Project description:SGLT2 inhibitors are plausible second-line drugs that provide powerful additional A1c-lowering effects while inducing weight loss without hypoglycemia.
Project description:In the last decade, attention has become greater to the relationship between neurodegeneration and abnormal insulin signaling in the central nervous system, as insulin in the brain is implicated in neuronal survival, plasticity, oxidative stress and neuroinflammation. Diabetes mellitus and Parkinson's disease are both aging-associated diseases that are turning into epidemics worldwide. Diabetes mellitus and insulin resistance not only increase the possibility of developing Parkinson's disease but can also determine the prognosis and progression of Parkinsonian symptoms. Today, there are no available curative or disease modifying treatments for Parkinson's disease, but the role of insulin and antidiabetic medications in neurodegeneration opens a door to treatment repurposing to fight against Parkinson's disease, both in diabetic and nondiabetic Parkinsonian patients. Furthermore, it is essential to comprehend how a frequent and treatable disease such as diabetes can influence the progression of neurodegeneration in a challenging disease such as Parkinson's disease. Here, we review the present evidence on the connection between Parkinson's disease and diabetes and the consequential implications of the existing antidiabetic molecules in the severity and development of Parkinsonism, with a particular focus on glucagon-like peptide-1 receptor agonists.
Project description:To achieve good metabolic control in diabetes and keep long term, a combination of changes in lifestyle and pharmacological treatment is necessary. Achieving near-normal glycated hemoglobin significantly, decreases risk of macrovascular and microvascular complications. At present there are different treatments, both oral and injectable, available for the treatment of type 2 diabetes mellitus (T2DM). Treatment algorithms designed to reduce the development or progression of the complications of diabetes emphasizes the need for good glycaemic control. The aim of this review is to perform an update on the benefits and limitations of different drugs, both current and future, for the treatment of T2DM. Initial intervention should focus on lifestyle changes. Moreover, changes in lifestyle have proven to be beneficial, but for many patients is a complication keep long term. Physicians should be familiar with the different types of existing drugs for the treatment of diabetes and select the most effective, safe and better tolerated by patients. Metformin remains the first choice of treatment for most patients. Other alternative or second-line treatment options should be individualized depending on the characteristics of each patient. This article reviews the treatments available for patients with T2DM, with an emphasis on agents introduced within the last decade.
Project description:The prevalence of type 2 diabetes is expected to increase gradually with the prolongation of population aging and life expectancy. In addition to macrovascular and microvascular complications of elderly patients of diabetes mellitus, geriatric syndromes such as cognitive impairment, depression, urinary incontinence, falling and polypharmacy are also accompanied by aging. Individual functional status in the elderly shows heterogeneity so that in these patients, there are many unanswered questions about the management of diabetes treatment. The goals of diabetes treatment in elderly patients include hyperglycemia and risk factors, as in younger patients. comorbid diseases and functional limitations of individuals should be taken into consideration when setting treatment targets. Thus, treatment should be individualized. In the treatment of diabetes in vulnerable elderly patients, hypoglycemia, hypotension, and drug interactions due to multiple drug use should be avoided. Since it also affects the ability to self-care in these patients, management of other concurrent medical conditions is also important.
Project description:Current guidelines for treatment of type 2 diabetes mellitus (T2DM) indicate a patient-centered approach that should go beyond glycemic control. Of the many antihyperglycemic agents available for treatment of T2DM, sodium-glucose cotransporter 2 (SGLT2) inhibitors offer the advantages of reduced glycated hemoglobin (A1C), body weight (BW), and systolic blood pressure (SBP) and are associated with a low risk of hypoglycemia when used either as monotherapy or with other agents not typically associated with increased risk of hypoglycemia. Collaborative, multidisciplinary teams are best suited to provide care to patients with diabetes, and clinical pharmacists can enhance the care provided by these teams. This review aims to provide insight into the mode of action, pharmacology, potential drug-drug interactions, clinical benefits, and safety considerations associated with use of the SGLT2 inhibitor canagliflozin in patients with T2DM and to provide information to enhance clinical pharmacists' understanding of canagliflozin.
Project description:More than 422 million people worldwide have diabetes, with 90-95% having type 2 diabetes (T2D). Glycemic control of T2D has demonstrated reductions in microvascular complications but recent data have demonstrated improvements in macrovascular outcomes with sodium-glucose cotransporter 2 (SGLT2) inhibitors. Ertugliflozin is the most recent SGLT2 inhibitor approved in the USA and Europe for the treatment of T2D. This narrative review aims to present and discuss the efficacy, safety, cardiovascular (CV), and renal outcomes related to the use of ertugliflozin in T2D. Ertugliflozin has been evaluated in eight clinical trials (n=5248) with a focus on glycemic control. These trials have demonstrated improvement in glycosylated hemoglobin (0.6-1%), fasting plasma glucose (30-50 mg/dL), 2-hour postprandial glucose (60-70 mg/dL), decreased body weight (2-3 kg), and lowering of blood pressure (3-5 mmHg) in patients with T2D when ertugliflozin is used as monotherapy or in addition to metformin, sitagliptin, insulin, and/or sulfonylureas. The findings from the VERTIS-CV trial (n=8246) were recently published and demonstrated that ertugliflozin use in patients with T2D and atherosclerotic CV disease is safe but did not demonstrate superiority in the lowering of major CV events compared to placebo. Other SGLT2 inhibitors, such as empagliflozin and canagliflozin, have demonstrated this benefit. The VERTIS-CV trial demonstrated that the use of ertugliflozin led to a decrease in the number of hospitalizations for heart failure and this lends further support that this benefit is a class effect of SGLT2 inhibitors.
Project description:There are several therapeutic approaches in type 2 diabetes mellitus (T2DM). When diet and exercise fail to control hyperglycemia, patients are forced to start therapy with antidiabetic agents. However, these drugs present several drawbacks that can affect the course of treatment. The major disadvantages of current oral modalities for the treatment of T2DM are mainly depicted in the low bioavailability and the immediate release of the drug, generating the need for an increase in frequency of dosing. In conjugation with the manifestation of adverse side effects, patient compliance to therapy is reduced. Over the past few years nanotechnology has found fertile ground in the development of novel delivery modalities that can potentially enhance anti-diabetic regimes efficacy. All efforts have been targeted towards two main vital steps: (a) to protect the drug by encapsulating it into a nano-carrier system and (b) efficiently release the drug in a gradual as well as controllable manner. However, only a limited number of studies published in the literature used in vivo techniques in order to support findings. Here we discuss the current disadvantages of modern T2DM marketed drugs, and the nanotechnology advances supported by in vivo in mouse/rat models of glucose homeostasis. The generation of drug nanocarriers may increase bioavailability, prolong release and therefore reduce dosing and thus, improve patient compliance. This novel approach might substantially improve quality of life for diabetics. Application of metal nanoformulations as indirect hypoglycemic agents is also discussed.
Project description:Objective: To detail studies investigating the efficacy/safety of semaglutide as a glucagon-like peptide-1 receptor agonist (GLP-1 RA) in the treatment of type 2 diabetes mellitus. Data Sources: A literature search in MEDLINE and ClinicalTrials.gov (January 2013 to May 2018) using the terms semaglutide, SUSTAIN, oral, and PIONEER resulted in 10 published articles and 14 ongoing/unpublished articles. Study Selection and Data Extraction: All English language phase 2 and 3 clinical trials evaluating efficacy/safety of semaglutide were included. Data Synthesis: In 9 phase 3, multicenter SUSTAIN trials, the efficacy and safety of semaglutide have been compared with placebo and other pharmacologic therapy for diabetes (PTD). In these trials, semaglutide resulted in lower hemoglobin A1c (HbA1c; approximately -1.5%) and weight reductions (approximately -4.5 kg) as comparable with dulaglutide for HbA1c lowering (approximately -1.5%). Semaglutide also has cardiovascular (CV) outcomes data that show significant reduction in risk of death from CV causes, nonfatal myocardial infarction, or nonfatal stroke (hazard ratio = 0.74; 95% confidence interval = 0.58-0.95). A safety finding that emerged from the CV outcomes trial was an association of semaglutide treatment with an increased risk of retinopathy complications in patients with preexisting diabetic retinopathy. Phase 3 trial data assessing semaglutide oral formulation have shown similar HbA1c (approximately -1.5% for 14 mg dose) and body weight (approximately -4.1 kg for 14 mg dose) reductions as compared with placebo. Across these studies, semaglutide was generally well tolerated with the most common adverse event reported as gastrointestinal side effects as seen in all GLP-1 RAs. Conclusions: These results suggest that semaglutide may have a place in therapy as a GLP-1 RA add-on therapy with higher weight loss as compared with other GLP-1 RAs and PTD and CV benefit.
Project description:IntroductionLipid control is essential in type 2 diabetes mellitus (T2DM). The aim of this study is to investigate factors associated with lipid therapy adherence and achievement of goals in real-life setting among patients with recently diagnosed T2DM.Research design and methodsThis is a longitudinal analysis in a center of comprehensive care for patients with diabetes. We include patients with T2DM, <5 years of diagnosis, without disabling complications (eg, amputation, myocardial infarct, stroke, proliferative retinopathy, glomerular filtration rate <60 mL/min/m2) and completed 2-year follow-up. The comprehensive diabetes care model includes 9 interventions in 4 initial visits and annual evaluations. Endocrinologists follow the clinic's guideline and adapt therapy to reach risk-based treatment goal. The main outcome measures were the proportion of patients meeting low-density lipoprotein cholesterol (c-LDL) (<100 mg/dL) and triglycerides (<150 mg/dL) and proportion of patients taking statin, fibrate or combination at baseline, 3 months and annual evaluations.ResultsWe included 288 consecutive patients (54±9 years, 53.8% women), time since T2DM diagnosis 1 (0-5) year. Baseline, 10.8% patients were receiving statin therapy (46.5% moderate-intensity therapy and 4.6% high-intensity therapy), 8.3% fibrates and 4.2% combined treatment. The proportion of patients with combined treatment increased to 41.6% at 3 months, decreased to 20.8% at 1 year and increased to 38.9% at 2 years of evaluation. Patients receiving treatment met LDL and triglycerides goals at 3 months (17% vs 59.7%, relative ratio (RR)=0.89, 95% CI 0.71 to 1.12), at 1 year (17% vs 26.7%, RR=0.62, 95% CI 0.41 to 0.95) and at 2 years (17% vs 29.9%, RR=0.63, 95% CI 0.43 to 0.93). Main reasons for medication suspension: patient considered treatment was not important (37.5%) and other physician suspended treatment (31.3%).Conclusion88.2% of patients with T2DM required lipid-lowering drugs. Education for patients and physicians is critical to achieve and maintain diabetes goals.Trial registration numberNCT02836808.