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Metformin AND GLP-1

Takeshi Osonoi, Miyoko Saito, Natsuyo Hariya, Moritaka Goto, Kazuki Mochizuki
Metformin, α-glucosidase inhibitors (α-GIs), and dipeptidyl peptidase 4 inhibitors (DPP-4Is) reduce hyperglycemia without excessive insulin secretion, and enhance postprandial plasma concentration of glucagon-like peptide-1 (GLP-1) in type-2 diabetes mellitus (T2DM) patients. We assessed add-on therapeutic effects of DPP-4I anagliptin in Japanese T2DM patients treated with metformin, an α-GI miglitol, or both drugs on postprandial responses of GLP-1 and glucose-dependent insulinotropic polypeptide (GIP), and on plasma concentration of the appetite-suppressing hormone leptin...
October 22, 2016: Peptides
Mark M Smits, Lennart Tonneijck, Marcel H A Muskiet, Trynke Hoekstra, Mhh Kramer, Michaela Diamant, Daniël H van Raalte
OBJECTIVE: To examine mechanisms underlying resting heart rate (RHR) increments of GLP-1 receptor agonists in type 2 diabetes patients. DESIGN: Acute and 12-week randomised placebo-controlled, double-blind, single-centre parallel-group trial. METHODS: 57 type 2 diabetes patients (mean±SD age 62.8±6.9 years; BMI 31.8±4.1 kg/m2; HbA1c 7.3±0.6%), treated with metformin and/or sulfonylureas, were included between July 2013 and August 2015...
October 24, 2016: European Journal of Endocrinology
Fabio Broglio, Edoardo Mannucci, Raffaele Napoli, Antonio Nicolucci, Francesco Purrello, Elena Nikonova, William Stager, Roberto Trevisan
AIMS: To evaluate long term efficacy and safety of lixisenatide, a short-acting, prandial GLP-1 RA (Glucagon-Like Peptide-1 Receptor Agonists) as add-on therapy in type 2 diabetes mellitus. METHODS: A meta-analysis of 76-week results of five placebo-controlled clinical trials from the GetGoal program was performed including 3,000 inadequately controlled adult diabetic patients where lixisenatide 20 µg once-daily was administered in combination with metformin (GetGoal-M and GetGoal-F1), sulphonylurea ± metformin (GetGoal-S), basal insulin ± metformin (GetGoal-L) or pioglitazone ± metformin (GetGoal-P)...
October 20, 2016: Diabetes, Obesity & Metabolism
Tongzhi Wu, Cong Xie, Hang Wu, Karen L Jones, Michael Horowitz, Christopher K Rayner
In rodents, metformin slows intestinal glucose absorption, potentially increasing exposure of the distal gut to glucose to enhance postprandial glucagon-like peptide-1 (GLP-1) secretion. We evaluated the effects of metformin on serum 3-O-methylglucose (3-OMG, a marker of glucose absorption) and plasma total GLP-1 concentrations during a standardised intraduodenal infusion of glucose and 3-OMG in patients with type 2 diabetes. 12 patients, treated with metformin 850 mg bd or placebo each for 7 days in a double-blind, randomised, crossover design (14 days 'washout' between treatments), were evaluated on days 5 or 8 of each treatment (6 each)...
October 20, 2016: Diabetes, Obesity & Metabolism
Mahalingam Balakumar, Durai Prabhu, Chandrakumar Sathishkumar, Paramasivam Prabu, Namita Rokana, Ramesh Kumar, Srividhya Raghavan, Avinash Soundarajan, Sunita Grover, Virender Kumar Batish, Viswanathan Mohan, Muthuswamy Balasubramanyam
PURPOSE: Diabetes and obesity are characterized by glucose intolerance, fat deposition, inflammation, and dyslipidemia. Recent reports postulated that distinct gut microbiota alterations were observed in obese/diabetic subjects and modulating gut microbiota beneficially through specific probiotics could be a potential therapeutic option for type 2 diabetes/obesity. Therefore, we attempted to study the efficacy of probiotics of Indian gut origin (Lactobacillus plantarum MTCC5690 and Lactobacillus fermentum MTCC5689) along with a positive control, Lactobacillus rhamnosus (LGG) on glucose/lipid homeostasis in high-fat-diet-induced diabetic animal model...
October 18, 2016: European Journal of Nutrition
Alexandre Baptista, Inês Teixeira, Sónia Romano, António Vaz Carneiro, Julian Perelman
OBJECTIVE: To conduct a systematic review of cost-effectiveness, cost-utility, and cost-benefit studies of DPP-4 inhibitors for diabetes treatment versus other antidiabetics. METHODS: Three investigators searched the CRD York, Tufts CEA Registry, and MEDLINE databases through 2015. We reviewed all potentially relevant titles and abstracts, and screened full-text articles, according to inclusion criteria. We established a quality score for each study based on a 35-item list...
October 17, 2016: European Journal of Health Economics: HEPAC: Health Economics in Prevention and Care
Na Wang, Jin-Ping Zhang, Xiao-Yan Xing, Zhao-Jun Yang, Bo Zhang, Xin Wang, Wen-Ying Yang
BACKGROUND: This post-hoc analysis investigated whether changes in endogenous glucagon-like peptide-1 (GLP-1) levels were associated with weight loss in newly diagnosed diabetes patients. METHODS: Seven hundred eighty-four subjects from the MARCH (Metformin and AcaRbose in Chinese as initial Hypoglycemic treatment) study were stratified by changes in GLP-1 levels (∆GLP-1). Changes in clinical and physiological parameters were evaluated across ∆GLP-1 subgroups to assess correlations between ∆GLP-1 and weight loss in acarbose vs...
September 22, 2016: Journal of Diabetes
Michael A Nauck, Melanie Kahle, Oleg Baranov, Carolyn F Deacon, Jens J Holst
AIMS/HYPOTHESIS: GLP-1 receptor agonists and DPP-4 inhibitors both stimulate GLP-1 receptors. Our objective was to determine, whether the addition of sitagliptin to pre-existing therapy with liraglutide changes glycaemic excursions after a mixed meal. METHODS: 16 subjects with type 2 diabetes treated with metformin and liraglutide (1.2 mg/d for ≥ 2 weeks) were randomized (sealed envelopes), within a cross-over design, to be studied on two occasions, after an overnight fast, with (a) sitagliptin (100 mg p...
October 6, 2016: Diabetes, Obesity & Metabolism
Soe Naing, Anapuma Poliyedath, Stutee Khandelwal, Teresa Sigala
Cardiovascular (CV) disease is the leading cause of death in patients with type 2 diabetes mellitus (T2DM). Most published trials of glucose-lowering agents have shown no significant CV benefit or increased risk of death or heart failure, with the exception of metformin. Three novel classes of glucose-lowering agents, dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptide 1 (GLP-1) receptor agonists, and sodium glucose cotransporter 2 (SGLT2) inhibitors, have been approved by the FDA for the treatment of T2DM in the United States and other parts of the world in the last decade...
October 4, 2016: Postgraduate Medicine
Ulrich Rohde, Cecilie A Federspiel, Peter Vilmann, Ebbe Langholz, Steffen U Friis, Martin Krakauer, Jens F Rehfeld, Jens J Holst, Tina Vilsbøll, Filip K Knop
AIMS: The duodenal-jejunal bypass sleeve ((DJBS) or EndoBarrier Gastrointestinal Liner) induces weight loss in obese subjects and may improve glucose homeostasis in patients with type 2 diabetes (T2D). To explore the underlying mechanisms, we evaluated postprandial physiology including glucose metabolism, gut hormone secretion, gallbladder emptying, appetite and food intake in patients undergoing DJBS treatment. MATERIAL AND METHODS: Ten normal glucose tolerant (NGT) obese subjects and nine age, body weight and body mass index-matched metformin-treated T2D patients underwent a liquid mixed meal test and a subsequent ad libitum meal test before implantation with DJBS and one (1w) and 26 weeks (26w) after implantation...
October 3, 2016: Diabetes, Obesity & Metabolism
Hitesh Soni
Diabesity is a new term for obesity-dependent diabetes, which is also associated with cardiovascular and other comorbidities with rising epidemic. Traditional treatments (sulfonylureas and thiazolidinediones) of diabetes are associated with weight gain, except metformin. Newer agents such as glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and Sodium glucose co-transporter 2 inhibitors (SGLT2i) are causing a modest weight reduction, whereas dipeptidyl peptidase-4 inhibitors (DPP-4i) are weight neutral...
October 2016: Medical Hypotheses
James G Johnson, Jennifer N Langan, Chen Gilor
An 8-yr-old male golden lion tamarin ( Leontopithecus rosalia ) was diagnosed with diabetes mellitus based on hyperglycemia and persistent glycosuria. Initial treatment consisted of the oral antihyperglycemic medications glipizide and metformin that resulted in decreased blood glucose concentrations; however, marked glycosuria persisted. Insufficient improvement on oral antihyperglycemic therapy and poor feasibility of daily subcutaneous insulin therapy led to an investigation into an alternative therapy with extended-release exenatide, a glucagon-like peptide-1 (GLP-1) mimetic, at a dosage of 0...
September 2016: Journal of Zoo and Wildlife Medicine: Official Publication of the American Association of Zoo Veterinarians
Juan P Frías, Cristian Guja, Elise Hardy, Azazuddin Ahmed, Fang Dong, Peter Öhman, Serge A Jabbour
BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose co-transporter-2 (SGLT2) inhibitors reduce glycaemia and weight, and improve cardiovascular risk factors via different mechanisms. We aimed to compare the efficacy and safety of co-initiation of the GLP-1 receptor agonist exenatide and the SGLT2 inhibitor dapagliflozin with exenatide or dapagliflozin alone in patients with type 2 diabetes inadequately controlled by metformin. METHODS: DURATION-8 was a 28 week, multicentre, double-blind, randomised, active-controlled phase 3 trial done at 109 sites in six countries...
September 15, 2016: Lancet Diabetes & Endocrinology
Mark M Smits, Lennart Tonneijck, Marcel H A Muskiet, Mark H H Kramer, Petra J W Pouwels, Indra C Pieters-van den Bos, Trynke Hoekstra, Michaela Diamant, Daniël H van Raalte, Djuna L Cahen
AIMS/HYPOTHESIS: Glucagon-like peptide (GLP)-1-based therapies have been suggested to improve hepatic steatosis. We assessed the effects of the GLP-1 receptor agonist liraglutide and the dipeptidyl peptidase (DPP)-4 inhibitor sitagliptin on hepatic steatosis and fibrosis in patients with type 2 diabetes. METHODS: In this 12 week, parallel, randomised, placebo-controlled trial, performed at the VU University Medical Center between July 2013 and August 2015, 52 overweight patients with type 2 diabetes treated with metformin and/or sulphonylurea agent ([mean ± SD] age 62...
September 15, 2016: Diabetologia
David Karásek
UNLABELLED: Despite a normal or higher bone mass, type 2 diabetes is associated with a higher risk of osteoporotic fractures. Besides a higher falls frequency the lower quality of diabetics bone plays the crucial role in this case. One of the factors affecting their fracture risk is a choice of antidiabetic treatment. So far, professional societies have warned before the thiazolidinediones use only, but gliflozines can be harmful for bone too. Metformin, sulfonylureas, GLP-1 agonists and DPP-4 inhibitors belong to the drugs without a negative effect on the fracture risk...
2016: Vnitr̆ní Lékar̆ství
Jianqiu Gu, Xin Meng, Yan Guo, Lei Wang, Hongzhi Zheng, Yixuan Liu, Bingshu Wu, Difei Wang
Liraglutide, a glucagon-like peptide (GLP-1) receptor agonist, has showed favorable effects in the glycaemic control and weight reduction in patients with type 2 diabetes mellitus (T2DM). The meta-analysis was to compare the efficacy and safety of liraglutide added to metformin with other treatments in patients with T2DM. A systematic literature search on PubMed, Embase, Web of Science and the Cochrane library databases were performed. Eligible studies were randomized controlled trials (RCTs) of patients with T2DM who received the combination treatment of liraglutide and metformin...
2016: Scientific Reports
P Kumarathurai, C Anholm, O K Kristiansen, O W Nielsen, S B Haugaard, A Sajadieh
OBJECTIVE: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown to reduce blood pressure in some clinical trials. Only a few studies have examined the effect of GLP-1 RAs on the 24-h variation of blood pressure. In this study, we explored the effect of the GLP-1 RA liraglutide on 24-h blood pressure and heart rate (HR) variation in patients with type 2 diabetes (T2DM) and coronary artery disease (CAD).(Figure is included in full-text article.) DESIGN AND METHOD: : Forty-one subjects were randomized to liraglutide plus metformin or placebo plus metformin in this this double-blind, placebo-controlled 12 plus 12 weeks cross-over study...
September 2016: Journal of Hypertension
Daniël H van Raalte, Mathijs C Bunck, Mark M Smits, T Hoekstra, Anja Cornér, Michaela Diamant, Bjorn Eliasson, Marja-RiittaTaskinen, Robert J Heine, Ulf Smith, HanneleYki-Järvinen, Andrea Mari
OBJECTIVE: Glucagon-like peptide (GLP)-1 receptor agonist treatment improves β-cell function. In this study, we investigated whether the improvements are sustained during a 3-year treatment period. RESEARCH DESIGN AND METHODS: Sixty-nine metformin-treated type 2 diabetes patients were randomised to the GLP1 receptor agonist, exenatide (EXE) twice daily (BID) or to insulin glargine (GLAR). β-cell function parameters were derived using the Mari model from standardised breakfast and lunch meals that were administered before treatment, and after 1 and 3 years of treatment...
October 2016: European Journal of Endocrinology
Mark M Smits, Lennart Tonneijck, Marcel H A Muskiet, Trynke Hoekstra, Mark H H Kramer, Michaela Diamant, Max Nieuwdorp, Albert K Groen, Djuna L Cahen, Daniël H van Raalte
AIMS: Treatment with glucagon-like peptide (GLP)-1 receptor agonists or dipeptidyl peptidase (DPP)-4 inhibitors might increase gallstone formation, yet involved mechanisms are unknown. We aimed to assess the effects of these drugs on gallbladder volume and bile acid profile. MATERIALS AND METHODS: 57 type 2 diabetes patients (mean±SD age 62.8 ± 6.9 years; BMI 31.8 ± 4.1 kg/m2; HbA1c 7.3 ± 0.6%), treated with metformin and/or sulfonylureas, were included in this 12-week randomised, placebo-controlled, double-blind, single-centre trial between July 2013 and August 2015 at the VU University Medical Center...
July 23, 2016: Diabetes, Obesity & Metabolism
Suetonia C Palmer, Dimitris Mavridis, Antonio Nicolucci, David W Johnson, Marcello Tonelli, Jonathan C Craig, Jasjot Maggo, Vanessa Gray, Giorgia De Berardis, Marinella Ruospo, Patrizia Natale, Valeria Saglimbene, Sunil V Badve, Yeoungjee Cho, Annie-Claire Nadeau-Fredette, Michael Burke, Labib Faruque, Anita Lloyd, Nasreen Ahmad, Yuanchen Liu, Sophanny Tiv, Natasha Wiebe, Giovanni F M Strippoli
IMPORTANCE: Numerous glucose-lowering drugs are used to treat type 2 diabetes. OBJECTIVE: To estimate the relative efficacy and safety associated with glucose-lowering drugs including insulin. DATA SOURCES: Cochrane Library Central Register of Controlled Trials, MEDLINE, and EMBASE databases through March 21, 2016. STUDY SELECTION: Randomized clinical trials of 24 weeks' or longer duration. DATA EXTRACTION AND SYNTHESIS: Random-effects network meta-analysis...
July 19, 2016: JAMA: the Journal of the American Medical Association
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