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1.
Front Mol Biosci ; 10: 1130625, 2023.
Article in English | MEDLINE | ID: covidwho-20242305

ABSTRACT

DPP-4 inhibition is an interesting line of therapy for treating Type 2 Diabetes Mellitus (T2DM) and is based on promoting the incretin effect. Here, the authors have presented a brief appraisal of DPP-4 inhibitors, their modes of action, and the clinical efficiency of currently available drugs based on DPP-4 inhibitors. The safety profiles as well as future directions including their potential application in improving COVID-19 patient outcomes have also been discussed in detail. This review also highlights the existing queries and evidence gaps in DPP-4 inhibitor research. Authors have concluded that the excitement surrounding DPP-4 inhibitors is justified because in addition to controlling blood glucose level, they are good at managing risk factors associated with diabetes.

2.
Clin Pract ; 12(1): 1-7, 2021 Dec 21.
Article in English | MEDLINE | ID: covidwho-2255130

ABSTRACT

Sodium-glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) agonists are important drugs in our armamentarium of treatment for Type 2 diabetes mellitus (DM). In addition to their glucose-lowering effects, they have effects on weight, other metabolic diseases and perhaps most importantly, a cardioprotective and reno-protective effect. Liraglutide is a long-acting GLP-1 agonist which was originally used at 1.8 mg daily for the treatment of DM. However, high-dose liraglutide-liraglutide 3 mg daily, has been demonstrated to be a safe and effective treatment for obesity, with or without DM. In this manuscript, I present two patients who had unusual responses to combination therapy with high-dose liraglutide and SGLT2 inhibitor-marked and/or rapid improvement in glycemic control and weight loss. Drawing from the observations in both cases, I discuss the complementary mechanisms of actions of both drugs, review the clinical effects of combination therapy and distil them into clinical pearls of practical utility for the physician. Given the "clash of the two pandemics" of obesity and COVID-19 and the burgeoning rates of obesity which loom in the near horizon, this is most timely.

3.
Endocr Pathol ; 34(1): 48-56, 2023 Mar.
Article in English | MEDLINE | ID: covidwho-2279637

ABSTRACT

The effects of many pharmacological agents on thyroid function are well known. Direct influences on measurements of thyroid function tests are also described. However, certain classes of drugs produce morphological changes in the gland. This review focuses on the significance of the following drug classes for the thyroid pathologist: iodine, antithyroid drugs, psychotropic drugs, antibiotics, cardiotropic drugs, antidiabetic drugs, and immunomodulatory agents. Radioactive iodine initially induces mild histologic changes; however, the long-term effects include marked follicular atrophy, fibrosis, and nuclear atypia-changes that vary depending on the pre-therapy condition of the gland. Some psychotropic drugs have been associated with a spectrum of inflammatory changes throughout the gland. The tetracycline class of antibiotics, namely minocycline, can lead to a grossly black thyroid gland with pigment seen in both colloid and follicular epithelial cells while variably present within thyroid nodules. The surgical pathologist most commonly sees an amiodarone-affected gland removed for hyperthyroidism, and the histologic findings again depend on the pre-therapy condition of the gland. While GLP-1 receptor agonists carry an FDA black box warning for patients with a personal or family history of multiple endocrine neoplasia or medullary thyroid carcinoma, the C cell hyperplasia originally noted in rats has not borne out in human studies. Finally, thyroiditis and hypothyroidism are well known complications of checkpoint inhibitor therapy, and rare cases of severe thyroiditis requiring urgent thyroidectomy have been reported with unique histologic findings. In this review, we describe the histologic findings for these drugs and more, in many cases including their functional consequences.


Subject(s)
Iodine , Thyroid Neoplasms , Thyroiditis , Humans , Animals , Rats , Iodine Radioisotopes , Pathologists , Anti-Bacterial Agents/pharmacology
4.
Diabetes Metab Res Rev ; : e3635, 2023 Mar 23.
Article in English | MEDLINE | ID: covidwho-2252403

ABSTRACT

AIMS: Endotoxemia commonly occurs in severe and fatal COVID-19, suggesting that concomitant bacterial stimuli may amplify the innate immune response induced by SARS-CoV-2. We previously demonstrated that the endogenous glucagon like peptide 1 (GLP-1) system in conjunction with increased procalcitonin (PCT) is hyperactivated in patients with severe Gram-negative sepsis and modulated by type 2 diabetes (T2D). We aimed to determine the association of COVID-19 severity with endogenous GLP-1 activation upregulated by increased specific pro-inflammatory innate immune response in patients with and without T2D. MATERIALS AND METHODS: Plasma levels of total GLP-1, IL-6, and PCT were estimated on admission and during hospitalisation in 61 patients (17 with T2D) with non-severe and severe COVID-19. RESULTS: COVID-19 patients demonstrated ten-fold increase of IL-6 levels regardless of disease severity. Increased admission GLP-1 levels (p = 0.03) accompanied by two-fold increased PCT were found in severe as compared with non-severe patients. Moreover, GLP-1 and PCT levels were significantly increased in non-survived as compared with survived patients at admission (p = 0.01 and p = 0.001, respectively) and at 5 to 6 days of hospitalisation (p = 0.05). Both non-diabetic and T2D patients demonstrated a positive correlation between GLP-1 and PCT response (r = 0.33, p = 0.03, and r = 0.54, p = 0.03, respectively), but the intensity of this joint pro-inflammatory/GLP-1 response was modulated by T2D. In addition, hypoxaemia down-regulated GLP-1 response only in T2D patients with bilateral lung damage. CONCLUSIONS: The persistent joint increase of endogenous GLP-1 and PCT in severe and fatal COVID-19 suggests a role of concomitant bacterial infection in disease exacerbation. Early elevation of endogenous GLP-1 may serve as a new biomarker of COVID-19 severity and fatal outcome.

5.
J Diabetes Complications ; 37(4): 108436, 2023 04.
Article in English | MEDLINE | ID: covidwho-2251594

ABSTRACT

BACKGROUND: Pulse wave velocity (PWV) and augmentation index (AIx) are indices used to assess arterial stiffness. We aim to compare the effect of empagliflozin, liraglutide and their sequential combination on arterial stiffness indices in patients with type 2 diabetes (T2D). METHODS: This was a randomized single blind study evaluating the effect of empagliflozin vs liraglutide in adult patients with T2D. Patients were randomized to liraglutide titrated gradually to 1.8 mg or empagliflozin 25 mg in 1:1 ratio. Three months later empagliflozin was added to the liraglutide group, and liraglutide was added to the empagliflozin group. Patients were assessed with non-invasive tests for arterial stiffness (i.e., carotid-femoral PWV and AIx of aortic pressure) at baseline, 3-month and 9-month visits (final visit was extended for 3 months from the initial design due to Covid 19 pandemic). The primary outcome was the between-group difference of PWV change (ΔPWV) and ΔAIx at 3 months. Secondary outcomes included the between-group difference of ΔPWV and ΔAIx at 9 months, as well as the ΔPWV and ΔAIx between baseline and 9-month visit when total study population was assessed. RESULTS: A total of 62 patients with T2D (30 started liraglutide; 32 empagliflozin, mean age 63 years, 25 % with established cardiovascular disease) participated in the study. We failed to show any significant between-group differences of ΔPWV and ΔΑΙx at 3 and 9 months, as well as between-group difference of ΔPWV and ΔAIx for the total study population between baseline and 9-month visit. In contrast, systemic vascular resistance and lipoprotein(a) levels improved, showing better results with liraglutide than empagliflozin. Favorable effects were also observed on body weight, body mass index, body and visceral fat, blood pressure, HbA1c, and uric acid levels. CONCLUSION: No evidence of a favorable change in arterial stiffness indices was seen with empagliflozin or liraglutide or their combination in this study. Well-designed powerful studies are needed to address any potential effects on arterial stiffness in selected populations.


Subject(s)
COVID-19 , Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Sodium-Glucose Transporter 2 Inhibitors , Vascular Stiffness , Humans , Middle Aged , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/prevention & control , Cardiovascular Diseases/complications , COVID-19/complications , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Liraglutide/adverse effects , Prospective Studies , Pulse Wave Analysis , Single-Blind Method , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/pharmacology
6.
J Diabetes ; 15(2): 86-96, 2023 Feb.
Article in English | MEDLINE | ID: covidwho-2213417

ABSTRACT

BACKGROUND: Patients with diabetes are more likely to suffer COVID-19 complications. Using noninsulin antihyperglycemic medications (AGMs) during COVID-19 infection has proved challenging. In this study, we evaluate different noninsulin AGMs in patients with COVID-19. METHODS: We searched Medline, Embase, Web of Science, and Cochrane on 24 January 2022. We used the following keywords (COVID-19) AND (diabetes mellitus) AND (antihyperglycemic agent). The inclusion criteria were studies reporting one or more of the outcomes. We excluded non-English articles, case reports, and literature reviews. Study outcomes were mortality, hospitalization, and intensive care unit (ICU) admission. RESULTS: The use of metformin rather than other glucose-lowering medications was associated with statistically significant lower mortality (risk ratio [RR]: 0.60, 95% confidence interval [CI]: 0.47, 0.77, p < .001). Dipeptidyl peptidase-4 inhibitor (DPP-4i) use was associated with statistically significantly higher hospitalization risk (RR: 1.44, 95% CI: 1.23, 1.68, p < .001) and higher risk of ICU admissions and/or mechanical ventilation vs nonusers (RR: 1.24, 95% CI: 1.04, 1.48, p < .02). There was a statistically significant decrease in hospitalization for SGLT-2i users vs nonusers (RR: 0.89, 95% CI: 0.84-0.95, p < .001). Glucagon-like peptide-1 receptor agonist (GLP-1RA) use was associated with a statistically significant decrease in mortality (RR: 0.56, 95% CI: 0.42, 073, p < 0.001), ICU admission, and/or mechanical ventilation (RR: 0.79, 95% CI: 0.69-0.89, p < .001), and hospitalization (RR: 0.73, 95% CI: 0.54, 0.98, p = .04). CONCLUSIONS: AGM use was not associated with increased mortality. However, metformin and GLP-1RA use reduced mortality risk statistically significantly. DPP-4i use was associated with a statistically significant increase in the risk of hospitalization and admission to the ICU.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Dipeptidyl-Peptidase IV Inhibitors , Metformin , Sodium-Glucose Transporter 2 Inhibitors , Humans , Hypoglycemic Agents/therapeutic use , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , COVID-19/epidemiology , COVID-19/complications , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Metformin/therapeutic use , Glucagon-Like Peptide-1 Receptor
7.
Open Medicinal Chemistry Journal ; 16 (no pagination), 2022.
Article in English | EMBASE | ID: covidwho-2197753

ABSTRACT

Glucagon-like peptide 1 (GLP-1) is a gut-derived hormone released after a meal, which alleviates hyperglycemia, increases beta-cell survival, reduces body weight, and reduces inflammation. These thrilling effects motivated clinical studies to discover the potential use of GLP-1 receptor agonists (GLP-1 RAs) in the management of T2D. GLP-1 RAs are potential anti-diabetic agents that can reduce blood pressure, glucose levels, HbA1c and, weight loss without hypoglycemia risk. This manuscript reviews the importance of GLP-1 RAs and their role in the management of T2D with or without COVID-19 infection. Hence, this manuscript can help physicians and researchers to choose the most appropriate drugs for the individualized treatment of subjects. Copyright © 2022 Mirzaei et al.

8.
Endocr Metab Immune Disord Drug Targets ; 23(8): 1041-1045, 2023.
Article in English | MEDLINE | ID: covidwho-2197842

ABSTRACT

BACKGROUND: The Italian population's habits changed dramatically during the "COVID- 19 lockdown" due to physical distancing and self-isolation. Moreover, medical consultations of patients with chronic diseases, such as type 2 diabetes (T2D), were suspended or postponed, unless urgent or semi-urgent, for several consecutive months. Thus, it is expected that the lockdown could have affected glucometabolic control in T2D. v Purpose: The aim of the study was to assess changes in glucometabolic control in a cohort of T2D patients before (T1) and after (T2) the COVID-19 lockdown (March-May 2020). METHODS: The study was approved by the Ethics Committee of the University of Bari, and all patients provided informed written consent to participate. Medical history, complete physical examination, and laboratory assessment were conducted as real-life clinical practice. Changes in clinical and laboratory variables between T1 and T2 were calculated. RESULTS: In detail, 13 patients were on metformin as monotherapy, 36 on GLP-1RA, 12 on sodiumglucose transporter 2 inhibitors (SGLT-2i), and 2 on dipeptidyl-peptidase 4 inhibitors (DPP4i). The mean age was 65.3 years (43-83). Study participants were mainly men (73%). The body weight (BW) ranged from 56 to 145 kg, and the waist circumference ranged from 88 to 146 cm. The mean HbA1c was 51.0 mmol/mol. At T2, no statistically significant changes were observed frombaseline except for BW [-1.6 (-2.60 to -0.62)] and HbA1c [-2.90 (-4.69; -1.12)]. CONCLUSION: We evaluated the effects of the COVID-19 lockdown on glucometabolic control in patients with background well-controlled T2D. We found that the lockdown had no adverse effects on metabolic profile regardless of background clinical characteristics and antihyperglycemic management. Despite limitations due to the nature of this study (sample size, retrospective observation, lack of data on lifestyle changes in our patients' everyday lives), T2D patients managed in our Diabetes Centers faced the lockdown-related restrictions without any detrimental consequence.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Male , Humans , Aged , Female , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Glycated Hemoglobin , Retrospective Studies , COVID-19/epidemiology , Communicable Disease Control , Hypoglycemic Agents/pharmacology , Body Weight
11.
World J Cardiol ; 14(6): 329-342, 2022 Jun 26.
Article in English | MEDLINE | ID: covidwho-1979528

ABSTRACT

Both GLP-1 receptor agonists (GLP-1RA) and SGLT-2 inhibitors (SGLT-2I) are newer classes of anti-diabetic agents that lower HbA1c moderately and decrease body weight and systolic blood pressure (SBP) modestly. Combination therapy with GLP-1RA plus SGLT-2I have shown a greater reduction in HbA1c, body weight, and SBP compared to either agent alone without any significant increase in hypoglycemia or other side effects. Since several agents from each class of these drugs have shown an improvement in cardiovascular (CV) and renal outcomes in their respective cardiovascular outcome trials (CVOT), combination therapy is theoretically expected to have additional CV and renal benefits. In this comprehensive opinion review, we found HbA1c lowering with GLP-1RA plus SGLT-2I to be less than additive compared to the sum of HbA1c lowering with either agent alone, although body weight lowering was nearly additive and the SBP lowering was more than additive. Our additional meta-analysis of CV outcomes with GLP-1RA plus SGLT-2I combination therapy from the pooled data of five CVOT found a similar reduction in three-point major adverse cardiovascular events compared to GLP-1RA or SGLT-2I alone, against placebo. Interestingly, a greater benefit in reduction of heart failure hospitalization with GLP-1RA plus SGLT-2I combination therapy was noted in the pooled meta-analysis of two randomized controlled trials. Future adequately powered trials can confirm whether additional CV or renal benefit is truly exerted by GLP-1RA plus SGLT-2I combination therapy.

12.
Clin Kidney J ; 15(9): 1657-1665, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1853009

ABSTRACT

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are highly effective in improving glycaemic control either as monotherapy or in combination with other hypoglycaemic drugs, and have low incidence of side effects, such as hypoglycaemia, nausea and weight gain, thus increasing patients' adherence to therapy. Methods: In this review we report the most recent studies demonstrating the beneficial effects of GLP-1RAs on renal outcomes, and also discuss the direct and indirect mechanisms through which they confer kidney protection. Finally, we discuss the metabolic and anti-inflammatory effects of GLP-1RAs in diabetic patients with COVID-19 disease. Results: GLP-1RAs have a nephroprotective action, which is expressed through both indirect (improvement of blood pressure and glycaemic control, weight loss) and direct (restoration of normal intrarenal haemodynamics, prevention of ischaemic and oxidative damage) effects. They have shown also metabolic and anti-inflammation beneficial effects in patients with COVID-19 disease. Conclusions: GLP-1RAs prevent albuminuria and slow the decline of renal function towards end stage renal disease in patients with diabetic kidney disease. They might be an opportunity to break the typical inflammation processes of COVID-19 disease.

13.
Biomedicines ; 10(4)2022 Mar 31.
Article in English | MEDLINE | ID: covidwho-1809692

ABSTRACT

Various important transcription factors in the pancreas are involved in the process of pancreas development, the differentiation of endocrine progenitor cells into mature insulin-producing pancreatic ß-cells and the preservation of mature ß-cell function. However, when ß-cells are continuously exposed to a high glucose concentration for a long period of time, the expression levels of several insulin gene transcription factors are substantially suppressed, which finally leads to pancreatic ß-cell failure found in type 2 diabetes mellitus. Here we show the possible underlying pathway for ß-cell failure. It is likely that reduced expression levels of MafA and PDX-1 and/or incretin receptor in ß-cells are closely associated with ß-cell failure in type 2 diabetes mellitus. Additionally, since incretin receptor expression is reduced in the advanced stage of diabetes mellitus, incretin-based medicines show more favorable effects against ß-cell failure, especially in the early stage of diabetes mellitus compared to the advanced stage. On the other hand, many subjects have recently suffered from life-threatening coronavirus infection, and coronavirus infection has brought about a new and persistent pandemic. Additionally, the spread of coronavirus infection has led to various limitations on the activities of daily life and has restricted economic development worldwide. It has been reported recently that SARS-CoV-2 directly infects ß-cells through neuropilin-1, leading to apoptotic ß-cell death and a reduction in insulin secretion. In this review article, we feature a possible molecular mechanism for pancreatic ß-cell failure, which is often observed in type 2 diabetes mellitus. Finally, we are hopeful that coronavirus infection will decline and normal daily life will soon resume all over the world.

14.
Cells ; 11(7)2022 04 01.
Article in English | MEDLINE | ID: covidwho-1779985

ABSTRACT

BACKGROUND & AIMS: ACE2, a carboxypeptidase that generates Ang-(1-7) from Ang II, is highly expressed in the lung, small intestine and colon. GPBAR1, is a G protein bile acid receptor that promotes the release of the insulinotropic factor glucagon-like peptide (GLP)-1 and attenuates intestinal inflammation. METHODS: We investigated the expression of ACE2, GLP-1 and GPBAR1 in two cohorts of Crohn's disease (CD) patients and three mouse models of colitis and Gpbar1-/- mice. Activation of GPBAR1 in these models and in vitro was achieved by BAR501, a selective GPBAR1 agonist. RESULTS: In IBD patients, ACE2 mRNA expression was regulated in a site-specific manner in response to inflammation. While expression of ileal ACE2 mRNA was reduced, the colon expression was induced. Colon expression of ACE2 mRNA in IBD correlated with expression of TNF-α and GPBAR1. A positive correlation occurred between GCG and GPBAR1 in human samples and animal models of colitis. In these models, ACE2 mRNA expression was further upregulated by GPABR1 agonism and reversed by exendin-3, a GLP-1 receptor antagonist. In in vitro studies, liraglutide, a GLP-1 analogue, increased the expression of ACE2 in colon epithelial cells/macrophages co-cultures. CONCLUSIONS: ACE2 mRNA expression in the colon of IBD patients and rodent models of colitis is regulated in a TNF-α- and GLP-1-dependent manner. We have identified a GPBAR1/GLP-1 mechanism as a positive modulator of ACE2.


Subject(s)
Angiotensin-Converting Enzyme 2 , Colitis , Crohn Disease , Glucagon-Like Peptide 1 , Receptors, G-Protein-Coupled , Angiotensin-Converting Enzyme 2/metabolism , Animals , Bile Acids and Salts , Glucagon-Like Peptide 1/metabolism , Humans , Inflammation , Mice , RNA, Messenger/genetics , Receptors, G-Protein-Coupled/metabolism , Tumor Necrosis Factor-alpha
15.
Cardiovasc Diabetol ; 21(1): 50, 2022 04 08.
Article in English | MEDLINE | ID: covidwho-1779649

ABSTRACT

The 7th Cardiovascular Outcome Trial (CVOT) Summit on Cardiovascular, Renal, and Glycemic Outcomes, was held virtually on November 18-19, 2021. Pursuing the tradition of the previous summits, this reference congress served as a platform for in-depth discussion and exchange on recently completed CVOTs. This year's focus was placed on the outcomes of EMPEROR-Preserved, FIGARO-DKD, AMPLITUDE-O, SURPASS 1-5, and STEP 1-5. Trial implications for diabetes and obesity management and the impact on new treatment algorithms were highlighted for endocrinologists, diabetologists, cardiologists, nephrologists, and general practitioners. Discussions evolved from outcome trials using SGLT2 inhibitors as therapy for heart failure, to CVOTs with nonsteroidal mineralocorticoid receptor antagonists and GLP-1 receptor agonists. Furthermore, trials for glycemic and overweight/obesity management, challenges in diabetes management in COVID-19, and novel guidelines and treatment strategies were discussed.Trial registration The 8th Cardiovascular Outcome Trial Summit will be held virtually on November 10-11, 2022 ( http://www.cvot.org ).


Subject(s)
Cardiovascular Diseases , Diabetes Mellitus , Blood Glucose , COVID-19 , Cardiovascular Diseases/drug therapy , Clinical Trials as Topic , Diabetes Mellitus/drug therapy , Humans , Hypoglycemic Agents/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Treatment Outcome
16.
Diabetes Ther ; 13(3): 453-464, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1682096

ABSTRACT

INTRODUCTION: The glucagon-like peptide-1 agonist (GLP1-RA) liraglutide is currently approved for the treatment of both obesity and type 2 diabetes (T2DM). We investigated whether the effect of this agent on cardiometabolic parameters in subjects with T2DM varied in relation to the concomitant presence of obesity. METHODS: One hundred thirty-five subjects (78 men and 57 women; age: 62 ± 10 years) naïve to incretin-based therapies were treated with low-dose liraglutide (1.2 mg/day) as an add-on to metformin for 18 months. Patients were divided into two subgroups based on their body-mass index (BMI): (a) obese (BMI ≥ 30) and (b) non-obese (BMI < 30). Clinical and laboratory analyses were assessed at baseline and every 6 months. RESULTS: During follow-up, significant improvements were seen in both groups in fasting glycemia, glycated hemoglobin, waist circumference, and carotid intima-media thickness (cIMT), while body weight, BMI, total cholesterol, and low-density lipoprotein cholesterol decreased significantly in obese subjects only. Correlation analysis revealed that changes in subclinical atherosclerosis (assessed by cIMT) were associated with changes in triglycerides (r = 0.488, p < 0.0001) in the obese group only. CONCLUSION: Liraglutide had beneficial actions on glycemic parameters and cardiometabolic risk factors in both non-obese and obese patients with T2DM, with a greater efficacy in the latter. These findings reinforce the benefits of liraglutide for the cardiometabolic outcomes of obese patients with T2DM in the real-world setting. This has critical importance during the current pandemic, since patients with diabetes and obesity are exposed globally to the most severe forms of COVID-19, related complications, and death. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01715428.

17.
Medicina (Kaunas) ; 58(1)2022 Jan 11.
Article in English | MEDLINE | ID: covidwho-1636386

ABSTRACT

The current management of Type 2 Diabetes Mellitus (T2DM) includes incretin-based treatments able to enhance insulin secretion and peripheral insulin sensitivity as well as improve body mass, inflammation, plasma lipids, blood pressure, and cardiovascular outcomes. Dietary Free Fatty Acids (FFA) regulate metabolic and anti-inflammatory processes through their action on incretins. Selective synthetic ligands for FFA1-4 receptors have been developed as potential treatments for T2DM. To comprehensively review the available evidence for the potential role of FFA receptor agonists in the treatment of T2DM, we performed an electronic database search assessing the association between FFAs, T2DM, inflammation, and incretins. Evidence indicates that FFA1-4 agonism increases insulin sensitivity, induces body mass loss, reduces inflammation, and has beneficial metabolic effects. There is a strong inter-relationship between FFAs and incretins. FFA receptor agonism represents a potential target for the treatment of T2DM and may provide an avenue for the management of cardiometabolic risk in susceptible individuals. Further research promises to shed more light on this emerging topic.


Subject(s)
Diabetes Mellitus, Type 2 , Insulin Resistance , Diabetes Mellitus, Type 2/drug therapy , Fatty Acids, Nonesterified , Humans
18.
Medicina Clínica (English Edition) ; 2022.
Article in English | ScienceDirect | ID: covidwho-1619674

ABSTRACT

Background and objectives One of the potential negative effects of a lockdown are changes in dietary and lifestyle patterns, which can lead to weight gain. Our objective was to assess the changes on dietary habits and eating patterns in a lockdown situation and their impact on weight. We aimed to determine whether the treatment with GLP1 analogues (aGLP1) could impact on these parameters. Material and methods 100 overweight/obese patients were consecutively recruited for a review at the end of the lockdown. A structured interview was designed to see changes in dietary habits, routines and exercise. Results 52% patients gained weight during lockdown. The percentage of subjects with an active history of depression or anxiety was higher among the group of patients who gained weight. The percentage of patients who worsened their hyperphagia was higher in those who gained weight (71.2% vs 10.6%;P < .0001);similar results were observed with binge eating (92% vs 10.6%;P < .0001) and cravings, both sweet and salty (69.2% vs 21.3% and 69.2% vs 14.9%;P < .0001 and P < .0001 respectively). Of the 48 patients who did not gain weight, 30 were under aGLP1 treatment (61.7%). The worsening of abnormal eating patterns was lower among patients treated with aGLP-1. Conclusions A lockdown is a vulnerable period to gain weight, especially in those patients with a psychopathological history. aGLP1 manage to control emotional eating, making them a valuable therapeutic option. Resumen Antecedentes y objetivos Uno de los potenciales efectos negativos de un confinamiento son los cambios en los patrones dietéticos y de estilo de vida, que pueden conllevar a una ganancia de peso. El objetivo fue ver los cambios sobre los hábitos higiénico-dietéticos y de patrones de ingesta en una situación de confinamiento y el impacto sobre el peso. Asimismo, ver si el estar bajo tratamiento con análogos de GLP1 (aGLP1) modificó estos parámetros. Material y métodos Se reclutaron de forma consecutiva 100 pacientes con sobrepeso/obesidad que acudieron a revisión al finalizar el confinamiento. Se diseñó una entrevista estructurada para ver los cambios en los hábitos dietéticos, rutinas y ejercicio. Resultados El 52% pacientes ganaron peso durante el confinamiento. El porcentaje de sujetos con historia activa de depresión o ansiedad fue superior entre el grupo de pacientes que ganó peso. El porcentaje de pacientes que empeoraron su hiperfagia ansiosa fue superior en aquellos que ganaron peso (71,2% vs 10,6%;P < ,0001);lo mismo ocurrió con los atracones (92% vs 10,6%;P < ,0001) y los cravings, dulces y salados (69,2% vs 21,3% y 69,2% vs 14,9%;P < ,0001 y P < ,0001 respectivamente). De los 48 pacientes que no ganaron peso, 30 estaban bajo tratamiento con aGLP1 (61,7%). El empeoramiento de los patrones anómalos de ingesta fue inferior entre los pacientes bajo tratamiento con aGLP-1. Conclusiones Un confinamiento es un período vulnerable para ganar peso, especialmente en aquellos pacientes con antecedentes psicopatológicos. Los aGLP1 consiguen controlar la ingesta emocional convirtiéndolos en una opción terapéutica valiosa.

19.
Rev Endocr Metab Disord ; 23(3): 521-539, 2022 06.
Article in English | MEDLINE | ID: covidwho-1611457

ABSTRACT

Semaglutide, a glucagon like peptide-1 (GLP-1) receptor agonist, is available as monotherapy in both subcutaneous as well as oral dosage form (first approved oral GLP-1 receptor agonist). It has been approved as a second line treatment option for better glycaemic control in type 2 diabetes and currently under scrutiny for anti-obesity purpose. Semaglutide has been proved to be safe in adults and elderly patients with renal or hepatic disorders demanding no dose modification. Cardiovascular (CV) outcome trials established that it can reduce various CV risk factors in patients with established CV disorders. Semaglutide is well tolerated with no risk of hypoglycaemia in monotherapy but suffers from gastrointestinal adverse effects. A large population affected with COVID-19 infection were diabetic; therefore use of semaglutide in diabetes as well as CV patients would be very much supportive in maintaining health care system during this pandemic situation. Hence, this peptidic drug can be truly considered as a quintessential of GLP-1 agonists for management of type 2 diabetes.


Subject(s)
COVID-19 Drug Treatment , Diabetes Mellitus, Type 2 , Aged , Diabetes Mellitus, Type 2/drug therapy , Glucagon-Like Peptide 1 , Glucagon-Like Peptide-1 Receptor/agonists , Glucagon-Like Peptide-1 Receptor/therapeutic use , Glucagon-Like Peptides , Humans , Hypoglycemic Agents/therapeutic use
20.
J Am Soc Nephrol ; 2021 Feb 18.
Article in English | MEDLINE | ID: covidwho-1496680

ABSTRACT

Obesity is a leading public health problem that currently affects over 650 million individuals worldwide. Although interest in the adverse effects of obesity has grown exponentially in recent years, less attention has been given to studying its management in individuals with CKD. This relatively unexplored area should be considered a high priority because of the rapid growth and high prevalence of obesity in the CKD population, its broad impact on health and outcomes, and its modifiable nature. This article begins to lay the groundwork in this field by providing a comprehensive overview that critically evaluates the available evidence related to obesity and kidney disease, identifies important gaps in our knowledge base, and integrates recent insights in the pathophysiology of obesity to help provide a way forward in establishing guidelines as a basis for managing obesity in CKD. Finally, the article includes a kidney-centric algorithm for management of obesity that can be used in clinical practice.

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