DOCSLIB.ORG

Potential of Albiglutide, a Long-Acting GLP-1 Receptor Agonist, in Type 2 Diabetes a Randomized Controlled Trial Exploring Weekly, Biweekly, and Monthly Dosing

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Potential of Albiglutide, a Long-Acting GLP-1 Receptor Agonist, in Type 2 Diabetes a Randomized Controlled Trial Exploring Weekly, Biweekly, and Monthly Dosing Emerging Treatments and Technologies ORIGINAL ARTICLE Potential of Albiglutide, a Long-Acting GLP-1 Receptor Agonist, in Type 2 Diabetes A randomized controlled trial exploring weekly, biweekly, and monthly dosing 1 5 JULIO ROSENSTOCK, MD FRED YANG, PHD ability of native GLP-1 to stimulate glu- 2,3 5 JANE REUSCH, MD MURRAY STEWART, DM, FRCP cose-dependent insulin secretion and 4 MARK BUSH, PHD FOR THE ALBIGLUTIDE STUDY GROUP suppress inappropriately elevated gluca- gon secretion (11,12). Native GLP-1 also slows gastric emptying and reduces food OBJECTIVE — To evaluate the efficacy, safety, and tolerability of incremental doses of albi- intake, which leads to modest weight loss glutide, a long-acting glucagon-like peptide-1 receptor agonist, administered with three dosing (11). However, native GLP-1 is rapidly schedules in patients with type 2 diabetes inadequately controlled with diet and exercise or inactivated (half-life 1–2 min) by dipepti- metformin monotherapy. dyl peptidase-4 (DPP-4), limiting its ther- RESEARCH DESIGN AND METHODS — In this randomized multicenter double- apeutic potential (13). Exenatide (half-life blind parallel-group study, 356 type 2 diabetic subjects with similar mean baseline characteris- 2.4 h) improves glycemic control in com- tics (age 54 years, diabetes duration 4.9 years, BMI 32.1 kg/m2, A1C 8.0%) received bination with metformin, a sulfonylurea, subcutaneous placebo or albiglutide (weekly [4, 15, or 30 mg], biweekly [15, 30, or 50 mg], or or a thiazolidinedione (14–18). Despite monthly [50 or 100 mg]) or exenatide twice daily as an open-label active reference (per labeling modest weight loss and improved glyce- in metformin subjects only) over 16 weeks followed by an 11-week washout period. The main mic control, gastrointestinal (GI) intoler- outcome measure was change from baseline A1C of albiglutide groups versus placebo at week ability and twice-daily administration 16. may lead to discontinuation (19). RESULTS — Dose-dependent reductions in A1C were observed within all albiglutide sched- Albiglutide (formerly known as alb- ules. Mean A1C was similarly reduced from baseline by albiglutide 30 mg weekly, 50 mg ugon) is a GLP-1 receptor agonist devel- biweekly (every 2 weeks), and 100 mg monthly (Ϫ0.87, Ϫ0.79, and Ϫ0.87%, respectively) oped through the fusion of two repeats of versus placebo (Ϫ0.17%, P Ͻ 0.004) and exenatide (Ϫ0.54%). Weight loss (Ϫ1.1 to Ϫ1.7 kg) human GLP-1 (7–36) molecules to re- was observed with these three albiglutide doses with no significant between-group effects. The combinant human albumin (20). The incidence of gastrointestinal adverse events in subjects receiving albiglutide 30 mg weekly was GLP-1 dimer was used to avoid potential less than that observed for the highest biweekly and monthly doses of albiglutide or exenatide. reductions of the interaction of the GLP-1 moiety of the monomer with its receptor CONCLUSIONS — Weekly albiglutide administration significantly improved glycemic con- in the presence of albumin. A single trol and elicited weight loss in type 2 diabetic patients, with a favorable safety and tolerability 3 profile. amino acid substitution (ala8 gly) ren- ders the molecule resistant to DPP-4. The Diabetes Care 32:1880–1886, 2009 structure of albiglutide provides an ex- tended half-life (ϳ5 days), which may al- arly intervention to improve glyce- the American Diabetes Association (ADA) low weekly or less frequent dosing. mic control reduces microvascular target A1C level (Ͻ7%) (6–8). Moreover, Furthermore, albiglutide is relatively im- E complications in type 2 diabetes weight gain and treatment-induced hypo- permeant to the central nervous system (1–4) and may provide long-term macro- glycemic episodes (9,10) are major barri- (21), which may have implications for GI vascular benefits (5). Despite numerous ers to achieving glycemic control (10). tolerability. In nonclinical studies, albig- available therapies, over half of patients Antidiabetic therapies based on glu- lutide stimulated cAMP production with type 2 diabetes are unable to achieve cagon-like peptide-1 (GLP-1) retain the through the GLP-1 receptor and induced ●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●● insulin secretion from INS-1 cells in vitro and in animal models (21–22). It also de- From the 1Dallas Diabetes and Endocrine Center at Medical City, Dallas, Texas; the 2Division of Endocri- nology, Metabolism and Diabetes, University of Colorado–Denver AMC, Denver, Colorado; the 3Denver layed gastric emptying and reduced food Veterans Affairs Medical Center, Denver, Colorado; 4GlaxoSmithKline, Research Triangle Park, North intake in rodents (21–23). Carolina; and 5GlaxoSmithKline, King of Prussia, Pennsylvania. This study was designed to explore a Corresponding author: Julio Rosenstock, [email protected]. wide range of doses (4–100 mg) and Received 24 February 2009 and accepted 6 July 2009. Published ahead of print at http://care.diabetesjournals.org on 10 July 2009. DOI: 10.2337/dc09-0366. schedules (weekly to monthly) to assess Clinical trial reg. no. NCT00518115, clinicaltrials.gov. glycemic control and adverse event pro- © 2009 by the American Diabetes Association. Readers may use this article as long as the work is properly files for albiglutide. Exenatide was in- cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons. cluded as an open-label reference to org/licenses/by-nc-nd/3.0/ for details. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby provide clinical perspective for a GLP-1 marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. receptor agonist. 1880 DIABETES CARE, VOLUME 32, NUMBER 10, OCTOBER 2009 care.diabetesjournals.org (5 (50 or 100 mg);(biweekly; or 15, open-label 30, or exenatide 50weekly mg), (4, or monthly 15, or(matched 30 to mg), albiglutide arms); every albiglutide 2treatment weeks arms: double-blindSubjects placebo were randomizedRandomization into 1 of 10 sessed safety data on ancommittee ongoing of basis. independentprescreening. experts A as- dataconsent safety was obtained monitoring from alltion subjects at of Helsinki.ducted Written in accordance informed an with institutional the review Declara- board and con- permitted. the-counter weight-loss drugsenrollment, and were no prescriptionat or over- the samemedications dose must for have 3 beenically months maintained prior significant. to Lipid-lowering tological profiles considered tomg/dl be (9 clin- mmol/l) ateases; screening; or fasting hema- serumbrovascular, triglycerides renal, or5 hepatobiliary years; dis- significant cardiovascular, cere- 12 weeks of 10 not used for insulin formin) antidiabetic monotherapy (except met- ( at 118 sites inducted the between U.S. April ( 2007 andcebo-controlled May parallel-group 2008 studyprospective con- randomized double-blind pla- METHODS RESEARCH DESIGN AND care.diabetesjournals.org D ple) were administered in the(same physician’s formulation without activetol, princi- 0.01% polysorbate-80)phosphate, and 4.2% placebo trehalose, 2.8% manni- lutide (formulated in 10 mmol/l sodium screening BMI ing). Additional inclusion criteria included for the exenatide arm (consistent with label- with metformin monotherapy were eligible to screening visit).months Only before prescreening subjects (1formin week treated prior monotherapy and(diet stable and exercise) for before screening. or Subjects were treated drugdiagnosed with naïve with type 2 met- diabetes 18–75 years) were eligiblewomen for of inclusion non-childbearing if potentialcontent/full/dc09-0366/DC1). (age Menable at and http://care.diabetesjournals.org/cgi/ Republic ( n ϭ ␮ The study protocol was approved by Exclusion criteria included any oral g twice daily for 4 weeks followed by 9), Chile ( Ն 20 and Ͻ Յ 1 month prior to screening and Ն n 3 months prior to screening or ϭ 7 and Ͼ 1) (online appendix 1, avail- — This phase II trial was a 7 days; pancreatitis within n Յ ϭ ␮ Յ 40 kg/m g twice daily). Albig- 2), and the Dominican 10%. n ϭ 2 106), Mexico and A1C at Ն 3 months Ն 800 Ͼ 3 Table 1—Change from baseline in glycemic parameters at 16 weeks Albiglutide Exenatide* Weekly Biweekly Monthly twice daily, Placebo 5–10 ␮g 4mg 15mg 30mg 15mg 30mg 50mg 50mg 100mg n (A1C data) 50 34 34 34 29 30 32 34 35 33 Baseline A1C (%) 7.8 Ϯ 0.9 8.0 Ϯ 0.9 8.2 Ϯ 1.0 8.0 Ϯ 0.9 8.0 Ϯ 0.9 8.2 Ϯ 1.0 8.0 Ϯ 1.0 7.9 Ϯ 0.7 7.9 Ϯ 0.8 8.1 Ϯ 1.0 ⌬A1C at 16 weeks vs. Ϫ Ϯ Ϫ Ϯ Ϫ Ϯ Ϫ Ϯ Ϫ Ϯ Ϫ Ϯ Ϫ Ϯ Ϫ Ϯ Ϫ Ϯ Ϫ Ϯ IABETES baseline 0.17 1.01 0.54 0.91 0.11 1.16 0.49 0.74 0.87 0.65† 0.56 0.97 0.79 0.98† 0.79 1.04† 0.55 1.01 0.87 0.87† n (FPG data) 47 33 32 32 29 28 32 32 34 33 Baseline FPG C Ϯ Ϯ Ϯ Ϯ Ϯ Ϯ Ϯ Ϯ Ϯ Ϯ ARE (mmol/l) 9.9 3.7 9.5 2.4 10.9 3.9 9.5 2.9 9.6 3.1 10.2 2.7 9.5 3.3 10.0 3.2 9.3 2.7 9.8 3.8 ⌬ , FPG at 16 VOLUME weeks vs. baseline (%) Ϫ0.10 Ϯ 2.90 Ϫ0.80 Ϯ 2.48 Ϫ0.47 Ϯ 3.12 Ϫ0.72 Ϯ 1.68 Ϫ1.44 Ϯ 2.03† Ϫ1.28 Ϯ 2.43 Ϫ1.58 Ϯ 2.06† Ϫ1.32 Ϯ 3.52† Ϫ0.72 Ϯ 2.77 Ϫ1.22 Ϯ 3.50† 32, Data are means Ϯ SD for the intent-to-treat population, last observation carried forward.
Load more

Recommended publications
  • Exenatide QW: a New Treatment Option for Type 2 Diabetes Offering Ease of Use, Improved Efficacy, and Reduced Side Effects
    FEATURE ARTICLE Commentary: Exenatide QW: A New Treatment Option for Type 2 Diabetes Offering Ease of Use, Improved Efficacy, and Reduced Side Effects Charles F. Shaefer, Jr., MD Editor’s note: Once-weekly exenatide, (also called incretin mimetics) cur- with GLP-1 receptor agonists is the which has recently been approved for rently in use.3,4 only form of anti-diabetes therapy patients with type 2 diabetes, has great Validation of the acceptance offering proven weight loss. Finally, potential as a new diabetes therapy in clinical practice of GLP-1 GLP-1 receptor agonist therapy is in the primary care setting. This receptor agonists can be found in one of the recommended treatment commentary and the feature article that the recently released American strategies offering a low incidence of follows it (p. 95) offer an overview of Diabetes Association (ADA)/ hypoglycemia, an important aspect this new therapeutic tool and important European Association for the Study of diabetes therapy learned from the insights about its clinical utility. In the of Diabetes (EASD) position state- Action to Control Cardiovascular interest of transparency, however, we ment on the management of type 2 Risk in Diabetes trial.6 want to point out that the authors of diabetes, which placed these drugs As clinicians consider what to do both articles are affiliated with Amylin alongside older, well-accepted agents when metformin and lifestyle change Pharmaceuticals, which manufactures such as sulfonylureas (SUs) and do not adequately control a patient’s exenatide QW and markets it under the thiozolidinediones (TZDs) as a sec- A1C, they frequently ask, “incretin 5 trade name Bydureon.
    [Show full text]
  • GLP-1 Receptor Agonists
    Cognitive Vitality Reports® are reports written by neuroscientists at the Alzheimer’s Drug Discovery Foundation (ADDF). These scientific reports include analysis of drugs, drugs-in- development, drug targets, supplements, nutraceuticals, food/drink, non-pharmacologic interventions, and risk factors. Neuroscientists evaluate the potential benefit (or harm) for brain health, as well as for age-related health concerns that can affect brain health (e.g., cardiovascular diseases, cancers, diabetes/metabolic syndrome). In addition, these reports include evaluation of safety data, from clinical trials if available, and from preclinical models. GLP-1 Receptor Agonists Evidence Summary GLP-1 agonists are beneficial for patients with type 2 diabetes and obesity. Some evidence suggests benefits for Alzheimer’s disease. It is unclear whether it is beneficial for individuals without underlying metabolic disease. Semaglutide seems to be most effective for metabolic dysfunction, though liraglutide has more preclinical data for Alzheimer’s disease. Neuroprotective Benefit: Evidence from many preclinical studies and a pilot biomarker study suggest some neuroprotective benefits with GLP-1 agonists. However, whether they may be beneficial for everyone or only a subset of individuals (e.g. diabetics) is unclear. Aging and related health concerns: GLP-1 agonists are beneficial for treating diabetes and cardiovascular complications relating to diabetes. It is not clear whether they have beneficial effects in otherwise healthy individuals. Safety: GLP-1 agonists are generally safe for most people with minor side effects. However, long-term side effects are not known. 1 Availability: Available Dose: Varies - see Chemical formula: C172H265N43O51 (Liraglutide) as a prescription chart at the end of MW: 3751.262 g/mol medicine.
    [Show full text]
  • The Activation of the Glucagon-Like Peptide-1 (GLP-1) Receptor by Peptide and Non-Peptide Ligands
    The Activation of the Glucagon-Like Peptide-1 (GLP-1) Receptor by Peptide and Non-Peptide Ligands Clare Louise Wishart Submitted in accordance with the requirements for the degree of Doctor of Philosophy of Science University of Leeds School of Biomedical Sciences Faculty of Biological Sciences September 2013 I Intellectual Property and Publication Statements The candidate confirms that the work submitted is her own and that appropriate credit has been given where reference has been made to the work of others. This copy has been supplied on the understanding that it is copyright material and that no quotation from the thesis may be published without proper acknowledgement. The right of Clare Louise Wishart to be identified as Author of this work has been asserted by her in accordance with the Copyright, Designs and Patents Act 1988. © 2013 The University of Leeds and Clare Louise Wishart. II Acknowledgments Firstly I would like to offer my sincerest thanks and gratitude to my supervisor, Dr. Dan Donnelly, who has been nothing but encouraging and engaging from day one. I have thoroughly enjoyed every moment of working alongside him and learning from his guidance and wisdom. My thanks go to my academic assessor Professor Paul Milner whom I have known for several years, and during my time at the University of Leeds he has offered me invaluable advice and inspiration. Additionally I would like to thank my academic project advisor Dr. Michael Harrison for his friendship, help and advice. I would like to thank Dr. Rosalind Mann and Dr. Elsayed Nasr for welcoming me into the lab as a new PhD student and sharing their experimental techniques with me, these techniques have helped me no end in my time as a research student.
    [Show full text]
  • 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]
  • Combining a Glucagon-Like Peptide-1 Receptor Agonist with Basal Insulin: the Why and How
    Combining a Glucagon-like Peptide-1 Receptor Agonist with Basal Insulin: The Why and How Case Study Mary is a 61 year-old female diagnosed with type 2 diabetes mellitus (T2DM) 8 years ago. She was initially managed with the combination of lifestyle modification and metformin. Since that time she was treated with a sulfonylurea, but it was discontinued due to symptomatic hypoglycemia. She was also treated with pioglitazone, but significant fluid retention led to it discontinuation. A year-and-a- half ago, basal insulin was added to her lifestyle and metformin management. She now administers 52 units (0.62 units/kg) once daily at bedtime. Since starting basal insulin, she has experienced 3 episodes of mild hypoglycemia. Since her diagnosis, Mary’s HbA1c has never been <7.0%; her current HbA1c is 7.9%. Over the past month, her fasting plasma glucose (FPG) has ranged from 103 mg/dL to 136 mg/dL and her postprandial glucose (PPG) from 164 mg/dL to 213 mg/dL. She has gained 2.6 kg since starting basal insulin and her body mass index is now 31 kg/m2. Her blood pressure is 134/82 mmHg. She experiences occasional tingling in her feet. Eye examination reveals grade 1 retinopathy. Current medications are: metformin 1000mg twice daily, basal insulin 52 units once daily at bedtime, and hydrochlorothiazide 25 mg once daily. Her family physician notes that Mary’s FPG is reasonably well-controlled, yet her HbA1c and PPG remain elevated. He is also concerned about her episodes of hypoglycemia and weight gain and the evidence indicating microvascular damage.
    [Show full text]
  • Predicting Immunogenicity of Peptide Drugs and Their Impurities
    Predicting Immunogenicity of Peptide Drugs and their Impurities using in Silico tools: Taspoglutide Case Study Aimee Mattei MS1, Frances Terry MPH1, Brian J Roberts PhD1, William Martin1, and Anne S De Groot MD1,2 1EpiVax, Inc.; 2Professor (Research) and Director, Institute for Immunology and Informatics, University of Rhode Island, USA Abstract What-if-Machine (WhIM) 15 Example Risk Profile for RLD A : . The peptide drug market is expected to generate $50B in revenue by 2024 but the FDA is Random Mimics the process of synthesizing High H ig h concerned about the number of impurities that may be introduced in the synthetic process. polypeptides and records theoretical Low 10 product impurities created through known . The peptide manufacturing process can result in synthesis-related impurities that can introduce Example Risk Profile for failures in the synthesis process. Random Peptides immunogenic epitopes within the amino acid sequence of the peptide, resulting in an unexpected 5 and undesired immune response against the drug. Each identified impurity is scored for Example Risk Profile for RLD B : putative T cell epitope content (EpiMatrix) Low 0 . EpiMatrix can be used to screen both the drug API sequence and its known peptide-related and cross conservation with the human Impurity Risk Score Risk Impurity impurities for the presence of putative T cell epitope content. proteome (JanusMatrix). -5 . When peptide-related impurities are unknown, the “What if Machine” (WhIM) can perform Impurities are weighted based on assumed probability of occurrence. Graphic for illustrative purposes only theoretical changes to the natural amino acid sequence of the drug substance and measure their -1 0 impact on the putative epitope content of the peptide.
    [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]
  • Exenatide: Role in Management of Type 2 Diabetes and Associated Cardiovascular Risk Factors
    Therapy in Practice Exenatide: role in management of Type 2 diabetes and associated cardiovascular risk factors Zin Z Htike1, Kamlesh Khunti2 & Melanie Davies* Practice Points Obesity in Type 2 diabetes poses a challenge in choosing the right combination of glucose-lowering agents, particularly due to the potential side effect of weight gain with many of the existing glucose-lowering medications. One of the incretin-based therapies, the glucagon-like peptide-1 analog, exenatide, is found to be a promising new agent that not only provides glucoregulatory effect in improving glycemic control without increase risk of hypoglycemia but also often results in weight loss. Treatment with exenatide results in reduction in HbA1c comparable to many of the existing glucose-lowering agents including basal insulin analog, galrgine or biphasic insulin aspart. Exenatide is of particular benefit in obese patients with Type 2 diabetes whose control in inadequate on a combination of oral glucose-lowering agents. To date, exenatide is not licensed for use in combination with insulin. SUMMARY Management of Type 2 diabetes, particularly in obese patients, is rather challenging as treatment with the majority of the available glucose-lowering t herapies is often associated with side effects of weight gain and hypoglycemia, in addition to failure to maintain durable glycemic control. The first available glucagon-like peptide-1 analog, exenatide, adds a new t herapeutic option to the currently available glucose-lowering agents for obese patients with Type 2 d iabetes. Both randomized controlled trials and retrospective observational s tudies have shown that treatment with exenatide not only improves glycemic control with a low risk of h ypoglycemia, but also results in concurrent weight loss with the additional benefit of i mprovement in cardiovascular risk factors of hypertension and hyperlipidemia.
    [Show full text]
  • A Network Meta-Analysis Comparing Exenatide Once Weekly with Other GLP-1 Receptor Agonists for the Treatment of Type 2 Diabetes Mellitus
    Diabetes Ther DOI 10.1007/s13300-016-0155-1 REVIEW A Network Meta-analysis Comparing Exenatide Once Weekly with Other GLP-1 Receptor Agonists for the Treatment of Type 2 Diabetes Mellitus Sheena Kayaniyil . Greta Lozano-Ortega . Heather A. Bennett . Kristina Johnsson . Alka Shaunik . Susan Grandy . Bernt Kartman To view enhanced content go to www.diabetestherapy-open.com Received: December 17, 2015 Ó The Author(s) 2016. This article is published with open access at Springerlink.com ABSTRACT treatment of adults with T2DM inadequately controlled on metformin monotherapy. Introduction: Exenatide is a glucagon-like Methods: A systematic literature review was peptide-1 receptor agonist (GLP-1 RA), conducted to identify randomized controlled approved for treatment of type 2 diabetes trials (RCTs) that investigated GLP-1 RAs mellitus (T2DM). There is limited direct (albiglutide, dulaglutide, exenatide, liraglutide, evidence comparing the efficacy and and lixisenatide) at approved doses in the tolerability of exenatide 2 mg once weekly United States/Europe, added on to metformin (QW) to other GLP-1 RAs. A network only and of 24 ± 6 weeks treatment duration. meta-analysis (NMA) was conducted to A Bayesian NMA was conducted. estimate the relative efficacy and tolerability of Results: Fourteen RCTs were included in the exenatide QW versus other GLP-1 RAs for the NMA. Exenatide QW obtained a statistically significant reduction in glycated hemoglobin (HbA1c) relative to lixisenatide 20 lg once daily. No other comparisons of exenatide QW Electronic supplementary material The online version of this article (doi:10.1007/s13300-016-0155-1) to other GLP-1 RAs were statistically significant contains supplementary material, which is available to for change in HbA1c.
    [Show full text]