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1.
Obesity management as a primary treatment goal for type 2 diabetes: time to reframe the conversation.
Lingvay, I, Sumithran, P, Cohen, RV, le Roux, CW
Lancet (London, England). 2022;(10322):394-405
Abstract
Obesity is now recognised as a disease that is associated with serious morbidity and increased mortality. One of its main metabolic complications is type 2 diabetes, as the two conditions share key pathophysiological mechanisms. Weight loss is known to reverse the underlying metabolic abnormalities of type 2 diabetes and, as such, improve glucose control; loss of 15% or more of bodyweight can have a disease-modifying effect in people with type 2 diabetes, an outcome that is not attainable by any other glucose-lowering intervention. Furthermore, weight loss in this population exerts benefits that extend beyond glycaemic control to improve risk factors for cardiometabolic disease and quality of life. We review the evidence supporting the role of weight loss in the management of type 2 diabetes and propose that many patients with type 2 diabetes would benefit from having a primary weight-centric approach to diabetes treatment. We discuss the logistical challenges to implementing a new weight-centric primary treatment goal in people with type 2 diabetes.
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2.
Potential role of Drug Repositioning Strategy (DRS) for management of tauopathy.
Zaki, MO, Elsherbiny, DA, Salama, M, Azab, SS
Life sciences. 2022;:120267
Abstract
Tauopathy is a term that has been used to represent a pathological condition in which hyperphosphorylated tau protein aggregates in neurons and glia which results in neurodegeneration, synapse loss and dysfunction and cognitive impairments. Recently, drug repositioning strategy (DRS) becomes a promising field and an alternative approach to advancing new treatments from actually developed and FDA approved drugs for an indication other than the indication it was originally intended for. This paradigm provides an advantage because the safety of the candidate compound has already been established, which abolishes the need for further preclinical safety testing and thus substantially reduces the time and cost involved in progressing of clinical trials. In the present review, we focused on correlation between tauopathy and common diseases as type 2 diabetes mellitus and the global virus COVID-19 and how tau pathology can aggravate development of these diseases in addition to how these diseases can be a risk factor for development of tauopathy. Moreover, correlation between COVID-19 and type 2 diabetes mellitus was also discussed. Therefore, repositioning of a drug in the daily clinical practice of patients to manage or prevent two or more diseases at the same time with lower side effects and drug-drug interactions is a promising idea. This review concluded the results of pre-clinical and clinical studies applied on antidiabetics, COVID-19 medications, antihypertensives, antidepressants and cholesterol lowering drugs for possible drug repositioning for management of tauopathy.
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3.
Non-alcoholic fatty liver disease (NAFLD): a review of pathophysiology, clinical management and effects of weight loss.
Pouwels, S, Sakran, N, Graham, Y, Leal, A, Pintar, T, Yang, W, Kassir, R, Singhal, R, Mahawar, K, Ramnarain, D
BMC endocrine disorders. 2022;(1):63
Abstract
Given the increasing prevalence of diabetes and obesity worldwide, the deleterious effects of non-alcoholic fatty liver disease (NAFLD) are becoming a growing challenge for public health. NAFLD is the most common chronic liver disease in the Western world. NAFLD is closely associated with metabolic disorders, including central obesity, dyslipidaemia, hypertension, hyperglycaemia and persistent abnormalities of liver function tests.In general NAFLD is a common denominer for a broad spectrum of damage to the liver, which can be due to hepatocyte injury, inflammatory processes and fibrosis. This is normally seen on liver biopsy and can range from milder forms (steatosis) to the more severe forms (non-alcoholic steatohepatitis (NASH), advanced fibrosis, cirrhosis and liver failure). In these patients, advanced fibrosis is the major predictor of morbidity and liver-related mortality, and an accurate diagnosis of NASH and NAFLD is mandatory. Histologic evaluation with liver biopsy remains the gold standard to diagnose NAFLD. Diagnosis of NAFLD is defined as presence of hepatic steatosis, ballooning and lobular inflammation with or without fibrosis. Weight loss, dietary modification, and the treatment of underlying metabolic syndrome remain the mainstays of therapy once the diagnosis is established. Dietary recommendations and lifestyle interventions, weight loss, and the treatment of underlying metabolic syndrome remain the mainstays of therapy once the diagnosis is established with promising results but are difficult to maintain. Pioglitazone and vitamin E are recommended by guidelines in selected patients. This review gives an overview of NAFLD and its treatment options.
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4.
Polycystic ovarian syndrome-current pharmacotherapy and clinical implications.
Rashid, R, Mir, SA, Kareem, O, Ali, T, Ara, R, Malik, A, Amin, F, Bader, GN
Taiwanese journal of obstetrics & gynecology. 2022;(1):40-50
Abstract
Polycystic ovary syndrome (PCOS), the most common endocrinopathy in women is characterized by polycystic ovaries, chronic anovulation and hyperandrogenism. The treatment in PCOS is mainly symptomatic and involves lifestyle interventions and medications such as Metformin, Oral contraceptives and Antiandrogens. However, the management of PCOS is challenging and current interventions are not able to deal with outcomes of this syndrome. This review encompasses latest pharmacotherapeutic and non-pharmacotherapeutic interventions currently in use to tackle various symptomatic contentions in PCOS. Our focus has been mainly on novel therapeutic modalities for treatment/management of PCOS, like use of newer insulin sensitizers viz., Inositols, Glucagon-like peptide-1(GLP-1) agonists, Dipeptidyl pepdidase-4 (DPP-4) inhibitors, and sodium-glucose transport protein 2 (SGLT2) inhibitors. Also, evidence suggesting the use of vitamin D, statins, and Letrozole as emerging therapies in PCOS have been summarized in this review. Additionally, novel cosmetic techniques like electrolysis, laser and use of topically applied eflornithine to tackle the most distressing feature of facial hirsutism associated with PCOS, non-pharmacological therapy like acupuncture and the role of herbal medicine in PCOS management have also been discussed.
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5.
Therapeutic Targeting of SGLT2: A New Era in the Treatment of Diabetes and Diabetic Kidney Disease.
Shaffner, J, Chen, B, Malhotra, DK, Dworkin, LD, Gong, R
Frontiers in endocrinology. 2021;:749010
Abstract
As the prevalence of diabetic kidney disease (DKD) continues to rise, so does the need for a novel therapeutic modality that can control and slow its progression to end-stage renal disease. The advent of sodium-glucose cotransporter-2 (SGLT2) inhibitors has provided a major advancement for the treatment of DKD. However, there still remains insufficient understanding of the mechanism of action and effectiveness of this drug, and as a result, its use has been very limited. Burgeoning evidence suggests that the SGLT2 inhibitors possess renal protective activities that are able to lower glycemic levels, improve blood pressure/hemodynamics, cause bodyweight loss, mitigate oxidative stress, exert anti-inflammatory and anti-fibrotic effects, reduce urinary albumin excretion, lower uric acid levels, diminish the activity of intrarenal renin-angiotensin-aldosterone system, and reduce natriuretic peptide levels. SGLT2 inhibitors have been shown to be safe and beneficial for use in patients with a GFR ≥30mL/min/1.73m2, associated with a constellation of signs of metabolic reprogramming, including enhanced ketogenesis, which may be responsible for the correction of metabolic reprogramming that underlies DKD. This article aims to provide a comprehensive overview and better understanding of the SGLT2 inhibitor and its benefits as it pertains to renal pathophysiology. It summarizes our recent understanding on the mechanisms of action of SGLT2 inhibitors, discusses the effects of SGLT2 inhibitors on diabetes and DKD, and presents future research directions and therapeutic potential.
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6.
Pharmacogenetics of new classes of antidiabetic drugs.
Imamovic Kadric, S, Kulo Cesic, A, Dujic, T
Bosnian journal of basic medical sciences. 2021;(6):659-671
Abstract
Type 2 diabetes (T2D) has a continuously rising prevalence worldwide. Pharmacogenetics has been recognized as a promising concept for pharmacological treatment of T2D, as antidiabetic drugs are not equally effective and safe for all patients, and the costs of diabetes treatment are increasing. The latest published guidelines on T2D treatment firmly endorse the use of newer antidiabetic drugs, sodium-glucose cotransporter-2 inhibitors (SGLT2i), dipeptidyl peptidase-4 inhibitors (DPP-IVi), and glucagon-like peptide-1 receptor agonists (GLP-1RA), considering their satisfactory pharmacological effect and good safety profile. Furthermore, SGLT2i and GLP-1RA show protective effects in patients with established atherosclerotic cardiovascular disease and chronic kidney disease. However, there has been growing evidence that the effectiveness and safety of these drug classes could depend on genetic variability. Here, we summarized the results of the published studies on the pharmacogenetic biomarkers for the three drug classes. A number of genetic variations have been investigated so far. The explored candidate genes mostly encode drug targets, drug-metabolizing enzymes, and genes linked to T2D risk. Although many of the results are promising, it is still necessary to obtain more information from larger controlled studies to confirm their clinical significance. This approach may lead towards more personalized treatment for patients with T2D.
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7.
CGMS and Glycemic Variability, Relevance in Clinical Research to Evaluate Interventions in T2D, a Literature Review.
Breyton, AE, Lambert-Porcheron, S, Laville, M, Vinoy, S, Nazare, JA
Frontiers in endocrinology. 2021;:666008
Abstract
Glycemic variability (GV) appears today as an integral component of glucose homeostasis for the management of type 2 diabetes (T2D). This review aims at investigating the use and relevance of GV parameters in interventional and observational studies for glucose control management in T2D. It will first focus on the relationships between GV parameters measured by continuous glucose monitoring system (CGMS) and glycemic control and T2D-associated complications markers. The second part will be dedicated to the analysis of GV parameters from CGMS as outcomes in interventional studies (pharmacological, nutritional, physical activity) aimed at improving glycemic control in patients with T2D. From 243 articles first identified, 63 articles were included (27 for the first part and 38 for the second part). For both analyses, the majority of the identified studies were pharmacological. Lifestyle studies (including nutritional and physical activity-based studies, N-AP) were poorly represented. Concerning the relationships of GV parameters with those for glycemic control and T2D related-complications, the standard deviation (SD), the coefficient of variation (CV), the mean blood glucose (MBG), and the mean amplitude of the glycemic excursions (MAGEs) were the most studied, showing strong relationships, in particular with HbA1c. Regarding the use and relevance of GV as an outcome in interventional studies, in pharmacological ones, SD, MAGE, MBG, and time in range (TIR) were the GV parameters used as main criteria in most studies, showing significant improvement after intervention, in parallel or not with glycemic control parameters' (HbA1c, FBG, and PPBG) improvement. In N-AP studies, the same results were observed for SD, MAGE, and TIR. Despite the small number of N-AP studies addressing both GV and glycemic control parameters compared to pharmacological ones, N-AP studies have shown promising results on GV parameters and would require more in-depth work. Evaluating CGMS-GV parameters as outcomes in interventional studies may provide a more integrative dimension of glucose control than the standard postprandial follow-up. GV appears to be a key component of T2D dysglycemia, and some parameters such as MAGE, SD, or TIR could be used routinely in addition to classical markers of glycemic control such as HbA1c, fasting, or postprandial glycemia.
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8.
Glucose-lowering action through targeting islet dysfunction in type 2 diabetes: Focus on dipeptidyl peptidase-4 inhibition.
Ahrén, B
Journal of diabetes investigation. 2021;(7):1128-1135
Abstract
Dipeptidyl peptidase-4 (DPP-4) inhibition is a glucose-lowering medication for type 2 diabetes. It works through stimulation of insulin secretion and inhibition of glucagon secretion in a glucose-dependent manner, resulting in lowered fasting and postprandial glycemia with low risk of hypoglycemia. As impaired insulin secretion and augmented glucagon secretion are key factors underlying hyperglycemia in type 2 diabetes, DPP-4 inhibition represents a therapy that targets the underlying mechanisms of the disease. If insufficient in monotherapy, it can preferably be used in combination with metformin, which targets insulin resistance, and also in combination with sodium-glucose cotransporter 2 inhibition, thiazolidinediones and insulin, which target other mechanisms. In individuals of East Asian origin, islet dysfunction is of particular importance for the development of type 2 diabetes. Consequently, it has been shown in several studies that DPP-4 is efficient in these populations. This mini-review highlights the islet mechanisms of DPP-4 inhibition, islet dysfunction as a key factor for hyperglycemia in type 2 diabetes and that, consequently, DPP-4 is of particular value in populations where islet dysfunction is central, such as in individuals of East Asian origin.
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9.
Pharmacotherapeutic considerations for the management of diabetes mellitus among hospitalized COVID-19 patients.
Hasan, SS, Kow, CS, Bain, A, Kavanagh, S, Merchant, HA, Hadi, MA
Expert opinion on pharmacotherapy. 2021;(2):229-240
Abstract
INTRODUCTION Diabetes mellitus is one of the most prevalent comorbidities identified in patients with coronavirus disease 2019 (COVID-19). This article aims to discuss the pharmacotherapeutic considerations for the management of diabetes in hospitalized patients with COVID-19. AREAS COVERED We discussed various aspects of pharmacotherapeutic management in hospitalized patients with COVID-19: (i) susceptibility and severity of COVID-19 among individuals with diabetes, (ii) glycemic goals for hospitalized patients with COVID-19 and concurrent diabetes, (iii) pharmacological treatment considerations for hospitalized patients with COVID-19 and concurrent diabetes. EXPERT OPINION The glycemic goals in patients with COVID-19 and concurrent type 1 (T1DM) or type 2 diabetes (T2DM) are to avoid disruption of stable metabolic state, maintain optimal glycemic control, and prevent adverse glycemic events. Patients with T1DM require insulin therapy at all times to prevent ketosis. The management strategies for patients with T2DM include temporary discontinuation of certain oral antidiabetic agents and consideration for insulin therapy. Patients with T2DM who are relatively stable and able to eat regularly may continue with oral antidiabetic agents if glycemic control is satisfactory. Hyperglycemia may develop in patients with systemic corticosteroid treatment and should be managed upon accordingly.
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10.
The Effects of Glucagon-Like Peptide-1 Receptor Agonists and Dipeptydilpeptidase-4 Inhibitors on Blood Pressure and Cardiovascular Complications in Diabetes.
Yaribeygi, H, Farrokhi, FR, Abdalla, MA, Sathyapalan, T, Banach, M, Jamialahmadi, T, Sahebkar, A
Journal of diabetes research. 2021;:6518221
Abstract
Glucagon-like peptide-1 receptor (GLP-1R) agonists are a class of newly introduced antidiabetic medications that potentially lower blood glucose by several molecular pathways. DPP-4 inhibitors are the other type of novel antidiabetic medications which act by preventing GLP-1 inactivation and thereby increasing the activity levels of GLP-1, leading to more glucose-induced insulin release from islet β-cells and suppression of glucagon release. Most patients with diabetes have concurrent hypertension and cardiovascular disorder. If antihyperglycemic agents can attenuate the risk of hypertension and cardiovascular disease, they will amplify their overall beneficial effects. There is conflicting evidence on the cardiovascular benefits of GLP-1R induction in laboratory studies and clinical trials. In this study, we have reviewed the main molecular mechanisms by which GLP-1R induction may modulate the cardiovascular function and the results of cardiovascular outcome clinical trials.