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Gliptins AND HbA1c

Ivan Tkáč, Ivana Gotthardová
Incretin effect enhancers are drugs used in the treatment of Type 2 diabetes and include GLP-1 receptor agonists and dipeptidyl peptidase-4 inhibitors (gliptins). Variants in several genes were shown to be involved in the physiology of incretin secretion. Only two gene variants have evidence also from pharmacogenetic studies. TCF7L2 rs7903146 C>T and CTRB1/2 rs7202877 T>G minor allele carriers were both associated with a smaller reduction in HbA1c after gliptin treatment when compared with major allele carriers...
May 2016: Pharmacogenomics
M Javorský, I Gotthardová, L Klimčáková, M Kvapil, J Židzik, Z Schroner, P Doubravová, I Gala, I Dravecká, I Tkáč
Gliptins act by increasing endogenous incretin levels. Glucagon-like peptide-1 receptor (GLP1R) and glucose-dependent insulinotropic peptide receptor (GIPR) are their indirect drug targets. Variants of GLP1R and GIPR have previously been associated with the incretin effect. The aim of the present pilot study was to examine associations of the GLP1R and GIPR gene variants with the glycaemic response to gliptins. A total of 140 consecutive patients with type 2 diabetes were followed-up 6 months after initiation of gliptin treatment...
September 2016: Diabetes, Obesity & Metabolism
Takashi Nakamura, Yoshitaka Iwanaga, Yuki Miyaji, Ryuji Nohara, Takao Ishimura, Shunichi Miyazaki
BACKGROUND: Gliptins should have beneficial effects beyond glycemic control, potentially on the pathophysiology of cardiovascular (CV) diseases, with some basic studies demonstrating this possibility. However, we are yet to answer whether there are any direct CV effects in the clinical setting. We aimed to examine the beneficial effects of sitagliptin in Japanese patients with diabetes and high CV risk for 12 months. METHODS: This was a prospective, multicenter, observational study of 205 patients with type 2 diabetes...
2016: Cardiovascular Diabetology
Pin Wang, Rong Huang, Sen Lu, Wenqing Xia, Haixia Sun, Jie Sun, Rongrong Cai, Shaohua Wang
OBJECTIVE: Whether lowering glycosylated haemoglobin (HbA1c) level below 7.0% improves macro-vascular outcomes in diabetes remains unclear. Here, we aimed to assess the effect of relatively tight glucose control resulting in a follow-up HbA1c level of less or more than 7.0% on cardiovascular outcomes in diabetic patients. RESEARCH DESIGN AND METHODS: We systematically searched Medline, Web of science and Cochrane Library for prospective randomized controlled trials published between Jan 1, 1996 and July 1, 2015 that recorded cardiovascular outcome trials of glucose-lowering drugs or strategies in patients with type 2 diabetes mellitus...
2015: Cardiovascular Diabetology
Se Hee Min, Soo Heon Kwak, Young Min Cho, Kyong Soo Park, Hye Seung Jung
BACKGROUND: Even though several oral anti-diabetic drugs (OAD) with various modes of action are replacing sulfonylurea (SU), some patients seem to be dependent on SU for adequate glycemic control. Therefore, we evaluated the clinical characteristics of such patients. METHODS: We selected the patients with type 2 diabetes who met following criteria from 2009 to 2014 at Seoul National University Hospital: glycated hemoglobin (HbA1c) was maintained below 7.5% for at least 6 months under small dose of SU (glimepiride ≤2 mg/day or equivalent dose); after discontinuation of SU, HbA1c increased ≥1...
December 2015: Endocrinology and Metabolism
(no author information available yet)
Metformin alone is the glucose-lowering drug of first choice for patients with type 2 diabetes. None of the other glucose-lowering drugs available in 2014 have any proven efficacy in preventing diabetes complications. How important are adverse effects in the choice of glucose-lowering alternatives to metformin for patients with type 2 diabetes? What about their effects on HbA1c levels? To answer these questions, we conducted a review of the literature using the standard Prescrire methodology. Sulphonylureas have been in use for many years...
May 2015: Prescrire International
Zdeněk Rušavý, Michal Žourek
Type 2 diabetes has become a pandemic disease over the past 50 years. Its incidence increases the most rapidly in the senior population, i.e. among people older than 65. In a number of countries 1/4 of the people with diabetes are now older than 65 years. Geriatrics now examines numerous differences regarding the senior patients, which often lead to somewhat different therapeutic procedures as compared to the treatment of other adult patients. This paper aims to show some different aspects of the treatment of an elderly patient with diabetes...
April 2015: Vnitr̆ní Lékar̆ství
Deep Dutta, Sanjay Kalra
Sodium glucose transporter 2 (SGLT2) inhibitors including dapagliflozin, canagliflozin and empagliflozin act by a novel insulin-independent mechanism by blocking glucose reabsorption in the proximal convoluted tubules resulting in markedly increased glycosuria, a mechanism not limited by the degree of insulin resistance or beta-cell dysfunction, and which results in weight loss due to loss of 300 to 400kcal/day. Currently dapagliflozin, canagliflozin and empagliflozin are the three primary drugs, which represent this group...
October 2014: JPMA. the Journal of the Pakistan Medical Association
Regin Elsa George, Siby Joseph
Diabetes resulting from both genetic and lifestyle factors causes high insulin deficiency or its resistance. As hyperglycemia and decreased insulin secretion and/or its sensitivity appear to be the primary defects associated with diabetes, available treatments focus on reducing those defects. A novel approach of treatment is to target the incretin mimetic hormones, which are secreted by intestinal cells in response to food intake, provoking glucose-dependent insulin secretion from the pancreas. Efficacy and safety studies of dipetidyl peptidase inhibitors (DPP-IV), sitagliptin, vildagliptin and linagliptin provide similar improvements in HbA1c levels when compared with metformin, sulfonylureas or glitazones without contributing to weight gain and hypoglycemia...
November 2014: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
K V S Hari Kumar, A K Gupta
AIMS: Dipeptidyl peptidase-4 inhibitors (DPP 4i) are oral hypoglycemic agents and are supposed to be beneficial in the early stages of diabetes. In this study, we evaluated the role of DPP4i in long standing type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: This retrospective data analysis was conducted from the patient records. All the patients (T2DM>5 years; Age>50 years; Gliptin use >12 months) were divided into 2 groups based on the duration of T2DM: Group A (<10 years) and Group B (>10 years)...
October 2015: Diabetes & Metabolic Syndrome
Dongsheng Cheng, Yang Fei, Yumei Liu, Junhui Li, Yuqiang Chen, Xiaoxia Wang, Niansong Wang
OBJECTIVE: To perform a systematic review and meta-analysis regarding the efficacy and safety of dipeptidyl peptidase-4 (DDP-4) inhibitors ("gliptins") for the treatment of type 2 diabetes mellitus (T2DM) patients with moderate to severe renal impairment. METHODS: All available randomized-controlled trials (RCTs) that assessed the efficacy and safety of DDP-4 inhibitors compared with placebo, no treatment, or active drugs were identified using PubMed, EMBASE, Cochrane CENTRAL, conference abstracts, clinical trials...
2014: PloS One
Chun-Jun Li, Xiao-Juan Liu, Lian Bai, Qian Yu, Qiu-Mei Zhang, Pei Yu, De-Min Yu
BACKGROUND: The oral DPP-4 inhibitors are new incretin-based therapies for treatment of type 2 diabetes. To assess the efficacy and safety of three DPP-4 inhibitors (Saxagliptin, Sitagliptin and Vildagliptin) as add-on therapy to dual combination of traditional oral hypoglycemic agents in Chinese type 2 diabetes patients. METHODS: In this 24-week, randomized, open-label, parallel clinical trial, we enrolled inadequately controlled (glycosylated haemoglobin A1c [HbA1c] ≥7...
2014: Diabetology & Metabolic Syndrome
Ananth Samith Shetty, Arun Nandith, Chamukuttan Snehalath, Ambady Ramachandran
OBJECTIVES: This retrospective analysis was done in type 2 diabetes patients to study whether treatment with either sitagliptin or other Dipeptidyl peptidase-4 (DPP-4) inhibitors increased the risk of pancreatitis. Comparison with patients treated with other Oral Antidiabetic Drugs (OADs) was done. METHODS: Asian Indian type 2 diabetic subjects (duration > or = 5 years) treated with sitagliptin or other DPP-4 inhibitors (n = 957) were selected from the clinic records...
August 2013: Journal of the Association of Physicians of India
Annalisa Capuano, Liberata Sportiello, Maria Ida Maiorino, Francesco Rossi, Dario Giugliano, Katherine Esposito
Type 2 diabetes mellitus is a complex and progressive disease that is showing an apparently unstoppable increase worldwide. Although there is general agreement on the first-line use of metformin in most patients with type 2 diabetes, the ideal drug sequence after metformin failure is an area of increasing uncertainty. New treatment strategies target pancreatic islet dysfunction, in particular gut-derived incretin hormones. Inhibition of the enzyme dipeptidyl peptidase-4 (DPP-4) slows degradation of endogenous glucagon-like peptide-1 (GLP-1) and thereby enhances and prolongs the action of the endogenous incretin hormones...
2013: Drug Design, Development and Therapy
Serge Halimi
Once lifestyle measures implemented, if hyperglycemia persists, above individual HbA1c targets, a medication should be started in type 2 diabetic patients (T2DM). First, unless exception, an oral antidiabetic drug. Except in case of intolerance, the initial monotherapy, metformin remains the strengthening treatment. Latter, combination of two oral drugs, now offers several options, mainly the choice to associate a "conventional insulin-secretor", sulfonylureas, glinide, or a "new one" belonging the class of "incretin", more readily a gliptine (DPP-4 inhibitors) rather than injectable GLP-1 analogue which can also be sometimes chosen at this stage...
May 2013: La Presse Médicale
Louis Monnier, Claude Colette, Andrea Comenducci, Denis Vallée, Sylvie Dejager
BACKGROUND: Oral hypoglycemic agents (OHAs) are usually divided into postprandial and basal drugs. As their actions are probably more complex, it is important to ascertain which factors can modulate their effects. SUBJECTS AND METHODS: Thirty-one type 2 diabetes patients treated with metformin (glycosylated hemoglobin [HbA1c] 6.5-9%; median, 7.3%) and enrolled in two randomized controlled studies were allocated to either rosiglitazone (Group 1, n = 8) or glimepiride (Group 2, n = 7) and to either vildagliptin or sitagliptin (Group 3 considered as a whole, n = 16)...
October 2012: Diabetes Technology & Therapeutics
Hélène Duez, Bertrand Cariou, Bart Staels
Although being a primary objective in the management of type 2 diabetes, optimal glycaemic control is difficult to achieve and usually not maintained over time. Type 2 diabetes is a complex pathology, comprising altered insulin sensitivity and impaired insulin secretion. Recent advances in the understanding of the physiological functions of incretins and their degrading enzyme dipeptidyl-peptidase (DPP)-4 have led to the 'discovery' of a new class of oral anti-diabetic drugs. Several DPP-4 inhibitors (or gliptins) with different chemical structures are now available...
April 1, 2012: Biochemical Pharmacology
Vishal Gupta, Sanjay Kalra
The treatment of type 2 diabetes mellitus (T2DM) has included the use of metformin and sulfonylurea (SU) as first-line anti-diabetic therapies world over since years. This remains, despite the knowledge that the combination results in a progressive decline in [beta]-cell function and by 3 years up to 50% of diabetic patients can require an additional pharmacological agent to maintain the glycosylated hemoglobin (HbA1c) <7.0% (UKPDS). Gliptins represent a novel class of agents that improve beta cell health and suppress glucagon, resulting in improved post-prandial and fasting hyperglycemia...
October 2011: Indian Journal of Endocrinology and Metabolism
B Ahrén, J E Foley, E Bosi
Several new oral antidiabetic agents, known as 'gliptins' or 'enzyme dipeptidyl peptidase-IV (DPP-4) inhibitors', have been developed for the treatment of type 2 diabetes and a key clinical use of the gliptins is in combination with metformin. There are important differences in the kinetics of the interaction of different gliptins with the catalytic site of DPP-4, which may lead to varying pharmacokinetics, pharmacodynamics and dosing regimens. Therefore, individual gliptins need to be characterized and here we discuss the extensively studied DPP-4 inhibitor vildagliptin, which has binding characteristics that ensure inhibition of the enzyme beyond the presence of detectable drug levels in plasma...
March 2011: Diabetes, Obesity & Metabolism
Gábor Firneisz, Tímea Varga, Gabriella Lengyel, János Fehér, Dóra Ghyczy, Barna Wichmann, László Selmeci, Zsolt Tulassay, Károly Rácz, Anikó Somogyi
BACKGROUND: In a cross-sectional study we studied the fasting serum DPP-4 enzymatic activity (sDPP-4) and the insulin resistance index (HOMA2-IR) in gliptin naïve patients with type 2 diabetes and in non-alcoholic fatty liver disease (NAFLD) and in healthy controls (CNTRL). METHODS AND FINDINGS: sDPP-4 was measured by kinetic assay in 39 NAFLD (F/M:19/20, mean age: 47.42 yrs) and 82 type 2 diabetes (F/M:48/34, 62.8 yrs) patients and 26 (F/M:14/12, 35.3 yrs) controls...
2010: PloS One
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