scholarly journals Cardiovascular benefits of sodium-glucose cotransporter 2 inhibitors in diabetic and nondiabetic patients

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Boyang Xiang ◽  
Xiaoya Zhao ◽  
Xiang Zhou
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Glycemic Control ◽  
Large Scale ◽  
Protective Effects ◽  
Beneficial Effects ◽  
Sodium Glucose Cotransporter ◽  
Outcome Trial

AbstractSodium-glucose cotransporter 2 inhibitors (SGLT2i) were developed as antidiabetic agents, but accumulating evidence has shown their beneficial effects on the cardiovascular system. Analyses of the EMPA-REG OUTCOME trial (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) suggested that these benefits are independent of glycemic control. Several large-scale outcome trials of SGLT2i also showed cardiovascular benefits in nondiabetic patients, strengthening this perspective. Extensive animal and clinical studies have likewise shown that mechanisms other than the antihyperglycemic effect underlie the cardiovascular benefits. Recent clinical guidelines recommend the use of SGLT2i in patients with type 2 diabetes mellitus and cardiovascular diseases because of the proven cardiovascular protective effects. Since the cardiovascular benefits are independent of glycemic control, the therapeutic spectrum of SGLT2i will likely be extended to nondiabetic patients.

Pharmacotherapy for Type 2 Diabetes Mellitus: What’s Up and Coming in the Glucagon-Like Peptide-1 (GLP-1) Pipeline?

2021 ◽  
pp. 089719002110490
Author(s):  
Mary J. Elder ◽  
Emily J. Ashjian
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Glycemic Control ◽  
Glucagon Secretion ◽  
New Drugs ◽  
Beneficial Effects ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-like peptide-1 (GLP-1), an incretin hormone, is known to lower glucose levels, suppress glucagon secretion, and slow gastric emptying. These properties make GLP-1 an ideal target in treating type 2 diabetes mellitus (T2DM). There are many FDA-approved GLP-1 agonists on the market today, several of which have demonstrated benefit beyond improving glycemic control. Given the beneficial effects of GLP-1 agonists in patients with T2DM, new drugs are in development that combine the mechanism of action of GLP-1 receptor agonism with novel mechanisms and with drugs that promote GLP-1 secretion. These agents are designed to improve glycemic control and target greater body weight reduction. This article discusses new GLP-1 drugs in the pipeline for the treatment of T2DM.

scholarly journals Pleiotropic effects of the dipeptidylpeptidase-4 inhibitors on the cardiovascular system

2014 ◽  
Vol 307 (4) ◽  
pp. H477-H492 ◽  
Author(s):  
Annayya R. Aroor ◽  
James R. Sowers ◽  
Guanghong Jia ◽  
Vincent G. DeMarco
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Glycemic Control ◽  
Molecular Mechanisms ◽  
Protective Effects ◽  
Inhibitory Peptide ◽  
Gastric Inhibitory Peptide ◽  
Dipeptidylpeptidase 4

Dipeptidylpeptidase-4 (DPP-4) is a ubiquitously expressed transmembrane protein that removes NH2-terminal dipeptides from various substrate hormones, chemokines, neuropeptides, and growth factors. Two known substrates of DPP-4 include the incretin hormones glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide, which are secreted by enteroendocrine cells in response to postprandial hyperglycemia and account for 60–70% of postprandial insulin secretion. DPP-4 inhibitors (DPP-4i) block degradation of GLP-1 and gastric inhibitory peptide, extend their insulinotropic effect, and improve glycemia. Since 2006, several DPP-4i have become available for treatment of type 2 diabetes mellitus. Clinical trials confirm that DPP-4i raises GLP-1 levels in plasma and improves glycemia with very low risk for hypoglycemia and other side effects. Recent studies also suggest that DPP-4i confers cardiovascular and kidney protection, beyond glycemic control, which may reduce the risk for further development of the multiple comorbidities associated with obesity/type 2 diabetes mellitus, including hypertension and cardiovascular disease (CVD) and kidney disease. The notion that DPP-4i may improve CVD outcomes by mechanisms beyond glycemic control is due to both GLP-1-dependent and GLP-1-independent effects. The CVD protective effects by DPP-4i result from multiple factors including insulin resistance, oxidative stress, dyslipidemia, adipose tissue dysfunction, dysfunctional immunity, and antiapoptotic properties of these agents in the heart and vasculature. This review focuses on cellular and molecular mechanisms mediating the CVD protective effects of DPP-4i beyond favorable effects on glycemic control.

Recent Advances in the Development of Type 2 Sodium-Glucose Cotransporter Inhibitors for the Treatment of Type 2 Diabetes Mellitus

2021 ◽  
Vol 21 ◽  
Author(s):  
Ana Karen Estrada ◽  
Timoteo Delgado-Maldonado ◽  
Edgar E. Lara-Ramírez ◽  
Ana Verónica Martínez-Vázquez ◽  
Eyra Ortiz-Lopez ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Clinical Trials ◽  
Type 2 Diabetes Mellitus ◽  
Adverse Effects ◽  
Clinical Results ◽  
Sglt2 Inhibitors ◽  
Beneficial Effects ◽  
Sodium Glucose Cotransporter

Background: Type 2 diabetes mellitus (T2DM) is one of the most serious and prevalent diseases worldwide. In the last decade, type 2 sodium-glucose cotransporter inhibitors (iSGLT2) were approved as alternative drugs for the pharmacological treatment of T2DM. The anti-hyperglycemic mechanism of action of these drugs involves glycosuria. In addition, SGLT2 inhibitors cause beneficial effects such as weight loss, a decrease in blood pressure, and others. Objective: This review aimed to describe the origin of SGLT2 inhibitors and analyze their recent development in preclinical and clinical trials. Results: In 2013, the FDA approved SGLT2 inhibitors as a new alternative for the treatment of T2DM. These drugs have shown good tolerance with few adverse effects in clinical trials. Additionally, new potential anti-T2DM agents based on iSGLT2 (O-, C-, and N-glucosides) have exhibited a favorable profile in preclinical evaluations, making them candidates for advanced clinical trials. Conclusion: The clinical results of SGLT2 inhibitors show the importance of this drug class as new anti-T2DM agents with a potential dual effect. Additionally, the preclinical results of SGLT2 inhibitors favor the design and development of more selective new agents. However, several adverse effects could be a potential risk for patients.

scholarly journals Effects of Consuming Calcium-Rich Foods on the Incidence of Type 2 Diabetes Mellitus

Nutrients ◽  
2018 ◽  
Vol 11 (1) ◽  
pp. 31 ◽  
Author(s):  
Jimin Jeon ◽  
Jiyoung Jang ◽  
Kyong Park
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Large Scale ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Protective Effects ◽  
Related Data ◽  
Korean Adults

The effect of calcium consumption in the prevention of type 2 diabetes mellitus (T2DM) remains controversial, and depends on food calcium sources. This prospective study aimed to evaluate the association between calcium-rich food consumption and T2DM incidence among Korean adults. We analyzed the data of 8574 adults aged 40–69 years, without a history of T2DM, cardiovascular disease, and cancer at the baseline from the Korean Genome and Epidemiology Study. The consumption of calcium-rich foods was assessed using a validated semi-quantitative food frequency questionnaire. T2DM-related data were collected using biennial questionnaires, health examinations, and clinical tests. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. In the multivariate-adjusted model, yogurt intake was inversely associated with T2DM risk (HR: 0.73; 95% CI: 0.61–0.88 in the fourth quartile as compared to the first quartile). However, the intakes of other calcium-rich foods, including milk and anchovies, were not significantly associated with T2DM risk. Yogurt may provide protective effects against T2DM in Korean adults, owing to the beneficial effects of probiotics. Further prospective large-scale cohort studies should be conducted to validate these findings.

scholarly journals Control of type 2 diabetes mellitus: problems and prospects for their solution

2009 ◽  
Vol 12 (4) ◽  
pp. 42-46
Author(s):  
Tatiana Ivanovna Romantsova ◽  
Irina Vladimirovna Glinkina
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Glycemic Control ◽  
Large Scale ◽  
Conclusive Evidence ◽  
Economic Implications ◽  
Postprandial Glycemia ◽  
Fasting Glycemia

Important medico-social and economic implications of type 2 diabetes mellitus (DM2) are determined by its continuously growing prevalence, frequencyand severity of complications related to inadequate glycemic control. Large-scale studies (UKPDS, VADT, ACCORD, ADVANCE) havedemonstrated controversial effect of intensive glycemic control (estimated from HbA1c dynamics) on diabetic macrovascular complication. At thesame time, epidemiological, experimental, and observational studies yielded conclusive evidence of postprandial glycemia (PPG) contribution tooverall glycemic control and its role in the development of macrovascular complications. For this reason, PPG control is currently given as much attentionas traditional parameters (HbA1c and fasting glycemia). Dipeptidyl peptidase-IV (DPP-IV) inhibitors are a new class of hypoglycemic agentsthat raise levels of incretins, glucagons-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) in blood by suppressing DPPIVactivity. The resulting recovery of physiological insulin secretion promotes reduction of fasting and postprandial glycemia and HbA1c level.

Weight Outcomes With Empagliflozin as Compared With Liraglutide in Veterans With Type 2 Diabetes Mellitus

2020 ◽  
Vol 54 (10) ◽  
pp. 981-987
Author(s):  
Ted Robert Grabarczyk ◽  
Natalie Koury Wissman
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Weight Loss ◽  
Type 2 Diabetes Mellitus ◽  
Glycemic Control ◽  
Sodium Glucose Cotransporter ◽  
Significant Difference ◽  
Weight Outcomes ◽  
Glucagon Like Peptide 1

Background: Glucagon-like peptide-1 agonists and sodium glucose cotransporter 2 inhibitors are associated with weight loss and improved cardiovascular outcomes, and are increasingly used in pharmacotherapy for type 2 diabetes mellitus (T2DM). Objectives: To compare weight loss outcomes of empagliflozin and liraglutide in patients with T2DM and overweight/obesity not yet prescribed insulin but requiring additional pharmacotherapy to improve glycemic control. Methods: This is an observational, multisite, cohort study of veterans with T2DM prescribed liraglutide or empagliflozin. Participants were prescribed either empagliflozin or liraglutide prior to November 1, 2017, had a hemoglobin A1C (A1C) ≥7.0%, had a body mass index ≥27 kg/m2, and were not treated with insulin at baseline. The primary outcome was change in weight after 1 year using multiple regression. Secondary outcomes were the proportion achieving ≥5% weight loss and change in A1C. Results: Weight loss was not significantly different between groups: −2.17 kg (95% CI: −2.91 to −1.42) in the liraglutide group (n = 298) and −2.81 kg (95% CI: −3.43 to −2.20) in the empagliflozin group (n = 247; P > 0.05). After adjusting for covariates, this effect remained nonsignificant. There was no difference in change in A1C between liraglutide (−0.83%; 95% CI: −1.05% to −0.62%) and empagliflozin (−0.71%; 95% CI: −0.89% to −0.53%; P > 0.05). Conclusions and Relevance: There was no significant difference in weight outcomes after 1 year in veterans treated with liraglutide versus empagliflozin. Because both medications did show modest weight loss, both remain good options for patients needing an additional medication to improve glycemic control that is at least weight neutral.

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