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Insuline + dpp4 inhibitor treatment in type 2 diabetes

Sayantan Nath, Sankar Kumar Ghosh, Yashmin Choudhury
INTRODUCTION: A murine model of type 2 diabetes mellitus was used to compare the antidiabetic effects of the dipeptidyl peptidase-4 (DPP4) inhibitor vildagliptin and biguanide, metformin. METHODS: Swiss albino mice (n=20 males; n=25 females) were given high fat diet (HFD) ad libitum for 3weeks followed by low dose (40mgkg(-1) body weight, bw daily) of streptozotocin (STZ) intraperitoneally five times from the 22nd day of treatment onwards, with HFD continued up to 26th day...
October 20, 2016: Journal of Pharmacological and Toxicological Methods
Heming Guo, Chen Fang, Yun Huang, Yufang Pei, Linqi Chen, Ji Hu
AIMS: Dipeptidyl peptidase-4 (DPP4) inhibitors are a novel class of antidiabetic medication in the treatment of type 2 diabetes mellitus. Several studies have indicated that DPP4 inhibitors could be used for type 1diabetes (T1DM). Here, we performed a meta-analysis to assess the efficacy and safety of DPP4 inhibitor therapy in patients with T1DM. METHODS: We conducted searches on Medline, Cochrane Library, Web of Science, and EMBASE for relevant studies published before November 21, 2015...
September 28, 2016: Diabetes Research and Clinical Practice
Neha Shrestha, Francisca Araújo, Mohammad-Ali Shahbazi, Ermei Mäkilä, Maria João Gomes, Mikko Airavaara, Esko I Kauppinen, Janne Raula, Jarno Salonen, Jouni Hirvonen, Bruno Sarmento, Hélder A Santos
Glucagon-like peptide-1 (GLP-1), an incretin hormone, is used for type 2 diabetes mellitus (T2DM) treatment because of its ability to stimulate insulin secretion and release in a glucose-dependent manner. Despite of its potent insulinotropic effect, oral GLP-1 delivery is greatly limited by its instability in the gastrointestinal tract, poor absorption efficiency and rapid degradation by dipeptidylpeptidase-4 (DPP4) enzyme leading to a short half-life (~2min). Thus, a multistage dual-drug delivery nanosystem was developed to deliver GLP-1 and DPP4 inhibitor simultaneously...
June 28, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Tsuyoshi Mashitani, Ryuichi Noguchi, Yasushi Okura, Tadashi Namisaki, Akira Mitoro, Hitoshi Ishii, Toshiya Nakatani, Eiryo Kikuchi, Hiroto Moriyasu, Masami Matsumoto, Shinya Sato, Tatsuichi An, Hiroshi Morita, Sigeyuki Aizawa, Yasunori Tokuoka, Masatoshi Ishikawa, Yoshinobu Matsumura, Hiromasa Ohira, Atsuko Kogure, Kazuhiro Noguchi, Hitoshi Yoshiji
Non-alcoholic fatty liver disease (NAFLD) represents one of the most common causes of chronic liver disease worldwide and is characterized by chronic liver inflammation and fibrosis leading to cirrhosis and increased risk of liver cancer in a proportion of patients. Effective anti-fibrotic agents have yet to be approved for the treatment of NAFLD. The present study aimed to evaluate the efficacy of dipeptidyl peptidase 4 inhibitors (DPP4-I) in the prevention of NAFLD progression in NAFLD patients with type 2 diabetes...
February 2016: Biomedical Reports
Kirsten Schulz, Jana Frahm, Susanne Kersten, Ulrich Meyer, Jürgen Rehage, Marion Piechotta, Maria Meyerholz, Gerhard Breves, Dania Reiche, Helga Sauerwein, Sven Dänicke
The inhibition of dipeptidyl peptidase-4 (DPP4) via specific inhibitors is known to result in improved glucose tolerance and insulin sensitivity and decreased accumulation of hepatic fat in type II diabetic human patients. The metabolic situation of dairy cows can easily be compared to the status of human diabetes and non-alcoholic fatty liver. For both, insulin sensitivity is reduced, while hepatic fat accumulation increases, characterized by high levels of non-esterified fatty acids (NEFA) and ketone bodies...
2015: PloS One
Bruno Detournay, Serge Halimi, Julien Robert, Céline Deschaseaux, Sylvie Dejager
AIM: We aimed to compare the frequency of severe hypoglycemia leading to hospitalization (HH) and emergency visits (EV) for any cause in patients with type 2 diabetes mellitus exposed to dipeptidyl peptidase 4 (DPP4) inhibitors (DPP4-i) versus those exposed to insulin secretagogues (IS; sulfonylureas or glinides). METHODS: Data were extracted from the EGB (Echantillon Généraliste des Bénéficiaires) database, comprising a representative sample of ~1% of patients registered in the French National Health Insurance System (~600,000 patients)...
2015: Vascular Health and Risk Management
Ele Ferrannini, Ralph A DeFronzo
Type 2 diabetes mellitus (T2DM) is characterized by multiple pathophysiologic abnormalities. With time, multiple glucose-lowering medications are commonly required to reduce and maintain plasma glucose concentrations within the normal range. Type 2 diabetes mellitus individuals also are at a very high risk for microvascular complications and the incidence of heart attack and stroke is increased two- to three-fold compared with non-diabetic individuals. Therefore, when selecting medications to normalize glucose levels in T2DM patients, it is important that the agent not aggravate, and ideally even improve, cardiovascular risk factors (CVRFs) and reduce cardiovascular morbidity and mortality...
September 7, 2015: European Heart Journal
Christian Meier, Ann V Schwartz, Andrea Egger, Beata Lecka-Czernik
Type 2 diabetes is associated with increased fracture risk and the mechanisms underlying the detrimental effects of diabetes on skeletal health are only partially understood. Antidiabetic drugs are indispensable for glycemic control in most type 2 diabetics, however, they may, at least in part, modulate fracture risk in exposed patients. Preclinical and clinical data clearly demonstrate an unfavorable effect of thiazolidinediones on the skeleton with impaired osteoblast function and activated osteoclastogenesis...
January 2016: Bone
Matteo Monami, Benedetta Ragghianti, Stefania Zannoni, Valentina Vitale, Besmir Nreu, Edoardo Mannucci
AIM: Basal insulin and DPP4 inhibitors are both possible options in patients with type 2 diabetes failing to oral drugs. The identification of clinical predictors of success with either one of the two approaches could be of help in personalizing therapy. METHODS: The retrospective study was performed on a consecutive series of patients with type 2 diabetes (n = 1,002) failing to at least one oral agent, who had been prescribed either basal insulin or DPP4 inhibitors in the previous 2 years, with a duration of follow-up of at least 6 months...
February 2016: Acta Diabetologica
Daisuke Ito, Kazuyuki Inoue, Kimie Kaneko, Morifumi Yanagisawa, Takashi Sumita, Yuichi Ikegami, Takuya Awata, Hitoshi Ishida, Shigehiro Katayama, Kouichi Inukai
BACKGROUND: In Japan, dipeptidyl peptidase 4 (DPP4) inhibitors have become standard therapeutic agents for type 2 diabetes, and numbers of patients receiving insulin therapy combined with DPP4 inhibitors, which is a highly effective regimen, are increasing. METHODS: In this study, we evaluated the efficacy of vildagliptin administered at the dose of 100 mg twice daily in 57 patients with type 2 diabetes already receiving insulin treatment. RESULTS: The 36 patients who simply received add-on vildagliptin showed a 0...
May 2015: Journal of Clinical Medicine Research
Eduardo José Abad Paniagua, Pedro Casado Escribano, José María Fernández Rodriguez, Francisco J Morales Escobar, Lourdes Betegón Nicolás, Joaquín Sánchez-Covisa, Max Brosa
OBJECTIVE: To assess the efficiency of the combined therapy with metformin and dapagliflozin, a new oral anti-diabetic drug with an insulin-independent mechanism of action, in the treatment of type-2 diabetes mellitus (T2DM) compared to DPP4 inhibitors, sulphonylureas and thiazolidindiones, also combined with metformin. DESIGN: Cost-effectiveness analysis using a discrete event simulation model based on the results of the available clinical trials and considering patient's entire life as time horizon...
October 2015: Atencion Primaria
Friedrich Mittermayer, Erica Caveney, Claudia De Oliveira, Loukas Gourgiotis, Mala Puri, Li-Jung Tai, J Rick Turner
The global burden of type 2 diabetes is increasing worldwide, and successful treatment of this disease needs constant provision of new drugs. Twelve classes of antidiabetic drugs are currently available, and many new drugs are under clinical development. These include compounds with known mechanisms of action but unique properties, such as once-weekly DPP4 inhibitors or oral insulin. They also include drugs with new mechanisms of action, the focus of this review. Most of these compounds are in Phase 1 and 2, with only a small number having made it to Phase 3 at this time...
2015: Current Diabetes Reviews
Gerald H Tomkin
In recent years the treatment focus for type 2 diabetes has shifted to prevention by lifestyle change and to more aggressive reduction of blood sugars during the early stage of treatment. Weight reduction is an important goal for many people with type 2 diabetes. Bariatric surgery is no longer considered a last resort treatment. Glucagon-like peptide-1 agonists given by injection are emerging as a useful treatment since they not only lower blood sugar but are associated with a modest weight reduction. The role of the oral dipeptidyl peptidase 4 inhibitors is emerging as second line treatment ahead of sulphonylureas due to a possible beneficial effect on the beta cell and weight neutrality...
October 15, 2014: World Journal of Diabetes
Sidra Azim, William L Baker, William B White
Type 2 diabetes increases the risk of developing cardiovascular (CV) complications such as myocardial infarction, heart failure, stroke, peripheral vascular disease, and CV-associated mortality. Strict glycemic control in diabetics has shown improvement in microvascular complications related to diabetes but has been unable to demonstrate major effects on macrovascular complications including myocardial infarction and stroke. Conventional therapies for diabetes that include insulin, metformin, sulfonylureas (SU), and alpha-glucosidase inhibitors have limited and/or controversial data on CV safety based on observational studies not designed or powered to assess CV safety of these medications...
November 2014: Current Cardiology Reports
Wendela Lucia de Ranitz-Greven, Joline Wilhelma Johanna Beulens, Lette Birgit Elisabeth Anne Hoeks, Gerdien Belle-van Meerkerk, Douwe Hedde Biesma, Harold Wessel de Valk
BACKGROUND: The addition of a DDP4-inhibitor to existing insulin therapy reduces HbA1c. However, no data exist about the addition of these agents at the beginning of insulin treatment in type 2 diabetes while this could especially be interesting because it is during this period that considerable residual beta cell function is still present. The benefit of such a strategy could be a lower insulin dose required for glycemic control. The hypothesis of our study was that adding a DPP4-inhibitor at the beginning of insulin treatment could lead to less exogenous insulin requirement, a reduction of hyperinsulinemia and side effects (hypoglycemia and weight gain), less glucose variability and improvement of insulin and glucagon dynamics during a mixed meal test...
2014: BMC Research Notes
Lorenzo Glorie, Geert J Behets, Lesley Baerts, Ingrid De Meester, Patrick C D'Haese, Anja Verhulst
Dipeptidyl peptidase IV (DPP IV) modulates protein activity by removing dipeptides. DPP IV inhibitors are currently used to improve glucose tolerance in type 2 diabetes patients. DPP IV substrates not only increase insulin secretion but also affect bone metabolism. In this study, the effect of DPP IV inhibitor sitagliptin on bone was evaluated in normal and streptozotocin-induced diabetic rats. This study included 64 male Wistar rats divided into four groups (n = 16): two diabetic and two control groups. One diabetic and one control group received sitagliptin through drinking water...
September 1, 2014: American Journal of Physiology. Endocrinology and Metabolism
Alfred Penfornis, Jean Frédéric Blicklé, Béatrice Fiquet, Stéphane Quéré, Sylvie Dejager
BACKGROUND AND AIM: Chronic kidney disease (CKD) is frequent in type 2 diabetes mellitus (T2DM), and therapeutic management of diabetes is more challenging in patients with renal impairment (RI). The place of metformin is of particular interest since most scientific societies now recommend using half the dosage in moderate RI and abstaining from use in severe RI, while the classic contraindication with RI has not been removed from the label. This study aimed to assess the therapeutic management, in particular the use of metformin, of T2DM patients with CKD in real life...
2014: Vascular Health and Risk Management
Sridhara Janardhan, G Narahari Sastry
Dipeptidyl peptidase IV (DPP4) is a promising target for the treatment of chronic metabolic type 2 diabetes mellitus (T2D). DPP4 is a highly specific serine protease involved in the regulation and cleavage of two incretin hormones, glucagon-like peptide (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). These incretin hormones are released by the gastrointestinal tract in response to ingestion of food and stimulate insulin secretion and thereby regulate glucose homeostasis with a low risk of hypoglycemia and glucagon secretion...
June 2014: Current Drug Targets
Daniël H Van Raalte, Renate E van Genugten, Björn Eliasson, Diane L Möller-Goede, Andrea Mari, Andrea Tura, Craig Wilson, Penny Fleck, Marja R Taskinen, Ulf Smith, Michaela Diamant
OBJECTIVE: Type 2 diabetes mellitus (T2DM) management requires continuous treatment intensification due to progressive decline in β-cell function in insulin resistant individuals. Initial combination therapy of a dipeptidyl peptidase (DPP)-4 inhibitor with a thiazolidinedione (TZD) may be rational. We assessed the effects of the DPP4 inhibitor alogliptin (ALO) combined with the TZD pioglitazone (PIO), vs ALO monotherapy or placebo (PBO), on β-cell function and glycemic control in T2DM...
April 2014: European Journal of Endocrinology
Teruo Jojima, Yoshimasa Aso
The increase proportion of older persons is continuously growing in worldwide, especially in Japan. Subsequently, the number of older adults with type 2 diabetes is also increasing. Older adults with diabetes are at substantial risk of frailty, cognitive impairment, and physical disability. They are also at greater risk for polypharmacy, depression, urinary incontinence, injurious fall, and persistent pain. Thus, older patients are a very heterogenous group of individuals. Hypoglycemia is a frequent adverse effect of treatment with sulfonylurea, glinides, or insulin in older adults with diabetes...
November 2013: Nihon Rinsho. Japanese Journal of Clinical Medicine
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