Campbell RK

References (7)

Title : Dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes mellitus - Neumiller_2010_Pharmacotherapy_30_463
Author(s) : Neumiller JJ , Wood L , Campbell RK
Ref : Pharmacotherapy , 30 :463 , 2010
Abstract : Type 2 diabetes mellitus traditionally has been characterized by insulin resistance and beta-cell dysfunction, leading to hyperglycemia and eventual micro- and macrovascular complications. Dipeptidyl peptidase-4 (DPP-4) inhibitors are a relatively new class of drugs available for the management of type 2 diabetes. In order to provide a comprehensive evaluation and comparison of the pharmacology, pharmacokinetics, efficacy, and safety of the DPP-4 inhibitors-sitagliptin, vildagliptin, saxagliptin, and alogliptin-in the treatment of type 2 diabetes, we conducted a MEDLINE search (1966-July 2009) for pertinent English-language articles. Abstracts of the annual meetings of the American Diabetes Association and European Association for the Study of Diabetes from 2005-2009 were also searched. As a drug class, the DPP-4 inhibitors have become widely accepted in clinical practice because of their low risk of hypoglycemia, favorable adverse-effect profile, and once-daily dosing. They are weight neutral (do not cause weight gain or loss) and appear to decrease beta-cell apoptosis and increase beta-cell survival. Because clinical studies directly comparing agents from this class have not, to our knowledge, been conducted, making comparisons in terms of efficacy and safety will become difficult for clinicians as more agents become available. Based on information from preclinical, clinical, and postmarketing data, there does not appear to be a compelling advantage of one DPP-4 inhibitor over another in terms of efficacy, safety, or ease of clinical use. Although theoretical advantages exist for agents with a higher specificity for DPP-4 inhibition versus inhibition of other isoenzymes associated with toxicity, comparative studies and/or increased clinical experience with this class of drug will determine the clinical advantages, if any, of one agent over another.
ESTHER : Neumiller_2010_Pharmacotherapy_30_463
PubMedSearch : Neumiller_2010_Pharmacotherapy_30_463
PubMedID: 20411998

Title : Saxagliptin: a dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes mellitus - Neumiller_2010_Am.J.Health.Syst.Pharm_67_1515
Author(s) : Neumiller JJ , Campbell RK
Ref : Am J Health Syst Pharm , 67 :1515 , 2010
Abstract : PURPOSE: The pharmacology, pharmacokinetics, efficacy, safety, and dosage and administration of saxagliptin are reviewed. SUMMARY: Saxagliptin is a selective, reversible inhibitor of dipeptidyl peptidase-4 (DPP-4) approved for the treatment of type 2 diabetes mellitus in adults. By inhibiting DPP-4, saxagliptin reduces the degradation of endogenous incretin hormones, resulting in increased glucose-dependent insulin release and decreased glucagon secretion from the pancreas. Saxagliptin is rapidly absorbed after oral administration, and its pharmacokinetic profile allows for once-daily oral administration. Clinical trials of saxagliptin as monotherapy and as combination therapy with other oral antidiabetic medications including metformin, glyburide, pioglitazone, and rosiglitazone have demonstrated clinical benefits in various glycemic endpoints, including glycosylated hemoglobin (HbA(1c)), fasting plasma glucose (FPG), and postprandial glucose (PPG) levels over 24 to 102 weeks of therapy. Due to its glucose-dependent mechanism of action, saxagliptin as monotherapy or in combination with metformin results in a low risk for hypoglycemia in patients with type 2 diabetes. Saxagliptin was generally well tolerated in clinical trials, with headache, upper-respiratory-tract infection, and urinary tract infection being the most common adverse events. Saxagliptin has demonstrated a low risk for drug-drug interactions. For patients with moderate or severe renal impairment or end-stage renal disease or patients taking a strong inhibitor of cytochrome P-450 isoenzyme 3A4 or 3A5, the recommended dosage is 2.5 mg once daily. CONCLUSION: Saxagliptin, a DPP-4 inhibitor approved for the treatment of type 2 diabetes, demonstrated safety and efficacy in lowering HbA(1c), FPG, and PPG levels as both monotherapy and in combination with other oral antidiabetic medications.
ESTHER : Neumiller_2010_Am.J.Health.Syst.Pharm_67_1515
PubMedSearch : Neumiller_2010_Am.J.Health.Syst.Pharm_67_1515
PubMedID: 20811029

Title : Looking to the future: focus on DPP-4 inhibitors for the treatment of type 2 diabetes and emerging therapies - Neumiller_2008_Diabetes.Educ_34_183
Author(s) : Neumiller JJ , Odegard PS , White JR, Jr. , Setter SM , Campbell RK
Ref : Diabetes Educ , 34 :183 , 2008
Abstract : Strong evidence exists demonstrating the benefits of tight glycemic control in type 1 and type 2 diabetes mellitus patients, but glycemic goals are not adequately achieved for many patients. Advancement in the knowledge surrounding the physiology of endogenous glucoregulatory peptide hormones, such as glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1, has led to new therapeutic targets for the treatment of type 2 diabetes mellitus. Dipeptidyl peptidase-4 (DPP-4) inhibitors provide practitioners with a novel mechanism of action to use for combination therapies for the treatment of type 2 diabetes mellitus. This article, part 3 of a 3-part series, reviews the new class of medications known as DPP-4 inhibitors as well as discusses a future buccal insulin formulation, Oral-Lyn, on the horizon for the treatment of diabetes mellitus.
ESTHER : Neumiller_2008_Diabetes.Educ_34_183
PubMedSearch : Neumiller_2008_Diabetes.Educ_34_183
PubMedID: 18375772

Title : More choices than ever before: emerging therapies for type 2 diabetes - Campbell_2008_Diabetes.Educ_34_518
Author(s) : Campbell RK , White JR, Jr.
Ref : Diabetes Educ , 34 :518 , 2008
Abstract : The goal of antidiabetes therapy is to reduce glycosylated hemoglobin (HbA(1c)) levels to prevent or minimize the microvascular complications associated with this disease, such as retinopathy, nephropathy, and neuropathy. Glycemic control, defined by the American Diabetes Association (ADA) as HbA(1c) <7.0%, is often difficult to achieve despite current treatments, including oral antidiabetes agents, such as biguanides (metformin), sulfonylureas, thiazolidinediones, dipeptidyl peptidase-IV (DPP-IV) inhibitors, meglitinides, and alpha-glucosidase inhibitors, as well as injectable agents, such as glucagon-like peptide-1 (GLP-1) analogues and insulin. In addition, antidiabetes treatments often become less effective over time as insulin resistance increases and pancreatic beta-cell function deteriorates. The latest ADA guidelines also recommend a range of interventions to control the multiple coexisting conditions associated with this chronic, progressive disease, including dyslipidemia and hypertension. This review highlights the new antidiabetes drug classes, which include incretin mimetics, cannabinoid receptor type 1 antagonists, and bile acid sequestrants, and compares these agents to established treatments with regard to efficacy and tolerability. The more recently developed antidiabetes drugs have been shown in clinical trials to produce glucose-lowering effects similar to those of established antidiabetes agents. Many of the new antidiabetes agents can be safely combined with established therapies to further improve glycemic control. In addition, the new agents may provide additional significant cardiometabolic benefits, including improving the lipid profile, lowering blood pressure, and reducing body weight. These new treatments may have the potential to greatly improve the management of type 2 diabetes.
ESTHER : Campbell_2008_Diabetes.Educ_34_518
PubMedSearch : Campbell_2008_Diabetes.Educ_34_518
PubMedID: 18535325

Title : Rationale for dipeptidyl peptidase 4 inhibitors: a new class of oral agents for the treatment of type 2 diabetes mellitus - Campbell_2007_Ann.Pharmacother_41_51
Author(s) : Campbell RK
Ref : Annals of Pharmacotherapy , 41 :51 , 2007
Abstract : OBJECTIVE: To review advances in understanding the pathophysiologic basis of type 2 diabetes mellitus and the pharmacology and mechanism of action of dipeptidyl peptidase 4 (DPP-4) inhibition in correcting the underlying defects in glycemic control. DATA SOURCES: Articles were identified through MEDLINE for the period 1966 through November 2006. Abstracts and presentations from the American Diabetes Association Scientific Sessions and the European Association for the Study of Diabetes (2002-2006) were also searched for scientific reports on DPP-4 inhibitors. STUDY SELECTION AND DATA EXTRACTION: Abstracts, original clinical and preclinical research reports, and review articles published in the English language were identified for review. Literature discussing glucose regulation, incretin hormones, type 2 diabetes pathophysiology, and DPP-4 inhibition were evaluated and selected based on consideration of their support for the proof of concept, mechanistic and in vivo findings, and timeliness. DATA SYNTHESIS: The search for new and effective therapies for type 2 diabetes has led to the identification of a novel therapeutic target, the incretin hormones, which play a role in mediating glucose homeostasis via effects on glucagon and insulin secretion from pancreatic islet alpha- and beta-cells, respectively. The incretins' glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide are rapidly inactivated by the enzyme DPP-4. DPP-4 inhibitor agents act by blocking the active site of DPP-4, thereby preventing inactivation of and prolonging the duration of action of incretins, which in turn helps to correct the defective insulin and glucagon secretion that marks type 2 diabetes. Clinical studies to date indicate that DPP-4 inhibitors effectively stimulate insulin secretion, suppress glucagon release, and improve glucose control in patients with type 2 diabetes. These agents are well tolerated and have a low incidence of adverse effects.
CONCLUSIONS: The DPP-4 inhibitors are novel agents for the treatment of type 2 diabetes. Compounds under development in this new class of oral antidiabetic drugs may be free of the limitations of current therapies.
ESTHER : Campbell_2007_Ann.Pharmacother_41_51
PubMedSearch : Campbell_2007_Ann.Pharmacother_41_51
PubMedID: 17190843

Title : The physiology of incretin hormones and the basis for DPP-4 inhibitors - McKennon_2007_Diabetes.Educ_33_55
Author(s) : McKennon SA , Campbell RK
Ref : Diabetes Educ , 33 :55 , 2007
Abstract : With the rising prevalence of diabetes, new therapies that provide glucose control are needed. Although many medications are available, tight glucose control is still a challenge. In this article, the physiology of glucose homeostasis is explored with respect to type 2 diabetes. The incretin effect is explained in detail, and the incretin hormones, glucose-dependent insulinotrophic polypeptide and glucagon-like peptide 1, are investigated as well as their contribution to type 2 diabetes therapy. Studies involving dipeptidyl-peptidase 4 (DPP-4) inhibitors are summarized as to their effects on glucose homeostasis. Specifically, vildagliptin (Galvus; Novartis International AG, Basel, Switzerland) and sitagliptin (Januvia; Merck & Co, Inc, Whitehouse Station, NJ) are described. The use and efficacy of the currently available incretin mimetic, exenatide (Byetta; Amylin Pharmaceuticals, Inc and Eli Lilly and Company, San Diego, Calif, and Indianapolis, Ind), are briefly discussed. Throughout this article, the rationale for the use of DPP-4 inhibitors is presented.
ESTHER : McKennon_2007_Diabetes.Educ_33_55
PubMedSearch : McKennon_2007_Diabetes.Educ_33_55
PubMedID: 17272793

Title : The draft genome of Ciona intestinalis: insights into chordate and vertebrate origins - Dehal_2002_Science_298_2157
Author(s) : Dehal P , Satou Y , Campbell RK , Chapman J , Degnan B , De Tomaso A , Davidson B , Di Gregorio A , Gelpke M , Goodstein DM , Harafuji N , Hastings KE , Ho I , Hotta K , Huang W , Kawashima T , Lemaire P , Martinez D , Meinertzhagen IA , Necula S , Nonaka M , Putnam N , Rash S , Saiga H , Satake M , Terry A , Yamada L , Wang HG , Awazu S , Azumi K , Boore J , Branno M , Chin-Bow S , DeSantis R , Doyle S , Francino P , Keys DN , Haga S , Hayashi H , Hino K , Imai KS , Inaba K , Kano S , Kobayashi K , Kobayashi M , Lee BI , Makabe KW , Manohar C , Matassi G , Medina M , Mochizuki Y , Mount S , Morishita T , Miura S , Nakayama A , Nishizaka S , Nomoto H , Ohta F , Oishi K , Rigoutsos I , Sano M , Sasaki A , Sasakura Y , Shoguchi E , Shin-I T , Spagnuolo A , Stainier D , Suzuki MM , Tassy O , Takatori N , Tokuoka M , Yagi K , Yoshizaki F , Wada S , Zhang C , Hyatt PD , Larimer F , Detter C , Doggett N , Glavina T , Hawkins T , Richardson P , Lucas S , Kohara Y , Levine M , Satoh N , Rokhsar DS
Ref : Science , 298 :2157 , 2002
Abstract : The first chordates appear in the fossil record at the time of the Cambrian explosion, nearly 550 million years ago. The modern ascidian tadpole represents a plausible approximation to these ancestral chordates. To illuminate the origins of chordate and vertebrates, we generated a draft of the protein-coding portion of the genome of the most studied ascidian, Ciona intestinalis. The Ciona genome contains approximately 16,000 protein-coding genes, similar to the number in other invertebrates, but only half that found in vertebrates. Vertebrate gene families are typically found in simplified form in Ciona, suggesting that ascidians contain the basic ancestral complement of genes involved in cell signaling and development. The ascidian genome has also acquired a number of lineage-specific innovations, including a group of genes engaged in cellulose metabolism that are related to those in bacteria and fungi.
ESTHER : Dehal_2002_Science_298_2157
PubMedSearch : Dehal_2002_Science_298_2157
PubMedID: 12481130
Gene_locus related to this paper: cioin-141645 , cioin-147959 , cioin-150181 , cioin-154370 , cioin-ACHE1 , cioin-ACHE2 , cioin-cxest , cioin-f6qcp0 , cioin-f6r8z1 , cioin-f6u176 , cioin-f6vac9 , cioin-f6x584 , cioin-f6xa69 , cioin-f6y403 , cioin-h2xqb4 , cioin-H2XTI0 , cioin-F6T1M3 , cioin-H2XUP7 , cioin-CIN.7233 , cioin-F6V269 , cioin-Cin16330 , cioin-h2xua2 , cioin-f6vaa5 , cioin-f6v9x6 , cioin-f6swc9 , cioin-f7amz2 , cioin-f6s021 , cioin-h2xxq9 , cioin-h2xne6 , cioin-f6ynr2