT2 inhibitors in different organelle functions.

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SGLT2 Inhibitors and the Mechanisms Involved in Weight Loss

Cited by 12 publications

References 90 publications

The Effect of Thiazolidinediones and SGLT-2 Inhibitors on Minerals,VIT.D3, Blood Glucose and Weight Gain in Wistar Rats Induced with Type 2 Diabetes

The Effect of Thiazolidinediones and SGLT-2 Inhibitors on Minerals,VIT.D3, Blood Glucose and Weight Gain in Wistar Rats Induced with Type 2 Diabetes

Unlocking the Full Potential of SGLT2 Inhibitors: Expanding Applications beyond Glycemic Control

SGLT2 inhibitors and AMPK: The road to cellular housekeeping?

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