Page last updated: 2024-11-04

biguanides

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Description

Biguanides: Derivatives of biguanide (the structure formula HN(C(NH)NH2)2) that are primarily used as oral HYPOGLYCEMIC AGENTS for the treatment of DIABETES MELLITUS, TYPE 2 and PREDIABETES. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

biguanides : A class of oral hypoglycemic drugs used for diabetes mellitus or prediabetes treatment. They have a structure based on the 2-carbamimidoylguanidine skeleton. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID5939
CHEMBL ID4297654
CHEBI ID3095
SCHEMBL ID8039
MeSH IDM0002471

Synonyms (35)

Synonym
CHEBI:3095
hbig
1,2,3-triimidodicarbonic diamide
imidodicarbonimidic diamide
h2n-c(=nh)-nh-c(=nh)-nh2
4911-98-2
guanylguanidine
56-03-1
biguanide
C07672
FT-0659014
1-(diaminomethylidene)guanidine
A830895
biguanides
AKOS006273502
ai3-52571
diguanide
einecs 200-251-8
unii-fb4q52i9k2
fb4q52i9k2 ,
AKOS015894538
SCHEMBL8039
guanidine, (aminoiminomethyl)-
duraplus
biguanide [mi]
isobiguanide
biguanide [who-dd]
XNCOSPRUTUOJCJ-UHFFFAOYSA-N
DTXSID7074664
DB13100
Q142880
CHEMBL4297654
[(diaminomethylidene)amino]methanimidamide
EN300-126001
carbamimidamidomethanimidamide

Research Excerpts

Overview

Biguanides are a class of antidiabetic drugs that includes phenformin and metformin. The former was withdrawn from approval in many countries due to its toxicity. Biguanides are a drug of choice for the treatment of type 2 diabetes mellitus.

ExcerptReferenceRelevance
"Biguanides are a class of antidiabetic drugs that includes phenformin and metformin; however, the former was withdrawn from approval in many countries due to its toxicity. "( Therapeutic Repurposing of Biguanides in Cancer.
Swanson, KD; Zhao, H; Zheng, B, 2021
)
2.36
"The biguanides are a family of drugs with diverse clinical applications. "( Molecular features of biguanides required for targeting of mitochondrial respiratory complex I and activation of AMP-kinase.
Agip, AN; Bridges, HR; Hirst, J; Sirviö, VA, 2016
)
1.31
"Biguanides are a drug of choice for the treatment of type 2 diabetes mellitus. "( The Dramatic Recovery of a Patient with Biguanide-associated Severe Lactic Acidosis Following Thiamine Supplementation.
Fujita, M; Godo, S; Kudo, D; Kushimoto, S; Nomura, R; Shimokawa, H; Yoshida, Y, 2017
)
1.9
"Biguanides are a class of drugs widely used as oral antihyperglycemic agents for the treatment of type 2 diabetes mellitus, but they are associated with lactic acidosis, a lethal side effect. "( Involvement of organic cation transporter 1 in the lactic acidosis caused by metformin.
Jonker, JW; Kato, Y; Kusuhara, H; Schinkel, AH; Sugiyama, Y; Wang, DS, 2003
)
1.76
"The biguanides are a class of oral hypoglycemic agents that are commonly used in the treatment of diabetes mellitus. "( Biguanide-associated lactic acidosis. Case report and review of the literature.
Arieff, AI; Barr, J; Gan, SC; Pearl, RG, 1992
)
0.84

Effects

ExcerptReferenceRelevance
"Biguanides have been used in treatment of diabetes mellitus for over 30 years now. "( [Value of biguanide in therapy of diabetes mellitus].
Haupt, E; Panten, U, 1997
)
1.74

Actions

Biguanides competitively inhibit the activity of ecDHFR, with the phenformin inhibition constant being 100-fold lower than that of metformin. Biguanides also inhibit mitochondrial ATP synthase, and two of them inhibit only ATP hydrolysis.

ExcerptReferenceRelevance
"The biguanides competitively inhibit the activity of ecDHFR, with the phenformin inhibition constant being 100-fold lower than that of metformin."( A Structural Basis for Biguanide Activity.
DeRose, EF; Duff, MR; Gabel, SA; Howell, EE; Krahn, JM; London, RE; Pedersen, LC, 2017
)
0.94
"Biguanides also inhibit mitochondrial ATP synthase, and two of them inhibit only ATP hydrolysis, not synthesis."( Effects of metformin and other biguanides on oxidative phosphorylation in mitochondria.
Bridges, HR; Hirst, J; Jones, AJ; Pollak, MN, 2014
)
1.41
"Biguanides inhibit mitochondrial complex I, but specific molecular features control the uptake of substituted biguanides into mitochondria, so only some biguanides inhibit mitochondrial respiration in vivo. "( Molecular features of biguanides required for targeting of mitochondrial respiratory complex I and activation of AMP-kinase.
Agip, AN; Bridges, HR; Hirst, J; Sirviö, VA, 2016
)
2.19

Toxicity

Lactic acidosis should be considered as a side effect of therapy with biguanides.

ExcerptReferenceRelevance
" In this, as an in earlier long-term study, there were no effects whatsoever to suggest that chlorhexidine treatment could give rise to any kind of tumourigenic effect or any other toxic sign."( Safety of Hibitane. I. Laboratory experiments.
Case, DE, 1977
)
0.26
" Only one significant adverse effect has been identified during medical use, namely, the production of sensorineural deafness after direct instillation into the middle ear, a property shared by several commonly used antiseptics."( Safety of Hibitane. II. Human experience.
Rushton, A, 1977
)
0.26
"A survey of the literature leads to the conclusion that lactic acidosis should be considered as a side effect of therapy with biguanides."( [The importance of lactate acidosis as a side effect of biguanide therapy].
Förster, H, 1976
)
0.46
" At the same time about 1/3 of these serious adverse drug reactions (ADR) was found to have been reported to the ADR-register."( Drug utilization and morbidity statistics for the evaluation of drug safety in Sweden.
Westerholm, B; Wiholm, BE, 1984
)
0.27
" At the same time, about 1/3 of these serious adverse drug reactions (ADRs) had been reported to the ADR register."( Drug utilization and morbidity statistics for the evaluation of drug safety in Sweden.
Westerholm, B; Wiholm, BE, 1984
)
0.27
" Neither the unpreserved saline solution nor the more highly concentrated multipurpose solution produced significant toxic effects on the corneal epithelial cells and compared favorably with previously reported incidences of desquamating cells in the normal corneal epithelium."( A masked quantitative cytologic study of the safety of a multipurpose contact lens solution applied to the in vivo rabbit eye.
Bergmanson, JP; Ross, RN, 1993
)
0.29
"Currently available oral agents for the treatment of type 2 diabetes mellitus include a variety of compounds from 5 different pharmacologic classes with differing mechanisms of action, adverse effect profiles, and toxicities."( Oral agents for the treatment of type 2 diabetes mellitus: pharmacology, toxicity, and treatment.
Beattie, P; Harrigan, RA; Nathan, MS, 2001
)
0.31
"To evaluate the cysticidal effect of polyhexamethylene biguanide (PHMB) and chlorhexidine on Acanthamoeba and its toxic effect on cultured human keratocytes."( Cysticidal effect on acanthamoeba and toxicity on human keratocytes by polyhexamethylene biguanide and chlorhexidine.
Choi, HY; Lee, JE; Lee, JS; Oum, BS; Yu, HS, 2007
)
0.34
" However, PHMB seemed to be more toxic to keratocytes than chlorhexidine."( Cysticidal effect on acanthamoeba and toxicity on human keratocytes by polyhexamethylene biguanide and chlorhexidine.
Choi, HY; Lee, JE; Lee, JS; Oum, BS; Yu, HS, 2007
)
0.34
"The secondary and adverse effects when biguanides, alpha-glycosidase inhibitor or thiazolidine derivative was used with sulphonylurea agent (SU) as compared with those with SU alone in Type 2 diabetes patients by using Systematic Review."( Lipids behavior and adverse effects for oral antidiabetic agents in patients with Type 2 diabetes treated with sulfonylureas alone based on systematic review.
Eto, M; Katsuyama, S; Miura, M; Mohri, K; Mouri, K; Mukai, J; Shoji, T; Suzuki, T; Tada, H; Watanabe, Y, 2007
)
0.61
"These new findings suggest that most of multipurpose solutions are toxic with oxidative stress and apoptosis induction."( Cytotoxicity of contact lens multipurpose solutions: role of oxidative stress, mitochondrial activity and P2X7 cell death receptor activation.
Baudouin, C; Dutot, M; Rat, P; Warnet, JM, 2008
)
0.35
" Any adverse event of the treatment has been monitored throughout the study."( The efficacy and safety of a single dose of polyhexamethylene biguanide gynaecologic solution versus a seven-dose regimen of vaginal clindamycin cream in patients with bacterial vaginosis.
Di Renzo, GC; Ferrari, A; Gerli, S; Minozzi, M; Papaleo, E,
)
0.13
" However, little is known about their potential toxic properties."( [A comparative in vitro study of cell toxicity of clinically used antiseptics].
Goertz, O; Hirsch, T; Jacobsen, F; Niederbichler, A; Rittig, A; Seipp, HM; Steinau, HU; Steinstraesser, L, 2009
)
0.35
"Lavasept showed only slight to moderate toxic effects on cellular vitality and proliferation."( [A comparative in vitro study of cell toxicity of clinically used antiseptics].
Goertz, O; Hirsch, T; Jacobsen, F; Niederbichler, A; Rittig, A; Seipp, HM; Steinau, HU; Steinstraesser, L, 2009
)
0.35
" Furthermore, antimicrobial efficacy and toxic properties must be included in the clinical decision process for optimal therapy of chronic wounds."( [A comparative in vitro study of cell toxicity of clinically used antiseptics].
Goertz, O; Hirsch, T; Jacobsen, F; Niederbichler, A; Rittig, A; Seipp, HM; Steinau, HU; Steinstraesser, L, 2009
)
0.35
" Our hypothesis was that antiseptics and supplemental irrigation with sodium chloride lavage are less toxic on human chondrocytes than treatment with antiseptics only."( Toxicity of antiseptics against chondrocytes: what is best for the cartilage in septic joint surgery?
Arnholdt, J; Kolar, P; Matziolis, G; Perka, C; Röhner, E; Seeger, JB; Thiele, K, 2011
)
0.37
" Polyhexanide possibly has more toxic potential than hydrogen peroxide against human chondrocytes after an application >15 minutes."( Toxicity of polyhexanide and hydrogen peroxide on human chondrocytes in vitro.
Dähn-Wollenberg, S; Hoff, P; Matziolis, G; Perka, C; Röhner, E; Seeger, JB, 2011
)
0.37
" Although formulated NB325 appeared generally safe for application in these studies, the low but observable level of toxicity suggests the need for improvements in the compound and/or formulation."( Cervicovaginal safety of the formulated, biguanide-based human immunodeficiency virus type 1 (HIV-1) inhibitor NB325 in a murine model.
Kish-Catalone, T; Krebs, FC; Labib, M; Lozenski, K; Pirrone, V; Rando, RF; Wigdahl, B, 2011
)
0.37
" Quantitative and qualitative analyses demonstrated the toxic effect of biguanide compounds on the viability of corneal epithelial cells, under single or in combination usage."( Antimicrobial action of biguanides on the viability of Acanthamoeba cysts and assessment of cell toxicity.
Carrijo-Carvalho, LC; Carvalho, FR; Chudzinski-Tavassi, AM; de Freitas, D; Foronda, AS; Mafra, CS; Taguchi, FM, 2013
)
0.7
"Both the QMix™ and NaOCl solutions were toxic to human bone marrow MSCs."( Cytotoxicity of QMix™ endodontic irrigating solution on human bone marrow mesenchymal stem cells.
Aldahmash, AM; Alkahtani, A; Alkahtany, SM; Anil, S; Elsafadi, MA; Mahmood, A, 2014
)
0.4
" The superficially adhering PHMB film produces no adverse effects on MG63 cells within a 48 h-cell culture, but promotes the initial attachment and spreading of the osteoblasts on the modified Ti6Al4V surface within 15 min."( Poly (hexamethylene biguanide) adsorption on hydrogen peroxide treated Ti-Al-V alloys and effects on wettability, antimicrobial efficacy, and cytotoxicity.
Benkhai, H; Finke, B; Friedrichs, W; Geist, N; Kramer, A; Langel, W; Matthes, R; Müller, G, 2014
)
0.4
" The most frequent adverse events with dulaglutide treatment were nasopharyngitis and gastrointestinal symptoms."( Efficacy and safety of once-weekly dulaglutide in combination with sulphonylurea and/or biguanide compared with once-daily insulin glargine in Japanese patients with type 2 diabetes: a randomized, open-label, phase III, non-inferiority study.
Araki, E; Imaoka, T; Inagaki, N; Oura, T; Takeuchi, M; Tanizawa, Y, 2015
)
0.42
" For the in vitro cytotoxic test with L929 mouse fibroblast cells, our novel dressing was not toxic to the cells and also promoted cell migration as good as the commercially available dressing, possibly due to the component of sericin released."( The safety and efficacy of bacterial nanocellulose wound dressing incorporating sericin and polyhexamethylene biguanide: in vitro, in vivo and clinical studies.
Aramwit, P; Napavichayanun, S; Yamdech, R, 2016
)
0.43
" Few adverse effects from the substance were reported."( Polyhexanide - safety and efficacy as an antiseptic.
Fjeld, H; Lingaas, E, 2016
)
0.43
" The overall incidence of treatment-emergent adverse events (TEAEs) was 75."( Long-term safety and efficacy of fasiglifam (TAK-875), a G-protein-coupled receptor 40 agonist, as monotherapy and combination therapy in Japanese patients with type 2 diabetes: a 52-week open-label phase III study.
Enya, K; Kaku, K; Matsuno, R; Nakaya, R; Ohira, T, 2016
)
0.43
" The discovery and establishment of safe and effective alternative antiseptics are important issues for the treatment of infected wounds."( Comparing two polymeric biguanides: chemical distinction, antiseptic efficacy and cytotoxicity of polyaminopropyl biguanide and polyhexamethylene biguanide.
Böhm, JK; Fromm-Dornieden, C; Rembe, JD; Schäfer, N; Stuermer, EK, 2016
)
0.74
" Further, the data available are derived from small, short-term registration trials and typically focus on relative rather than absolute risks of any given drug and do not address the potential adverse outcomes if a patient's diabetes remains untreated."( Should Side Effects Influence the Selection of Antidiabetic Therapies in Type 2 Diabetes?
Grunberger, G, 2017
)
0.46
" No sign of infection or adverse event was observed after treatment with both dressings."( Inflammatory reaction, clinical efficacy, and safety of bacterial cellulose wound dressing containing silk sericin and polyhexamethylene biguanide for wound treatment.
Ampawong, S; Angspatt, A; Aramwit, P; Harnsilpong, T; Napavichayanun, S, 2018
)
0.48
" Adverse events, tolerability and vital signs were assessed before, during, after and at the end of the treatment period."( Tolerability and safety of urotainer® polihexanide 0.02% in catheterized patients: a prospective cohort study.
Everaert, K; Kesselring, J; Möhr, S; Pannek, J; Van der Aa, F; Vance, W, 2020
)
0.56
"There was no serious adverse event in the study."( Tolerability and safety of urotainer® polihexanide 0.02% in catheterized patients: a prospective cohort study.
Everaert, K; Kesselring, J; Möhr, S; Pannek, J; Van der Aa, F; Vance, W, 2020
)
0.56
" The Panel reviewed relevant data relating to the safety of this ingredient and concluded that Polyaminopropyl Biguanide is safe in cosmetics in the present practices of use and concentration described in the safety assessment, when formulated to be nonirritating and nonsensitizing, which may be based on a quantitative risk assessment or other accepted methodologies."( Safety Assessment of Polyaminopropyl Biguanide (Polyhexamethylene Biguanide Hydrochloride) as Used in Cosmetics.
Belsito, DV; Bergfeld, WF; Boyer, I; Heldreth, B; Hill, RA; Johnson, W; Klaassen, CD; Liebler, DC; Marks, JG; Shank, RC; Slaga, TJ; Snyder, PW; Zhu, J,
)
0.13
" The rates of dose-limiting adverse events (DLAEs) leading to interruption of dosing, mild adverse events (AEs) (not dose limiting) and incidental AEs (unrelated to treatment) were compared."( Safety and tolerability of topical polyhexamethylene biguanide: a randomised clinical trial in healthy adult volunteers.
Asero, N; Dart, JKG; Minassian, DC; Overweel, J; Papa, V; Rottey, S; Sallet, G; van der Meulen, I, 2022
)
0.72
" Secondary outcomes included: central line-associated infection; primary bloodstream infection; local infection; skin complications; device/dressing dwell time; serious adverse events, and cost-effectiveness."( Polyhexamethylene biguanide discs versus unmedicated dressings for prevention of central venous catheter-associated infection in the intensive care unit: A pilot randomised controlled trial to assess protocol safety and feasibility.
Corley, A; Irvine, L; Larsen, E; Marsh, N; McGuinness, N; Pearse, I; Pelecanos, A; Rapchuk, IL; Rickard, CM; Ullman, AJ; Ziegenfuss, M, 2022
)
0.72
"Polyhexamethylene biguanide discs appear safe for central venous catheter infection prevention."( Polyhexamethylene biguanide discs versus unmedicated dressings for prevention of central venous catheter-associated infection in the intensive care unit: A pilot randomised controlled trial to assess protocol safety and feasibility.
Corley, A; Irvine, L; Larsen, E; Marsh, N; McGuinness, N; Pearse, I; Pelecanos, A; Rapchuk, IL; Rickard, CM; Ullman, AJ; Ziegenfuss, M, 2022
)
0.72

Pharmacokinetics

ExcerptReferenceRelevance
" The basic pharmacokinetic properties of these agents are discussed with a view to efficient and safe treatment."( Pharmacokinetic optimisation of oral hypoglycaemic therapy.
di Carlo, A; Giannarelli, R; Marchetti, P; Navalesi, R, 1991
)
0.28
" By using labelled compounds or measuring the circulating concentrations, the main pharmacokinetic properties of oral hypoglycaemic agents have been assessed and, in some cases, their pharmacokinetic-pharmacodynamic relationships have been evaluated."( Pharmacokinetic-pharmacodynamic relationships of oral hypoglycaemic agents. An update.
Marchetti, P; Navalesi, R, 1989
)
0.28
" The pharmacokinetic properties of proguanil were similar during and after pregnancy."( Single dose pharmacokinetics of proguanil and its metabolites in pregnancy.
Moody, RR; Nosten, F; Taylor, RB; ter Kuile, F; Wangboonskul, J; White, NJ, 1993
)
0.29
" Herein, a physiologically-based pharmacokinetic (PBPK) and pharmacodynamic framework is proposed for integrating information on physicochemical, cell-based, animal, and human studies of various biguanides to identify gaps in knowledge and to build a systems model that may facilitate the planning of randomized cancer chemoprevention trials of metformin."( A systems pharmacokinetic and pharmacodynamic approach to identify opportunities and pitfalls in energy stress-mediated chemoprevention: the use of metformin and other biguanides.
Thompson, HJ; Thompson, MD, 2012
)
0.76
" The depletion of moroxydine hydrochloride in gibel carp was slower with a longer half-life period, especially at lower water temperature that was tested."( Pharmacokinetics and tissue residues of moroxydine hydrochloride in gibel carp, Carassius gibelio after oral administration.
Chen, J; Liu, W; Ma, J; Xu, J; Zeng, L; Zhou, Y, 2016
)
0.43

Compound-Compound Interactions

ExcerptReferenceRelevance
"From July 1996 to March 1997, three cases of Acanthamoeba keratitis combined with fungal infection were diagnosed and treated at our ophthalmic department."( Treatment of Acanthamoeba keratitis combined with fungal infection with polyhexamethylene biguanide.
Sheu, MM; Tien, SH, 1999
)
0.3
" Polyhexanide was tested alone and in combination with oxacillin, penicillin G, ampicillin, cefazolin, cefuroxime, imipenem, gentamicin, erythromycin, doxycycline, levoflocaxin, linezolid and vancomycin."( In-vitro activity of polyhexanide alone and in combination with antibiotics against Staphylococcus aureus.
Fabry, W; Kock, HJ, 2014
)
0.4
" aureus alone and in combination with antibiotics."( In-vitro activity of polyhexanide alone and in combination with antibiotics against Staphylococcus aureus.
Fabry, W; Kock, HJ, 2014
)
0.4
" This study is designed to assess the effect of antimicrobial-impregnated dressing (AMD) combined with negative-pressure wound therapy (NPWT) on skin graft survival."( Antimicrobial-impregnated dressing combined with negative-pressure wound therapy increases split-thickness skin graft engraftment: a simple effective technique.
Chen, CC; Chew, KY; Kuo, YR; Wu, CC, 2015
)
0.42
" Cultured human corneal epithelial (HCE) cells and Acanthamoeba were treated with polyhexamethylene biguanide (PHMB) combined with cellulose synthesis inhibitors to evaluate the CPE as an antiamebic agent."( Potential Value of Cellulose Synthesis Inhibitors Combined With PHMB in the Treatment of Acanthamoeba Keratitis.
Chung, DI; Goo, YK; Hong, Y; Kong, HH; Moon, EK, 2015
)
0.42
"The aim of the study was to assess the antibacterial efficacy of photon-initiated photoacoustic streaming (PIPS) using an Er:YAG laser and sonic-activated irrigation combined with QMiX irrigant or sodium hypochlorite against Enterococcus faecalis intracanal biofilm."( The efficacy of photon-initiated photoacoustic streaming and sonic-activated irrigation combined with QMiX solution or sodium hypochlorite against intracanal E. faecalis biofilm.
Anić, I; Bago, I; Balić, M; Jakovljević, S; Lucić, R; Mehadžić, K; Plečko, V, 2016
)
0.43

Bioavailability

The results suggest that inhibition of mitochondrial metabolism by Metformin or Phenformin is associated with increased leukemia cell susceptibility. The results provide a rationale for clinical studies exploring the efficacy of combining biguanides with ABT-737, Venetoclax.

ExcerptReferenceRelevance
" Chlorhexidine is poorly absorbed after oral administration, well tolerated after parenteral administration and its percutaneous absorption is abolutely minimal."( Safety of Hibitane. I. Laboratory experiments.
Case, DE, 1977
)
0.26
" The bioavailability of the biguanides ranges from 40 to 60%."( Pharmacokinetic optimisation of oral hypoglycaemic therapy.
di Carlo, A; Giannarelli, R; Marchetti, P; Navalesi, R, 1991
)
0.58
" There were higher absorption rate (t1/2ka ) and longer elimination half-lives (t1/2ke ) at 15 °C (4."( Pharmacokinetics and tissue residues of moroxydine hydrochloride in gibel carp, Carassius gibelio after oral administration.
Chen, J; Liu, W; Ma, J; Xu, J; Zeng, L; Zhou, Y, 2016
)
0.43
" Taken together, our results suggest that inhibition of mitochondrial metabolism by Metformin or Phenformin is associated with increased leukemia cell susceptibility to induction of intrinsic apoptosis, and provide a rationale for clinical studies exploring the efficacy of combining biguanides with the orally bioavailable derivative of ABT-737, Venetoclax."( Biguanides sensitize leukemia cells to ABT-737-induced apoptosis by inhibiting mitochondrial electron transport.
Andreeff, M; Bornmann, W; Duque, JE; Enciso, L; Jaramillo, D; Konopleva, M; Krystal, G; Lee, JT; Lopez, C; Morales, L; Pan, R; Samudio, I; Suarez, M; Velez, J, 2016
)
2.05
" Alexidine Dihydrochloride (AD), an orally bioavailable bis-biguanide compound, is an apoptosis stimulating reagent."( Repurposing of Alexidine Dihydrochloride as an Apoptosis Initiator and Cell Cycle Inhibitor in Human Pancreatic Cancer.
Aydemir, E; Bayrak, OF; Kasikci, E; Sahin, F; Yogurtcu, BM, 2020
)
0.56

Dosage Studied

ExcerptRelevanceReference
" Since the dosage regimes for chlorhexidine in the two studies were comparable, the mode of delivery would appear to be important in the therapeutic effectiveness."( Hibitane in the treatment of aphthous ulceration.
Addy, M, 1977
)
0.26
" No consistent relationship was demonstrable between the serum biguanide level, administered dosage and time of administration."( [Biguanide-induced and - associated lactic acidosis: serum and tissue biguanide levels in hyperlactaemia and lactic acidosis (author's transl)].
Irsigler, K; Kaspar, L; Kritz, H; Regal, H, 1979
)
0.26
" Among the sulfonamide derivatives are preparations which are highly effective, low dosed and have few side effects."( [Twenty years of oral diabetic therapy (author's transl)].
Dietze, G; Mehnert, H, 1975
)
0.25
" We, therefore, consider a preventive administration of biguanides to be effective in long term or high dosage administration of glucocorticoides."( [Antagonistic action of prednisolone and buformin in the carbohydrate metabolism of healthy persons (author's transl)].
Bottermann, P; Ermler, R; Schweigart, U, 1976
)
0.5
" DTT treatment also markedly shifted the dose-response curve of NMDA to the left."( Redox modulation of N-methyl-D-aspartate-stimulated neurotransmitter release from rat brain slices.
Blair, R; Woodward, JJ, 1991
)
0.28
" In the presence of 100 microM 2-Me5-HT, the upper part of the 5-HT dose-response curve was shifted to the right but reached the same maximum value as in the absence of 2-Me5-HT."( The agonist properties of m-chlorophenylbiguanide and 2-methyl-5-hydroxytryptamine on 5-HT3 receptors in N1E-115 neuroblastoma cells.
Lummis, SC; Martin, IL; Sepúlveda, MI, 1991
)
0.28
" Injection into the fourth ventricle of ICI 174864 (100-300nmol) or DAMGO (100-300pmol) had no effects on the dose-response relationships for phenylbiguanide or nicotine."( Chemosensitive cardiopulmonary afferents and the haemodynamic response to simulated haemorrhage in conscious rabbits.
Evans, RG; Ludbrook, J, 1991
)
0.28
" The dose-response curves for left atrial and pulmonary artery injection of 1-PBG were shifted successively to the right by intravenous infusion of the 5-HT3 antagonist MDL72222 (0."( Characteristics of cardiovascular reflexes originating from 5-HT3 receptors in the heart and lungs of unanaesthetized rabbits.
Evans, RG; Ludbrook, J; Michalicek, J, 1990
)
0.28
" All doses of PDG which affected respiration uniformly produced initial apnea, whose duration, in any given animal and trial session, exhibited a consistent dose-response relationship."( The respiratory response to stimulation of juxta-pulmonary capillary receptors in the non-anesthetized cat.
Ginzel, KH; Lucas, EA, 1985
)
0.27
" Serum pancreatic enzyme concentrations were not related to glycosylated haemoglobin concentrations, the dosage of insulin, or the age of onset of diabetes."( Exocrine pancreatic function in diabetes mellitus.
Beckett, AG; Dandona, P; Foo, Y; Freedman, DB; Katrak, A; Mikhailidis, DP; Perkins, J; Rosalki, SB, 1984
)
0.27
" On the other hand, 2-methyl-5-HT produced only a vasoconstriction, and the dose-response curve was shifted to the right in parallel by treatment with either ketanserin or bunazosin, although methysergide and granisetron had no antagonistic effect."( 2-Methyl-5-HT-induced vasoconstrictions mediated via alpha 1-adrenoceptors in rabbit common carotid arteries.
Chiba, S; Fujiwara, T, 1994
)
0.29
" Dose-response curves to chemical stimulation (spikes/s vs."( Daily spontaneous running did not alter vagal afferent reactivity.
Collins, HL; DiCarlo, SE; Scislo, TJ, 1993
)
0.29
" Dose-response curves relating right atrial injections of bradykinin (0."( Effect of bradykinin on respiratory rate in anaesthetized rabbits; role of rapidly adapting receptors.
Hargreaves, M; Kappagoda, CT; Ravi, K, 1993
)
0.29
" The currently recommended dosage regimen appears to be appropriate for extensive metabolisers of proguanil."( The multiple dose pharmacokinetics of proguanil.
Breckenridge, AM; Edwards, G; Helsby, NA; Ward, SA, 1993
)
0.29
" Due to frequent occurrence of lactic acidosis, particularly in patients with serious contraindications to biguanide therapy and in cases of non-compliance with dosage instructions, buformin and phenformin were taken off the market in most European countries at the end of the seventies."( [Value of biguanide in therapy of diabetes mellitus].
Haupt, E; Panten, U, 1997
)
0.3
"The risk of lactic acidosis can probably be eliminated entirely if dosage instructions and contraindications are observed carefully."( [Value of biguanide in therapy of diabetes mellitus].
Haupt, E; Panten, U, 1997
)
0.3
"6 mg/kg), significantly shifted the methamphetamine dose-response curve to the left."( Effects of various serotonin agonists, antagonists, and uptake inhibitors on the discriminative stimulus effects of methamphetamine in rats.
Goldberg, SR; Kutkat, SW; Laufert, MD; Munzar, P; Nováková, J, 1999
)
0.3
" When multiple dosages of a drug were tested, the results of the highest approved dosage were used."( Oral antihyperglycemic therapy for type 2 diabetes: scientific review.
Inzucchi, SE, 2002
)
0.31
"In patients with type 2 diabetes mellitus, the traditional method of initiating therapy with a sulfonylurea and increasing the dosage until maximum levels are reached before adding an insulin-sensitizing agent has persisted and should be re-evaluated."( A comparison of agents used to manage type 2 diabetes mellitus: need for reappraisal of traditional approaches.
Bell, DS, 2004
)
0.32
"The exposure of human osteoblasts and endothelial cells to polyhexanide at concentrations with questionable antibacterial activity resulted in severe cell damage whereas exposure to high dosed gentamicin did not."( Effect of polyhexanide and gentamycin on human osteoblasts and endothelial cells.
Eulert, J; Hendrich, C; Ince, A; Jakob, F; Löhr, JF; Schütze, N, 2007
)
0.34
" In addition, the Sphingomonads were the only isolates capable of growth in axenic cultures dosed with PHMB."( Microbial degradation of the biocide polyhexamethylene biguanide: isolation and characterization of enrichment consortia and determination of degradation by measurement of stable isotope incorporation into DNA.
Collins, AN; O'Malley, LP; Shaw, CH, 2007
)
0.34
" As the prevalence of children diagnosed with type 2 diabetes continues to rise, the need for adequate information regarding the safety, efficacy, and appropriate dosing of oral diabetes medications in the pediatric population likewise increases."( The utility of oral diabetes medications in type 2 diabetes of the young.
Abu-Baker, A; Busch, RS; Kane, MP, 2005
)
0.33
" These data include information regarding drug safety and efficacy and/or drug pharmacokinetic and drug dosing information."( The utility of oral diabetes medications in type 2 diabetes of the young.
Abu-Baker, A; Busch, RS; Kane, MP, 2005
)
0.33
"Timely identification of the pathogen, with repeated culture and smear if necessary, as well as adequate dosage to prevent recurrence is highly recommended in order to preclude the need for therapeutic penetrating keratoplasty."( Medical treatment for combined Fusarium and Acanthamoeba keratitis.
Hsiao, CH; Huang, SC; Lin, HC; Lin, MY; Ma, DH; Tan, HY; Yeh, LK, 2009
)
0.35
" The dose-response curve was bell-shaped."( Interactions between the anxiogenic effects of CB1 gene disruption and 5-HT3 neurotransmission.
Aliczki, M; Halasz, J; Haller, J; Mikics, E; Vas, J, 2009
)
0.35
" The presence of impaired kidney function with reduced glomerular filtration rate should influence choices, dosing, and monitoring of hypoglycemic agents, as some agents require a dosing adjustment in patients with kidney disease and some are entirely contraindicated."( Selection and dosing of medications for management of diabetes in patients with advanced kidney disease.
Berns, JS; Reilly, JB,
)
0.13
"5 hour after dosing were 21."( Liver uptake of biguanides in rats.
Kitamura, A; Komuro, S; Sogame, Y; Yabuki, M, 2011
)
0.72
" The MTT assay showed significant dose-response decreases of 500 nm absorbance for all MPS-treated cells."( Cytotoxicity and effects on metabolism of contact lens care solutions on human corneal epithelium cells.
Boost, MV; Cho, P; Choy, CK, 2012
)
0.38
" Furthermore, the double-biguanide application had a statistically significant decrease in the deleterious effect on endothelial cells at higher dosage and concentration."( Antimicrobial action of biguanides on the viability of Acanthamoeba cysts and assessment of cell toxicity.
Carrijo-Carvalho, LC; Carvalho, FR; Chudzinski-Tavassi, AM; de Freitas, D; Foronda, AS; Mafra, CS; Taguchi, FM, 2013
)
0.7
" The objective of this review is to evaluate the evidence regarding the use of oral hypoglycemic agents (with particular attention to the DPP-4 inhibitors) in diabetes type 2 with chronic kidney disease stage III- IV and ESRD, while in case of eGFR > 60 ml / min no dosage adjustment is usually required."( [Oral hypoglycemic drugs in chronic kidney disease: which limitations in the clinical setting].
D'anna, G; Di Nicolò, P; Fatuzzo, P; Fiorini, F; Granata, A; Insalaco, M; Lentini, P; Russo, L; Scarfia, VR,
)
0.13
" However, use of these drugs in DM-CKD should be evaluated carefully, mainly because of the higher risk of hypoglycemia that requires dosing adjustments."( [Anti-diabetics and chronic kidney disease].
Camocardi, A; Conte, G; De Nicola, L; Garofalo, C; Iazzetta, N; Iodice, C; Minutolo, R; Pacilio, M,
)
0.13
" Conclusion In many cases in the therapeutic inertia group only a single type of hypoglycaemic drug was prescribed or the dosage remained unchanged."( Therapeutic inertia and intensified treatment in diabetes mellitus prescription patterns: A nationwide population-based study in Taiwan.
Huang, LY; Lai, MS; Shau, WY; Su, S; Yang, MC; Yeh, HL, 2016
)
0.43
" The increasing incidence of hemangiosarcomas highly probably resulted from increased endothelial proliferation, triggered by the exceedingly high dosage fed, because PHMB is not genotoxic and there is no evidence for epigenetic effects."( Re-evaluation of polihexanide use in wound antisepsis in order to clarify ambiguities of two animal studies.
Assadian, O; Dissemond, J; Eberlein, T; Kramer, A; Müller, G, 2019
)
0.51
" The percentage of patients with good adherence (the proportion of days in which patients took all pills as prescribed in the past 7 days ≥80%) was high (≥90%) in any dosing regimen with no significant difference among the groups."( [Adherence to Oral Antihyperglycemic Agents (Dipeptidyl Peptidase-4 Inhibitors and Biguanides) and Its Associated Factors in Patients with Type 2 Diabetes].
Hayashi, A; Kamei, M; Kubo, T; Okuyama, K; Tokita, S, 2019
)
0.74
" Studies over the last decade have focused on the design and development of advanced oral delivery dosage forms using bio nano technologies and novel drug carrier systems."( Biguanide Pharmaceutical Formulations and the Applications of Bile Acid-Based Nano Delivery in Chronic Medical Conditions.
Al-Salami, H; Atlas, MD; Brown, D; Chester, J; Foster, T; Ionescu, CM; Johnston, E; Jones, M; Kovacevic, B; Kuthubutheen, J; Mikov, M; Mooranian, A; Wagle, SR; Walker, D, 2022
)
0.72
" In this study, it was newly revealed that biguanide-modified chitosan (Bi-Ch) possessed ideal mitochondria depression capacity, leading to the following decreased dosage needed to disrupt mitochondrial function to reverse tumor hypoxia and depress MDR-1 expression."( Chitosan biguanide induced mitochondrial inhibition to amplify the efficacy of oxygen-sensitive tumor therapies.
Deng, H; Liu, Y; Luo, W; Shen, J; Zheng, C; Zhou, Z, 2022
)
0.72
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Drug Classes (1)

ClassDescription
guanidinesAny organonitrogen compound containing a carbamimidamido (guanidino) group. Guanidines have the general structure (R(1)R(2)N)(R(3)R(4)N)C=N-R(5) and are related structurally to amidines and ureas.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Research

Studies (3,161)

TimeframeStudies, This Drug (%)All Drugs %
pre-19901697 (53.69)18.7374
1990's339 (10.72)18.2507
2000's399 (12.62)29.6817
2010's573 (18.13)24.3611
2020's153 (4.84)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 72.42

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be very strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index72.42 (24.57)
Research Supply Index8.21 (2.92)
Research Growth Index4.55 (4.65)
Search Engine Demand Index130.53 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (72.42)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials262 (7.71%)5.53%
Reviews342 (10.07%)6.00%
Case Studies133 (3.92%)4.05%
Observational7 (0.21%)0.25%
Other2,653 (78.10%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (31)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
Incretin-based Drugs and the Risk of Heart Failure: A Multi-center Network Observational Study [NCT02456428]1,499,650 participants (Actual)Observational2014-03-31Completed
The Use of Incretin-based Drugs and the Risk of Acute Pancreatitis in Patients With Type 2 Diabetes [NCT02476760]1,417,914 participants (Actual)Observational2014-03-31Completed
Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes [NCT00006305]Phase 32,368 participants (Actual)Interventional2000-09-30Completed
Randomized, Active-Controlled, Phase 3 Study to Evaluate Efficacy, Safety and Tolerability of 0.08% PHMB Ophthalmic Solution in Comparison With 0.02% PHMB + 0.1% Propamidine Combination Therapy in Subjects Affected by Acanthamoeba Keratitis [NCT03274895]Phase 3135 participants (Actual)Interventional2017-08-13Completed
Reduction of Postoperative Wound Infections by Antiseptica? [NCT04055233]Phase 3456 participants (Actual)Interventional2015-02-01Completed
Improving the Response of Recurrent Glioma to Radiation Therapy Through Metabolic Intervention [NCT02149459]Phase 118 participants (Anticipated)Interventional2014-06-30Recruiting
Effects of Metformin Versus Oral Contraceptives on PED/PEA-15 Protein Expression in Obese Women With Polycystic Ovary Syndrome [NCT00948402]Phase 320 participants (Actual)Interventional2006-12-31Completed
An Open-Label, Multicenter 52-Week Study Assessing the Safety and Tolerability of Lixisenatide in Combination With Oral Anti-Diabetic Treatment in Patients With Type 2 Diabetes [NCT01940965]Phase 3294 participants (Actual)Interventional2013-09-30Completed
EXCEED - A Pan-European Post-Authorisation Safety Study: Risk of Pancreatic Cancer Among Type 2 Diabetes Patients Who Initiated Exenatide as Compared With Those Who Initiated Other Non-Glucagon-Like Peptide 1 Receptor Agonists Based Glucose Lowering Drugs [NCT05663515]2,400 participants (Anticipated)Observational2024-01-01Not yet recruiting
Long-term Safety Study of MP-513 as Monotherapy or in Combination With Oral Antihyperglycaemic Agent in Japanese Patients With Type 2 Diabetes Mellitus [NCT01301833]Phase 3462 participants (Actual)Interventional2011-02-28Completed
Glucose Metabolism in South Asian Women With IGT or IFG. DIAbetes in South Asians - DIASA 3: A 12-week Intervention Trial With Oral Antidiabetic Medication to Improve Hepatic and Whole Body Insulin Sensitivity [NCT04662866]Phase 264 participants (Anticipated)Interventional2021-02-10Recruiting
Effect of Antigravity Treadmill Training on the Gait Performance and Functional Balance in Patients With Diabetic Peripheral Neuropathy. Randomized Controlled Trial [NCT05565924]68 participants (Actual)Interventional2022-01-02Completed
Effects on Re-endothelialisation With Bydureon Treatment Add on to Insulin Versus Insulin Alone, Both in Combination With Metformin in Type 2 Diabetic Subjects [NCT02621489]Phase 438 participants (Actual)Interventional2015-12-31Completed
Exploratory Study to Investigate the Suppressive Effect of Oral Anti-Diabetic Drug (TZD) on Progression of Diabetic Nephropathy on [NCT00846716]400 participants (Anticipated)Interventional2008-03-31Recruiting
[NCT01740245]Phase 40 participants InterventionalCompleted
Randomized, Double-Masked, Placebo-Controlled Multiple-Dose Phase 1 Study to Evaluate the Safety and Tolerability of Different Doses of Preservative-free Polyhexamethylene Biguanide (PHMB) Ophthalmic Solution in Healthy Subjects [NCT02506257]Phase 190 participants (Actual)Interventional2015-11-30Completed
Antimicrobial Activity of Two Mouthwashes [NCT02375178]30 participants (Actual)Interventional2014-08-31Completed
A 52-Week, Open-Label, Long-Term Safety Study of LY2189265 in Combination With Monotherapy of Oral Antihyperglycemic Medications in Patients With Type 2 Diabetes Mellitus [NCT01468181]Phase 3394 participants (Actual)Interventional2011-11-30Completed
ORAL ANTIDIABETICS EFFECT ON VISCERAL FAT MEASURED BY BIOIMPEDANCE IN TYPE 2 DIABETES PATIENTS. Pilot Study. [NCT05032001]30 participants (Anticipated)Interventional2021-08-01Enrolling by invitation
Clinical Study Evaluating the Efficacy and Safety of Metformin Versus Empagliflozin for Halting Chronic Kidney Disease Progression [NCT05373680]Phase 2/Phase 390 participants (Anticipated)Interventional2022-01-01Recruiting
A Phase 3, Open Label, Randomized, Parallel, 26 Week Treatment Study Comparing LY2605541 With Insulin Glargine as Basal Insulin Treatment in Combination With Oral Anti Hyperglycemia Medications in Asian Insulin Naïve Patients With Type 2 Diabetes Mellitus [NCT01894568]Phase 3388 participants (Actual)Interventional2013-07-31Completed
Dapagliflozin Effect in Cognitive Impairment in Stroke Trial [NCT05565976]Phase 2/Phase 3270 participants (Anticipated)Interventional2020-08-01Recruiting
A Randomized, Double Blind, Trial of Metformin and Atorvastatin in Delaying Androgen Deprivation Therapy Among Men With Rising PSA Following Radical Prostatectomy or Radiotherapy: The LIGAND (LIpitor and biGuanide to Androgen Delay) Trial [NCT02497638]Phase 20 participants (Actual)Interventional2021-12-31Withdrawn(stopped due to Drug intervention no longer relevant for the proposed population)
"Randomized, Double-blind, Placebo-controlled Study to Assess the Effect of Metformin, an Activator of AMPK, on Cognitive Measures of Progression in Huntington's Disease Patients" [NCT04826692]Phase 360 participants (Anticipated)Interventional2021-12-10Recruiting
Pilot Biomarker Modulation Study of Metformin and Omega-3 Fatty Acids in Woman With a History of Early Stage Breast Cancer [NCT02278965]Phase 119 participants (Actual)Interventional2015-01-22Completed
Metabolic and Endocrine Effects of Combination of Metformin and DPP-4 Inhibitor Saxagliptin Compared to Saxagliptin or Metformin XR Monotherapy in Patients With PCOS and Impaired Glucose Regulation: A Single-blinded Randomized Pilot Study [NCT02022007]Phase 338 participants (Actual)Interventional2014-03-31Completed
The Use of Incretin-based Drugs and the Risk of Pancreatic Cancer in Patients With Type 2 Diabetes [NCT02475499]886,172 participants (Actual)Observational2014-03-31Completed
Comparison of Antimicrobial Action of Sodium Hypochlorite and Polyhexamethylene Biguanide as Root Canal Irrigants in Patients Reporting With Non-vital Necrotic Pulp and Apical Periodontitis [NCT05306431]Phase 260 participants (Actual)Interventional2022-06-01Completed
A 52-Week, Open-Label, Multicenter Study to Determine the Long Term Safety and Efficacy of Albiglutide in Combination With Monotherapy of Oral Antihyperglycemic Medications in Japanese Patients With Type 2 Diabetes Mellitus [NCT01777282]Phase 3374 participants (Actual)Interventional2013-02-23Completed
A Randomized Phase II Study of Metformin Plus Paclitaxel/Carboplatin/Bevacizumab in Patients With Previously Untreated Advanced/Metastatic Pulmonary Adenocarcinoma [NCT01578551]Phase 225 participants (Actual)Interventional2012-05-31Terminated(stopped due to Low enrollment)
A Phase 3 Study of LY2189265 Compared to Insulin Glargine in Patients With Type 2 Diabetes Mellitus on a Sulfonylurea and/or Biguanide [NCT01584232]Phase 3361 participants (Actual)Interventional2012-04-30Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT00006305 (2) [back to overview]Number of Participants With All-Cause Mortality
NCT00006305 (2) [back to overview]Number of Participants With Death, Myocardial Infarction, or Stroke
NCT01301833 (5) [back to overview]Change From Baseline in Fasting Glucagon at Week 52
NCT01301833 (5) [back to overview]Change From Baseline in Fasting Immuno Reactive Insulin (IRI) at Week 52
NCT01301833 (5) [back to overview]Change From Baseline in Fasting Plasma Glucose at Week 52
NCT01301833 (5) [back to overview]Change From Baseline in HbA1c at Week 52
NCT01301833 (5) [back to overview]Number of Participants With Adverse Events
NCT01468181 (8) [back to overview]Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG)
NCT01468181 (8) [back to overview]Change From Baseline in Body Weight
NCT01468181 (8) [back to overview]Change From Baseline in Fasting Blood Glucose (FBG)
NCT01468181 (8) [back to overview]Change From Baseline in Glycosylated Hemoglobin (HbA1c)
NCT01468181 (8) [back to overview]Change From Baseline in Updated Homeostasis Model Assessment (HOMA2)
NCT01468181 (8) [back to overview]Percentage of Participants Who Achieve HbA1c ≤6.5% or <7%
NCT01468181 (8) [back to overview]Percentage of Participants With Hypoglycemic Episodes
NCT01468181 (8) [back to overview]Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
NCT01578551 (3) [back to overview]Progression Free Survival (PFS)
NCT01578551 (3) [back to overview]Overall Survial
NCT01578551 (3) [back to overview]Response to Therapy
NCT01584232 (6) [back to overview]Change From Baseline in Body Weight at 26 Weeks
NCT01584232 (6) [back to overview]Change From Baseline in Fasting Blood Glucose (FBG) at 26 Weeks
NCT01584232 (6) [back to overview]Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 26 Weeks
NCT01584232 (6) [back to overview]Percentage of Participants With Hypoglycemic Episodes
NCT01584232 (6) [back to overview]Change From Baseline in 8-Point Self-Monitored Blood Glucose (SMBG) at 26 Weeks
NCT01584232 (6) [back to overview]Percentage of Participants Who Achieved Glycosylated Hemoglobin (HbA1c) <=6.5% or <7% at 26 Weeks
NCT01777282 (7) [back to overview]Percentage of Participants Achieving Clinically Meaningful Levels of HbA1c (i.e., the Percentage of Participants Achieving Treatment Goal of <6.5% and <7.0% at Week 52)
NCT01777282 (7) [back to overview]Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE)
NCT01777282 (7) [back to overview]Time to Study Withdrawal Due to Hyperglycemia
NCT01777282 (7) [back to overview]Number of Participants With Any Hypoglycemic Event
NCT01777282 (7) [back to overview]Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 52
NCT01777282 (7) [back to overview]Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52
NCT01777282 (7) [back to overview]Change From Baseline in Body Weight at Week 52
NCT01894568 (18) [back to overview]Change From Baseline to 26 Weeks in Adult Low Blood Sugar Survey (LBSS) Scores
NCT01894568 (18) [back to overview]Change From Baseline of European Quality of Life-5 Dimensions - 3 Levels (EuroQoL-5D-3L ) Index Score and Visual Analog Scale (VAS) Health State Score at Week 26
NCT01894568 (18) [back to overview]Change From Baseline to 12 Weeks in Hemoglobin A1c (HbA1c)
NCT01894568 (18) [back to overview]30-Day Adjusted Rate of Total and Nocturnal Hypoglycemic Events
NCT01894568 (18) [back to overview]Change From Baseline to Week 26 in Body Weight
NCT01894568 (18) [back to overview]Change From Baseline to Week 26 in Hemoglobin A1c (HbA1c)
NCT01894568 (18) [back to overview]Insulin Dose Per Kilogram (kg) of Body Weight
NCT01894568 (18) [back to overview]Intra-Participant Variability of the Fasting Blood Glucose (FBG)
NCT01894568 (18) [back to overview]Percent Hemoglobin A1c at Week 26
NCT01894568 (18) [back to overview]Percentage of Participants Achieving Steady-State of Basal Insulin Dose at 26 Weeks (Time to Steady State for Basal Insulin [Stable Maximum Dose])
NCT01894568 (18) [back to overview]Percentage of Participants With Total and Nocturnal Hypoglycemic Events (HE)
NCT01894568 (18) [back to overview]9-Point Self-Monitored Blood Glucose (SMBG)
NCT01894568 (18) [back to overview]Percentage of Participants With HbA1c ≤6.5%
NCT01894568 (18) [back to overview]Percentage of Participants With Detectable Anti-Insulin Peglispro Antibodies at Week 26
NCT01894568 (18) [back to overview]Concentration of Triglycerides, Total Cholesterol, Low-Density Lipoprotein (LDL-C), and High-Density Lipoprotein Cholesterol (HDL-C) at Week 26
NCT01894568 (18) [back to overview]Fasting Blood Glucose (FBG)
NCT01894568 (18) [back to overview]Fasting Serum Glucose (FSG)
NCT01894568 (18) [back to overview]Insulin Treatment Satisfaction Questionnaire (ITSQ) Score
NCT02022007 (12) [back to overview]Number of Participants With No Clinically Significant Changes in Liver Enzyme Levels or Positive Pregnancy Tests
NCT02022007 (12) [back to overview]Oral Disposition Index
NCT02022007 (12) [back to overview]Pancreatic ß-cell Compensatory Function
NCT02022007 (12) [back to overview]Triglyceride (TRG) /HDL-cholesterol Ratio
NCT02022007 (12) [back to overview]Body Mass Index at 16 Weeks
NCT02022007 (12) [back to overview]Fasting Glucose
NCT02022007 (12) [back to overview]Free Androgen Index (FAI)
NCT02022007 (12) [back to overview]Glucose Metabolism
NCT02022007 (12) [back to overview]Matsuda Index of Insulin-Sensitivity (SI OGTT)
NCT02022007 (12) [back to overview]Mean Blood Glucose During the OGTT
NCT02022007 (12) [back to overview]Menstrual Cycle Interval at 16 Weeks
NCT02022007 (12) [back to overview]Waist Circumference at 16 Weeks
NCT02506257 (6) [back to overview]Visual Acuity
NCT02506257 (6) [back to overview]Systolic Blood Pressure
NCT02506257 (6) [back to overview]Ocular Surface Disease Index-OSDI
NCT02506257 (6) [back to overview]Plasma Concentration of PHMB
NCT02506257 (6) [back to overview]Number of Subjects With Dose-limiting Adverse Events
NCT02506257 (6) [back to overview]Conjunctival Examination
NCT03274895 (3) [back to overview]Clinical Resolution Rate
NCT03274895 (3) [back to overview]Visual Acuity
NCT03274895 (3) [back to overview]Time to Cure

Number of Participants With All-Cause Mortality

(NCT00006305)
Timeframe: five years

Interventionparticipants (Number)
Revascularization and Insulin Providing (IP)80
Revascularization and Insulin Sensitizing (IS)75
Medical Therapy and Insulin Providing (IP)80
Medical Therapy and Insulin Sensitizing (IS)81

[back to top]

Number of Participants With Death, Myocardial Infarction, or Stroke

(NCT00006305)
Timeframe: five years

Interventionparticipants (Number)
Revascularization and Insulin Providing (IP)145
Revascularization and Insulin Sensitizing (IS)121
Medical Therapy and Insulin Providing (IP)143
Medical Therapy and Insulin Sensitizing (IS)140

[back to top]

Change From Baseline in Fasting Glucagon at Week 52

(NCT01301833)
Timeframe: Baseline and 52 weeks

Interventionpg / mL (Mean)
Teneligliptin2.8
Teneligliptin and Glinide5.3
Teneligliptin and Biguanide5.0
Teneligliptin and Alpha-glucosidase Inhibitor6.9

[back to top]

Change From Baseline in Fasting Immuno Reactive Insulin (IRI) at Week 52

(NCT01301833)
Timeframe: Baseline and 52 weeks

InterventionμU / mL (Mean)
Teneligliptin0.988
Teneligliptin and Glinide0.211
Teneligliptin and Biguanide-0.173
Teneligliptin and Alpha-glucosidase Inhibitor-0.330

[back to top]

Change From Baseline in Fasting Plasma Glucose at Week 52

(NCT01301833)
Timeframe: Baseline and 52 weeks

Interventionmg / dL (Mean)
Teneligliptin-11.7
Teneligliptin and Glinide-13.7
Teneligliptin and Biguanide-12.7
Teneligliptin and Alpha-glucosidase Inhibitor-19.5

[back to top]

Change From Baseline in HbA1c at Week 52

(NCT01301833)
Timeframe: Baseline and 52 weeks

InterventionPercent (Mean)
Teneligliptin-0.63
Teneligliptin and Glinide-0.76
Teneligliptin and Biguanide-0.78
Teneligliptin and Alpha-glucosidase Inhibitor-0.89

[back to top]

Number of Participants With Adverse Events

Treatment-emergent adverse events (TEAE) were defined as any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product reported from first dose of study drug through 14 days after receiving the last dose of study drug. (NCT01301833)
Timeframe: 52 Weeks

,,,
Interventionparticipants (Number)
Serious Adverse EventOther Adverse Event
Teneligliptin14182
Teneligliptin and Alpha-glucosidase Inhibitor659
Teneligliptin and Biguanide681
Teneligliptin and Glinide372

[back to top]

Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG)

Participants were to test and record SMBG concentrations in their study diaries before each meal (breakfast, lunch, and dinner), approximately 2 hours after the start of each meal. For the mean of all 7-point blood glucose values, the daily mean was calculated as the average of 7 blood glucose values collected on a particular day. The mean of all 7-point blood glucose values at each visit was calculated as the average of 2 daily means. The change from baseline was calculated as the mean of all 7-point blood glucose values at endpoint minus the mean of all 7-point blood glucose values at baseline. (NCT01468181)
Timeframe: Baseline, up to 26 weeks and up to 52 weeks

,,,,
Interventionmg/dL (Mean)
Pre-morning mean at 26 Weeks (n=131,61,64,66,71)Pre-morning mean at 52 Weeks (n=131,61,64,66,71)2hr postmorning meal at 26Weeks(n=131,61,65,66,71)2hr postmorning meal at 52Weeks(n=131,61,65,66,71)Pre-midday meal at 26 Weeks (n=131,61,65,66,71)Pre-midday meal at 52 Weeks (n=131,61,65,66,71)2hr postmidday meal at 26 Weeks(n=131,60,65,66,71)2hr postmidday meal at 52 Weeks(n=131,60,65,66,71)Pre-evening meal at 26 Weeks (n=130,61,65,66,70)Pre-evening meal at 52 Weeks (n=130,61,65,66,70)2hr postevening meal at 26Weeks(n=128,61,65,66,69)2hr postevening meal at 52Weeks(n=128,61,65,66,69)Bedtime at 26 Weeks (n=128, 61, 65, 63, 67)Bedtime at 52 Weeks (n=128, 61, 65, 63, 67)
LY2189265 + a-GI-45.97-45.69-73.43-73.62-54.75-55.96-67.70-63.47-57.82-54.66-71.15-63.82-63.98-66.74
LY2189265 + BG-34.60-37.19-64.23-63.81-26.26-33.34-50.03-52.70-25.66-25.34-45.41-48.61-49.98-52.70
LY2189265 + Glinides-48.26-46.45-67.99-73.78-54.51-56.07-68.49-65.46-46.85-51.64-68.75-64.22-64.01-64.41
LY2189265 + SU-44.70-42.93-69.66-58.50-49.95-43.90-67.24-57.27-44.57-43.90-62.24-58.98-61.07-54.07
LY2189265 + TZD-35.40-39.83-65.73-67.51-51.80-50.21-80.02-81.64-43.22-42.15-66.14-69.30-66.19-68.42

[back to top]

Change From Baseline in Body Weight

(NCT01468181)
Timeframe: Baseline, up to 26 weeks and up to 52 weeks

,,,,
Interventionkilograms (kg) (Mean)
26 Weeks52 Weeks
LY2189265 + a-GI-1.22-1.24
LY2189265 + BG-0.74-0.87
LY2189265 + Glinides0.190.04
LY2189265 + SU0.020.10
LY2189265 + TZD0.781.02

[back to top]

Change From Baseline in Fasting Blood Glucose (FBG)

(NCT01468181)
Timeframe: Baseline, up to 26 weeks and up to 52 weeks

,,,,
Interventionmilligrams/deciliters (mg/dL) (Mean)
26 Weeks52 Weeks
LY2189265 + a-GI-46.8-47.0
LY2189265 + BG-37.9-36.0
LY2189265 + Glinides-42.7-45.8
LY2189265 + SU-46.8-43.2
LY2189265 + TZD-42.1-39.6

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Change From Baseline in Glycosylated Hemoglobin (HbA1c)

(NCT01468181)
Timeframe: Baseline, up to 26 Weeks and up to 52 Weeks

,,,,
Interventionpercentage of HbA1c (Mean)
26 Weeks52 Weeks
LY2189265 + a-GI-1.67-1.65
LY2189265 + BG-1.58-1.57
LY2189265 + Glinides-1.80-1.65
LY2189265 + SU-1.93-1.67
LY2189265 + TZD-1.71-1.69

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Change From Baseline in Updated Homeostasis Model Assessment (HOMA2)

The HOMA2 is a computer model that uses fasting plasma insulin and glucose concentrations to estimate steady state pancreatic beta cell function (%B) and to estimate insulin sensitivity (%S) as a percentage of a normal reference population (normal young adults). The normal reference population was set at 100%. The change from baseline for fasting insulin concentrations are presented as insulin secretion (HOMA2-%B) and insulin sensitivity (HOMA2-%S). (NCT01468181)
Timeframe: Baseline, up to 26 weeks and up to 52 weeks

,,,,
Interventionpercentage of HOMA2 (Mean)
HOMA2-%B, 26 WeeksHOMA2-%B, 52 WeeksHOMA2-%S, 26 WeeksHOMA2-%S, 52 Weeks
LY2189265 + a-GI30.8828.067.576.86
LY2189265 + BG28.1526.05-3.48-3.83
LY2189265 + Glinides26.9333.51-4.41-5.51
LY2189265 + SU29.1026.06-4.80-3.99
LY2189265 + TZD27.3425.38-5.500.47

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Percentage of Participants Who Achieve HbA1c ≤6.5% or <7%

(NCT01468181)
Timeframe: 26 weeks and 52 weeks

,,,,
Interventionpercentage of participants (Number)
HbA1c ≤6.5% at Week 26HbA1c ≤6.5% at Week 52HbA1c <7.0% at Week 26HbA1c <7.0% at Week 52
LY2189265 + a-GI72.370.881.583.1
LY2189265 + BG54.157.473.873.8
LY2189265 + Glinides53.547.969.062.0
LY2189265 + SU35.131.361.848.9
LY2189265 + TZD60.657.672.777.3

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Percentage of Participants With Hypoglycemic Episodes

The percentage of participants with hypoglycemic episodes was calculated by dividing the number of participants with at least 1 hypoglycemic episode over the 52-week treatment period by the total number of participants analyzed, multiplied by 100%. All classifications of hypoglycemia (documented symptomatic, asymptomatic, severe, nocturnal, non-nocturnal, probable symptomatic, relative, and unspecified) were included, except for episodes of relative hypoglycemia that were not severe. A summary of serious and other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module. (NCT01468181)
Timeframe: Baseline through 52 Weeks

Interventionpercentage of participants (Number)
LY2189265 + SU33.6
LY2189265 + BG3.3
LY2189265 + a-GI6.2
LY2189265 + TZD6.1
LY2189265 + Glinides9.9

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Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)

A TEAE was defined as an event that first occurs or worsens (increases in severity) after baseline, regardless of causality or severity. The percentage of participants with TEAEs was calculated by dividing the number of participants with at least 1 TEAE over the 52-week treatment period by the total number of participants analyzed, multiplied by 100%. A summary of serious and other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module. (NCT01468181)
Timeframe: Baseline through 52 Weeks

Interventionpercentage of participants (Number)
LY2189265 + SU85.5
LY2189265 + BG83.6
LY2189265 + a-GI70.8
LY2189265 + TZD80.3
LY2189265 + Glinides73.2

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Progression Free Survival (PFS)

Number of months without evidence of progression after 1 year of the combination of metformin and standard chemotherapy in patients with previously untreated advanced or metastatic pulmonary adenocarcinoma. (NCT01578551)
Timeframe: 1 year

Interventionmonths (Median)
Arm A9.6
Arm B6.7

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Overall Survial

Number of months alive after 1 year of the combination of metformin with standard chemotherapy in patients with previously untreated advanced or metastatic pulmonary adenocarcinoma. (NCT01578551)
Timeframe: up to 2 years

Interventionmonths (Median)
Arm A15.9
Arm B13.9

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Response to Therapy

Percentage of participants with complete or partial response to combination of metformin with standard chemotherapy in patients with previously untreated advanced or metastatic pulmonary adenocarcinoma as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (NCT01578551)
Timeframe: 2 years

Interventionpercentage of participants (Number)
Arm A56
Arm B33

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Change From Baseline in Body Weight at 26 Weeks

Least squares (LS) means were calculated using a mixed-effects model for repeated measures (MMRM) analysis with treatment, visit, treatment-by-visit, oral antihyperglycemic medication regimen (sulfonylureas only, biguanides only, or both), and baseline body mass index (BMI) group (<25 or >=25 kilograms per meter squared [kg/m^2]) as fixed effects, baseline body weight as a covariate, and participant as a random effect. (NCT01584232)
Timeframe: Baseline, 26 weeks

Interventionkilograms (kg) (Least Squares Mean)
LY2189265 + OAM-0.48
Insulin Glargine + OAM0.94

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Change From Baseline in Fasting Blood Glucose (FBG) at 26 Weeks

Least squares (LS) means were calculated using a mixed-effects model for repeated measures (MMRM) analysis with treatment, visit, treatment-by-visit, oral antihyperglycemic medication regimen (sulfonylureas only, biguanides only, or both), and baseline body mass index (BMI) group (<25 or >=25 kilograms per meter squared [kg/m^2]) as fixed effects, baseline FBG as a covariate, and participant as a random effect. (NCT01584232)
Timeframe: Baseline, 26 weeks

Interventionmilligrams per deciliter (mg/dL) (Least Squares Mean)
LY2189265 + OAM-34.3
Insulin Glargine + OAM-37.8

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Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 26 Weeks

Least squares (LS) means were calculated using a mixed-effects model for repeated measures (MMRM) analysis with treatment, visit, treatment-by-visit, oral antihyperglycemic medication regimen (sulfonylureas only, biguanides only, or both), and baseline body mass index (BMI) group (<25 or >=25 kilograms per meter squared [kg/m^2]) as fixed effects, baseline HbA1c as a covariate, and participant as a random effect. (NCT01584232)
Timeframe: Baseline, 26 weeks

Interventionpercentage of HbA1c (Least Squares Mean)
LY2189265 + OAM-1.44
Insulin Glargine + OAM-0.90

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Percentage of Participants With Hypoglycemic Episodes

The percentage of participants with hypoglycemic episodes was calculated by dividing the number of participants with at least one hypoglycemic episode over the 26-week treatment period by the total number of participants analyzed, multiplied by 100%. All classifications of hypoglycemia (documented symptomatic, asymptomatic, severe, nocturnal, non-nocturnal, probable symptomatic, relative, and unspecified) were included, except for episodes of relative hypoglycemia that were not severe. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. (NCT01584232)
Timeframe: Baseline through 26 Weeks

Interventionpercentage of participants (Number)
LY2189265 + OAM26.0
Insulin Glargine + OAM47.8

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Change From Baseline in 8-Point Self-Monitored Blood Glucose (SMBG) at 26 Weeks

Participants were to test and record SMBG concentrations in their study diaries before each meal (breakfast, lunch, and dinner), approximately 2 hours after the start of each meal, at bedtime, and before breakfast the next morning (second pre-morning meal). Least squares (LS) means were calculated using analysis of covariance (ANCOVA) model with treatment, oral antihyperglycemic medication regimen (sulfonylureas only, biguanides only, or both), and baseline body mass index (BMI) group (<25 or >=25 kilograms per meter squared [kg/m^2]) as fixed effects and baseline SMBG as a covariate. (NCT01584232)
Timeframe: Baseline, Up to 26 weeks

,
Interventionmilligrams per deciliter (mg/dL) (Least Squares Mean)
Pre-morning meal (n=178, 179)2 hours post-morning meal (n=178, 179)Pre-midday meal (n=178, 179)2 hours post-midday meal (n=178, 179)Pre-evening meal (n=178, 179)2 hours post-evening meal (n=177, 178)Bedtime (n=177, 172)Second pre-morning meal (n=178, 179)
Insulin Glargine + OAM-38.66-36.14-27.94-20.30-17.50-15.55-17.79-37.02
LY2189265 + OAM-33.49-49.54-36.16-43.51-31.14-46.68-41.53-30.81

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Percentage of Participants Who Achieved Glycosylated Hemoglobin (HbA1c) <=6.5% or <7% at 26 Weeks

The percentage of participants achieving HbA1c level less than 7.0% and less than or equal to 6.5% was analyzed with a longitudinal logistic regression model with treatment, visit, treatment-by-visit, oral antihyperglycemic medication regimen (sulfonylureas only, biguanides only, or both), and baseline body mass index (BMI) group (<25 or >=25 kilograms per meter squared [kg/m^2]) as fixed effects, baseline HbA1c as a covariate, and participant as a random effect. (NCT01584232)
Timeframe: Up to 26 weeks

,
Interventionpercentage of participants (Number)
HbA1c <=6.5%HbA1c <7%
Insulin Glargine + OAM24.045.8
LY2189265 + OAM51.171.3

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Percentage of Participants Achieving Clinically Meaningful Levels of HbA1c (i.e., the Percentage of Participants Achieving Treatment Goal of <6.5% and <7.0% at Week 52)

HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over a 2- to 3 month period. The Baseline HbA1c value is defined as the last non-missing value before the start of treatment. Participants who discontinued from study treatment before Week 52 had their last on-treatment, post-Baseline HbA1c observation carried forward for the analysis. Clinically meaningful levels of response in HbA1c are defined as <6.5% and <7.0%. (NCT01777282)
Timeframe: Week 52

,,,,
InterventionPercentage of participants (Number)
HbA1c <6.5%HbA1c <7.0%
Albiglutide Plus (+) Background OAD (Biguanide)26.959.7
Albiglutide Plus (+) Background OAD (Glinide)24.652.3
Albiglutide Plus (+) Background OAD (Sulfonylurea)20.054.2
Albiglutide Plus (+) Background OAD (Thiazolidinedione)45.980.3
Albiglutide Plus (+) Background OAD (α-Glucosidase Inhibitor)26.267.2

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Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE)

An AE is defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, or is an event of possible drug-induced liver injury. Refer to the general AE/SAE module for a list of non-serious AEs and SAEs. Non-serious hypoglycemia events are not included. (NCT01777282)
Timeframe: From Baseline through Week 52

,,,,
InterventionParticipants (Number)
Any AEAny SAE
Albiglutide Plus (+) Background OAD (Biguanide)470
Albiglutide Plus (+) Background OAD (Glinide)581
Albiglutide Plus (+) Background OAD (Sulfonylurea)972
Albiglutide Plus (+) Background OAD (Thiazolidinedione)492
Albiglutide Plus (+) Background OAD (α-Glucosidase Inhibitor)433

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Time to Study Withdrawal Due to Hyperglycemia

Participants who experienced persistent hyperglycemia after uptitration were to be withdrawn from the study. Hyperglycemia is defined as a fasting plasma glucose >=280 mg/dL (>=15.5 mmol/L) from >=Week 2 to =230 mg/dL (>=12.8 mmol/L) from >=Week 12 to NCT01777282)
Timeframe: Week 52

InterventionWeeks (Mean)
Albiglutide Plus (+) Background OAD (Sulfonylurea)13.0
Albiglutide Plus (+) Background OAD (Glinide)16.5

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Number of Participants With Any Hypoglycemic Event

Hypoglycemia events are defined with respect to low plasma glucose level, mostly accompanied by typical symptoms and/or assistance needed from third party with glucose administration. These events were reported by the investigators upon verification of the plasma glucose levels, symptoms and assistance recorded by the participants, and/or plasma glucose values obtained from laboratory evaluations. (NCT01777282)
Timeframe: From Baseline through Week 52

InterventionParticipants (Number)
Albiglutide Plus (+) Background OAD (Sulfonylurea)17
Albiglutide Plus (+) Background OAD (Biguanide)1
Albiglutide Plus (+) Background OAD (Glinide)4
Albiglutide Plus (+) Background OAD (Thiazolidinedione)2
Albiglutide Plus (+) Background OAD (α-Glucosidase Inhibitor)0

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Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 52

HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over a 2- to 3-month period. The Baseline HbA1c value is defined as the last non-missing value before the start of treatment. Change from Baseline was calculated as the value at Week 52 minus the value at Baseline. Participants who discontinued from study treatment before Week 52 had their last on-treatment, post-Baseline HbA1c observation carried forward for the analysis. (NCT01777282)
Timeframe: Baseline and Week 52

InterventionPercentage of HbA1c in the blood (Mean)
Albiglutide Plus (+) Background OAD (Sulfonylurea)-1.04
Albiglutide Plus (+) Background OAD (Biguanide)-0.94
Albiglutide Plus (+) Background OAD (Glinide)-0.95
Albiglutide Plus (+) Background OAD (Thiazolidinedione)-1.42
Albiglutide Plus (+) Background OAD (α-Glucosidase Inhibitor)-1.39

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Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52

FPG is an indicator of efficacy. The Baseline FPG value is defined as the last non-missing value before the start of treatment. Change from Baseline was calculated as the FPG value at Week 52 minus the FPG value at Baseline. Participants who discontinued from study treatment before Week 52 had their last on-treatment, post-Baseline FPG observation carried forward for the analysis. (NCT01777282)
Timeframe: Baseline and Week 52

InterventionMilligrams per deciliter (mg/dL) (Mean)
Albiglutide Plus (+) Background OAD (Sulfonylurea)-16.4
Albiglutide Plus (+) Background OAD (Biguanide)-24.3
Albiglutide Plus (+) Background OAD (Glinide)-16.4
Albiglutide Plus (+) Background OAD (Thiazolidinedione)-32.1
Albiglutide Plus (+) Background OAD (α-Glucosidase Inhibitor)-33.2

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Change From Baseline in Body Weight at Week 52

The Baseline body weight value is defined as the last non-missing value before the start of treatment. Change from Baseline was calculated as the body weight value at Week 52 minus the value at Baseline. Participants who discontinued from study treatment before Week 52 had their last on-treatment, post-Baseline weight observation carried forward for the analysis. (NCT01777282)
Timeframe: Baseline and Week 52

InterventionKilograms (kg) (Mean)
Albiglutide Plus (+) Background OAD (Sulfonylurea)0.25
Albiglutide Plus (+) Background OAD (Biguanide)-0.33
Albiglutide Plus (+) Background OAD (Glinide)-0.04
Albiglutide Plus (+) Background OAD (Thiazolidinedione)0.52
Albiglutide Plus (+) Background OAD (α-Glucosidase Inhibitor)-0.13

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Change From Baseline to 26 Weeks in Adult Low Blood Sugar Survey (LBSS) Scores

LBSS is a validated, participant-reported 33-item questionnaire with items rated on a 5-point Likert scale, where 0 = never and 5 - always. The LBSS measures behaviors to avoid hypoglycemia and its negative consequences (15 items) and worries about hypoglycemia and its negative consequences (18 items). Total score is the sum of all items (range 0 to 132). Higher total scores reflect greater fear of hypoglycemia. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) with country, treatment and metformin use as fixed effects and baseline score as a covariate. LBSS was assessed during screening visit (baseline) and again at Week 26. (NCT01894568)
Timeframe: Baseline, Week 26

Interventionunits on a scale (Least Squares Mean)
Insulin Peglispro1.51
Insulin Glargine1.62

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Change From Baseline of European Quality of Life-5 Dimensions - 3 Levels (EuroQoL-5D-3L ) Index Score and Visual Analog Scale (VAS) Health State Score at Week 26

The EuroQoL-5D-3L questionnaire is a generic, multidimensional, health-related, quality-of-life instrument. The profile allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression using a 3-level scale of 1 to 3 (no problem, some problems, and extreme problems). These combinations of attributes are converted into a weighted health-state Index Score according to the United States population-based algorithm. Scores ranged from -0.11 to 1.0 where a score of 1.0 indicates perfect health. Overall health state score was self-reported using a VAS marked on a scale of 0 to 100 (0 indicates worst imaginable health state and 100 indicates best imaginable health state. LS means were calculated using analysis of covariance (ANCOVA) for actual measures and changes from baseline at endpoint using LOCF method: adjusting for treatment, stratification factors (region, HbA1c and SU/meglitin. (NCT01894568)
Timeframe: Baseline, Week 26

,
Interventionunits on a scale (Least Squares Mean)
Change from Baseline to Endpoint EQ-5D-3L ScoreChange from Baseline VAS Health State Score
Insulin Glargine0.003.66
Insulin Peglispro0.012.29

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Change From Baseline to 12 Weeks in Hemoglobin A1c (HbA1c)

Hemoglobin A1c (HbA1c) is a test that measures a participant's average blood glucose level over the past 2 to 3 months.LS means were calculated using a MMRM with baseline HbA1C measurement, stratification factors (country, HbA1c, LDL-C [< 100 mg/dL and ≥ 100 mg/dL], and SU/meglitinide use), treatment, visit, and treatment-by-visit interaction as fixed effects. (NCT01894568)
Timeframe: Baseline, Week 12

Interventionpercent of HbA1c (Least Squares Mean)
Insulin Peglispro-1.43
Insulin Glargine-1.22

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30-Day Adjusted Rate of Total and Nocturnal Hypoglycemic Events

Hypoglycemia Events (HE) occurs when blood glucose level ≤ 70 milligram per deciliter (mg/dL) (<3.9 micromoles per liter [mmol/L]). Nocturnal HE includes any total HE that occurred between bedtime and waking. Group mean rates of nocturnal hypoglycemia (per 30 days) are presented and were calculated from negative binomial regression models with treatment, baseline sulfonylurea/meglitinide use, baseline total hypoglycemia event rate, log (exposure/30 days) as the offset in the model. Group Mean is estimated by taking the inverse link function on individual participant covariates first and then averages over all participants. (NCT01894568)
Timeframe: Baseline to Week 26

,
InterventionNumber of events per participant per 30d (Mean)
Total HENocturnal HE
Insulin Glargine1.210.27
Insulin Peglispro1.280.19

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Change From Baseline to Week 26 in Body Weight

LS Means were calculated using MMRM analysis adjusting for baseline, treatment, stratification factor (region, HbA1c, LDL-C, and SU/meglitinide use), visit and treatment-by-visit interaction. (NCT01894568)
Timeframe: Baseline, Week 26

InterventionKilogram (kg) (Least Squares Mean)
Insulin Peglispro1.06
Insulin Glargine1.57

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Change From Baseline to Week 26 in Hemoglobin A1c (HbA1c)

Hemoglobin A1c (HbA1c) is a test that measures a participant's average blood glucose level over the past 2 to 3 months. Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis adjusting for treatment, stratification factors (region, sulfonylureas/meglitinide use, baseline Low-Density Lipoprotein [LDL-C], visit, treatment-by-visit interaction, and baseline HbA1c as fixed effects and participants as the random effect. P-value is from MMRM with terms for treatment, visit, treatment-by-visit interaction, stratification, and baseline HbA1C. (NCT01894568)
Timeframe: Baseline, Week 26

Interventionpercent of HbA1c (Least Squares Mean)
Insulin Peglispro-1.61
Insulin Glargine-1.36

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Insulin Dose Per Kilogram (kg) of Body Weight

LS means were calculated using MMRM analysis adjusting for baseline, treatment, stratification factor (region, HbA1c, LDL-C, and SU/meglitinide), visit, and treatment-by-visit interaction. (NCT01894568)
Timeframe: Week 26

Interventionunits per kg (Least Squares Mean)
Insulin Peglispro0.26
Insulin Glargine0.26

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Intra-Participant Variability of the Fasting Blood Glucose (FBG)

Intra-participant variability of Fasting Blood Glucose (FBG), which was measured by Self Monitored Blood Glucose (SMBG), was assessed by the standard deviation of the FBG measurement at the Week 26 visit. LS means were calculated using a MMRM with baseline fasting blood glucose measurement, stratification factors (country, HbA1c, LDL-C [< 100 mg/dL and ≥ 100 mg/dL], and SU/meglitinide use), treatment, visit, and treatment-by-visit interaction as fixed effects. (NCT01894568)
Timeframe: Week 26

Interventionmg/dL (Least Squares Mean)
Insulin Peglispro14.97
Insulin Glargine15.12

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Percent Hemoglobin A1c at Week 26

HbA1c is a test that measures a participant's average blood glucose level over the past 2 to 3 months. LS means were calculated using a MMRM with baseline HbA1C measurement, stratification factors (country, HbA1c, LDL-C [< 100 mg/dL and ≥ 100 mg/dL], and SU/meglitinide use), treatment, visit, and treatment-by-visit interaction as fixed effects. (NCT01894568)
Timeframe: Week 26

Interventionpercent of HbA1c (Least Squares Mean)
Insulin Peglispro6.92
Insulin Glargine7.17

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Percentage of Participants Achieving Steady-State of Basal Insulin Dose at 26 Weeks (Time to Steady State for Basal Insulin [Stable Maximum Dose])

(NCT01894568)
Timeframe: Week 26

Interventionpercentage of participants (Number)
Insulin Peglispro96.9
Insulin Glargine97.2

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Percentage of Participants With Total and Nocturnal Hypoglycemic Events (HE)

Percentage of participants with hypoglycemic events (total or nocturnal) to Week 26 based on BG Threshold 70mg/dL. (NCT01894568)
Timeframe: Baseline to Week 26

,
Interventionpercentage of participants (Number)
Nocturnal Hypoglycemia BG 70mg/dLTotal Hypoglycemia BG 70mg/dL
Insulin Glargine29.676.5
Insulin Peglispro26.677.1

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9-Point Self-Monitored Blood Glucose (SMBG)

LS means were calculated using MMRM analysis adjusting for baseline, treatment, stratification factor (region, HbA1c, LDL-C, and SU/meglitinide use), visit and treatment-by-visit interaction. The 9-point SMBG are measured at: Pre-morning meal, 2 hours(hr) post morning meal, pre-midday meal, 2 hr post midday meal, pre-evening meal, 2 hr post pre-evening meal, bedtime, 0300 hr, and pre-morning meal next day, and should be performed on 2 non-consecutive days. (NCT01894568)
Timeframe: Week 0 and Week 26

,
Interventionmg/dL (Least Squares Mean)
Morning Pre-meal Wk0Morning Pre-meal Wk26Morning Post-meal Wk0Morning Post-meal Wk26Mid-day Pre-meal Wk0Mid-day Pre-meal Wk26Mid-day Post-meal Wk0Mid-day Post-meal Wk26Evening Pre-meal Wk0Evening Pre-meal Wk26Evening Post-meal Wk0Evening Post-meal Wk26Bed Time Wk0Bed Time Wk260300 Hours (Hrs) Wk00300 Hrs Wk26Pre-morning Meal Next Day Wk0Pre-morning Meal Next Day Wk26
Insulin Glargine162.83108.71233.37176.93166.68122.85226.11183.88172.83135.55219.54182.80197.68161.44162.13114.77159.96105.18
Insulin Peglispro160.19108.24237.19176.97169.24122.01224.22182.32176.49131.65219.45176.23198.64153.41158.82115.18156.28108.42

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Percentage of Participants With HbA1c ≤6.5%

Percentage of participants with HbA1c ≤6.5% at Week 26 were made using a logistic regression model for endpoint used last observation carried forward (LOCF) method including treatment, baseline HbA1c value. (NCT01894568)
Timeframe: Week 26

InterventionPercentage of participants (Number)
Insulin Peglispro29.8
Insulin Glargine22.7

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Percentage of Participants With Detectable Anti-Insulin Peglispro Antibodies at Week 26

For participants with detectable anti-insulin peglispro antibody level, the percentage of participants with positive cross-react with endogenous insulin was summarized. (NCT01894568)
Timeframe: Week 26

Interventionpercentage of participants (Number)
Insulin Peglispro24.6
Insulin Glargine32.5

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Concentration of Triglycerides, Total Cholesterol, Low-Density Lipoprotein (LDL-C), and High-Density Lipoprotein Cholesterol (HDL-C) at Week 26

LS means were calculated using MMRM analysis adjusting for baseline, treatment, stratification factor (region, HbA1c, LDL-C, and SU/meglitinide use), visit, and treatment-by-visit interaction. (NCT01894568)
Timeframe: Week 26

,
Interventionmg/dL (Least Squares Mean)
Cholesterol Wk26HDL Wk26Triglycerides Wk26LDL Wk26
Insulin Glargine177.9052.99122.83101.07
Insulin Peglispro175.7651.64132.4397.95

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Fasting Blood Glucose (FBG)

LS Means were calculated using MMRM analysis adjusting for baseline, treatment, stratification factor (region, HbA1c, LDL-C, and SU/meglitinide use), visit and treatment-by-visit interaction. (NCT01894568)
Timeframe: Weeks 0 and 26

,
Interventionmg/dL (Least Squares Mean)
Week 0Week 26
Insulin Glargine161.19108.22
Insulin Peglispro159.53108.39

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Fasting Serum Glucose (FSG)

LS means were calculated using MMRM analysis adjusting for baseline, treatment, stratification factor (region, HbA1c, LDL-C, and sulfonylurea [SU]/meglitinide use), visit, and treatment-by-visit interaction. (NCT01894568)
Timeframe: Weeks 0 and 26

,
Interventionmg/dL (Least Squares Mean)
Week 0Week 26
Insulin Glargine166.61110.32
Insulin Peglispro164.31103.85

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Insulin Treatment Satisfaction Questionnaire (ITSQ) Score

The Insulin Treatment Satisfaction Questionnaire is a validated instrument containing 22 items that assessed treatment satisfaction for participants with diabetes on insulin. The questionnaire measures satisfaction from the following 5 domains: Inconvenience of Regimen, Lifestyle Flexibility, Glycemic Control, Hypoglycemic Control, and Insulin Delivery Device. Data presented are the transformed score on a scale of 0-100, where a higher score indicate better treatment satisfaction. LS means was achieved using a MMRM model for post-baseline measures with stratification factors (country, HbA1c, and SU/meglitinide use) treatment, visit, treatment-by-visit as fixed effects. ITSQ was assessed at Week 4 (baseline) and Week 26. (NCT01894568)
Timeframe: Week 4 and 26

,
Interventionunits on a scale (Least Squares Mean)
ITSQ Wk4ITSQ Wk26
Insulin Glargine75.9478.29
Insulin Peglispro74.1378.73

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Number of Participants With No Clinically Significant Changes in Liver Enzyme Levels or Positive Pregnancy Tests

The safety criteria will include laboratory values for liver enzymes and document the absence of pregnancy in all participants during the trial (NCT02022007)
Timeframe: 16 weeks

InterventionParticipants (Count of Participants)
Metformin XR0
Saxagliptin0
Saxagliptin-Metformin XR0

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Oral Disposition Index

Post-treatment in insulin-sensitivity-secretion index . The insulin secretion-sensitivity index (IS-SI) provides an estimate of β-cell compensation relative to the prevailing insulin resistance, not absolute insulin secretion. It is derived by applying the concept of the disposition index (DI) to measurements obtained during the 2-h OGTT. The IS-SI, a surrogate measure of the DI derived from the OGTT (IGI multiplied by the SIOGTT], was calculated as the product of acute β-cell response [IGI] and Matsuda index (SIOGTT) based on the existence of the predicted hyperbolic relationship between these two measures (NCT02022007)
Timeframe: 16 weeks

Interventionindex (Mean)
Metformin XR208
Saxagliptin359
Saxagliptin-Metformin XR532

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Pancreatic ß-cell Compensatory Function

Post-treatment corrected early phase insulin secretion index (IGI/HOMA-IR). . Early pancreatic β-cell response is estimated as the insulinogenic index (IGI) derived from the ratio of the increment of insulin to that of glucose 30 minutes after a glucose load (insulin 30 min - insulin 0 min/glucose 30 min - glucose 0 min) corrected for by the relative level of insulin resistance (IGI/HOMA-IR which is estimated by homeostasis model assessment of insulin resistance using fasting insulin and glucose levels). (NCT02022007)
Timeframe: 16 weeks

InterventionRatio (Mean)
Metformin XR0.46
Saxagliptin1.4
Saxagliptin-Metformin XR1.03

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Triglyceride (TRG) /HDL-cholesterol Ratio

The measure of TRG levels and HDL- cholesterol levels are used as an estimate of insulin sensitivity. A TRG/HDL-C ratio of greater than 3.0 is used as an indirect measure of insulin resistance (NCT02022007)
Timeframe: 16 weeks

InterventionRatio (Mean)
Metformin XR4.2
Saxagliptin2.9
Saxagliptin-Metformin XR3.0

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Body Mass Index at 16 Weeks

Height and weight measurements were used to calculate body mass index (BMI), defined as kg/m2. (NCT02022007)
Timeframe: 16 weeks

Interventionkg/mg2 (Mean)
Metformin XR42
Saxagliptin36.7
Saxagliptin-Metformin XR42

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Fasting Glucose

Post-treatment fasting glucose levels (NCT02022007)
Timeframe: 16 weeks

Interventionmmol/L (Mean)
Metformin XR5.4
Saxagliptin5.3
Saxagliptin-Metformin XR5.0

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Free Androgen Index (FAI)

Hyperandrogenism is measured by a combination of total testosterone (T) and sex hormone binding globulin (SHBG). The FAI was calculated as the quotient 100 x T/SHBG; hyperandrogenism was defined by a FAI value >3.85. (NCT02022007)
Timeframe: 16 weeks

Interventionindex (Mean)
Metformin XR6.3
Saxagliptin5.5
Saxagliptin-Metformin XR4.3

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Glucose Metabolism

Glucose metabolic secretory status after drug treatment (normal, impaired or diabetic). We used the American Diabetes Association (ADA) definition of impairment which is fasting glucose greater than 100 mg/dL and/or 2 hour glucose greater than 140 mg/dL. (NCT02022007)
Timeframe: 16 weeks

InterventionParticipants (Count of Participants)
Metformin XR3
Saxagliptin6
Saxagliptin-Metformin XR10

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Matsuda Index of Insulin-Sensitivity (SI OGTT)

Post-treatment insulin sensitivity index. The Matsuda index of whole-body insulin sensitivity is calculated from an oral glucose tolerance test (10,000/square root of [fasting glucose x fasting insulin] x [mean glucose x mean insulin during OGTT]), and is highly correlated with the rate of whole-body glucose disposal during the euglycemic insulin clamp (NCT02022007)
Timeframe: 16 weeks

InterventionIndex (Mean)
Metformin XR2.5
Saxagliptin3.5
Saxagliptin-Metformin XR4.1

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Mean Blood Glucose During the OGTT

Post-treatment mean blood glucose levels. Mean blood glucose (MBG) concentrations were calculated by summing glucose values obtained at 0,30,60 and 120 minutes during the OGTT and dividing by 4. (NCT02022007)
Timeframe: 16 weeks

Interventionmmol/L (Mean)
Metformin XR7.9
Saxagliptin7.1
Saxagliptin-Metformin XR6.2

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Menstrual Cycle Interval at 16 Weeks

The number of menstrual cycles during the previous year was recorded and the average menstrual interval calculated by dividing 365 by the number of menstrual cycles in the previous year . During the study period, the patients in a menstrual diary recorded vaginal bleeding over 16 weeks. The effects of treatment intervention on menstrual cycle interval was calculated evaluated by dividing 112 days by the number of menstrual cycles recorded in each patient's menstrual cycle diary. (NCT02022007)
Timeframe: 16 weeks

Interventiondays between menstrual cycles (Mean)
Metformin XR81
Saxagliptin58
Saxagliptin-Metformin XR36

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Waist Circumference at 16 Weeks

The circumference measurement was taken in the upright position using a 15-mm width flexible metric tape held close to the body but not tight enough to indent the skin. Waist circumference (WC) was measured in centimeters at the narrowest level midway between the lowest ribs and the iliac crest. (NCT02022007)
Timeframe: 16 weeks

Interventioncentimeters (Mean)
Metformin XR109
Saxagliptin99.6
Saxagliptin-Metformin XR106

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Visual Acuity

Change from baseline Visual acuity. Best corrected visual acuity was reported in decimal fraction. A decrease of visual acuity during treatment was considered a negative safety outcome. (NCT02506257)
Timeframe: Baseline and Day 14

Interventiondecimals (Mean)
0.04% PHMB0.3
0.06% PHMB0.3
0.08% PHMB0.3
PHMB Vehicle0.3

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Systolic Blood Pressure

Change from baseline systolic blood pressure (NCT02506257)
Timeframe: Baseline and Day 14

InterventionmmHg (Mean)
0.04% PHMB-0.7
0.06% PHMB0.6
0.08% PHMB-0.9
PHMB Vehicle1.0

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Ocular Surface Disease Index-OSDI

Change from baseline OSDI at D 14. Score range was betwwen 0-100. An increase of OSDI values with treatment represent a negative outcome. (NCT02506257)
Timeframe: Baseline and Day 14

Interventionscores on a scale (Mean)
0.04% PHMB1.5
0.06% PHMB1.3
0.08% PHMB4.2
PHMB Vehicle-2.2

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Plasma Concentration of PHMB

(NCT02506257)
Timeframe: Day14

Interventionmicrograms/ml (Mean)
0.04% PHMB0
0.06% PHMB0
0.08% PHMB0
PHMB Vehicle0

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Number of Subjects With Dose-limiting Adverse Events

(NCT02506257)
Timeframe: up to 21 days from date of randomization

Interventionparticipants (Number)
0.04% PHMB0
0.06% PHMB2
0.08% PHMB3
PHMB Vehicle0

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Conjunctival Examination

Change from baseline conjunctival staining at Day 14. Staining with lissamine green was used. The density of staining was graded with the Oxford Score. Score range was between 0-15. An increase in the score after treatment represent a negative outcome (NCT02506257)
Timeframe: Baseline and Day 14

Interventionscores on a scale (Mean)
0.04% PHMB0.7
0.06% PHMB1.2
0.08% PHMB1.7
PHMB Vehicle1.0

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Clinical Resolution Rate

Percentage of patients cured 30 days after discontinuing all study therapies, within 12 months of randomization (NCT03274895)
Timeframe: 12 months

Interventionpercentage of participants (Number)
PHMB 0.08% Plus Placebo84.8
PHMB 0.02% Plus Propamidine 0.1%88.5

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Visual Acuity

Final visual acuity (best corrected) (NCT03274895)
Timeframe: maximum 12 months

InterventionLogMAR (Median)
PHMB 0.08% Plus Placebo0.000
PHMB 0.02% Plus Propamidine 0.1%0.000

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Time to Cure

Time needed to reach a clinical resolution (NCT03274895)
Timeframe: maximum 12 months

Interventiondays (Median)
PHMB 0.08% Plus Placebo140
PHMB 0.02% Plus Propamidine 0.1%114

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