scholarly journals Effects of Incretin-Related Diabetes Drugs on Bone Formation and Bone Resorption

2021 ◽  
Vol 22 (12) ◽  
pp. 6578
Author(s):  
Hideki Kitaura ◽  
Saika Ogawa ◽  
Fumitoshi Ohori ◽  
Takahiro Noguchi ◽  
Aseel Marahleh ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Bone Resorption ◽  
Bone Formation ◽  
Current Knowledge ◽  
Osteoclast Differentiation ◽  
Glucose Absorption ◽  
Dipeptidyl Peptidase 4 ◽  
Increased Risk ◽  
Glucagon Like Peptide 1

Patients with type 2 diabetes have an increased risk of fracture compared to the general population. Glucose absorption is accelerated by incretin hormones, which induce insulin secretion from the pancreas. The level of the incretin hormone, glucagon-like peptide-1 (GLP-1), shows an immediate postprandial increase, and the circulating level of intact GLP-1 is reduced rapidly by dipeptidyl peptidase-4 (DPP-4)-mediated inactivation. Therefore, GLP-1 receptor agonists and DPP-4 inhibitors are effective in the treatment of type 2 diabetes. However, these incretin-related diabetic agents have been reported to affect bone metabolism, including bone formation and resorption. These agents enhance the expression of bone markers, and have been applied to improve bone quality and bone density. In addition, they have been reported to suppress chronic inflammation and reduce the levels of inflammatory cytokine expression. Previously, we reported that these incretin-related agents inhibited both the expression of inflammatory cytokines and inflammation-induced bone resorption. This review presents an overview of current knowledge regarding the effects of incretin-related diabetes drugs on osteoblast differentiation and bone formation as well as osteoclast differentiation and bone resorption. The mechanisms by which incretin-related diabetes drugs regulate bone formation and bone resorption are also discussed.

scholarly journals Renoprotective Effects of the Dipeptidyl Peptidase-4 Inhibitor Sitagliptin: A Review in Type 2 Diabetes

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Cristina Mega ◽  
Edite Teixeira-de-Lemos ◽  
Rosa Fernandes ◽  
Flávio Reis
Keyword(s):  
Type 2 Diabetes ◽  
Current Knowledge ◽  
Diabetic Patients ◽  
Dipeptidyl Peptidase 4 ◽  
Dipeptidyl Peptidase 4 Inhibitor ◽  
Increased Risk ◽  
Long Time ◽  
Stage Renal Disease ◽  
End Stage

Diabetic nephropathy (DN) is now the single commonest cause of end-stage renal disease (ESRD) worldwide and one of the main causes of death in diabetic patients. It is also acknowledged as an independent risk factor for cardiovascular disease (CVD). Since sitagliptin was approved, many studies have been carried out revealing its ability to not only improve metabolic control but also ameliorate dysfunction in various diabetes-targeted organs, especially the kidney, due to putative underlying cytoprotective properties, namely, its antiapoptotic, antioxidant, anti-inflammatory, and antifibrotic properties. Despite overall recommendations, many patients spend a long time well outside the recommended glycaemic range and, therefore, have an increased risk for developing micro- and macrovascular complications. Currently, it is becoming clearer that type 2 diabetes mellitus (T2DM) management must envision not only the improvement in glycaemic control but also, and particularly, the prevention of pancreatic deterioration and the evolution of complications, such as DN. This review aims to provide an overview of the current knowledge in the field of renoprotective actions of sitagliptin, namely, improvement in diabetic dysmetabolism, hemodynamic factors, renal function, diabetic kidney lesions, and cytoprotective properties.

scholarly journals Incretin Hormones and Type 2 Diabetes—Mechanistic Insights and Therapeutic Approaches

Biology ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 473
Author(s):  
Geke Aline Boer ◽  
Jens Juul Holst
Keyword(s):  
Type 2 Diabetes ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Incretin Hormones ◽  
Postprandial Metabolism ◽  
Dipeptidyl Peptidase 4 ◽  
Receptor Agonists ◽  
Control Of Diabetes ◽  
Glucagon Like Peptide 1

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are secreted from the gut upon nutrient stimulation and regulate postprandial metabolism. These hormones are known as classical incretin hormones and are responsible for a major part of postprandial insulin release. The incretin effect is severely reduced in patients with type 2 diabetes, but it was discovered that administration of GLP-1 agonists was capable of normalizing glucose control in these patients. Over the last decades, much research has been focused on the development of incretin-based therapies for type 2 diabetes. These therapies include incretin receptor agonists and inhibitors of the incretin-degrading enzyme dipeptidyl peptidase-4. Especially the development of diverse GLP-1 receptor agonists has shown immense success, whereas studies of GIP monotherapy in patients with type 2 diabetes have consistently been disappointing. Interestingly, both GIP-GLP-1 co-agonists and GIP receptor antagonists administered in combination with GLP-1R agonists appear to be efficient with respect to both weight loss and control of diabetes, although the molecular mechanisms behind these effects remain unknown. This review describes our current knowledge of the two incretin hormones and the development of incretin-based therapies for treatment of type 2 diabetes.

scholarly journals Incretin Hormones and Type 2 Diabetes – Mechanistic Insights and Therapeutic Approaches

2020 ◽  
Author(s):  
Geke Aline Boer ◽  
Jens Juul Holst
Keyword(s):  
Type 2 Diabetes ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Incretin Hormones ◽  
Postprandial Metabolism ◽  
Dipeptidyl Peptidase 4 ◽  
Receptor Agonists ◽  
Control Of Diabetes ◽  
Glucagon Like Peptide 1

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are secreted from the gut upon nutrient stimulation and regulate postprandial metabolism. These hormones are known as classical incretin hormones and are responsible for a major part of postprandial insulin release. The incretin effect is severely reduced in patients with type 2 diabetes, but it was discovered that administration of GLP-1 agonists was capable of normalizing glucose control in these patients. Over the last decades, much research has been focused on the development of incretin-based therapies for type 2 diabetes. These therapies include incretin receptor agonists and inhibitors of the incretin-degrading enzyme dipeptidyl peptidase-4. Especially the development of diverse GLP-1 receptor agonists has shown immense success, whereas studies of GIP monotherapy in patients with type 2 diabetes have consistently been disappointing. Interestingly, both GIP-GLP-1 co-agonists and GIP receptor antagonists administered in combination with GLP-1R agonists appear to be efficient with respect to both weight loss and control of diabetes, although the molecular mechanisms behind these effects remain unknown. This review describes our current knowledge of the two incretin hormones and the development of incretin-based therapies for treatment of type 2 diabetes.

scholarly journals Incretin-based Therapies for Type 2 Diabetes—Comparisons Between Glucagon-like Peptide-1 Receptor Agonists and Dipeptidyl Peptidase-4 Inhibitors

2011 ◽  
Vol 07 (02) ◽  
pp. 82 ◽  
Author(s):  
Timothy Bailey ◽  
Keyword(s):  
Type 2 Diabetes ◽  
Glycosylated Hemoglobin ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase 4 ◽  
Receptor Agonists ◽  
Increased Risk ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Type 2 diabetes exerts a huge toll on both morbidity and mortality, despite an expanding range of antiglycemic drugs and epidemiological evidence highlighting the benefits of effective glycemic control. Incretin-based agents offer important benefits, including a meal-dependent mode of action that may protect against hypoglycemia, and weight loss—in contrast to other antihyperglycemic drugs that cause weight gain. There are now two glucagon-like peptide-1 (GLP-1) receptor agonists and three dipeptidyl peptidase-4 (DPP-4) inhibitors approved for the management of type 2 diabetes in the US. Clinical trials have established the efficacy of incretin-based agents in controlling fasting and post-prandial blood glucose levels as well as glycosylated hemoglobin (HbA1c), both as monotherapy (including as first-line pharmacological treatment) and in combination with other antihyperglycemic treatments. GLP-1 receptor agonists and DPP-4 inhibitors have different mechanisms of action, which may explain their inconsistent efficacy results in direct comparator trials; for example, liraglutide has better efficacy than sitagliptin. However, GLP-1 receptor agonists can cause transient nausea in some patients. There is also evidence of different effects of individual agents within the same class; for example, liraglutide has shown superior efficacy to exenatide when added to metformin and/or sulfonylurea. Linagliptin is not cleared through renal mechanisms, unlike sitagliptin and saxagliptin. Isolated cases of pancreatitis led to concerns about a putative link with incretin-based therapies. However, the data currently available do not support a mechanistic or epidemiological link, although there does appear to be an increased risk of pancreatitis in people with diabetes that is independent of incretin-based treatment. Ongoing studies aim to extend our longer-term understanding of these agents, and hence, allow us to develop an optimal approach to patient management.

Glucagon-like peptide-1 (GLP-1) Biological Role in Patients of Type 2 Diabetes and Metabolic Syndrome

2019 ◽  
Vol 56 (2) ◽  
pp. 227
Author(s):  
Mohammedziyad Abu Awad
Keyword(s):  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Glucagon Secretion ◽  
Diabetic Patients ◽  
Metabolic Disturbances ◽  
Cvd Risk ◽  
First Line Therapy ◽  
Increased Risk ◽  
Glucagon Like Peptide 1

<p style="margin: 0in 0in 10pt; text-align: justify; line-height: 200%;">Type2 diabetes is estimated to affect 380 million people worldwide in 2025. Patients of this disease are at increased risk of cardiovascular diseases (CVD).The CVD risk is greater when diabetic patients have metabolic syndrome. Thus, the management of metabolic syndrome and CVD is crucial for diabetic patient’s life progress. GLP-1 has positive biological influences on glucose metabolism control by inhibiting glucagon secretion, enhancing insulin secretion and protecting the effects of cells. GLP-1 was also found to have other positive influences including weight loss, appetite sensation and food intake. These are important factors in metabolic disturbances control and CVD management. The paper reviewed several studies regarding the GLP-1 positive concerns. In conclusion, the paper supports the modern proposal of GLP-1 RAs as a first line therapy in initially diagnosed type 2 diabetes patients.</p>

scholarly journals Treatment of Heart Failure with Sodium-Glucose Cotransporter 2 Inhibitors and Other Anti-diabetic Drugs

2019 ◽  
Vol 5 (1) ◽  
pp. 27-30 ◽  
Author(s):  
Thomas A Zelniker ◽  
Eugene Braunwald
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Renal Failure ◽  
Cardiovascular Death ◽  
Cardiovascular Outcomes ◽  
Sodium Glucose Cotransporter ◽  
Increased Risk ◽  
Patients With Diabetes ◽  
Glucagon Like Peptide 1

Patients with type 2 diabetes are at increased risk of developing heart failure, cardiovascular death and renal failure. The recent results of three large sodium-glucose cotransporter 2 inhibitor cardiovascular outcomes trials have demonstrated a reduction in heart failure hospitalisation and progressive renal failure. One trial also showed a fall in cardiovascular and total death. A broad spectrum of patients with diabetes benefit from these salutary effects in cardiac and renal function and so these trials have important implications for the management of patients with type 2 diabetes. Selected glucagon-like peptide 1 receptor agonists have also been shown to reduce adverse cardiovascular outcomes.

scholarly journals Treatment of type 2 diabetes: the stability of the effectiveness of hypoglycemic medications

2016 ◽  
Vol 13 (3) ◽  
pp. 32-36
Author(s):  
Tat'yana Morgunova ◽  
Valentin Fadeev
Keyword(s):  
Type 2 Diabetes ◽  
Meta Analysis ◽  
Original Research ◽  
Dipeptidyl Peptidase 4 ◽  
Sodium Glucose Cotransporter ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
The Stability

This article is dedicated to the problem of glycaemic durability of drugs used in treatment of type 2 diabetes. The results of studies comparing durability of glycemic control as monotherapy or in combination of metformin with different drugs: dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, sulfonylurea, inhibitors of sodium-glucose cotransporter-2 are shown. The article discusses the results of original research and meta-analysis.

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