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1.
Endocr Pract ; 27(4): 334-341, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33685669

RESUMEN

OBJECTIVE: Adults with type 2 diabetes (T2D) face increased risk of many long-term adverse outcomes. While managing patients with T2D, clinicians are challenged to stay informed regarding all new therapies and must consider potential risks and benefits resultant to their use. Metformin (MET) is typically prescribed as first-line therapy, but a second line is often needed, given MET can be insufficient for maintaining long-term glycemic control. Our objective was to develop a predictive decision-making tool to help clinicians use an outcome-based approach to select second-line therapies for patients when MET monotherapy is insufficient for glycemic control. METHODS: Electronic health records of 19 277 adults with T2D on MET monotherapy and ≥3 months of either GLP-1RA, DPP-4i, Insulin, SGLT-2i, SFU, or TZD therapy were reviewed at Cleveland Clinic from patient visits occurring between 2005 and 2019. Separate models were developed to predict likelihood of each main outcome measure (stroke, myocardial infarction, worsening hypertension, renal failure, and death). Discrimination and calibration were assessed with bootstrapping. RESULTS: The median follow-up time for those without an event was 3.6 years (interquartile range 1.9, 6.3). Model discrimination ability was evaluated by concordance indices (goodness of fit metric with values ranging between 0 and 1: 1 indicates perfect discrimination ability; 0.5 reflects same discrimination ability as chance) demonstrating strong discrimination ability, with concordance index values for outcomes as follows: myocardial infarction (0.786), stroke (0.805), worsening hypertension (0.855), renal failure (0.808), and death (0.827). CONCLUSION: A decision-making tool has been developed that may afford clinicians a more objective and individualized approach to choosing a second-line therapy to control glycemia for persons with T2D.


Asunto(s)
Diabetes Mellitus Tipo 2 , Inhibidores de la Dipeptidil-Peptidasa IV , Metformina , Adulto , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Quimioterapia Combinada , Humanos , Hipoglucemiantes/efectos adversos , Metformina/uso terapéutico
2.
Curr Cardiol Rep ; 23(4): 24, 2021 03 02.
Artículo en Inglés | MEDLINE | ID: mdl-33655453

RESUMEN

PURPOSE OF THE REVIEW: The purpose of this review is to examine recent evidence supporting CV safety profile and improvement of CV outcomes of some of the newer classes of diabetic medications. RECENT FINDINGS: Diabetes mellitus (DM) is associated with increased risk of cardiovascular disease (CVD). Thus, CVD management is critical in diabetic patients. Since 2008, the US Food and Drug Administration (FDA) has mandated that all newer diabetic medications should establish cardiovascular safety before it is approved for use. Diabetic medications that also lower CV risk would be a significant advancement as shown in recent studies. There are 3 new class of diabetic medications: Dipeptidyl peptidase-4 inhibitors (DPP-4), glucagon-like peptide receptor agonists (GLP-1 RA), and sodium-glucose cotransporter type 2 (SGLT 2) inhibitors which have established both CV safety and improvement in CV outcomes with some drugs. In patients with type 2 diabetes and established atherosclerotic cardiovascular disease, multiple atherosclerotic cardiovascular disease risk factors, or diabetic kidney disease, a sodium-glucose cotransporter 2 inhibitor, or a glucagon-like peptide 1 receptor agonist with demonstrated cardiovascular benefit is recommended to reduce the risk of major adverse cardiovascular events.


Asunto(s)
Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Inhibidores de la Dipeptidil-Peptidasa IV , Preparaciones Farmacéuticas , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Glucosa , Humanos , Hipoglucemiantes/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico
3.
Diabetes Metab J ; 45(2): 251-259, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33752274

RESUMEN

BACKGROUND: Dipeptidyl peptidase-4 inhibitor (DPP-4i) and renin-angiotensin system (RAS) blockade are reported to affect the clinical course of coronavirus disease 2019 (COVID-19) in patients with diabetes mellitus (DM). METHODS: As of May 2020, analysis was conducted on all subjects who could confirm their history of claims related to COVID-19 in the National Health Insurance Review and Assessment Service (HIRA) database in Korea. Using this dataset, we compared the short-term prognosis of COVID-19 infection according to the use of DPP-4i and RAS blockade. Additionally, we validated the results using the National Health Insurance Service (NHIS) of Korea dataset. RESULTS: Totally, data of 67,850 subjects were accessible in the HIRA dataset. Of these, 5,080 were confirmed COVID-19. Among these, 832 subjects with DM were selected for analysis in this study. Among the subjects, 263 (31.6%) and 327 (39.3%) were DPP4i and RAS blockade users, respectively. Thirty-four subjects (4.09%) received intensive care or died. The adjusted odds ratio for severe treatment among DPP-4i users was 0.362 (95% confidence interval [CI], 0.135 to 0.971), and that for RAS blockade users was 0.599 (95% CI, 0.251 to 1.431). These findings were consistent with the analysis based on the NHIS data using 704 final subjects. The adjusted odds ratio for severe treatment among DPP-4i users was 0.303 (95% CI, 0.135 to 0.682), and that for RAS blockade users was 0.811 (95% CI, 0.391 to 1.682). CONCLUSION: This study suggests that DPP-4i is significantly associated with a better clinical outcome of patients with COVID-19.


Asunto(s)
Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Diabetes Mellitus/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , /mortalidad , Bases de Datos Factuales , Diabetes Mellitus/mortalidad , Diabetes Mellitus/virología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Programas Nacionales de Salud/estadística & datos numéricos , Sistema Renina-Angiotensina/efectos de los fármacos , República de Corea , Resultado del Tratamiento
4.
Nutr Metab Cardiovasc Dis ; 31(4): 1257-1266, 2021 04 09.
Artículo en Inglés | MEDLINE | ID: mdl-33618922

RESUMEN

BACKGROUND AND AIMS: Dipeptidyl-peptidase inhibitors might be useful in type 2 diabetes prevention. ACCES (ACute and Chronic Effects of Saxagliptin) was a randomized, placebo-controlled, double-blind, controlled phase 2, pilot study aiming to examine in obese patients with impaired glucose tolerance (IGT) the acute effects and the effects after 12 weeks of treatment by saxagliptin on glucose levels at fasting and postprandially after a standard breakfast, and on glucose tolerance. METHODS AND RESULTS: We included 24 obese patients with IGT. Patients were randomized to receive saxagliptin 5 mg or placebo in the morning. The treatment was taken on Visit 1 before breakfast, then continued for 12 weeks. Biochemical measurements were performed before, one, two and three hours after a standard breakfast including 75 g of carbohydrates, during Visit 1 and Visit 2 (12 weeks). Glucose variability (GV) was evaluated at Visit 1 from 24-h continuous glucose monitoring including the breakfast. A second OGTT was performed at Visit 3 (3-5 days after Visit 2). Compared with placebo-treated patients, saxagliptin-treated patients had lower 1 h and 2 h post-meal plasma glucose levels at Visit 1 and similar changes at Visit 2 (p < 0.01 to p < 0.004), with lower GV indexes after breakfast at Visit 1. At Visit 3, all patients but one in saxagliptin group and only 4 patients in placebo group turned to normal glucose tolerance. Lower glucose response to breakfast at Visit 1 was predictive of recovery of glucose tolerance. CONCLUSION: Saxagliptin has metabolically beneficial effects in glucose-intolerant obese patients by significantly lowering postprandial blood glucose levels. CLINICAL TRIAL REGISTRATION NUMBER: NCT01521312: https://clinicaltrials.gov/ct2/show/NCT01521312.


Asunto(s)
Adamantano/análogos & derivados , Glucemia/efectos de los fármacos , Diabetes Mellitus Tipo 2/prevención & control , Dipéptidos/uso terapéutico , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Intolerancia a la Glucosa/tratamiento farmacológico , Obesidad/complicaciones , Periodo Posprandial , Adamantano/efectos adversos , Adamantano/uso terapéutico , Adulto , Biomarcadores/sangre , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/etiología , Dipéptidos/efectos adversos , Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Método Doble Ciego , Femenino , Francia , Intolerancia a la Glucosa/sangre , Intolerancia a la Glucosa/diagnóstico , Intolerancia a la Glucosa/etiología , Humanos , Masculino , Persona de Mediana Edad , Obesidad/diagnóstico , Proyectos Piloto , Factores de Tiempo , Resultado del Tratamiento
5.
JAMA Netw Open ; 4(2): e2035792, 2021 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-33523188

RESUMEN

Importance: Glucagonlike peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter-2 inhibitors (SGLT2i), and dipeptidyl peptidase-4 inhibitors (DPP-4i) are associated with low rates of hypoglycemia, and postmarketing trials of GLP-1RA and SGLT2i demonstrated that these medications improved cardiovascular and kidney outcomes. Objective: To compare trends in initiation of treatment with GLP-1RA, SGLT2i, and DPP-4i by older adults with type 2 diabetes insured by Medicare Advantage vs commercial health plans. Design, Setting, and Participants: This retrospective cohort study used administrative claims data from a deidentified database of commercially insured and Medicare Advantage beneficiaries. Adults aged 58 to 66 years with type 2 diabetes who filled any medication prescription to lower glucose levels from January 1, 2016, to December 31, 2019, were compared between groups. Exposure: Enrollment in a Medicare Advantage or commercial health insurance plan. Main Outcomes and Measures: The odds of initiating GLP-1RA, SGLT2i, and DPP-4i treatment were examined for Medicare Advantage vs commercial insurance beneficiaries using 3 separate logistic regression models adjusted for year and demographic and clinical factors. These models were used to calculate adjusted annual rates of medication initiation by health plan. Results: A total of 382 574 adults with pharmacologically treated type 2 diabetes (52.9% men; mean [SD] age, 62.4 [2.7] years) were identified, including 172 180 Medicare Advantage and 210 394 commercial beneficiaries. From 2016 to 2019, adjusted rates of initiation of GLP-1RA, SGLT2i, and DPP-4i treatment increased among all beneficiaries, from 2.14% to 20.02% for GLP-1RA among commercial insurance beneficiaries and from 1.50% to 11.44% among Medicare Advantage beneficiaries; from 2.74% to 18.15% for SGLT2i among commercial insurance beneficiaries and from 1.57% to 8.51% among Medicare Advantage beneficiaries; and from 3.30% to 11.71% for DPP-4i among commercial insurance beneficiaries and from 2.44% to 7.68% among Medicare Advantage beneficiaries. Initiation rates for all 3 drug classes were consistently lower among Medicare Advantage than among commercial insurance beneficiaries. Within each calendar year, the odds of initiating GLP-1RA treatment ranged from 0.28 (95% CI, 0.26-0.29) to 0.70 (95% CI, 0.65-0.75) for Medicare Advantage and commercial insurance beneficiaries, respectively; SGLT2i, from 0.21 (95% CI, 0.20-0.22) to 0.57 (95% CI, 0.53-0.61), respectively; and DPP-4i, from 0.37 (95% CI, 0.34-0.39) to 0.73 (95% CI, 0.69-0.78), respectively (P < .001 for all). The odds of starting GLP-1RA and SGLT2i increased with income; for an income of $200 000 and higher vs less than $40 000, the odds ratio for GLP-1RA was 1.23 (95% CI, 1.15-1.32) and for SGLT2i was 1.16 (95% CI, 1.09-1.24). Conclusions and Relevance: These findings suggest that Medicare Advantage beneficiaries may be less likely than commercially insured beneficiaries to be treated with newer medications to lower glucose levels, with greater disparities among lower-income patients. Better understanding of nonclinical factors contributing to treatment decisions and efforts to promote greater equity in diabetes management appear to be needed.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Hipoglucemiantes/uso terapéutico , Incretinas/uso terapéutico , Seguro de Salud , Medicare Part C , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Anciano , Femenino , Receptor del Péptido 1 Similar al Glucagón/agonistas , Disparidades en Atención de Salud , Humanos , Renta/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Estados Unidos
7.
J Assoc Physicians India ; 69(2): 25-29, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33527807

RESUMEN

Achieving adequate glycemic control in type 2 diabetes mellitus (T2DM) remains a difficult but achievable goal. Oral agents (OADs) are important option for management of T2DM. Most T2DM patients require more than one medication for adequate glycemic control. Metformin based combination therapy is recommended when monotherapy is insufficient. Evogliptin is a recently developed dipeptidyl peptidase-4 (DPP-4) inhibitor, which can to be combined with metformin for treating T2DM. Combination therapy of Evogliptin and Metformin lowers blood glucose via augmentation of insulin secretion, suppression of glucagon secretion, and insulin sensitization. Co-administration of Evogliptin and Metformin showed no clinically relevant pharmacokinetic differences compared to the administration of each drug alone. Combination therapy of Evogliptin and Metformin also provides significantly better glycemic control compared to the respective monotherapies. Efficacy and safety of Evogliptin and Metformin had been demonstrated in several multicentre randomized clinical trials conducted in various countries like South Korea, Russia and India. Consequently, fixed dose combination (FDC) of Evogliptin and Metformin is approved in South Korea and India. Complexity of the treatment regimen and polypharmacy are well-known factors of poor medication adherence and FDCs have the potential to improve adherence by reducing the pill burden. Adoption of this combination therapy in clinical practice for management of T2DMs will provide a greater degree of HbA1c reduction than that observed with the use of either drug as monotherapy, and is unlikely to cause significant hypoglycemia. Combination therapy of Evogliptin and Metformin is a promising strategy in the treatment of T2DM.


Asunto(s)
Diabetes Mellitus Tipo 2 , Inhibidores de la Dipeptidil-Peptidasa IV , Metformina , Glucemia , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Quimioterapia Combinada , Hemoglobina A Glucada , Humanos , Hipoglucemiantes/uso terapéutico , India , Metformina/uso terapéutico , Piperazinas , Federación de Rusia
8.
Arch Immunol Ther Exp (Warsz) ; 69(1): 1, 2021 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-33527308

RESUMEN

A novel coronavirus disease, COVID-19, has emerged as a global public health issue. Clinical course of disease significantly correlates with the occurrence of some comorbidities, among them type 2 diabetes. According to recent structural studies the dipeptidyl peptidase 4, a key molecule in the pathophysiology of diabetes, may influence the course of COVID-19. Since DPP4 inhibitors, gliptins, are widely used in diabetes patients, the exact role of DPP4 modulation in SARS-CoV-2 infection, at least in that group, urgently needs to be clarified. In this short review, we discuss this issue with more detail.


Asunto(s)
Antivirales/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Dipeptidil Peptidasa 4/metabolismo , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , /efectos de los fármacos , Antivirales/farmacología , /enzimología , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Humanos
9.
Life Sci ; 274: 119069, 2021 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-33460667

RESUMEN

As a complicated metabolic disorder, type 2 diabetes mellitus (T2DM) is becoming a major health concern worldwide. Drugs including acarbose, saxagliptin and vildagliptin are applied, but their efficacy is still required to be compared. Therefore, the study aimed to evaluate the efficacy and safety of acarbose, saxagliptin and vildagliptin in the treatment of T2DM. Ninety patients diagnosed with T2DM were treated with acarbose, saxagliptin and vildagliptin, respectively (30 patients for each drug). All patients were examined at 0, 4 and 12 weeks after treatment with vital signs recorded. Fasting blood glucose and blood biochemical indices were analyzed. In addition, fecal samples were taken for microbial macrogenome sequencing and safety evaluation within 12 weeks after treatment. Blood glucose level decreased at 4 and 12 weeks after treatment, and the total cholesterol (TC) and high-density lipoprotein (HDL) levels at 12 weeks were different. Genus abundance of intestinal flora was altered at different time points. Acarbose increased Butyricimonas level first and then decreased it during drug treatment. Saxagliptin increased Megamonas and decreased Turicibacter genus level gradually. Pseudomonas, Klebsiella, Blautia, Faecalibacterium and Roseburia levels fluctuated after Vildagliptin treatment, which increased fasting C-peptide level greater than the other two drugs. Saxagliptin showed higher adverse reactions than acarbose and vildagliptin. Collectively, acarbose, vildagliptin, and saxagliptin can effectively reduce the HbA1c level and affect the intestinal flora distribution in T2DM patients, and the adverse reactions of acarbose and vildagliptin are less than saxagliptin, providing alternative strategies for the treatment of T2DM.


Asunto(s)
Acarbosa/uso terapéutico , Adamantano/análogos & derivados , Biomarcadores/análisis , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Dipéptidos/uso terapéutico , Hipoglucemiantes/uso terapéutico , Vildagliptina/uso terapéutico , Adamantano/uso terapéutico , Glucemia/análisis , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Femenino , Estudios de Seguimiento , Hemoglobina A Glucada/análisis , Inhibidores de Glicósido Hidrolasas/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Pronóstico
10.
N Engl J Med ; 384(1): 11-19, 2021 01 07.
Artículo en Inglés | MEDLINE | ID: mdl-33406328

RESUMEN

BACKGROUND: Dipeptidyl peptidase 4 (DPP-4; also known as CD26), a transmembrane receptor expressed on T cells, has a costimulatory function in activating T cells. In a mouse model, down-regulation of CD26 prevented graft-versus-host disease (GVHD) but preserved graft-versus-tumor effects. Whether inhibition of DPP-4 with sitagliptin may prevent acute GVHD after allogeneic stem-cell transplantation is not known. METHODS: We conducted a two-stage, phase 2 clinical trial to test whether sitagliptin plus tacrolimus and sirolimus would reduce the incidence of grade II to IV acute GVHD from 30% to no more than 15% by day 100. Patients received myeloablative conditioning followed by mobilized peripheral-blood stem-cell transplants. Sitagliptin was given orally at a dose of 600 mg every 12 hours starting the day before transplantation until day 14 after transplantation. RESULTS: A total of 36 patients who could be evaluated, with a median age of 46 years (range, 20 to 59), received transplants from matched related or unrelated donors. Acute GVHD occurred in 2 of 36 patients by day 100; the incidence of grade II to IV GVHD was 5% (95% confidence interval [CI], 1 to 16), and the incidence of grade III or IV GVHD was 3% (95% CI, 0 to 12). Nonrelapse mortality was zero at 1 year. The 1-year cumulative incidences of relapse and chronic GVHD were 26% (95% CI, 13 to 41) and 37% (95% CI, 22 to 53), respectively. GVHD-free, relapse-free survival was 46% (95% CI, 29 to 62) at 1 year. Toxic effects were similar to those seen in patients undergoing allogeneic stem-cell transplantation. CONCLUSIONS: In this nonrandomized trial, sitagliptin in combination with tacrolimus and sirolimus resulted in a low incidence of grade II to IV acute GVHD by day 100 after myeloablative allogeneic hematopoietic stem-cell transplantation. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT02683525.).


Asunto(s)
Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Fosfato de Sitagliptina/uso terapéutico , Adulto , Inhibidores de la Dipeptidil-Peptidasa IV/administración & dosificación , Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Quimioterapia Combinada , Femenino , Humanos , Inmunosupresores/uso terapéutico , Leucemia Mieloide/terapia , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Recurrencia , Sirolimus/uso terapéutico , Fosfato de Sitagliptina/administración & dosificación , Fosfato de Sitagliptina/efectos adversos , Análisis de Supervivencia , Tacrolimus/uso terapéutico , Trasplante Homólogo , Adulto Joven
11.
Rev Med Liege ; 76(1): 7-12, 2021 Jan.
Artículo en Francés | MEDLINE | ID: mdl-33443322

RESUMEN

Sulphonylureas (SU) for a long time occupied an essential role in the management of type 2 diabetes (T2D). However, the launch of new oral antidiabetic drugs (OAD), firstly DPP-4 inhibitors (gliptins) and more recently SGLT2 inhibitors (gliflozins), has markedly changed the scene. Indeed, in contrast to SU, these new OAD (of course more expensive) offer the advantage of a very low risk of hypoglycaemia and a beneficial impact on bodyweight. Furthermore, gliflozins have proven to exert a cardiovascular and renal protection in patients at high risk. SU keep a place in the management of T2D, yet it becomes more and more limited. For sure, SU should be avoided among elderly frailty people and patients at high risk of hypoglycaemia.


Asunto(s)
Diabetes Mellitus Tipo 2 , Inhibidores de la Dipeptidil-Peptidasa IV , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Anciano , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Humanos , Hipoglucemiantes/efectos adversos , Compuestos de Sulfonilurea
12.
Diabetes Res Clin Pract ; 172: 108580, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33316313

RESUMEN

AIMS: To assess the order of glucose-lowering medication (GLM) discontinuation following bariatric surgery among patients taking ≥2 GLMs. METHODS: Patients with diabetes mellitus taking ≥2 GLM classes who underwent bariatric surgery were identified using health claims data from the United States. The order of discontinuation was assessed in patients taking ≥2 GLM classes by comparing each GLM class to the other classes in aggregate. Descriptive statistics and Poisson regression were used to assess the order of discontinuation and changes in trends in the order of discontinuation. RESULTS: Overall, 12,244 of 26,651 patients with type 2 diabetes who underwent bariatric surgery were taking ≥2 GLM classes. When each GLM class was assessed separately, fewer than 50% of patients had metformin, sulfonylurea, thiazolidinedione, DPP-4 inhibitor, SGLT2 inhibitor, glucosidase inhibitor, or insulin discontinued first when compared to the other classes in aggregate. Between 2008 and 2014, thiazolidinediones were increasingly more likely to be the first GLM discontinued (p = 0.0432). Slightly more than 50% of patients whose GLM regimen included a sulfonylurea discontinued the sulfonylurea first despite clinical recommendations. CONCLUSIONS: From a population level, there was no consistent approach in the order of discontinuation of GLM classes in patients following bariatric surgery.


Asunto(s)
Cirugía Bariátrica/métodos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/cirugía , Hipoglucemiantes/uso terapéutico , Cumplimiento de la Medicación/estadística & datos numéricos , Privación de Tratamiento/estadística & datos numéricos , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Femenino , Humanos , Hipoglucemiantes/clasificación , Insulina/uso terapéutico , Masculino , Metformina/uso terapéutico , Persona de Mediana Edad , Estudios Retrospectivos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Compuestos de Sulfonilurea/uso terapéutico
13.
Diabetes Obes Metab ; 23(4): 910-915, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33319440

RESUMEN

AIM: To estimate the proportion of individuals with type 2 diabetes mellitus (T2DM) undergoing changes in glucose-lowering therapy in 2019 and 2020. METHOD: Individuals with T2DM who had at least one consultation in one of 940 general (including diabetologist) practices in Germany between January and July 2019 (N = 79 268) and between January and July 2020 (N = 85 046) were included. Therapy changes were defined as the prescription of new glucose-lowering drugs, with or without the discontinuation of previous treatments (therapy switch and add-on therapy, respectively). The number of T2DM patients with at least one medication regimen change was calculated for the periods 1 January to 14 March in 2019 and 2020, and for the periods 15 March to 31 July in 2019 and 2020. March 2020 corresponded to the beginning of the lockdown in Germany. RESULTS: Overall, there was a decrease in the number of patients with at least one medication regimen change in the period 15 March to 31 July 2019 compared with 15 March to 31 July 2020 (dipeptidyl peptidase-4 inhibitors: -15%; sodium-glucose co-transporter-2 inhibitors: -3%; glucagon-like peptide-1 receptor agonists: 0%; other oral glucose-lowering drugs: -6%; and insulin: -21%). CONCLUSIONS: The coronavirus disease-2019 (COVID-2019) pandemic had a strong impact on glucose-lowering drug use in T2DM patients in Germany. More research is warranted to further investigate the treatment and management of T2DM individuals during the COVID-19 era in Germany and elsewhere.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Sustitución de Medicamentos/tendencias , Quimioterapia Combinada/tendencias , Femenino , Alemania , Receptor del Péptido 1 Similar al Glucagón/agonistas , Humanos , Insulina/uso terapéutico , Masculino , Persona de Mediana Edad , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Adulto Joven
14.
Diabetes Metab Syndr ; 15(1): 159-167, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33352455

RESUMEN

BACKGROUND & AIMS: Several observational studies have recently reported the outcomes of non-insulin anti-diabetic agents (ADA) in patients with T2DM and coronavirus disease 2019 (COVID-19). We sought to review the literature to appraise the clinicians on these outcomes. METHODS: A literature search using the specific keywords was carried out in the database of PubMed, MedRxiv and Google Scholar up till December 11, 2020 applying Boolean method. Full text of all the relevant articles that reported the outcomes of ADA in patients with T2DM and COVID-19 were retrieved. Subsequently, an appraisal of literature report was narratively presented. RESULTS: Available studies that reported the outcomes of ADA are either case series or retrospective cohorts or prospective observational studies, in absence of the randomized controlled trials (RCTs). Results from these observational studies suggest that amongst all the non-insulin ADA, metformin users prior to the hospitalization had improved outcomes compared to the non-users. Data for dipeptidyl-peptidase-4 inhibitors (DPP-4i) are encouraging although inconsistent. No documentation of any harm or benefit has been observed for sulfonylureas (SUs), sodium glucose co-transporter-2 inhibitors (SGLT-2i) and glucagon-like peptide receptor agonists (GLP-1RAs). No data is yet available for pioglitazone. CONCLUSION: Metformin and DPP-4i should be continued in patients with T2DM until hospitalization or unless contraindicated. No evidence of harm suggests that SUs, SGLT-2i or GLP-1RAs may not be stopped unless very sick, hospitalized or contraindicated. The results from RCTs are needed to claim any meaningful benefit with either metformin or DPP-4i in patients with T2DM and COVID-19.


Asunto(s)
/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Hipoglucemiantes/uso terapéutico , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Humanos , Hipoglucemiantes/farmacología , Metformina/farmacología , Metformina/uso terapéutico , Estudios Prospectivos , Estudios Retrospectivos , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico
15.
Ann Pharmacother ; 55(1): 65-79, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32571083

RESUMEN

OBJECTIVE: To evaluate glucagon-like peptide 1 receptor agonists (GLP-1 RAs), dipeptidyl-peptidase IV (DPP-4) inhibitors, and sodium-glucose cotransporter 2 (SGLT) inhibitors to treat nondiabetic and type 2 diabetes mellitus (T2DM) nonalcoholic fatty liver disease (NAFLD) as it relates to improvement in hepatosteatosis (HS) or steatohepatitis (SH). DATA SOURCES: MEDLINE and CINAHL were searched from inception through May 1, 2020. Search terms included nonalcoholic steatohepatitis, nonalcoholic fatty liver disease, fatty liver, dipeptidyl-peptidase IV inhibitors, glucagon-like peptide-1 receptor agonists, and sodium-glucose transporter 2 inhibitors. STUDY SELECTION AND DATA EXTRACTION: Full-text observational and randomized controlled studies in English were included. Patients diagnosed with NAFLD, treated with GLP-1 RAs, DPP-4 inhibitors, and SGLT2 inhibitors, with measures to evaluate HS or SH were evaluated. DATA SYNTHESIS: Eight GLP-1 RA trials were reviewed; 7 GLP-1 RA trials showed improvement in HS. Two studies demonstrated improvement in liver histology in patients with SH. Seven SGLT2 inhibitor studies were reviewed; 6 studies demonstrated improvements in NAFLD. Five studies showed improvements in HS, whereas 1 displayed improvement in liver histology in NASH. Six studies that included DPP-4 inhibitors were evaluated, and only 2 demonstrated improvement in NASH. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Based on evidence reviewed, GLP-1 RAs and SGLT2 inhibitors decreased HS and SH in NAFLD patients, whereas DPP-4 inhibitor therapy was not effective for patients with HS. CONCLUSIONS: Based on study data utilizing imaging studies and biopsy results, GLP-1 RAs or SGLT2 inhibitors can benefit NAFLD T2DM patients. Clinical trials with larger patient populations may augment these results.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Receptor del Péptido 1 Similar al Glucagón/agonistas , Hipoglucemiantes/uso terapéutico , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Humanos , Hipoglucemiantes/administración & dosificación , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Estudios Observacionales como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento
16.
Acta Pharm ; 71(2): 175-184, 2021 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-33151168

RESUMEN

Recently, an outbreak of a fatal coronavirus, SARS-CoV-2, has emerged from China and is rapidly spreading worldwide. Possible interaction of SARS-CoV-2 with DPP4 peptidase may partly contribute to the viral pathogenesis. An integrative bioinformatics approach starting with mining the biomedical literature for high confidence DPP4-protein/gene associations followed by functional analysis using network analysis and pathway enrichment was adopted. The results indicate that the identified DPP4 networks are highly enriched in viral processes required for viral entry and infection, and as a result, we propose DPP4 as an important putative target for the treatment of COVID-19. Additionally, our protein-chemical interaction networks identified important interactions between DPP4 and sitagliptin. We conclude that sitagliptin may be beneficial for the treatment of COVID-19 disease, either as monotherapy or in combination with other therapies, especially for diabetic patients and patients with pre-existing cardiovascular conditions who are already at higher risk of COVID-19 mortality.


Asunto(s)
Infecciones por Coronavirus/tratamiento farmacológico , Dipeptidil Peptidasa 4/efectos de los fármacos , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Fosfato de Sitagliptina/farmacología , Fosfato de Sitagliptina/uso terapéutico , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/tratamiento farmacológico , Biología Computacional , Infecciones por Coronavirus/complicaciones , Cristalografía por Rayos X , Minería de Datos , Complicaciones de la Diabetes/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Reposicionamiento de Medicamentos , Redes Reguladoras de Genes , Humanos , Estructura Molecular , Pandemias , Neumonía Viral/complicaciones
17.
Nefrología (Madrid) ; 40(6): 664-671, nov.-dic. 2020. tab, graf
Artículo en Inglés | IBECS | ID: ibc-197203

RESUMEN

BACKGROUND: Linagliptin does not require dose adjustment in diabetes mellitus patients with chronic kidney disease (CKD). But, renal effects of linagliptin are not clear. Our aim was to examine the effect of linagliptin on renal disease progression in only insulin dependent type 2 diabetes mellitus (DM) patients with CKD. METHODS: Stage 3-4 CKD patients were randomized into 2 groups in this prospective randomized controlled study. In the first group, linagliptin 5mg was added in addition to the background insulin therapy. In the second group, patients continued their insulin therapy. Patients were followed up at 3-month intervals for one year. RESULTS: The study population consisted of 164 patients (90 patients in linagliptin group, 74 patients in other group) with a mean age of 67.5 ± 8.8 years. eGFR significantly increased in linagliptin group (p = 0.033), but decreased in other group (p = 0.003). No significant change was observed in total insulin dose in linagliptin group (p = 0.111), but in other group, total insulin dose significantly increased (p < 0.001). Proteinuria levels decreased in both groups, but there was no significant change. In the multiple logistic regression analysis, male gender and proteinuria emerged as variables that showed significant association with increased risk and the use of linagliptin emerged as variable that showed significant association with decreased risk for CKD progression. CONCLUSION: Linagliptin in DM patients with CKD was able to improve renal progression without significant effect on proteinuria and glucose control. With regard to treating diabetic nephropathy, linagliptin may offer a new therapeutic approach


ANTECEDENTES: La linagliptina no precisa un ajuste de la dosis en pacientes con diabetes mellitus y enfermedad renal crónica (ERC). No obstante, los efectos renales de la linagliptina no están claros. Nuestro objetivo fue examinar el efecto de la linagliptina en la evolución de la enfermedad renal únicamente en pacientes con diabetes mellitus de tipo 2 insulinodependientes con ERC. MÉTODOS: En este estudio prospectivo, aleatorizado y controlado, se asignaron de forma aleatoria pacientes con ERC en estadios 3-4 en 2 grupos. En el primer grupo se añadió linagliptina 5 mg además de la insulinoterapia de base. En el segundo grupo, los pacientes siguieron con su insulinoterapia. Los pacientes fueron objeto de seguimiento a intervalos de 3 meses durante un año. RESULTADOS: La población del estudio estuvo compuesta por 164 pacientes (90 pacientes en el grupo de linagliptina, 74 pacientes en el otro grupo) con una edad media de 67,5 ± 8,8 años. La TFGe aumentó significativamente en el grupo de linagliptina (p = 0,033), pero disminuyó en el otro grupo (p = 0,003). No se observó ningún cambio significativo en la dosis total de insulina en el grupo de la linagliptina (p = 0,111), pero, en el otro grupo, la dosis total de insulina aumentó significativamente (p < 0,001). Los niveles de proteinuria disminuyeron en ambos grupos, pero no hubo cambios significativos. En el análisis de regresión logística múltiple, el género masculino y la proteinuria destacaron como variables que mostraban una asociación significativa con el aumento del riesgo y el uso de la linagliptina destacó como variable con una asociación significativa con la disminución del riesgo de progresión de la enfermedad renal crónica. CONCLUSIÓN: La linagliptina en pacientes con DM y ERC consiguió mejorar la evolución renal sin un efecto significativo sobre la proteinuria y el control glucémico. En lo que respecta al tratamiento de la nefropatía diabética, la linagliptina puede ofrecer un nuevo enfoque terapéutico


Asunto(s)
Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Linagliptina/uso terapéutico , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Insuficiencia Renal Crónica/tratamiento farmacológico , Diabetes Mellitus Tipo 2/fisiopatología , Insuficiencia Renal Crónica/fisiopatología , Progresión de la Enfermedad , Estudios Prospectivos , Proteinuria/orina , Estadísticas no Paramétricas , Hemoglobina A Glucada , Modelos Logísticos , Resultado del Tratamiento
18.
BMC Med ; 18(1): 359, 2020 11 16.
Artículo en Inglés | MEDLINE | ID: mdl-33190637

RESUMEN

BACKGROUND: Limited evidence exists on the role of glucose-lowering drugs in patients with COVID-19. Our main objective was to examine the association between in-hospital death and each routine at-home glucose-lowering drug both individually and in combination with metformin in patients with type 2 diabetes mellitus admitted for COVID-19. We also evaluated their association with the composite outcome of the need for ICU admission, invasive and non-invasive mechanical ventilation, or in-hospital death as well as on the development of in-hospital complications and a long-time hospital stay. METHODS: We selected all patients with type 2 diabetes mellitus in the Spanish Society of Internal Medicine's registry of COVID-19 patients (SEMI-COVID-19 Registry). It is an ongoing, observational, multicenter, nationwide cohort of patients admitted for COVID-19 in Spain from March 1, 2020. Each glucose-lowering drug user was matched with a user of other glucose-lowering drugs in a 1:1 manner by propensity scores. In order to assess the adequacy of propensity score matching, we used the standardized mean difference found in patient characteristics after matching. There was considered to be a significant imbalance in the group if a standardized mean difference > 10% was found. To evaluate the association between treatment and study outcomes, both conditional logit and mixed effect logistic regressions were used when the sample size was ≥ 100. RESULTS: A total of 2666 patients were found in the SEMI-COVID-19 Registry, 1297 on glucose-lowering drugs in monotherapy and 465 in combination with metformin. After propensity matching, 249 patients on metformin, 105 on dipeptidyl peptidase-4 inhibitors, 129 on insulin, 127 on metformin/dipeptidyl peptidase-4 inhibitors, 34 on metformin/sodium-glucose cotransporter 2 inhibitor, and 67 on metformin/insulin were selected. No at-home glucose-lowering drugs showed a significant association with in-hospital death; the composite outcome of the need of intensive care unit admission, mechanical ventilation, or in-hospital death; in-hospital complications; or long-time hospital stays. CONCLUSIONS: In patients with type 2 diabetes mellitus admitted for COVID-19, at-home glucose-lowering drugs showed no significant association with mortality and adverse outcomes. Given the close relationship between diabetes and COVID-19 and the limited evidence on the role of glucose-lowering drugs, prospective studies are needed.


Asunto(s)
Infecciones por Coronavirus/mortalidad , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Hipoglucemiantes/normas , Insulina/uso terapéutico , Metformina/uso terapéutico , Neumonía Viral/mortalidad , Respiración Artificial/estadística & datos numéricos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Anciano , Anciano de 80 o más Años , Betacoronavirus , Estudios de Cohortes , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/terapia , Diabetes Mellitus Tipo 2/complicaciones , Quimioterapia Combinada , Femenino , Mortalidad Hospitalaria , Hospitalización , Humanos , Hipoglucemiantes/uso terapéutico , Unidades de Cuidados Intensivos , Tiempo de Internación/estadística & datos numéricos , Modelos Logísticos , Masculino , Ventilación no Invasiva/estadística & datos numéricos , Pandemias , Neumonía Viral/complicaciones , Neumonía Viral/terapia , Estudios Prospectivos , España
19.
Diabetes Care ; 43(12): 3042-3049, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33023989

RESUMEN

OBJECTIVE: Diabetes may unfavorably influence the outcome of coronavirus disease 19 (COVID-19), but the determinants of this effect are still poorly understood. In this monocentric study, we aimed at evaluating the impact of type 2 diabetes, comorbidities, plasma glucose levels, and antidiabetes medications on the survival of COVID-19 patients. RESEARCH DESIGN AND METHODS: This was a case series involving 387 COVID-19 patients admitted to a single center in the region of Lombardy, the epicenter of the severe acute respiratory syndrome coronavirus 2 pandemic in Italy, between 20 February and 9 April 2020. Medical history, pharmacological treatments, laboratory findings, and clinical outcomes of patients without diabetes and patients with type 2 diabetes were compared. Cox proportional hazards analysis was applied to investigate risk factors associated with mortality. RESULTS: Our samples included 90 patients (23.3%) with type 2 diabetes, who displayed double the mortality rate of subjects without diabetes (42.3% vs. 21.7%, P < 0.001). In spite of this, after correction for age and sex, risk of mortality was significantly associated with a history of hypertension (adjusted hazard ratio [aHR] 1.84, 95% CI 1.15-2.95; P = 0.011), coronary artery disease (aHR 1.56, 95% CI 1.04-2.35; P = 0.031), chronic kidney disease (aHR 2.07, 95% CI 1.27-3.38; P = 0.003), stroke (aHR 2.09, 95% CI 1.23-3.55; P = 0.006), and cancer (aHR 1.57, 95% CI 1.08-2.42; P = 0.04) but not with type 2 diabetes (P = 0.170). In patients with diabetes, elevated plasma glucose (aHR 1.22, 95% CI 1.04-1.44, per mmol/L; P = 0.015) and IL-6 levels at admission (aHR 2.47, 95% CI 1.28-4.78, per 1-SD increase; P = 0.007) as well as treatment with insulin (aHR 3.05, 95% CI 1.57-5.95; P = 0.001) and ß-blockers (aHR 3.20, 95% CI 1.50-6.60; P = 0.001) were independently associated with increased mortality, whereas the use of dipeptidyl peptidase 4 inhibitors was significantly and independently associated with a lower risk of mortality (aHR 0.13, 95% CI 0.02-0.92; P = 0.042). CONCLUSIONS: Plasma glucose levels at admission and antidiabetes drugs may influence the survival of COVID-19 patients affected by type 2 diabetes.


Asunto(s)
Infecciones por Coronavirus , Coronavirus , Diabetes Mellitus Tipo 2 , Inhibidores de la Dipeptidil-Peptidasa IV , Pandemias , Neumonía Viral , Betacoronavirus , Glucemia , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Humanos , Italia/epidemiología , Factores de Riesgo , Fosfato de Sitagliptina
20.
Medicine (Baltimore) ; 99(41): e22592, 2020 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-33031311

RESUMEN

BACKGROUND: DM is a common chronic metabolic disease. COVID-19 is a large-scale infectious disease. Some studies have shown that DM is an independent risk factor that increases COVID-19 mortality or other adverse outcomes. There is currently no specific and effective drug treatment. More and more people realize that DPP-4 inhibitors may play a huge role in fighting COVID-19 combined with diabetes. However, there is no evidence-based medicine to confirm the effectiveness and safety of DPP-4 inhibitors in the treatment of COVID-19 patients with diabetes. Therefore, we will conduct a systematic review and meta-analysis to synthesize the existing clinical evidence. METHODS AND ANALYSIS: Electronic databases include CNKI, Wanfang, VIP, CBM database, Cochrane Library, PubMed, Web of Science, EMBASE, etc. We will retrieve each database from December 2019 to September 2020. At the same time, we will look for clinical trial registration and gray literature. This study only included clinical randomized controlled trials. The reviewers independently conduct literature selection, data analysis, quality analysis, and evaluation. The primary outcomes include mortality rate, morbidity, interleukin-6, tumor necrosis factor-alpha, clinical improvement, symptoms improvement, fasting blood glucose, 2-hour postprandial blood glucose, glycosylated hemoglobin, fasting insulin, adverse reactions, etc. Finally, we will conducted a meta-analysis through Review Manager Software version 5.3. RESULTS: The results will be published in peer-reviewed journals and presented at a relevant conference. CONCLUSION: This study will explore the effectiveness and safety of DPP-4 inhibitors in the treatment of COVID-19 patients with diabetes. It will provide evidence-based medical evidence for DPP-4 inhibitors in the treatment of diabetes with COVID-19. REGISTRATION NUMBER: INPLASY202090015.


Asunto(s)
Infecciones por Coronavirus/tratamiento farmacológico , Complicaciones de la Diabetes/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Betacoronavirus , Humanos , Metaanálisis como Asunto , Pandemias , Revisiones Sistemáticas como Asunto
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