DOCSLIB.ORG

Use of Dipeptidyl Peptidase-4 Inhibitors and the Reporting of Infections: a Disproportionality Analysis in the World Health Organization Vigibase

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Use of Dipeptidyl Peptidase-4 Inhibitors and the Reporting of Infections: a Disproportionality Analysis in the World Health Organization Vigibase Epidemiology/Health Services Research ORIGINAL ARTICLE Use of Dipeptidyl Peptidase-4 Inhibitors and the Reporting of Infections: A Disproportionality Analysis in the World Health Organization VigiBase 1,2 1,4 MARJOLEIN J. WILLEMEN, PHARMD RON H. MEYBOOM, PHD by reducing fasting and postprandial glu- 1,2 1,5 AUKJE K. MANTEL-TEEUWISSE, PHD TOINE C. EGBERTS, PHD 2,3 1,2 cose concentrations in patients with type 2 SABINE M. STRAUS, PHD HUBERT G. LEUFKENS, PHD diabetes (1). DPP-4 is assumed to have many other functions in the human physiology due — OBJECTIVE Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of antidiabetic drugs. to its presence on the surface of many They inactivate incretin hormones but also have many other effects throughout the body, among different cell types, but these effects are which are effects on the immune system. This might result in an increased infection risk. This study assessed the association between use of DPP-4 inhibitors and the reporting of infections. still largely unknown. The role of DPP-4 in immune regulation is better defined RESEARCH DESIGN AND METHODS—A nested case-control was conducted using and includes induction of transforming VigiBase, the World Health Organization-Adverse Drug Reactions (WHO-ADR) database. The growth factor-b1 in activated T cells and base cohort consisted of ADRs for antidiabetic drugs (Anatomical Therapeutic Chemical code suppression of production of inflamma- A10). Cases were defined as ADRs of infection according to the Medical Dictionary for Regulatory fi tory cytokines by T cells (4), effects on cell Activities (MedDRA) classi cation system. All other ADRs were considered controls. Reporting growth, differentiation, and apoptosis odds ratios (RORs) were calculated to estimate the strength of the association between different (5,6). The immunomodulating effect has classes of antidiabetic drugs and the reporting of infections. given rise to concerns regarding a possible RESULTS—We identified 305,415 suspected ADRs involving antidiabetic drugs in 106,469 increase in the occurrence of infections case reports, of which 8,083 involved DPP-4 inhibitors monotherapy. Overall, the reporting of (1–3). infections was higher for patients using DPP-4 inhibitors compared with users of biguanides Nasopharyngitis, upper respiratory (ROR 2.3 [95% CI 1.9–2.7]). Reporting of upper respiratory tract infections (ROR 12.3 [95% CI tract (URTI), and related infections (acute – fi 8.6 17.5]) was signi cantly associated with use of DPP-4 inhibitors. bronchitis, pharyngitis, sinusitis, and rhi- CONCLUSIONS—This study indicates an increased reporting of infections, in particular nitis) were the most commonly reported upper respiratory tract infections, for users of DPP-4 inhibitors compared with users of other infections for the active substances com- antidiabetic drugs. However, the limitations of spontaneous reporting systems (e.g., underre- pared with the reference intervention in porting, the Weber-effect, reporting bias) should be taken into account. Therefore, further re- clinical trial programs (1–3). However, search is needed to evaluate this suspicion and the underlying mechanism. pooled analyses for vildagliptin and saxagliptin did not indicate an increased – Diabetes Care 34:369 374, 2011 risk of infections compared with the ref- erence group (7,8). In the three European ipeptidyl peptidase-4 (DPP-4) inhib- peptide-1 and glucose-dependent insuli- Union (EU) Risk Management Plans (a Ditors are a new class of antidiabetic notropic polypeptide) by DPP-4 inhibitors mandatory part of marketing applications drugs, with three products currently results in a rise in insulin from pancreatic since November 2005 [9]) for the ap- available on the market: sitagliptin, vilda- b-cells and a decrease in glucagon from proved DPP-4 inhibitors, “infections” gliptin, and saxagliptin (1–3). The inacti- pancreatic a-cells. As a consequence, were defined as important identified risks vation of incretin hormones (glucagon-like DPP-4 inhibitors improve glycemic control that require further evaluation. Postau- thorization safety studies specifically eval- uating the risk of hospitalization due to ccccccccccccccccccccccccccccccccccccccccccccccccc infections are currently being conducted From the 1Division of Pharmacoepidemiology and Clinical Pharmacology, Faculty of Science, Utrecht Institute for vildagliptin and saxagliptin (2,3). For for Pharmaceutical Sciences, Utrecht, the Netherlands; the 2Medicines Evaluation Board, The Hague, the 3 sitagliptin, the risk for infections will be Netherlands; the Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, the Netherlands; the 4World Health Organization Collaborating Centre for International Drug Monitoring, further evaluated through an in-depth Uppsala Monitoring Centre, Uppsala, Sweden; and the 5Department of Clinical Pharmacy, University analysis of the safety results of the ongo- Medical Center Utrecht, Utrecht, the Netherlands. ing and planned clinical trials (1). Corresponding author: Aukje K. Mantel-Teeuwisse, [email protected]. Data on a possible direct relation Received 14 September 2010 and accepted 5 November 2010. DOI: 10.2337/dc10-1771 between diabetes mellitus and infections This article contains Supplementary Data online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/ are inconclusive. Several studies investi- dc10-1771/-/DC1. gated a possible association between di- The opinions and conclusions are those of the authors and not necessarily those of the Uppsala Monitoring abetes mellitus and alterations of the Centre, the National Centers, or the World Health Organization. © 2011 by the American Diabetes Association. Readers may use this article as long as the work is properly immune system (10,11). Some epidemi- cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/ ologic studies showed that these patients licenses/by-nc-nd/3.0/ for details. are at an increased risk for common care.diabetesjournals.org DIABETES CARE, VOLUME 34, FEBRUARY 2011 369 DPP-4 inhibitors and reporting of infections infections (12–15), but evidence from through a manual search were defined as the high-level group terms URTI, LRTI, and clinical trials is limited and inconsistent cases. All reports containing other ADRs UTI. Adjusted analyses were conducted (16). Disease progression may have an ef- were considered as controls. We grouped with all potential confounders included in fect on the occurrence of infections; thus, the infections on the first sublevel (high- the model. more severely ill patients might be at an level group terms) of MedDRA and looked More ADRs were usually reported for increased risk of infections (17). To our at URTI (e.g., sinusitis and nasopharyngi- onecasereport,andthereforeitwas knowledge, no studies have specifically tis), lower respiratory tract infections possible that one case report contained investigated the relation between the use (LRTI, e.g., bronchitis and pneumonia), more than one ADR of an infection. To of DPP-4 inhibitors and infections as ad- and urinary tract infections (UTI; e.g., cys- test the effect of multiple ADRs reported verse drug reactions (ADRs). Therefore, titis and pyelonephritis). Because of low in one case report, we analyzed the data the aim of the current study was to assess numbers, all other infections were com- on the level of case reports (one case the relation between different classes of bined. report generally represented one patient). antidiabetic drugs and the reporting of In the U.S., DPP-4 inhibitors are in- fi infections. Exposure de nition dicated for monotherapy for the treat- Exposure to antidiabetic drugs was the ment of diabetes mellitus, whereas in the RESEARCH DESIGN AND determinant that was investigated. Anti- EU, these medicines are only indicated for METHODS diabetic drugs were subclassified based combination therapies. To check whether on the Anatomical Therapeutic Chemical this affected the results of this study, we Setting and study design (ATC) classification system of the WHO performed a sensitivity analysis by ana- Data were obtained from the International (www.whocc.no): biguanides (ATC code lyzing the data for the U.S. and the rest of Drug Monitoring Program of the World A10BA), sulfonylurea derivatives (A10BB), the world separately. In addition, to study Health Organization (WHO). The WHO thiazolidinediones (A10BG), DPP-4 in- the effect of the type of reporter (health global individual case safety report (ICSR) hibitors (A10BH), insulins, and analogs care professional or consumer) on the database, VigiBase, is maintained by the (A10A). When multiple antidiabetic drugs outcome, we performed a sensitivity anal- Uppsala Monitoring Centre and contains were reported for a certain ADR, this was ysis in which the reports were assessed summaries of suspected spontaneous case classified as combination therapy, irrespec- according to the type of reporter. Statisti- reports originally summated by health tive of whether a drug reported was classi- cal analysis was done using SPSS 16.0 care professionals and patients to national fied as “suspected” or as a comedication. statistical software (SPSS Inc., Chicago, IL). pharmacovigilance centers in 98 coun- tries worldwide. As of May 2010, this Potential confounding factors RESULTS—From the WHO VigiBase database contained .5 million case re- Potential confounding factors retrieved we identified 305,415 suspected ADRs ports of suspected ADRs regarding spe-
Load more

Recommended publications
  • Effect of Glucose/Sulfonylurea Interaction on Release of Insulin
    Proc. Nati. Acad. Sci. USA Vol. 76, No. 11, pp. 5901-5904, November 1979 Medical Sciences Effect of glucose/sulfonylurea interaction on release of insulin, glucagon, and somatostatin from isolated perfused rat pancreas (glibenclamide) SUAD EFENDIt*, FRANZ ENZMANNf, ANITA NYLtN*, KERSTIN UVNAS-WALLENSTENt, AND ROLF LUFT* *Department of Endocrinology, Karolinska Hospital, 104 01 Stockholm; tDepartment of Pharmacology, Karolinska Institute, 104 01 Stockholm, Sweden; and tHoechst Aktiengesellschaft, Medizinische Abteilung, Frankfurt, West Germany Contributed by Rolf Luft, July 27, 1979 ABSTRACT The effect of a sulfonylurea, glibenclamide, method and separated on CM-cellulose column. The antibodies on the release of insulin, glucagon, and somatostatin was studied produced in our laboratory were used at a final dilution of 1: in the isolated perfused rat pancreas. At concentrations glucose 56,000. Crossreactivity of the antibody was less than 0.01% with of 1.1 mM or less, the drug stimulated somatostatin release, whereas glucagon release, after 2-3 min of increase, was insulin, glucagon, substance P, luliberin, vasopressin, and ox- markedly inhibited. Insulin release was moderately stimulated, ytocin. The antigenic specificity of the antibodies was deter- and maximal release occurred relatively late. A moderate glu- mined by using somatostatin analogues (11). Phosphate buffer cose load (6.7 mM) inhibited glibenclamide-induced release of (0.04 M, pH 7.4) containing 1% bovine serum albumin was used somatostatin, whereas the two in combination exerted an ad- as the diluent for all components in this radioimmunoassay. ditive action on insulin release. Greater glucose loads, which by themselves would stimulate somatostatin release, only Incubations were for 48 hr at 4°C.
    [Show full text]
  • 1 Annex I Annex I Summary of Product Characteristics
    ANNEX I ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS 1 1. NAME OF THE MEDICINAL PRODUCT VENVIA 1 mg film-coated tablets. 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each tablet contains rosiglitazone maleate corresponding to 1 mg rosiglitazone. For excipients see 6.1. 3. PHARMACEUTICAL FORM Film-coated tablets Yellow film-coated tablets marked "SB" on one side and "1" on the other. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Rosiglitazone is indicated only in oral combination treatment of type 2 diabetes mellitus in patients with insufficient glycaemic control despite maximal tolerated dose of oral monotherapy with either metformin or a sulphonylurea: − in combination with metformin only in obese patients. − in combination with a sulphonylurea only in patients who show intolerance to metformin or for whom metformin is contraindicated. 4.2 Posology and method of administration Treatment should only be initiated by a physician experienced in the treatment of type 2 diabetes. Experience from clinical trials with rosiglitazone is currently limited to 2 years. The long-term benefits of therapy with rosiglitazone have not been demonstrated (see section 5.1). Rosiglitazone therapy is usually initiated at 4 mg/day. Combination with Metformin This dose can be increased to 8 mg/day after 8 weeks if greater glycaemic control is required. Combination with sulphonylurea There is currently no experience with doses of rosiglitazone above 4 mg/day in combination with sulphonylureas. Rosiglitazone may be given once or twice a day. Rosiglitazone may be taken with or without food. Elderly No dose adjustment is required in the elderly. 2 Patients with renal impairment No dose adjustment is required in patients with mild and moderate renal insufficiency.
    [Show full text]
  • Journal of Diabetes and Obesity
    Journal of Diabetes and Obesity Research Article Open Access The Different Association between Metformin and Sulfony- lurea Derivatives and the Risk of Cancer May be Confounded by Body Mass Index Catherine E. de Keyser1,2, Loes E. Visser1, Albert Hofman1, Bruno H. Stricker1,2*, Rikje Ruiter1# 1 Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands 2 The Health Care Inspectorate, The Hague, the Netherlands *Corresponding author: Bruno H. Stricker, Department of Epidemiology, Erasmus MC, P.O. Box 2040, 3000CA Rotterdam, the Netherlands, Tel: +31-10-7044958; Fax: +31-10-7044657; E-mail: [email protected] #Submitting author: Rikje Ruiter, Department of Epidemiology, Erasmus MC, P.O. Box 2040, 3000CA Rotterdam, the Nether- lands, Tel: +31-10-7044958; Fax: +31-10-7044657; E-mail: [email protected] Abstract Received date: July 09, 2016 Aim: Several studies in large databases suggest that in comparison to glucose-low- Accepted date: : September 05, 2016 ering sulfonylurea derivatives, metformin is associated with a reduced risk of cancer Publication date: September 12, 2016 in patients with diabetes. As many databases miss relevant confounder data, our objective was to investigate whether the determinants age, body mass index (BMI), alcohol consumption, and renal function were associated with dispensing of either Citation: Stricker, B.H., et al. The Dif- metformin or sulfonylurea derivatives as first drug therapy for type 2 diabetes mel- ferent Association between Metformin and litus while taking into account calendar time. Sulfonylurea Derivatives and the Risk of Methods: We identified 639 incident metformin users and 934 incident sulfonylurea Cancer May be Confounded by Body Mass derivatives users in the Rotterdam Study, a prospective population-based cohort Index.
    [Show full text]
  • Marked Improvement in Glycemic Control with Exenatide on Addition
    Journal of Diabetes Mellitus, 2018, 8, 152-159 http://www.scirp.org/journal/jdm ISSN Online: 2160-5858 ISSN Print: 2160-5831 Marked Improvement in Glycemic Control with Exenatide on Addition to Metformin, Sulfonylurea and Insulin Glargine in Type 2 Diabetes Mellitus, a Real World Experience Salina Esmail1, Sonal Banzal2, Udaya M. Kabadi2,3* 1University of Iowa, Iowa City, IA, USA 2MGM College of Medicine, Indore, India 3Broadlawns Medical Center, Des Moines, IA, USA How to cite this paper: Esmail, S., Banzal, S. Abstract and Kabadi, U.M. (2018) Marked Improve- ment in Glycemic Control with Exenatide on Background: The major effect of Exenatide is attributed to lowering of Addition to Metformin, Sulfonylurea and post-prandial glycemia, whereas insulin glargine mainly improves fasting Insulin Glargine in Type 2 Diabetes Mellitus, glycemia [FPG]. Objective: Therefore, we assessed effect of Exenatide a Real World Experience. Journal of Diabetes Mellitus, 8, 152-159. administration at 6 months and for at 1 year on glycemic control, lipids, body https://doi.org/10.4236/jdm.2018.84015 weight [BW], daily insulin dose and hypoglycemic events. Methods: Records of 164 subjects, 126 men and 38 women administered Exenatide between Received: August 27, 2018 January 2011 and December 2013 are included in this report. Exenatide was Accepted: November 12, 2018 Published: November 15, 2018 initiated at 5 mcg subcutaneously twice daily [BID] in obese subjects, BMI > 30 kg/m2, with C-peptide > 1 ng/d, and HbA1c 7.5% - 9.5%, while receiving Copyright © 2018 by authors and daily metformin 2000 mg, Sulfonylurea Glimepiride 8 mg and insulin Glar- Scientific Research Publishing Inc.
    [Show full text]
  • Diabetes in the Elderly: Matching Meds to Needs
    Barbara Keber, MD; Jennifer Fiebert, PharmD Hofstra Northwell School of Diabetes in the elderly: Medicine, Northwell Health, Glen Cove, NY Matching meds to needs [email protected] The authors reported no Elderly patients, whose insulin resistance is complicated potential conflict of interest relevant to this article. by age-related loss of beta-cell function and concomitant diseases, require personalized Tx considerations. s members of the baby boomer generation (adults PRACTICE ≥65 years) age, the number of people at risk for dia- RECOMMENDATIONS betes increases. Already nearly one-quarter of people ❯ Allow higher A1C goals for A 1 over age 65 have type 2 diabetes (T2DM). With a proliferation elderly patients who have of new medications to treat diabetes, deciding which ones to such comorbid conditions use in older patients is becoming complex. as cognitive dysfunction, dementia, or cardiovascu- In this article we review the important issues to consider lar or renal disease. B when prescribing and monitoring diabetes medications in older adults. To provide optimal patient-centered care, it’s nec- ❯ Look to metformin first essary to assess comorbid conditions as well as the costs, risks, in most instances if there are no contraindications. and benefits of each medication. Determining appropriate Monitor renal function goals of therapy and selecting agents that minimize the risk of frequently and vitamin B12 hypoglycemia will help ensure safe and effective management levels periodically. B of older patients with diabetes. ❯ Consider glucagon-like peptide-1 receptor agonists for patients who also have What makes elderly patients unique established cardiovascular The pathophysiology of T2DM in the elderly is unique in that disease, or consider starting it involves not just insulin resistance but also age-related loss basal insulin instead of using of beta-cell function, leading to reduced insulin secretion and multiple oral agents.
    [Show full text]
  • Liraglutide for the Treatment of Diabetes Mellitus in Japan
    REVIEW Liraglutide for the treatment of diabetes mellitus in Japan Kohei Kaku† A once‑daily 0.9 mg dose of liraglutide administered to Japanese subjects with Type 2 diabetes mellitus provides a significant glycated reduction hemoglobin of 1.5% or more from the baseline with few Points hypoglycemic episodes. Stepwise dose titration by 0.3‑mg increments at intervals of 1 week significantly reduces the frequency of gastrointestinal symptoms. Practice When liraglutide is used in combination with sulfonylurea, dose reduction of sulfonylurea should be considered to avoid a risk of hypoglycemia. A once‑daily 0.9‑mg dose of liraglutide is not always sufficient to suppress bodyweight gain. The use of liraglutide in insulin‑dependent patients should be strictly avoided. The safety of liraglutide is not established in pregnant patients or in pediatric patients. SUMMARY Impaired b‑cell function in Type 2 diabetes mellitus (T2DM) is generally progressive. The commonly used sulfonylureas (SU) lose efficacy over time and are associated with impaired b‑cell function, and undesirable events such as weight gain and hypoglycemia. Thus, there is a strong need to develop antidiabetic agents that control glycemia without weight gain and hypoglycemia, and preserve b‑cell function. Glucagon‑like‑peptide‑1 (GLP‑1) is known to improve glycemic control by enhancement of glucose‑stimulated insulin secretion, preserving b‑cell function, and minimizing hypoglycemia and weight gain. Liraglutide, a human GLP‑1 analog, has recently been approved for use in Japanese patients with T2DM. To assess liraglutide in management of Japanese patients with T2DM, the results of clinical studies in Japan is summarized and also compared with the data from Europe and the USA.
    [Show full text]
  • Are Metformin, Statin and Aspirin Use Still Associated with Overall Mortality Among Colorectal Cancer Patients with Diabetes If Adjusted for One Another? Zanders, M
    Tilburg University Are metformin, statin and aspirin use still associated with overall mortality among colorectal cancer patients with diabetes if adjusted for one another? Zanders, M. M. J.; van Herk-Sukel, M. P. P.; Vissers, P. A. J.; Herings, R. M. C.; Haak, H. R.; van de Poll-Franse, L. V. Published in: The British Journal of Cancer DOI: 10.1038/bjc.2015.259 Publication date: 2015 Document Version Publisher's PDF, also known as Version of record Link to publication in Tilburg University Research Portal Citation for published version (APA): Zanders, M. M. J., van Herk-Sukel, M. P. P., Vissers, P. A. J., Herings, R. M. C., Haak, H. R., & van de Poll- Franse, L. V. (2015). Are metformin, statin and aspirin use still associated with overall mortality among colorectal cancer patients with diabetes if adjusted for one another? The British Journal of Cancer, 113(3), 403-410. https://doi.org/10.1038/bjc.2015.259 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.
    [Show full text]
  • Sulfonylureas
    Therapeutic Class Overview Sulfonylureas INTRODUCTION In the United States (US), diabetes mellitus affects more than 30 million people and is the 7th leading cause of death (Centers for Disease Control and Prevention [CDC] 2018). Type 2 diabetes mellitus (T2DM) is the most common form of diabetes and is characterized by elevated fasting and postprandial glucose concentrations (American Diabetes Association [ADA] 2019[a]). It is a chronic illness that requires continuing medical care and ongoing patient self-management education and support to prevent acute complications and to reduce the risk of long-term complications (ADA 2019[b]). ○ Complications of T2DM include hypertension, heart disease, stroke, vision loss, nephropathy, and neuropathy (ADA 2019[a]). In addition to dietary and lifestyle management, T2DM can be treated with insulin, one or more oral medications, or a combination of both. Many patients with T2DM will require combination therapy (Garber et al 2019). Classes of oral medications for the management of blood glucose levels in patients with T2DM focus on increasing insulin secretion, increasing insulin responsiveness, or both, decreasing the rate of carbohydrate absorption, decreasing the rate of hepatic glucose production, decreasing the rate of glucagon secretion, and blocking glucose reabsorption by the kidney (Garber et al 2019). Pharmacologic options for T2DM include sulfonylureas (SFUs), biguanides, thiazolidinediones (TZDs), meglitinides, alpha-glucosidase inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) analogs, amylinomimetics, sodium-glucose cotransporter 2 (SGLT2) inhibitors, combination products, and insulin (Garber et al 2019). SFUs are the oldest of the oral antidiabetic medications, and all agents are available generically. The SFUs can be divided into 2 categories: first-generation and second-generation.
    [Show full text]
  • Actos II-10-11
    ANNEX I ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS 1 1. NAME OF THE MEDICINAL PRODUCT Actos 15 mg tablets. 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each tablet contains 15 mg of pioglitazone as hydrochloride. For excipients, see 6.1. 3. PHARMACEUTICAL FORM Tablet. The tablets are white to off-white, round, convex and marked ‘15’ on one face. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Pioglitazone is indicated as oral monotherapy in type 2 diabetes mellitus patients, particularly overweight patients, inadequately controlled by diet and exercise for whom metformin is inappropriate because of contraindications or intolerance. Pioglitazone is also indicated for oral combination treatment in type 2 diabetes mellitus patients with insufficient glycaemic control despite maximal tolerated dose of oral monotherapy with either metformin or sulphonylurea: - in combination with metformin particularly in overweight patients - in combination with a sulphonylurea only in patients who show intolerance to metformin or for whom metformin is contraindicated 4.2 Posology and method of administration The long-term benefits of therapy with pioglitazone have not been demonstrated (see section 5.1). Pioglitazone tablets are taken orally once daily with or without food. Dosage in adults: Pioglitazone may be initiated at 15mg or 30mg once daily. The dose may be increased in increments up to 45mg once daily. In combination with metformin, the current metformin dose can be continued upon initiation of pioglitazone therapy. In combination with sulphonylurea, the current sulphonylurea dose can be continued upon initiation of pioglitazone therapy. If patients report hypoglycaemia, the dose of sulphonylurea should be decreased. 2 Elderly: No dosage adjustment is necessary for elderly patients (see section 5.2).
    [Show full text]
  • Utah Medicaid Pharmacy and Therapeutics Committee Drug
    Utah Medicaid Pharmacy and Therapeutics Committee Drug Class Review DPP-4 Inhibitor Products AHFS Classification: 68:20.05 Dipeptidyl Peptidase-4 Inhibitors Alogliptin (Nesina) Alogliptin and Metformin (Kazano) Alogliptin and Pioglitazone (Oseni) Linagliptin (Tradjenta) Linagliptin and Empagliflozin (Glyxambi) Linagliptin and Metformin (Jentadueto, Jentadueto XR) Saxagliptin (Onglyza) Saxagliptin and Dapagliflozin (Qtern) Saxagliptin and Metformin (Kombiglyze XR) Sitagliptin (Januvia) Sitagliptin and Metformin (Janumet, Janumet XR) Final Report November 2017 Review prepared by: Elena Martinez Alonso, B.Pharm., MSc MTSI, Medical Writer Valerie Gonzales, Pharm.D., Clinical Pharmacist Vicki Frydrych, Pharm.D., Clinical Pharmacist Joanita Lake, B.Pharm., MSc EBHC (Oxon), Assistant Professor University of Utah College of Pharmacy Michelle Fiander, MA, MLIS, Systematic Review/Evidence Synthesis Librarian Joanne LaFleur, Pharm.D., MSPH, Associate Professor University of Utah College of Pharmacy University of Utah College of Pharmacy, Drug Regimen Review Center Copyright © 2017 by University of Utah College of Pharmacy Salt Lake City, Utah. All rights reserved 1 Contents List of Abbreviations .................................................................................................................................... 3 Executive Summary ...................................................................................................................................... 4 Introduction ..................................................................................................................................................
    [Show full text]
  • (Glyburide) Tablets USP 1.25, 2.5 and 5 Mg DESCRIPTION Diaßeta
    Diaßeta® (glyburide) Tablets USP 1.25, 2.5 and 5 mg DESCRIPTION Diaßeta® (glyburide) is an oral blood-glucose-lowering drug of the sulfonylurea class. It is a white, crystalline compound, formulated as tablets of 1.25 mg, 2.5 mg, and 5 mg strengths for oral administration. Diaßeta tablets USP contain the active ingredient glyburide and the following inactive ingredients: dibasic calcium phosphate USP, magnesium stearate NF, microcrystalline cellulose NF, sodium alginate NF, talc USP. Diaßeta 1.25 mg tablets USP also contain D&C Yellow #10 Aluminum Lake and FD&C Red #40 Aluminum Lake. Diaßeta 2.5 mg tablets USP also contain FD&C Red #40 Aluminum Lake. Diaßeta 5 mg tablets USP also contain D&C Yellow #10 Aluminum Lake, and FD&C Blue #1. Chemically, Diaßeta is identified as 1-[[p-[2-(5-Chloro-o-anisamido)ethyl]phenyl]sulfonyl]-3-cyclohexylurea. The CAS Registry Number is 10238-21-8. The structural formula is: Cl CONHCH2CH2 SO2NHCONH OCH3 The molecular weight is 493.99. The aqueous solubility of Diaßeta increases with pH as a result of salt formation. CLINICAL PHARMACOLOGY Diaßeta appears to lower the blood glucose acutely by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta cells in the pancreatic islets. The mechanism by which Diaßeta lowers blood glucose during long-term administration has not been clearly established. With chronic administration in Type II diabetic patients, the blood glucose lowering effect persists despite a gradual decline in the insulin secretory response to the drug. Extrapancreatic effects may play a part in the mechanism of action of oral sulfonylurea hypoglycemic drugs.
    [Show full text]
  • Glucagon-Like Peptide-1 Receptor Agonists
    Clinical Policy: Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists Reference Number: HIM.PA.53 Effective Date: 03.01.18 Last Review Date: 02.21 Line of Business: HIM Revision Log See Important Reminder at the end of this policy for important regulatory and legal information. Description The following agents contain a synthetic glucagon-like peptide-1 (GLP-1) receptor agonist and require prior authorization: dulaglutide (Trulicity®), exenatide ER (Bydureon®, Bydureon BCise®), exenatide IR (Byetta®), liraglutide (Victoza®), liraglutide/insulin degludec (Xultophy®), lixisenatide (Adlyxin®), lixisenatide/insulin glargine (Soliqua®), and semaglutide (Ozempic®, Rybelsus®). FDA Approved Indication(s) GLP-1 receptor agonists are indicated as adjunct to diet and exercise to improve glycemic control with type 2 diabetes mellitus. Victoza is indicated in patients 10 years of age and older, while the other GLP-1 receptor agonists are indicated in adults. Ozempic, Trulicity and Victoza are also indicated to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes mellitus and: • Established cardiovascular disease (Ozempic, Trulicity, Victoza); • Cardiovascular risk factors (Trulicity only). Limitation(s) of use: • Trulicity, Bydureon, Bydureon BCise, and Xultophy are not recommended as a first-line therapy for patients inadequately controlled on diet and exercise. • Other than Soliqua and Xultophy which contains insulin, GLP-1 receptor agonists are not a substitute for insulin. They should not be used for the treatment of type 1 diabetes or diabetic ketoacidosis. • Other than Trulicity, concurrent use with prandial insulin has not been studied and cannot be recommended. • GLP-1 receptor agonists have not been studied in patients with a history of pancreatitis.
    [Show full text]