Compounds > insulin glulisine
Page last updated: 2024-11-12

insulin glulisine

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Description

insulin glulisine: provides greater beta-cell protective action [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID16136701
MeSH IDM0456627

Synonyms (13)

Synonym
insulin glulisine
hmr 1964
insulin, lysyl(b3)-glutamyl(b29)-
(3(sup b)-l-lysine,29(sup b)-l-glutamic acid)insulin (human)
apidra solostar
unii-7xiy785azd
apidra
insulin glulisine [usan:inn:jan]
7xiy785azd ,
b3-lysyl-b29-glutamylinsulin
insulin (human), 3b-l-lysine-29b-l-glutamic acid-
insulin (human),3(sup b)-l-lysine,29(sup b)-l-glutamic acid-
insulin, lys(b3)-glu(b29)-

Research Excerpts

Overview

Insulin glulisine (Apidra) is a human insulin analogue approved for the improvement of glycaemic control in adults, adolescents and children with diabetes mellitus. It is a rapid-acting insulin with a faster onset of action than the other insulin analogs of its class, which are insulin aspart (Asp) and insulin lispro (Lisp)

ExcerptReferenceRelevance
"Insulin glulisine is a new rapid-acting analogue and has characteristics nearly identical to those of its predecessors."( New insulin analogues and routes of delivery: pharmacodynamic and clinical considerations.
Roach, P, 2008)		1.07
"Insulin glulisine is a rapid-acting insulin with relative equivalence in efficacy and safety to other short- and rapid-acting insulins. "( Insulin glulisine: an evaluation of its pharmacodynamic properties and clinical application.
Helms, KL; Kelley, KW, 2009)		3.24
"Insulin glulisine is a safe and effective rapid-acting insulin analog for the treatment of adults with diabetes. "( Insulin glulisine: an evaluation of its pharmacodynamic properties and clinical application.
Helms, KL; Kelley, KW, 2009)		3.24
"Insulin glulisine (Apidra) is a human insulin analogue approved for the improvement of glycaemic control in adults, adolescents and children with diabetes mellitus. "( Insulin glulisine: a review of its use in the management of diabetes mellitus.
Garnock-Jones, KP; Plosker, GL, 2009)		3.24
"Insulin glulisine (Glu) is a rapidly-acting insulin analog with a faster onset of action than the other insulin analogs of its class, which are insulin aspart (Asp) and insulin lispro (Lisp). "( Comparison of daily glucose excursion by continuous glucose monitoring between type 2 diabetic patients receiving preprandial insulin aspart or postprandial insulin glulisine.
Arai, K; Asai, S; Fukuda, H; Katabami, T; Kato, H; Nagai, Y; Nishine, A; Ohta, A; Sada, Y; Tanaka, Y, 2013)		2.03
"Insulin glulisine is a novel analog of human insulin designed for use as a rapid-acting insulin. "( Insulin glulisine provides improved glycemic control in patients with type 2 diabetes.
Dailey, G; Moses, RG; Rosenstock, J; Ways, K, 2004)		3.21
"Insulin glulisine is a new rapid-acting insulin analog. "( A comparison of the steady-state pharmacokinetics and pharmacodynamics of a novel rapid-acting insulin analog, insulin glulisine, and regular human insulin in healthy volunteers using the euglycemic clamp technique.
Becker, RH; Burger, F; Frick, AD; Potgieter, JH; Scholtz, H, 2005)		1.98
"Insulin glulisine is a rapid-acting human insulin analogue that has a faster onset of action and shorter duration of action than regular human insulin (RHI) in patients with type 1 or 2 diabetes mellitus and is efficacious in controlling prandial blood glucose levels in these patients. "( Insulin glulisine.
Robinson, DM; Wellington, K, 2006)		3.22
"Insulin glulisine (Apidra) is a rapid-acting insulin analogue created by substituting lysine for asparagine at position B3 and glutamic acid for lysine at position B29 on the B chain of human insulin."( Combining insulins for optimal blood glucose control in type I and 2 diabetes: focus on insulin glulisine.
Garg, SK; Snyder, B; Ulrich, H, 2007)		1.28

Effects

Insulin glulisine has a good safety profile in children with type 1 diabetes aged 6-12 years, with generally low rates of severe hypoglycaemia and few adverse reactions. It can be administered immediately before or after meals.

ExcerptReferenceRelevance
"Insulin glulisine has a good safety profile in children with type 1 diabetes aged 6-12 years, with generally low rates of severe hypoglycaemia and few adverse reactions. "( Safety results from OCAPI: a European Observational Cohort Study of insulin glulisine-treated children aged 6-12 years with type 1 diabetes.
Cali, A; Danne, T; Konstantinova, M; Loizeau, V; Pilorget, V, 2014)		2.08
"Insulin glulisine has a flexible administration period, as it can be administered immediately before or after meals."( Insulin glulisine: a review of its use in the management of diabetes mellitus.
Garnock-Jones, KP; Plosker, GL, 2009)		2.52
"Insulin glulisine has a higher efficacy in reducing postprandial glucose excursions and in restoring normal postprandial microcirculation than rapid human insulin. "( Micro- and macrovascular outcomes in Type 2 diabetic patients treated with insulin glulisine or human regular insulin: a retrospective database analysis.
Dippel, FW; Giani, G; Kostev, K; Kress, S; Rathmann, W, 2012)		2.05
"Insulin glulisine has a favorable safety profile, which is not significantly different from that of regular human insulin."( Insulin glulisine.
Cox, SL, 2005)		2.49
"Insulin glulisine has been designed to exhibit intrinsic stability while maintaining rapid deployment of insulin monomers."( Insulin glulisine complementing basal insulins: a review of structure and activity.
Becker, RH, 2007)		2.5

Toxicity

Insulin glulisine has a good safety profile in children with type 1 diabetes aged 6-12 years, with generally low rates of severe hypoglycaemia and few adverse reactions.

ExcerptReferenceRelevance
" Insulin glulisine was safe and well tolerated."( Pharmacokinetics, prandial glucose control, and safety of insulin glulisine in children and adolescents with type 1 diabetes.
Becker, RH; Bittner, C; Danne, T; Frick, AD; Heise, T; Rave, K, 2005)		1.48
" Further, these initial data indicate that insulin glulisine is safe and well tolerated in this patient population."( Pharmacokinetics, prandial glucose control, and safety of insulin glulisine in children and adolescents with type 1 diabetes.
Becker, RH; Bittner, C; Danne, T; Frick, AD; Heise, T; Rave, K, 2005)		0.84
"2 %), daily insulin doses, blood glucose profiles and adverse event rates were similar in both groups."( Safety of insulin glulisine when given by continuous subcutaneous infusion using an external pump in patients with type 1 diabetes.
Hoogma, RP; Schumicki, D, 2006)		0.74
" Frequency and type of adverse events, serious adverse events, or hypoglycemia reported as serious adverse events were similar between both groups."( Comparable efficacy and safety of insulin glulisine and insulin lispro when given as part of a Basal-bolus insulin regimen in a 26-week trial in pediatric patients with type 1 diabetes.
Arslanian, S; Blatniczky, L; Danne, T; Peterkova, V; Philotheou, A; Souhami, E, 2011)		0.65
"Insulin glulisine has a good safety profile in children with type 1 diabetes aged 6-12 years, with generally low rates of severe hypoglycaemia and few adverse reactions."( Safety results from OCAPI: a European Observational Cohort Study of insulin glulisine-treated children aged 6-12 years with type 1 diabetes.
Cali, A; Danne, T; Konstantinova, M; Loizeau, V; Pilorget, V, 2014)		2.08
"Given the current lack of clinical data, this study will provide evidence supporting safe and effective glycemic control using basal insulin glargine-based therapy plus OADs compared with twice-daily premixed insulin in Chinese patients with T2DM after short-term IIT."( Efficacy and Safety of Basal Insulin-Based Treatment Versus Twice-Daily Premixed Insulin After Short-Term Intensive Insulin Therapy in Patients with Type 2 Diabetes Mellitus in China: Study Protocol for a Randomized Controlled Trial (BEYOND V).
Cui, N; Guo, L; Jiang, X; Liu, J; Mu, Y; Wang, G; Xu, B; Zhang, X, 2020)		0.56
" Overall, the number of adverse events per person was similar between groups (2."( A Phase II, Single-Center, Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Therapeutic Efficacy of Intranasal Glulisine in Amnestic Mild Cognitive Impairment and Probable Mild Alzheimer's Disease.
Barclay, TR; Frey, W; Hage, L; Hanson, LR; Kashyap, B; O'Keefe, LR; Pyle, M; Rosenbloom, M; Svitak, A, 2021)		0.62
"Intranasal glulisine was relatively safe and well-tolerated and did not consistently impact peripheral glucose or insulin levels."( A Phase II, Single-Center, Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Therapeutic Efficacy of Intranasal Glulisine in Amnestic Mild Cognitive Impairment and Probable Mild Alzheimer's Disease.
Barclay, TR; Frey, W; Hage, L; Hanson, LR; Kashyap, B; O'Keefe, LR; Pyle, M; Rosenbloom, M; Svitak, A, 2021)		0.62

Pharmacokinetics

insulin glulisine has shown an absorption profile with a peak insulin concentration approximately twice that of regular human insulin, which is reached in approximately half the time. The pharmacokinetic profile for insulinglulisine was similar for children and adolescents, whereas the pharmacodynamic profile for RHI demonstrated a 64% higher concentration in adolescents.

ExcerptReferenceRelevance
" The pharmacokinetic profile for insulin glulisine was similar for children and adolescents, whereas the pharmacokinetic profile for RHI demonstrated a 64% higher concentration in adolescents."( Pharmacokinetics, prandial glucose control, and safety of insulin glulisine in children and adolescents with type 1 diabetes.
Becker, RH; Bittner, C; Danne, T; Frick, AD; Heise, T; Rave, K, 2005)		0.85
" Pharmacokinetic studies with insulin glulisine have shown an absorption profile with a peak insulin concentration approximately twice that of regular human insulin, which is reached in approximately half the time."( Clinical pharmacokinetics and pharmacodynamics of insulin glulisine.
Becker, RH; Frick, AD, 2008)		0.89
" Insulin aspart and insulin lispro have nearly identical pharmacokinetic and pharmacodynamic profiles and provide better postprandial glucose control and less hypoglycaemia (primarily nocturnal and severe hypoglycaemia in type 1 diabetes mellitus) than regular insulin."( New insulin analogues and routes of delivery: pharmacodynamic and clinical considerations.
Roach, P, 2008)		0.35
"To evaluate the pharmacodynamic properties, efficacy, safety, and clinical application of insulin glulisine, a rapid-acting insulin analog, in the treatment of diabetes mellitus in ambulatory and hospitalized patients."( Insulin glulisine: an evaluation of its pharmacodynamic properties and clinical application.
Helms, KL; Kelley, KW, 2009)		2.02
"To compare how the rapid-acting insulin analogues (RAIAs) aspart, lispro, and glulisine perform in continuous subcutaneous insulin infusion (CSII) therapy regarding (1) pharmacokinetic properties, (2) chemical and physical stability, and (3) pump compatibility."( Comparison of pharmacokinetic properties, physicochemical stability, and pump compatibility of 3 rapid-acting insulin analogues-aspart, lispro, and glulisine.
Bode, BW, )		0.13
"These RAIAs have pharmacokinetic profiles that more closely mimic endogenous insulin in comparison with regular human insulin and tend to produce less hypoglycemia."( Comparison of pharmacokinetic properties, physicochemical stability, and pump compatibility of 3 rapid-acting insulin analogues-aspart, lispro, and glulisine.
Bode, BW, )		0.13
"A multinational, randomized, double-blind, two-way crossover trial to compare the pharmacokinetic and pharmacodynamic properties of bolus, subcutaneously administered insulin glulisine (glulisine) and insulin aspart (aspart) in insulin-naÏve, obese subjects with type 2 diabetes."( Comparative pharmacodynamic and pharmacokinetic characteristics of subcutaneous insulin glulisine and insulin aspart prior to a standard meal in obese subjects with type 2 diabetes.
Bolli, GB; Charbonnel, B; Luzio, S; Marzotti, S; Owens, DR; Porcellati, F; Sert-Langeron, C; Zair, Y, 2011)		0.79
" The pharmacodynamic and pharmacokinetic data indicate that this cyclodextrin-based formulation may have potential for further research as an oral insulin dosage form."( Physicochemical, pharmacokinetic and pharmacodynamic analyses of amphiphilic cyclodextrin-based nanoparticles designed to enhance intestinal delivery of insulin.
Bazile, D; Brayden, DJ; Hunger, C; McCartney, F; Nellen, S; O'Driscoll, CM; Presas, E; Sultan, E; V Alvarez, C; Werner, U, 2018)		0.48

Compound-Compound Interactions

ExcerptReferenceRelevance
"Better A1c reductions were obtained with premeal GLU, but postmeal administration of GLU was as safe and effective as premeal GLU or RHI in combination with insulin glargine and was not associated with weight gain."( Optimized Basal-bolus insulin regimens in type 1 diabetes: insulin glulisine versus regular human insulin in combination with Basal insulin glargine.
Garg, SK; Rosenstock, J; Ways, K, )		0.37
"A total of 180 hospitalized patients with type 2 diabetes received either glulisine (n = 88) or regular insulin (n = 92) before each meal in combination with insulin glargine at bedtime in a randomized double-blind fashion."( Glulisine versus human regular insulin in combination with glargine in noncritically ill hospitalized patients with type 2 diabetes: a randomized double-blind study.
Boron, A; Meyer, C; Plummer, E; Vedda, R; Voltchenok, M, 2010)		0.36

Bioavailability

ExcerptReferenceRelevance
"The insulin analog LysB3,GluB29-insulin (glulisine) displays accelerated in vivo bioavailability compared with native insulin."( Effects of the rapid-acting insulin analog glulisine on cultured human skeletal muscle cells: comparisons with insulin and insulin-like growth factor I.
Aroda, V; Carter, L; Ciaraldi, TP; Henry, RR; Mudaliar, S; Phillips, SA, 2005)		0.33

Dosage Studied

The prandial insulin glulisine dosage for arm A and arm B was 9. The study compared the dosing accuracy of the FT with that of the manually operated SoloSTAR (SS)

ExcerptRelevanceReference
" These data highlight the flexibility in the dosing schedule with insulin glulisine."( Insulin glulisine: a new rapid-acting insulin analogue for the treatment of diabetes.
Ellis, SL; Garg, SK; Ulrich, H, 2005)		2.01
" The information provided is tailored to diabetes educators and includes mechanism of action, pharmacokinetics, drug interactions, clinical trials, dosage and administration guidelines, side effects, and educational pearls for each insulin discussed."( Update in the pharmacologic treatment of diabetes: focus on insulin detemir, insulin glulisine, and inhaled dry powdered insulin.
Campbell, RK; Iltz, JL; Odegard, PS; Setter, SM, )		0.36
"This study assessed insulin dose and dosing patterns required to optimize glycemic control with an insulin pump in patients with type 2 diabetes."( Insulin pump therapy in patients with type 2 diabetes safely improved glycemic control using a simple insulin dosing regimen.
Bailey, TS; Bode, BW; Brunelle, R; Chen, X; Edelman, SV; Frias, JP; Kipnes, MS, 2010)		0.36
"Insulin pump therapy using a simple dosing regimen significantly improved glycemic control in patients with type 2 diabetes."( Insulin pump therapy in patients with type 2 diabetes safely improved glycemic control using a simple insulin dosing regimen.
Bailey, TS; Bode, BW; Brunelle, R; Chen, X; Edelman, SV; Frias, JP; Kipnes, MS, 2010)		0.36
"Postprandial glulisine administration provided similar glycaemic control and was non-inferior to preprandial administration on weight gain, without additional risk of severe hypoglycaemia, showing dosing flexibility and the feasibility of such approach when clinically indicated."( Influence of preprandial vs. postprandial insulin glulisine on weight and glycaemic control in patients initiating basal-bolus regimen for type 2 diabetes: a multicenter, randomized, parallel, open-label study (NCT00135096).
Brusco, O; Nakhle, S; Ratner, R; Rendell, M; Vlajnic, A; Wynne, A, 2011)		0.63
"Reduction of initial glargine/glulisine insulin weight-based dosing in hospitalized patients with diabetes and renal insufficiency reduced the frequency of hypoglycemia by 50% without compromising the control of hyperglycemia."( A randomized trial of two weight-based doses of insulin glargine and glulisine in hospitalized subjects with type 2 diabetes and renal insufficiency.
Baldwin, D; DeLange-Hudec, S; Emanuele, MA; Glossop, V; Lee, H; Molitch, M; Munoz, C; Raghu, P; Smallwood, K; Zander, J, 2012)		0.38
" While insulin Glu is usually injected just before meals, postprandial injection may help to avoid unexpected postprandial hypoglycemia or hyperglycemia by adjusting the insulin dosage according to food intake."( Comparison of daily glucose excursion by continuous glucose monitoring between type 2 diabetic patients receiving preprandial insulin aspart or postprandial insulin glulisine.
Arai, K; Asai, S; Fukuda, H; Katabami, T; Kato, H; Nagai, Y; Nishine, A; Ohta, A; Sada, Y; Tanaka, Y, 2013)		0.59
" The present study compared the dosing accuracy of the FT with that of the manually operated SoloSTAR® (SS; Sanofi; insulin glulisine)."( Dosing accuracy and insulin flow rate characteristics of a new disposable insulin pen, FlexTouch, compared with SoloSTAR.
Abdel-Tawab, M; Bohnet, J; Kamlot, S; Schmitz, M, 2013)		0.6
"Thirty unused pens from one batch of each pen type were used to test dosing accuracy at minimum (1 U), mid (40 U), and maximum dose (80 U)."( Dosing accuracy and insulin flow rate characteristics of a new disposable insulin pen, FlexTouch, compared with SoloSTAR.
Abdel-Tawab, M; Bohnet, J; Kamlot, S; Schmitz, M, 2013)		0.39
"Both insulin pens revealed excellent dosing accuracy, delivering all doses within the limits set by ISO 11608-1:2000."( Dosing accuracy and insulin flow rate characteristics of a new disposable insulin pen, FlexTouch, compared with SoloSTAR.
Abdel-Tawab, M; Bohnet, J; Kamlot, S; Schmitz, M, 2013)		0.39
"This study demonstrated excellent dosing accuracy for the SS and FT at all tested dosage levels."( Dosing accuracy and insulin flow rate characteristics of a new disposable insulin pen, FlexTouch, compared with SoloSTAR.
Abdel-Tawab, M; Bohnet, J; Kamlot, S; Schmitz, M, 2013)		0.39
" This analysis discusses several features and design alternatives of insulin pens and comments on a new study by Bohnet and coauthors in this issue of Journal of Diabetes Science and Technology that compared the dosing accuracy of the spring-driven FlexTouch® (FT; Novo Nordisk; insulin aspart) with that of the manually operated SoloSTAR® (Sanofi; insulin glulisine)."( Analysis and perspective of Dosing accuracy and insulin flow rate characteristics of a new disposable insulin pen, FlexTouch, compared with SoloSTAR.
Ignaut, DA; Yeager, HK, 2013)		0.56
" The pharmacodynamic and pharmacokinetic data indicate that this cyclodextrin-based formulation may have potential for further research as an oral insulin dosage form."( Physicochemical, pharmacokinetic and pharmacodynamic analyses of amphiphilic cyclodextrin-based nanoparticles designed to enhance intestinal delivery of insulin.
Bazile, D; Brayden, DJ; Hunger, C; McCartney, F; Nellen, S; O'Driscoll, CM; Presas, E; Sultan, E; V Alvarez, C; Werner, U, 2018)		0.48
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (154)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's59 (38.31)29.6817
2010's86 (55.84)24.3611
2020's9 (5.84)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 85.37

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 Index85.37 (24.57)
Research Supply Index5.46 (2.92)
Research Growth Index4.57 (4.65)
Search Engine Demand Index151.00 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (85.37)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials67 (39.88%)5.53%
Reviews37 (22.02%)6.00%
Case Studies13 (7.74%)4.05%
Observational4 (2.38%)0.25%
Other47 (27.98%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (79)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
A Study of Effectiveness and Safety of Apidra in Combination With Lantus Therapy in Basal-bolus Insulin Regimen in Inadequately Controlled Children and Adolescents With Type 1 Diabetes in the Russian Federation. [NCT01202474]Phase 4100 participants (Actual)Interventional2011-05-31Completed
Safety and Efficacy of Insulin Glargine Injection [rDNA Origin] Treatment in Place of the TZD or the Sulfonylurea or Metformin in Triple Agent Therapy for T2DM Adult Subjects With Unsatisfactory Control [NCT00283049]Phase 4390 participants (Actual)Interventional2006-02-28Terminated(stopped due to Due to technical issues relating to the Electronic diary data.)
A 24-week, Open, Multicenter, Comparative Study of 2 Strategies (Including Insulin Glargine Versus Premixed Insulin) for the Therapeutic Management of Patients With Type 2 Diabetes Failing Oral Agents [NCT01121835]Phase 4934 participants (Actual)Interventional2010-02-28Completed
A Randomized, Double Blind Study to Assess the Pharmacodynamic and Pharmacokinetic Effects of Insulin Glulisine in Obese Subjects With Type 2 Diabetes After a Standard Meal in Comparison to Insulin Aspart [NCT01159353]Phase 137 participants (Actual)Interventional2007-09-30Completed
Phase IV, Multicenter, International, Non-comparative, Open Label Study of Efficacy and Safety of Basal Bolus Therapy (Insulin Glargine + Insulin Glulisine) in Patients With T1 Diabetes Previously Uncontrolled on Any Insulin Regimen. [NCT01204593]Phase 4206 participants (Actual)Interventional2010-11-30Completed
Efficacy and Safety of Intensive Insulin Therapy With Insulin Glulisine in Patients With Type 2 Diabetes Inadequately Controlled With Basal Insulin and Oral Glucose-lowering Drugs [NCT01203111]Phase 4207 participants (Actual)Interventional2010-12-31Completed
National, Phase IV, Multicentric, Open Label, Comparative Study to Evaluate the Efficacy and Safety of Insulin Glargine Plus Glulisine and Sliding Scale Plus Glulisine in Hospitalized Patients With Diabetes Metabolism Type II Under Enteral Nutrition. [NCT01081938]Phase 415 participants (Actual)Interventional2010-02-28Terminated(stopped due to Recruitment challenges)
Better Acceptance of a Single Injection Apidra (Insulin Glulisine) Added to Once Daily Lantus (Insulin Glargine) Versus Twice Daily Premixed Insulin in a Real Life Use Setting [NCT01079364]Phase 452 participants (Actual)Interventional2010-01-31Terminated(stopped due to Slow recruitment)
A Randomized Controlled Trial Comparing Glargine U300 and Glargine U100 for the Inpatient and Post-Hospital Discharge Management of Medicine and Surgery Patients With Type 2 Diabetes [NCT03013985]Phase 4247 participants (Actual)Interventional2017-05-17Completed
Phase 4 Crossover Study Comparing the Effect of Insulin Glulisine to Insulin Aspart on Breakfast Post Prandial Blood Glucose Levels in Prepubertal Children With Type 1 Diabetes Mellitus on Multiple Daily Insulin Injection Therapy [NCT00913497]Phase 416 participants (Actual)Interventional2009-06-30Completed
National (Brazil), Phase IV, Multicentric, Open Label, Parallel, Comparative Study of the Use of Insulin Glargine + Glulisine or Insulin Regular + NPH Insulin (Isophane Insulin) in Type 2 Diabetes Mellitus Patients With Moderate Renal Failure. [NCT01122979]Phase 472 participants (Actual)Interventional2010-07-31Completed
Comparison of a Basal Plus (Insulin Glargine/Insulin Glulisine) Regimen to Biphasic Insulin (InsulinAspart/Insulin Aspart Protamine 30/70) in T2DM Patients Who Require Insulin Intensification After Basal Insulin Optimization. [NCT01212913]Phase 4161 participants (Actual)Interventional2010-08-31Completed
A Comparative Study to Evaluate the Prandial Treatment Adjustment Effect Via Continuous Glucose Monitoring on Type 2 DM Patients Uncontrolled With a Basal Insulin or Premix Once a Day [NCT01234597]Phase 4219 participants (Actual)Interventional2012-12-31Completed
Basal Bolus Versus Basal Insulin Regimen for the Treatment of Hospitalized Patients With Type 2 Diabetes Mellitus [NCT00979628]Phase 4375 participants (Actual)Interventional2010-01-31Completed
An Open-Label, Randomized, Two-Period, Crossover Study to Characterize the Insulin Exposure and Glucose Response to Meals in Type 1 Diabetic Subjects Administered Two Different Insulin Regimens Compared to the Endogenous Insulin Exposure and Glucose Respo [NCT00927524]24 participants (Actual)Interventional2005-04-30Completed
A Canadian, Phase IV, Multicenter, Comparative, Open-label Study Evaluating 2 Approaches of Blood Glucose Monitoring and Insulin Titration (Patient-managed vs Health Care Professional) in T2DM Patients While Receiving the Addition of 1 Injection of Insuli [NCT01013571]Phase 4493 participants (Actual)Interventional2009-10-31Completed
Multicentre, Open, Non-randomised Controlled Phase IV Clinical Trial of Efficacy and Safety for Insulin Glulisine Injected Subcutaneously in Patients With Type 1 Diabetes Mellitus Using Also Insulin Glargine [NCT00964574]Phase 468 participants (Actual)Interventional2009-07-31Completed
A Phase 4, Randomized, Open Label, Parallel Group, Multicenter Study to Characterize Regimens of Basal Insulin Intensified With Either Symlin® or Rapid Acting Insulin in Patients With Type 2 Diabetes [NCT00467649]Phase 4112 participants (Actual)Interventional2007-05-31Completed
Effect of Insulin Glulisine Compared to Insulin Aspart and Insulin Lispro When Administered by Continuous Subcutaneous Insulin Infusion (CSII) on Specific Pump Parameters in Patient With Type 1 Diabetes Mellitus [NCT00607087]Phase 4289 participants (Actual)Interventional2008-01-31Completed
Comparison of a Basal Plus One Insulin Regimen (Insulin Glargine/Insulin Glulisine) With a Biphasic Insulin Regimen (Insulin Aspart/Insulin Aspart Protamine 30/70) in Type 2 Diabetes Patients Following Basal Insulin Optimisation [NCT00965549]Phase 4463 participants (Actual)Interventional2009-07-31Completed
A Randomised, Open-labelled, 2-period Crossover Trial Investigating Pharmacodynamics and Pharmacokinetics of Biphasic Insulin Aspart 30 Thrice Daily and Basal-bolus Therapy With Insulin Glargine & Insulin Glulisine in Subjects With Type 2 Diabetes [NCT00824668]Phase 124 participants (Actual)Interventional2007-08-31Completed
Insulin Requirement for Pure- Protein Meal in Children With Type 1 Diabetes Treated With Continuous Subcutaneous Insulin Infusion - a Cross-over, Randomized Trial. [NCT02685449]Phase 470 participants (Anticipated)Interventional2016-02-29Recruiting
An International Multicentre Randomized Controlled Trial of Intensive Insulin Therapy Targeting Normoglycemia In Acute Myocardial Infarction: the RECREATE (REsearching Coronary REduction by Appropriately Targeting Euglycemia) Pilot Study [NCT00640991]Phase 3500 participants (Anticipated)Interventional2008-04-30Completed
RAndomized Study of Basal Bolus Insulin Therapy in the Inpatient Management of Patients With Type 2 Diabetes Undergoing General Surgery (RABBIT 2 Surgery) [NCT00596687]Phase 4234 participants (Actual)Interventional2007-12-31Completed
A Multi-center, Phase 3b, Stratified, Randomized, Open-label Clinical Trial to Evaluate the Efficacy of Intensive Apidra®/Lantus® Therapy vs Sliding Scale Insulin on Infarct Size in Hyperglycemic Subjects With Anterior STEMI (ST Elevation Myocardial Infar [NCT00670228]Phase 334 participants (Actual)Interventional2008-04-30Terminated(stopped due to Due to Negative feasibility assessment of recruiting the planned number of subjects within the study timelines)
A Phase II, Randomized, Double Blind, 2-Way Crossover Safety and Efficacy Study of Subcutaneously Injected Prandial Insulins: Lispro-PH20 or Aspart-PH20 Compared to Insulin Lispro (Humalog®) in Patients With Type 1 Diabetes [NCT01194245]Phase 2135 participants (Actual)Interventional2010-08-31Completed
All to Target Trial Lantus® (Insulin Glargine) With Stepwise Addition of APIDRA® (Insulin Glulisine) or Lantus With One Injection of Apidra vs a Twice-Daily Premixed Insulin Regimen (Novolog® Mix 70/30) in Adult Subjects With Type 2 Diabetes Failing Dual [NCT00384085]Phase 4588 participants (Actual)Interventional2006-05-31Completed
Treatment Satisfaction of Insulin Glargine Plus Insulin Apidra Compared With NPH Insulin Plus Insulin Apidra in Recently Diagnosed Type 1 Diabetes Children and Adolescents [NCT00925977]44 participants (Actual)Interventional2009-07-31Terminated
Study of Safety and Effectiveness of Apidra® in Combination With Basal Insulin in Patients With Type 1 & 2 Diabetes Mellitus [NCT00526513]Phase 4188 participants (Actual)Interventional2007-07-31Completed
Comparison of Three Therapeutic Strategies for Treating Type 2 Diabetes Mellitus Patients Poorly Controlled With Basal Insulin Associated With Oral Antidiabetic Drugs [NCT00174642]Phase 3811 participants (Actual)Interventional2004-12-31Completed
INHALE-1: A 26-week Primary Treatment Phase, With 26-week Extension, Open-label, Randomized Clinical Trial Evaluating the Efficacy and Safety of Afrezza® Versus Rapid-acting Insulin Analog Injections, Both in Combination With a Basal Insulin, in Pediatric [NCT04974528]Phase 3264 participants (Anticipated)Interventional2021-09-29Recruiting
Comparison of Two Therapeutic Strategies for Treating Type 2 Diabetic Patients Poorly Controlled With Basal Insulin Associated With Oral Antidiabetic Drugs : 6-month Proof of Concept Study. [NCT00360698]Phase 4106 participants (Actual)Interventional2006-07-31Completed
Effect of Prandial Treatment With Insulin Glulisine Compared to Regular Human Insulin on Postprandial Endothelial Function and Microvascular Stress in Type 2 Diabetic Patients [NCT00562133]Phase 315 participants (Actual)Interventional2006-12-31Completed
Comparison of Pharmacodynamics and Pharmacokinetics of the Two Fast-acting Insulin Analogs Insulin Glulisine and Insulin Aspart in Healthy Volunteers [NCT00969592]Phase 112 participants (Actual)Interventional2007-11-30Completed
A Randomized, 24-week, Controlled, Open Label, Parallel Arm, Multicenter Study Comparing the Efficacy and Safety of the Insulin Glargine/Lixisenatide Fixed Ratio Combination to Insulin Glargine in Type 2 Diabetes Patients, Inadequately Controlled on Basal [NCT03529123]Phase 3247 participants (Actual)Interventional2018-06-19Completed
Glargine Dosing in Hospitalized Patients With Type 2 Diabetes and Renal Insufficiency [NCT00911625]Phase 4114 participants (Actual)Interventional2009-01-21Completed
A Phase II, Randomized, Double Blind, 2-Way Crossover Safety and Efficacy Study of Subcutaneously Injected Prandial Insulins: Lispro-PH20 or Aspart-PH20 Compared to Insulin Lispro (Humalog®) in Patients With Type 2 Diabetes [NCT01194258]Phase 2132 participants (Actual)Interventional2010-08-31Completed
Human Insulin Analogs: Evaluation of Inflammatory mRNA Expression of Macrophages and Endothelial Function of Short-acting Insulin - HERMES Pilot Study [NCT01417897]Phase 412 participants (Anticipated)Interventional2011-09-30Active, not recruiting
Phase IV, Open Label, Non-comparative, Multi-center, Study of the Effects of Both Insulin Glargine & Insulin Glulisine in Type I Diabetes Mellitus Patients. [NCT00539448]Phase 498 participants (Actual)Interventional2007-04-30Completed
A Randomized, Double-blind, Single-dose, 2-Treatment, 2-Period, 2-Sequence Crossover Bioequivalence Study Comparing Two Formulations of Insulin Glulisine (Insulin Glulisine 300 Units/mL Versus Insulin Glulisine 100 Units/mL Marketed as Apidra® 100 Units/m [NCT02910518]Phase 144 participants (Actual)Interventional2017-02-17Completed
Phase 1, Randomized, Double-Blind, Pharmacokinetic and Glucodynamic, 6-Way Crossover Study of Subcutaneously Administered Insulin Analogs With Recombinant Human Hyaluronidase (rHuPH20) Compared to Insulin Analogs Alone in Healthy Volunteers [NCT00979875]Phase 114 participants (Actual)Interventional2009-09-30Completed
12-week, Multicenter, Controlled, Open, 3:1 Randomized, Parallel Clinical Trial Comparing Insulin Glulisine With Regular Human Insulin (Insulin Lispro) Injected Subcutaneously in Subjects With Type 1 or 2 Diabetes Mellitus Also Using Lantus (Insulin Glarg [NCT00467376]Phase 3485 participants (Actual)Interventional2007-01-31Completed
Influence of Insulin Therapy in Patients Admitted to Hospital With Acute Exacerbations of Chronic Obstructive Pulmonary Disease [NCT00467636]51 participants (Actual)Interventional2007-07-31Terminated(stopped due to Difficulty recruiting (early discharge scheme initiated))
A Phase 4, Mono-center, Randomized, Open Label, Comparator-controlled, Parallel-group, Mechanistic Intervention Trial to Assess the Effect of 8-week Treatment With the Glucagon-like Peptide-1 Receptor Agonist Lixisenatide Versus Insulin Glulisine on Renal [NCT02276196]Phase 440 participants (Actual)Interventional2014-09-30Completed
The Optimal Type of Bolus Following a High-protein Meal in Type 1 Diabetic Children Treated With Insulin Pumps [NCT02276859]Phase 470 participants (Actual)Interventional2014-10-31Completed
Comparison of Apidra to Regular Insulin in Hospitalized Patients [NCT00528918]300 participants (Actual)Interventional2007-06-30Completed
Dose-Exposure-Response Relationship of Insulin Glulisine (HMR1964) in Subjects With Type 1 Diabetes Mellitus Assessed With the Euglycemic Clamp Technique Using the Biostator (TM) [NCT00368394]Phase 118 participants Interventional2004-01-31Completed
A Randomized, Open Label, Two-arm, Cross-over Design Study to Compare the Pharmacodynamics and Pharmacokinetics of Insulin Glulisine and Insulin Lispro in Obese Patients With Type 2 Diabetes. [NCT00310297]Phase 10 participants Interventional2004-11-30Completed
Pharmacodynamic and Pharmacokinetic Properties of Insulin Glulisine (Apidra) in Comparison to Insulin Lispro (Humalog) in Healthy Lean and Obese Subjects [NCT00311077]Phase 10 participants Interventional2004-04-30Completed
A Single-center, Randomized, Double-blind, 3-period Cross-over Trial to Compare the Effect of Insulin Glulisine, Insulin Lispro and Unmodified Human Insulin on the Endogenous Glucose Production in Type 1 Diabetic Patients. [NCT00297583]Phase 10 participants Interventional2004-04-30Completed
Insulin Glulisine Administered in a Fixed Bolus Regimen Versus Variable Bolus Regimen Based on Carbohydrate Counting in Adult Subjects With Type 2 Diabetes Receiving Insulin Glargine as Basal Insulin [NCT00135057]Phase 3281 participants Interventional2004-04-30Completed
APIDRA® (Insulin Glulisine) Administered Premeal vs Postmeal in Adult Subjects With Type 2 Diabetes Mellitus Receiving LANTUS® (Insulin Glargine) as Basal Insulin: a Multicenter, Randomized, Parallel, Open Label Clinical Study [NCT00135096]Phase 3345 participants (Actual)Interventional2004-08-31Completed
Local, Open, Non-Randomized, Phase IV Clinical Study for the Collection of Data Regarding the Drug Portability Received During the Treatment With Subcutaneous Injection of Apidra Glulisine (HMR1964) to Patients With Diabetes Mellitus 1st Type [NCT00489190]Phase 445 participants (Actual)Interventional2005-08-31Completed
One Versus Two Versus Three Daily Rapid-acting Insulin Injections of APIDRA (Insulin Glulisine) as add-on to Lantus® and Oral Sensitizer Basal Therapy in Type 2 Diabetes: a Multicenter, Randomized, Parallel, Open-label Clinical Study [NCT00135083]Phase 3347 participants (Actual)Interventional2004-08-31Completed
Insulin Glargine Plus Insulin Glulisine MDI Versus Premix Insulin Treatment in Subjects With Diabetes Mellitus (Type 1 or Type 2) Evaluating Differences in Patient Reported Outcomes [NCT00135941]Phase 3582 participants (Actual)Interventional2005-08-31Completed
52-week, Open, Randomized, Multinational, Multicenter Clinical Trial Comparing Insulin Glulisine in Combination With Insulin Glargine in an Intensified Insulin Regimen to a Two-injection Conventional Insulin Regimen in Type 2 Diabetes Mellitus Patients Wi [NCT00174668]Phase 3311 participants (Actual)Interventional2004-11-30Completed
Efficacy and Safety of Insulin Glulisine Compared With Insulin Lispro in Children and Adolescents With Type 1 Diabetes Mellitus: A 26 Week, Multicenter, Open, Parallel Clinical Trial [NCT00115570]Phase 3572 participants (Actual)Interventional2005-04-30Completed
12-Week, Multinational, Multicenter, Controlled, Open, 1:1 Randomized, Parallel Clinical Trial Comparing the Safety of HMR1964 and Insulin Aspart Used in Continuous Subcutaneous Insulin Infusion (CSII) in Subjects With Type 1 Diabetes Mellitus [NCT00046150]Phase 359 participants (Actual)Interventional2002-05-31Completed
Multicenter, Open, Non-randomised Phase III Clinical Study of Efficacy and Safety of Insulin Glulisine Injected Subcutaneously in Patients With Type 1 Diabetes Mellitus Using Also Insulin Glargine [NCT00397553]Phase 3104 participants (Actual)Interventional2005-01-31Completed
Comparison of Effectiveness of Glulisine and Lispro in Decreasing Post-Prandial Hyperglycemia in a Real-World Setting [NCT01621776]107 participants (Actual)Interventional2011-06-30Completed
Glucodynamic Response to Pre- and Postmeal Subcutaneous Injection of 0.15 IU/kg HMR1964 Insulin and RHI in Type 1 Diabetic Subjects in an Open, Randomized, Four-way Crossover Study [NCT00290043]Phase 120 participants Interventional2001-12-31Completed
A Crossover, Multicentre, Randomised Trial Comparing the Effect on the Control of Blood Glucose Concentration of Insulin Glargine and Insulin Detemir, Combined With Insulin Glulisine, Used as a Bolus, in Type 1 Diabetic Patients [NCT00271284]Phase 388 participants (Actual)Interventional2005-10-31Completed
Evaluation of Efficacy and Safety of HMR1964 (Insulin Glulisine) in Subjects With Type 1 Diabetes Mellitus; Insulin Lispro Controlled, Open, Randomized, Parallel Group, Non-inferiority Study, for 28 Weeks [NCT00290979]Phase 3250 participants Interventional2004-12-31Completed
Optimisation of Insulin Treatment of Type 2 Diabetes Mellitus by Telecare Assistance for Self Monitoring of Blood Glucose (SMBG). [NCT00272064]Phase 3352 participants (Actual)Interventional2005-10-31Completed
Efficacy and Safety of Insulin Glulisine Given as a Single Injection at Breakfast + Insulin Glargine+OAD (Oral Antidiabetic Drug) vs Insulin Glulisine Given as a Single Injection at Main Meal+Insulin Glargine+OAD in Type 2 Diabetic Patients for Which Glyc [NCT00272012]Phase 3396 participants (Actual)Interventional2004-07-31Completed
Evaluation of Efficacy and Safety of HMR1964 Intensive Therapy in Subjects With Type 2 Diabetes Mellitus Not Optimally Controlled With Oral Hypoglycemic Agents (OHA); OHA Therapy Controlled, Open, Randomized, Parallel Group, Comparative (Superiority), 16- [NCT00290927]Phase 3390 participants Interventional2003-12-31Completed
Establishing Cardiovascular Biomarkers to Define Preferred Lantus® Use. [NCT01500850]Phase 460 participants (Anticipated)Interventional2011-10-31Recruiting
Non-inferiority Trial Comparing Insulin Glulisine to Insulin Lispro as Part of a Basal-bolus Insulin Regimen for the Treatment of Gestational Diabetes. [NCT01662921]Phase 217 participants (Actual)Interventional2013-04-30Completed
The Impact Of Insulin Glulisine In Comparison With Aspart On Postprandial Glycemia After The High-Glycemic Index Meal In Children With Type 1 Diabetes - Cross-Over Double-Blind, Randomized Clinical Trial. [NCT01678235]Phase 464 participants (Actual)Interventional2011-09-30Completed
Effects of Super-Bolus on Postprandial Glycemia After High Glycemic Index Meal in Children With Type 1 Diabetes Mellitus- Randomized Study [NCT04019821]Phase 472 participants (Actual)Interventional2020-01-01Completed
A Double-Blind, Placebo-Controlled Single Dose Study of the Safety and Efficacy of Glulisine on Cognitive Function and Memory in Individuals Diagnosed With Probable Mild to Moderate Alzheimer's Disease/Intranasal Insulin Study. [NCT01436045]Phase 212 participants (Actual)Interventional2011-09-30Completed
A Randomized, Comparative Study of Basal-bolus Insulin Versus Conventional Sliding-scale Regular Insulin Therapy in Management of Non-critically Ill Patients Hospitalized in the Medical Ward. [NCT01594060]Phase 436 participants (Actual)Interventional2012-06-30Completed
Diabetes Care in Nursing Home Residents: A Randomized Controlled Study [NCT01131052]Phase 4150 participants (Actual)Interventional2011-03-31Completed
A Phase II, Single Center, Randomized, Double-Blind, Placebo-Controlled Study of the Safety and the Therapeutic Effectiveness of Intranasal Glulisine in Amnestic Mild Cognitive Impairment and Probable Mild Alzheimer's Disease [NCT02503501]Phase 249 participants (Actual)Interventional2015-09-28Terminated(stopped due to Study will not have power to show a difference between groups.)
The Impact of Two Different Insulin Dose Calculation on Postprandial Glycemia After Mixed Meal in Children With Type 1 Diabetes Mellitus- Randomized Study. [NCT04124302]Phase 470 participants (Anticipated)Interventional2019-11-30Not yet recruiting
CONtinuous Subcutaneous Insulin Infusion STudy ENrolling Type 1 (CONSISTENT 1): Evaluation of Metabolic Outcomes and Safety of Hylenex Recombinant (Hyaluronidase Human Injection) Used as a Preadministration Infusion Site Treatment in Subjects With Type 1 [NCT01848990]Phase 4456 participants (Actual)Interventional2013-03-31Completed
A Randomized, Open-label, Active-controlled, 3-arm Parallel-group, 26-week Study Comparing the Efficacy and Safety of Lixisenatide to That of Insulin Glulisine Once Daily and Insulin Glulisine Three Times Daily in Patients With Type 2 Diabetes Insufficien [NCT01768559]Phase 3894 participants (Actual)Interventional2013-01-31Completed
A 26-Week, Multi-Center, Open-label, Randomized, Parallel-group Study to Evaluate the Efficacy and Safety of Two Treatment Regimens in Patients With Type 2 Diabetes After Short-Term Intensive Insulin Therapy: Basal Insulin Based Treatment (With Prandial O [NCT03359837]Phase 4384 participants (Actual)Interventional2018-01-20Completed
A Double-Blind, Placebo-Controlled Pilot Investigation of the Safety of Intranasal Glulisine in Down Syndrome [NCT02432716]Phase 112 participants (Actual)Interventional2015-04-30Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT00283049 (3) [back to overview]Change in Hemoglobin A1c (HbA1c) From Baseline to Week 12
NCT00283049 (3) [back to overview]Occurrences of Hypoglycemia, Symptomatic Hypoglycemia, Severe Hypoglycemia, and Serious Hypoglycemia
NCT00283049 (3) [back to overview]Rate of Hypoglycemia, Symptomatic Hypoglycemia, Severe Hypoglycemia and Serious Hypoglycemia
NCT00360698 (11) [back to overview]Glycosylated Haemoglobin (HbA1c) Value
NCT00360698 (11) [back to overview]Daily Mean Plasma Glucose
NCT00360698 (11) [back to overview]Rate of Symptomatic Hypoglycemia With Plasma Glucose < 70mg/dL
NCT00360698 (11) [back to overview]Daily Dose of Insulin Glulisine
NCT00360698 (11) [back to overview]Daily Dose of Insulin Glargine
NCT00360698 (11) [back to overview]Change in Daily Mean Plasma Glucose
NCT00360698 (11) [back to overview]Change in Glycosylated Haemoglobin (HbA1c) Value
NCT00360698 (11) [back to overview]Change in Weight
NCT00360698 (11) [back to overview]Rate of Nocturnal Symptomatic Hypoglycemia With Plasma Glucose < 70mg/dL
NCT00360698 (11) [back to overview]Rate of Severe Symptomatic Hypoglycemia
NCT00360698 (11) [back to overview]Patients With Glycosylated Haemoglobin (HbA1c) Value < 7%
NCT00384085 (8) [back to overview]Percentage of Patients Achieving Glycosylated Hemoglobin A1c (HbA1c) <7.0% at Week 60 Without a Severe Hypoglycemic Event or a Symptomatic Hypoglycemic Event With an Self Monitoring Blood Glucose (SMBG) <50 mg/dl
NCT00384085 (8) [back to overview]Percentage of Patients Achieving Glycosylated Hemoglobin A1c (HbA1c) < 7.0% at Week 60 (Lantus/Apidra-3 Versus Novolog Mix 70/30 - ITT Population With All Sites) (Sensitivity Analysis)
NCT00384085 (8) [back to overview]Percentage of Patients Achieving Glycosylated Hemoglobin A1c (HbA1c) < 7.0% at Week 60 (Lantus/Apidra-3 Versus Novolog Mix 70/30 - Intent To Treat (ITT) Population Without Good Clinical Practices (GCP) Noncompliant Sites)
NCT00384085 (8) [back to overview]Adjusted Incidence Rate of Hypoglycemia
NCT00384085 (8) [back to overview]Adjusted Hypoglycemic Event Rates (Event/Patient-year)
NCT00384085 (8) [back to overview]Percentage of Patients Achieving Glycosylated Hemoglobin A1c (HbA1c) <7.0% at Week 60 (Lantus/Apidra-1 Versus Novolog Mix 70/30)
NCT00384085 (8) [back to overview]Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) at Week 60 (Lantus/Apidra-1 Versus Novolog Mix 70/30)Per Protocol Population
NCT00384085 (8) [back to overview]Absolute Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) at Week 60 (Lantus/Apidra-3 Versus Novolog Mix 70/30)
NCT00467649 (12) [back to overview]Change in Fasting Plasma Glucose From Baseline at Week 24
NCT00467649 (12) [back to overview]Change in HbA1c From Baseline at Week 24
NCT00467649 (12) [back to overview]Change in Waist Circumference From Baseline at Week 24
NCT00467649 (12) [back to overview]Percentage of Patients Achieving HbA1c <=7% at Week 24
NCT00467649 (12) [back to overview]Percentage of Patients With a Severe Hypoglycemia Adverse Event
NCT00467649 (12) [back to overview]Percentage of Patients With no Weight Gain at Week 24
NCT00467649 (12) [back to overview]The Percentage of Patients Achieving HbA1c <=7% at Week 24 With no Gain in Body Weight From Baseline and no Incidence of Severe Hypoglycemia
NCT00467649 (12) [back to overview]Fasting Serum Lipids Change From Baseline to Week 24
NCT00467649 (12) [back to overview]Hypoglycemia Adverse Events
NCT00467649 (12) [back to overview]Phase 2: Change in Body Weight at Week 36
NCT00467649 (12) [back to overview]Phase 2: Change in HbA1c at Week 36
NCT00467649 (12) [back to overview]Change in Body Weight From Baseline at Week 24
NCT00596687 (2) [back to overview]# Participants With Hypoglycemic Events
NCT00596687 (2) [back to overview]Mean Blood Glucose Concentration
NCT00607087 (17) [back to overview]Monthly Rate of Unexplained Hyperglycemia and/ or Confirmed Infusion Set Occlusion
NCT00607087 (17) [back to overview]Patients With at Least One Site Infection, Site Inflammation/Erythema, Pruritus or Isolated Pain at Injection Site
NCT00607087 (17) [back to overview]Glycosylated Hemoglobin: HbA1c
NCT00607087 (17) [back to overview]Percentage of Patients With at Least One Episode of Significant Ketosis and/ or Risk Level for Impending Diabetic Ketoacidosis
NCT00607087 (17) [back to overview]Percentage of Patients With at Least One Unexplained Hyperglycemia
NCT00607087 (17) [back to overview]Percentage of Patients With at Least One Unexplained Hyperglycemia and/ or Confirmed Infusion Set Occlusion
NCT00607087 (17) [back to overview]Rate of Nocturnal Symptomatic Hypoglycemia With a Plasma Glucose (PG) ≤70 mg/dL Per Patient-year
NCT00607087 (17) [back to overview]Rate of Severe Symptomatic Hypoglycemia Per Patient-year
NCT00607087 (17) [back to overview]Rate of Symptomatic Hypoglycemia With a Plasma Glucose (PG) ≤ 70 mg/dL Per Patient-year
NCT00607087 (17) [back to overview]Time Interval Between Infusion Set Changes in Routine
NCT00607087 (17) [back to overview]Time Interval Between Infusion Set Changes: All Changes
NCT00607087 (17) [back to overview]Total Daily Basal Insulin Infusion
NCT00607087 (17) [back to overview]Total Daily Bolus Insulin Dose
NCT00607087 (17) [back to overview]Percentage of Patients With at Least One Confirmed Infusion Set Occlusion
NCT00607087 (17) [back to overview]Monthly Rate of Confirmed Infusion Set Occlusion
NCT00607087 (17) [back to overview]Monthly Rate of Episode of Significant Ketosis and/ or Risk Level for Impending Diabetic Ketoacidosis
NCT00607087 (17) [back to overview]Monthly Rate of Unexplained Hyperglycemia
NCT00670228 (4) [back to overview]Infarct Size Absolute Change From Baseline at Day 60
NCT00670228 (4) [back to overview]Left Ventricular (LV) Function Evaluated by Cardiac Magnetic Resonance Imaging (MRI)
NCT00670228 (4) [back to overview]Occurrence of the Major Adverse Cardiovascular Events (MACE)
NCT00670228 (4) [back to overview]Biomarkers of Inflammation Measurement: CRP (C-Reactive Protein)
NCT00911625 (1) [back to overview]Average Blood Glucose Over 6 Days
NCT00913497 (2) [back to overview]Difference in the Two Hour and Four Hour Post Prandial Blood Glucose Levels Following Administration of Insulin Glulisine Versus Insulin Aspart at the End of the Twenty Study Days
NCT00913497 (2) [back to overview]Occurrence of Hypoglycemia;
NCT00979628 (2) [back to overview]Number of Patients With Hypoglycemia Events (Blood Glucose Levels < 70 mg/dL) During Their Hospital Stay That Are Treated With Basal Plus, Basal-bolus and SSRI Treatments
NCT00979628 (2) [back to overview]Mean Blood Glucose Levels (Measured in mg/dL) at Randomization Are Compared to Mean Blood Glucose Levels After First Day of Treatment Among Subjects Treated With Basal Plus, Basal -Bolus and SSRI Treatments
NCT00979875 (6) [back to overview]Area Under the Concentration-time Curve for Serum Insulin From Time 0 to 60 Minutes (AUC0-60)
NCT00979875 (6) [back to overview]Time to Maximum Glucose Infusion Rate (tGIR[Max])
NCT00979875 (6) [back to overview]Time to Maximum Serum Insulin Concentration (Tmax)
NCT00979875 (6) [back to overview]Percentage of Total Area Under the Concentration-time Curve for Serum Insulin Attained by Time t (AUC0-t)
NCT00979875 (6) [back to overview]Time to Early and Late 50% Maximum Serum Insulin Concentration (t[50%Max])
NCT00979875 (6) [back to overview]Time to Percentage of Total Insulin Exposure
NCT01131052 (8) [back to overview]Mean Blood Glucose Concentration
NCT01131052 (8) [back to overview]Mean of Daily Blood Glucose Concentration
NCT01131052 (8) [back to overview]Mean of Glycosylated Hemoglobin (hbA1c)
NCT01131052 (8) [back to overview]Mean of Glycosylated Hemoglobin (hbA1c)
NCT01131052 (8) [back to overview]Mean of Glycosylated Hemoglobin (hbA1c)
NCT01131052 (8) [back to overview]Mean of Weekly Fasting Blood Glucose Concentration
NCT01131052 (8) [back to overview]Percent of Participants With a Mean Blood Glucose Concentration of Less Than 40 mg/dL
NCT01131052 (8) [back to overview]Percent of Participants With a Mean Blood Glucose Concentration of Less Than 70 mg/dL
NCT01194245 (6) [back to overview]Mean Daily Insulin Dose
NCT01194245 (6) [back to overview]Mean Daily Postprandial Glucose (PPG) Excursions
NCT01194245 (6) [back to overview]Rates of Hypoglycemia at the End of Each Treatment Period
NCT01194245 (6) [back to overview]Percentage of Participants Meeting Glucose Targets
NCT01194245 (6) [back to overview]Change From Baseline in Body Weight at the End of Each Treatment Period
NCT01194245 (6) [back to overview]Change From Baseline in Glycosylated Hemoglobin A1C (HbA1c) at the End of Each Treatment Period
NCT01194258 (6) [back to overview]Change From Baseline in Body Weight at the End of Each Treatment Period
NCT01194258 (6) [back to overview]Change From Baseline in Glycosylated Hemoglobin A1C (HbA1C) at the End of Each Treatment Period
NCT01194258 (6) [back to overview]Mean Daily Insulin Dose as Recorded During 10-Point Glucose Monitoring
NCT01194258 (6) [back to overview]Mean Daily PPG Excursions
NCT01194258 (6) [back to overview]Percentage of Participants Meeting Glucose Targets at Least 2/3 of the Time
NCT01194258 (6) [back to overview]Rates of Hypoglycemia at the End of Each Treatment Period
NCT01436045 (4) [back to overview]Olfactory Function
NCT01436045 (4) [back to overview]Cognitive Performance
NCT01436045 (4) [back to overview]Trails B - Errors
NCT01436045 (4) [back to overview]Trails B - Seconds
NCT01621776 (3) [back to overview]Difference Between Pre- and 120 Minute Post-prandial Blood Glucose Concentrations at Dinner
NCT01621776 (3) [back to overview]The Difference Between Pre- and 120 Minute Post-prandial Blood Glucose Concentrations at Lunch.
NCT01621776 (3) [back to overview]Difference Between Pre- and 120 Minute Post-prandial Blood Glucose Concentrations at Breakfast
NCT01768559 (15) [back to overview]Change in Insulin Glargine Dose From Baseline to Week 26
NCT01768559 (15) [back to overview]Change in Average 7-point SMPG Profiles From Baseline to Week 26
NCT01768559 (15) [back to overview]Change in PPG From Baseline to Week 26 (in Participants Who Had an Injection of Investigational Medicinal Product [IMP] Before Breakfast)
NCT01768559 (15) [back to overview]Insulin Glulisine Dose at Week 26
NCT01768559 (15) [back to overview]Percentage of Participants Who Reached the Target of HbA1c <7% and Had no Weight Gain at Week 26
NCT01768559 (15) [back to overview]Percentage of Participants Who Reached the Target of HbA1c <7% at Week 26 and Did Not Experienced Documented (Plasma Glucose <60 mg/dL) Symptomatic Hypoglycemia During 26 Week Treatment Period
NCT01768559 (15) [back to overview]Percentage of Participants With no Weight Gain at Week 26
NCT01768559 (15) [back to overview]Total Insulin Dose at Week 26
NCT01768559 (15) [back to overview]Percentage of Participants With Documented Symptomatic and Severe Symptomatic Hypoglycemia
NCT01768559 (15) [back to overview]Percentage of Participants With HbA1c Level <7% and ≤6.5% at Week 26
NCT01768559 (15) [back to overview]Percentage of Participants Who Reached the Target of HbA1c <7%, Had no Weight Gain at Week 26, and Did Not Experience Documented (Plasma Glucose <60 mg/dL) Symptomatic Hypoglycemia During 26-Week Treatment Period
NCT01768559 (15) [back to overview]Change in Body Weight From Baseline to Week 26
NCT01768559 (15) [back to overview]Change in FPG From Baseline to Week 26
NCT01768559 (15) [back to overview]Change in Glucose Excursions From Baseline to Week 26 (in Participants Who Had an Injection of IMP Before Breakfast)
NCT01768559 (15) [back to overview]Change in HbA1c From Baseline to Week 26
NCT01848990 (27) [back to overview]Time Per Day <56 Milligrams Per Deciliter (mg/dL), ≤70 mg/dL, >70 mg/dL, <140 mg/dL, ≥140 mg/dL, Outside of 71 to 180 mg/dL, and Outside of 71 to 139 mg/dL
NCT01848990 (27) [back to overview]Number of Participants With the Indicated Responses to the Device Handling Questions
NCT01848990 (27) [back to overview]Standard Deviation of Self-Monitoring Blood Glucose Values at 12 Months
NCT01848990 (27) [back to overview]Standard Deviation of Self-Monitoring Blood Glucose Values at 6 Months
NCT01848990 (27) [back to overview]Area Per Day <56 mg/dL, ≤70 mg/dL, ≥140 mg/dL, Outside of 71 to 180 mg/dL, and Outside of 71 to 139 mg/dL
NCT01848990 (27) [back to overview]Average Glucose, Median Glucose, and Average Daily Standard Deviation
NCT01848990 (27) [back to overview]Rates of Hyperglycemia Events to Month 12
NCT01848990 (27) [back to overview]Average of Bolus Times Relative to Meal Times
NCT01848990 (27) [back to overview]Average of Daily Insulin Doses (Bolus, Basal, and Total)
NCT01848990 (27) [back to overview]Change From Baseline in Body Weight to Month 12
NCT01848990 (27) [back to overview]Change From Baseline in DTSQs and DTSQc at Month 12
NCT01848990 (27) [back to overview]Change From Baseline in Weighted Impact ADDQoL Values at Month 12
NCT01848990 (27) [back to overview]Mean Glucose Excursions at 12 Months
NCT01848990 (27) [back to overview]Mean Glucose Excursions at 6 Months
NCT01848990 (27) [back to overview]Number of Participants Achieving HbA1c <7.0% and HbA1c ≤6.5% at Month 12
NCT01848990 (27) [back to overview]Rates of HEs to Month 12
NCT01848990 (27) [back to overview]Average Carbohydrate Factor (CarbF) Values
NCT01848990 (27) [back to overview]Average Correction Factor (CorrF) Values
NCT01848990 (27) [back to overview]Change From Baseline in Average Weighted Impact ADDQoL Values at Month 12
NCT01848990 (27) [back to overview]Change From Baseline to 12 Months in HbA1c
NCT01848990 (27) [back to overview]Change From Baseline to 6 Months in Glycosylated Hemoglobin (HbA1c)
NCT01848990 (27) [back to overview]Mean Additional Time for Hylenex Pre-administration
NCT01848990 (27) [back to overview]Mean Time to Change Infusion Site
NCT01848990 (27) [back to overview]Mean Times Per Week Participants Said They Were Eating to Avoid Going Low Due to Late Insulin Action
NCT01848990 (27) [back to overview]Number of Participants With the Indicated Responses to the Question Regarding the Difficulty of Infusion Site Change
NCT01848990 (27) [back to overview]Rates of Hyperglycemia Events to Month 6
NCT01848990 (27) [back to overview]Rates of Hypoglycemia Events (HE) to Month 6
NCT02432716 (5) [back to overview]Memory Retention Measured by Fuld Object-Memory Evaluation (FOME)
NCT02432716 (5) [back to overview]Memory Retention Measured by Rivermead Behavioral Memory Test (RBMT-C).
NCT02432716 (5) [back to overview]Safety Measured by Adverse Events
NCT02432716 (5) [back to overview]Cognitive Change Measured by Fuld Object-Memory Evaluation (FOME)
NCT02432716 (5) [back to overview]Cognitive Change Measured by Rivermead Behavioral Memory Test (RBMT-C)
NCT02503501 (3) [back to overview]Change in Cognition as Measured by the Alzheimer's Disease Assessment Scale - Cognitive 13 (ADAS-Cog 13)
NCT02503501 (3) [back to overview]Change in Functional Performance as Measured by the Clinical Dementia Rating (CDR) Scale
NCT02503501 (3) [back to overview]Change in Functional Performance as Measured by the Functional Activities Questionnaire (FAQ)
NCT03013985 (14) [back to overview]Percent of Blood Glucose 70-180 Measured by Point of Care Test
NCT03013985 (14) [back to overview]Number Subjects With Cardiac Complications
NCT03013985 (14) [back to overview]Number of Patients With Acute Renal Failure
NCT03013985 (14) [back to overview]Mean Daily Glucose in Patients With Length of Stay Shorter Than 5 Days
NCT03013985 (14) [back to overview]Mean Daily Glucose in Patients With Length of Stay Shorter Than 3 Days
NCT03013985 (14) [back to overview]Number of Days of Hospital Stay
NCT03013985 (14) [back to overview]Mean Daily Glucose in Patients With Admission HbA1c Lower Than 8%
NCT03013985 (14) [back to overview]Mean Daily Glucose in Patients With Admission HbA1c Higher Than 8%
NCT03013985 (14) [back to overview]Mean Daily Blood Glucose Concentration Inpatient
NCT03013985 (14) [back to overview]Mean Daily Blood Glucose Concentration After Hospital Discharge
NCT03013985 (14) [back to overview]Hospital Mortality
NCT03013985 (14) [back to overview]Percent of Subjects With Severe Hypoglycemia
NCT03013985 (14) [back to overview]Percent of Subjects With Hypoglycemic Events
NCT03013985 (14) [back to overview]Mean Daily Glucose in Patients With Length of Stay Longer Than 5 Days

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

(NCT00283049)
Timeframe: 12 weeks from Baseline

InterventionPercentage (Mean)
Insulin Glargine + Sulfonylurea (SU) + Thiazolidinedione (TZD)-1.2
Insulin Glargine + Metformin (MET) + Thiazolidinedione (TZD)-1.2
Insulin Glargine + Metformin (MET) + Sulfonylurea (SU)-1.2

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Occurrences of Hypoglycemia, Symptomatic Hypoglycemia, Severe Hypoglycemia, and Serious Hypoglycemia

"Symptomatic hypoglycemia (BG<70 mg/dL, BG<50 mg/dL): including 1 or more symptoms: headache, dizziness, general feeling of weakness, drowsiness, confusion, pallor, irritability, trembling, sweating, rapid heartbeat & a cold, clammy feeling.~Mild-to-moderate hypoglycemia: SMBG ≥ 36 mg/dL but <70 mg/dL~Severe hypoglycemia: assistance of another party is required & either:~SMBG of <36 mg/dL, or~with prompt response to treatment with oral carbohydrates, IV glucose or glucagon.~Serious hypoglycemia:~Hypoglycemia with coma/loss of consciousness Or Hypoglycemia seizure/convulsion." (NCT00283049)
Timeframe: 60 weeks from Baseline

,,
InterventionParticipants (Number)
Any reported symptomatic Hypoglycemic eventSymptomatic events with Self-monitored BG (SMBG)SMBG <70 mg/dL with symptomSMBG <50mg/dL with symptomSMBG <36 mg/dL with symptomSevere HypoglycemiasSevere only due to SMBG <36mg/dLSevere: Prompt response to CHO countermeasureSevere:SMBG<36mg/dL, prompt response to CHOSerious hypoglycemiaComa/Loss of Consciousness
Insulin Glargine + Metformin (MET) + Sulfonylurea (SU)1121121128535504200
Insulin Glargine + Metformin (MET) + Thiazolidinedione (TZD)10710610271241015411
Insulin Glargine + Sulfonylurea (SU) + Thiazolidinedione (TZD)1101091077423814333

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Rate of Hypoglycemia, Symptomatic Hypoglycemia, Severe Hypoglycemia and Serious Hypoglycemia

"Symptomatic hypoglycemia (BG<70 mg/dL, BG<50 mg/dL): including 1 or more symptoms: headache, dizziness, general feeling of weakness, drowsiness, confusion, pallor, irritability, trembling, sweating, rapid heartbeat & a cold, clammy feeling.~Mild-to-moderate hypoglycemia: SMBG ≥ 36 mg/dL but <70 mg/dL~Severe hypoglycemia: assistance of another party is required & either:~SMBG of <36 mg/dL, or~with prompt response to treatment with oral carbohydrates, IV glucose or glucagon.~Serious hypoglycemia:~Hypoglycemia with coma/loss of consciousness Or Hypoglycemia seizure/convulsion." (NCT00283049)
Timeframe: 60 Weeks from Baseline

,,
Interventionevents/ patient-year (Mean)
Exposure (Patient-years)Hypoglycemic (HE) event with SMBG <70mg/dLHE with SMBG <50mg/dLHE with SMBG <36mg/dLSevere HE (BG<36mg/dL or prompt response to CHOSerious HE (coma/loss of consciousness,seizure)
Insulin Glargine + Metformin (MET) + Sulfonylurea (SU)0.96725.35.60.60.10.0
Insulin Glargine + Metformin (MET) + Thiazolidinedione (TZD)0.94316.53.30.30.10.0
Insulin Glargine + Sulfonylurea (SU) + Thiazolidinedione (TZD)0.94130.14.90.30.10.0

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Glycosylated Haemoglobin (HbA1c) Value

(NCT00360698)
Timeframe: at the end of treatment (week 24)

Interventionpercent (Mean)
Insulin Glulisine+Insulin Glargine+Metformin+Glimepiride7.5
Insulin Glargine+Metformin+Glimepiride7.8

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Daily Mean Plasma Glucose

(NCT00360698)
Timeframe: at the end of treatment (week 24)

Interventionmg/dL (Mean)
Insulin Glulisine+Insulin Glargine+Metformin+Glimepiride154.7
Insulin Glargine+Metformin+Glimepiride165.8

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Rate of Symptomatic Hypoglycemia With Plasma Glucose < 70mg/dL

(NCT00360698)
Timeframe: during treatment period (12 weeks)

InterventionNumber of hypoglycemia per patient-year (Mean)
Insulin Glulisine+Insulin Glargine+Metformin+Glimepiride8.19
Insulin Glargine+Metformin+Glimepiride7.68

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Daily Dose of Insulin Glulisine

Mean of 3 daily doses reported during the week prior to the final visit (NCT00360698)
Timeframe: at the end of treatment (week 24)

Interventionunits of insulin glulisine per day (Mean)
Insulin Glulisine+Insulin Glargine+Metformin+Glimepiride12.8

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Daily Dose of Insulin Glargine

Mean of 3 daily doses reported during the week prior to the final visit (NCT00360698)
Timeframe: at the end of treatment (week 24)

Interventionunits of insulin glargine per day (Mean)
Insulin Glulisine+Insulin Glargine+Metformin+Glimepiride54.7
Insulin Glargine+Metformin+Glimepiride62.2

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Change in Daily Mean Plasma Glucose

(NCT00360698)
Timeframe: from baseline to the end of treatment (week 24)

Interventionmg/dL (Least Squares Mean)
Insulin Glulisine+Insulin Glargine+Metformin+Glimepiride-15.01
Insulin Glargine+Metformin+Glimepiride-2.07

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Change in Glycosylated Haemoglobin (HbA1c) Value

(NCT00360698)
Timeframe: from baseline to the end of treatment (week 24)

Interventionpercent (Least Squares Mean)
Insulin Glulisine+Insulin Glargine+Metformin+Glimepiride-0.37
Insulin Glargine+Metformin+Glimepiride-0.11

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Change in Weight

(NCT00360698)
Timeframe: from baseline to the end of treatment (week 24)

Interventionkg (Least Squares Mean)
Insulin Glulisine+Insulin Glargine+Metformin+Glimepiride0.46
Insulin Glargine+Metformin+Glimepiride0.22

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Rate of Nocturnal Symptomatic Hypoglycemia With Plasma Glucose < 70mg/dL

(NCT00360698)
Timeframe: during treatment period (12 weeks)

InterventionNumber of hypoglycemia per patient-year (Mean)
Insulin Glulisine+Insulin Glargine+Metformin+Glimepiride1.62
Insulin Glargine+Metformin+Glimepiride3.95

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Rate of Severe Symptomatic Hypoglycemia

(NCT00360698)
Timeframe: during treatment period (12 weeks)

InterventionNumber of hypoglycemia per patient-year (Mean)
Insulin Glulisine+Insulin Glargine+Metformin+Glimepiride0.00
Insulin Glargine+Metformin+Glimepiride0.20

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Patients With Glycosylated Haemoglobin (HbA1c) Value < 7%

Glycosylated Haemoglobin (HbA1c) is a biological parameter that reflects the blood glucose concentration over a long period of time. It is the standard parameter for glycemic control follow -up in diabetic patients. this parameter is expressed in percentage (%) and the target in diabetes management is to reach a HbA1c <7% (NCT00360698)
Timeframe: at the end of treatment (week 24)

Interventionpercentage of participants (Number)
Insulin Glulisine+Insulin Glargine+Metformin+Glimepiride22.4
Insulin Glargine+Metformin+Glimepiride8.8

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Percentage of Patients Achieving Glycosylated Hemoglobin A1c (HbA1c) <7.0% at Week 60 Without a Severe Hypoglycemic Event or a Symptomatic Hypoglycemic Event With an Self Monitoring Blood Glucose (SMBG) <50 mg/dl

"Severe hypoglycemia was defined as an event with clinical symptoms that are considered to result from hypoglycemia in which the patient required assistance of another person and one of the following: the event was associated with a measured blood glucose level below 36 mg/dL or the event was associated with prompt recovery after oral carbohydrate, iv glucose, or glucagon administration.~A symptomatic hypoglycemic event was defined as a hypoglycemic episode with an associated SMBG value of <50 mg/dL with reported symptoms." (NCT00384085)
Timeframe: At week 60

,,
Interventionpercentage of participants (Number)
HbA1c < 7.0%HbA1c ≥ 7.0%Missing data
Lantus/Apidra-125.052.222.8
Lantus/Apidra-323.055.721.3
Novolog Mix 70/3014.158.427.6

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Percentage of Patients Achieving Glycosylated Hemoglobin A1c (HbA1c) < 7.0% at Week 60 (Lantus/Apidra-3 Versus Novolog Mix 70/30 - ITT Population With All Sites) (Sensitivity Analysis)

Responders defined as patients who achieved an HbA1c value <7.0% versus nonresponders. Patients who did not achieve an HbA1c value <7.0% and patients with a missing HbA1c value at Week 60 were considered to be nonresponders. (NCT00384085)
Timeframe: At week 60

,
Interventionpercentage of participants (Number)
HbA1c < 7.0%HbA1c ≥ 7.0%Missing data
Lantus/Apidra-344.134.421.5
Novolog Mix 70/3038.132.029.9

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Percentage of Patients Achieving Glycosylated Hemoglobin A1c (HbA1c) < 7.0% at Week 60 (Lantus/Apidra-3 Versus Novolog Mix 70/30 - Intent To Treat (ITT) Population Without Good Clinical Practices (GCP) Noncompliant Sites)

Responders defined as patients who achieved an HbA1c value <7.0% versus nonresponders. Patients who did not achieve an HbA1c value <7.0% and patients with a missing HbA1c value at Week 60 were considered to be nonresponders. (NCT00384085)
Timeframe: At week 60

,
Interventionpercentage of participants (Number)
HbA1c < 7.0%HbA1c ≥ 7.0%Missing data
Lantus/Apidra-343.335.321.4
Novolog Mix 70/3038.632.329.1

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Adjusted Incidence Rate of Hypoglycemia

"Adjusted incidence rate of hypoglycemia: estimated percent of patients having at least 1 event of a given type of hypoglycemia.~A severe Hypoglycemic Event (HE) is one where patient requires assistance. It is confirmed either by a prompt response to certain countermeasures or by a blood Glucose (BG) <36 mg/dL during or soon after the event.~A serious HE is one where the patient has loss of consciousness, coma, seizure, or convulsion.~Nocturnal = events occurring between 00:00 & 06:00 based on a 24-hour clock.~An event is included if the HE start date is within the treatment period." (NCT00384085)
Timeframe: Week 60

,,
Interventionestimated percentage per patient (Mean)
Self-Monitored Blood Glucose (SMBG) < 70 mg/dlSMBG< 70 mg/dl with symptomsSMBG< 70 mg/dl, nocturnalSMBG< 70 mg/dl with symptoms, nocturnalSMBG< 50 mg/dlSMBG< 50 mg/dl with symptomsSMBG< 50 mg/dl, nocturnalSMBG< 50 mg/dl with symptoms, nocturnalSMBG< 36 mg/dlSevere hypoglycemiasSerious hypoglycemias
Lantus/Apidra-174.7862.5040.3133.5539.5532.5611.297.498.637.190.00
Lantus/Apidra-374.4060.1446.3037.0339.7731.5112.056.9310.8910.100.41
Novolog Mix 70/3083.1571.9842.5335.6853.1445.9212.588.8814.328.232.29

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Adjusted Hypoglycemic Event Rates (Event/Patient-year)

"Adjusted Hypoglycemic event rate: Total # of events for a given type of hypoglycemia divided by the total exposure to study drug (patient-years). Rates are estimated from a general linear model adjusted for baseline BMI and oral agent combination of antidiabetic medications on which the patient entered the study.~An event is included if the hypoglycemic event start date is within the treatment period (i.e., from the Randomization date to & including 1 day after the date of last dose of study drug)." (NCT00384085)
Timeframe: Week 60

,,
Interventionevent per patient year (Mean)
Self-Monitored Blood Glucose (SMBG) < 70 mg/dlSMBG< 70 mg/dl with symptomsSMBG< 70 mg/dl, nocturnalSMBG< 70 mg/dl with symptoms, nocturnalSMBG< 50 mg/dlSMBG< 50 mg/dl with symptomsSMBG< 50 mg/dl, nocturnalSMBG< 50 mg/dl with symptoms, nocturnalSMBG< 36 mg/dlSevere hypoglycemiasSerious hypoglycemias
Lantus/Apidra-112.857.111.841.101.170.830.180.090.100.10NA
Lantus/Apidra-314.507.231.901.161.380.890.200.100.150.17NA
Novolog Mix 70/3020.4212.231.681.162.421.910.270.180.230.17NA

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Percentage of Patients Achieving Glycosylated Hemoglobin A1c (HbA1c) <7.0% at Week 60 (Lantus/Apidra-1 Versus Novolog Mix 70/30)

Patients who achieved an HbA1c value <7.0% were defined as responders. Patients who did not achieve HbA1c values <7.0% and patients with missing HbA1c values were considered nonresponders. (NCT00384085)
Timeframe: At week 60

Interventionpercentage of participants (Number)
Lantus/Apidra-151.1
Novolog Mix 70/3039.5

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Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) at Week 60 (Lantus/Apidra-1 Versus Novolog Mix 70/30)Per Protocol Population

Absolute Change in HbA1c from Baseline to Week 60. If the Week 60 HbA1c evaluation was missing, the patient was counted as having not completed per protocol. (NCT00384085)
Timeframe: At week 60

,
Interventionpercent HbA1c (Least Squares Mean)
baseline HbA1cAbsolute change in HbA1c from baseline
Lantus/Apidra-19.30-2.30
Novolog Mix 70/309.06-1.97

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Absolute Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) at Week 60 (Lantus/Apidra-3 Versus Novolog Mix 70/30)

Absolute Change in HbA1c from Baseline to Week 60. (NCT00384085)
Timeframe: From baseline to week 60

Interventionpercent HbA1c (Least Squares Mean)
Lantus/Apidra-3-2.45
Novolog Mix 70/30-2.13

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Change in Fasting Plasma Glucose From Baseline at Week 24

Baseline values are presented in the Baseline Characteristics section (NCT00467649)
Timeframe: From Baseline to Week 24

Interventionmg/dL (Mean)
Group A (Phase 1 SYMLIN)-29.0
Group B (Phase 1 RA Insulin)-37.8

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Change in HbA1c From Baseline at Week 24

Baseline values are presented in the Baseline Characteristics section (NCT00467649)
Timeframe: From Baseline to Week 24

InterventionPercent (Least Squares Mean)
Group A (Phase 1 SYMLIN)-1.11
Group B (Phase 1 RA Insulin)-1.27

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Change in Waist Circumference From Baseline at Week 24

Baseline values are presented in the Baseline Characteristics section (NCT00467649)
Timeframe: From Baseline to Week 24

Interventioncm (Least Squares Mean)
Group A (Phase 1 SYMLIN)-0.63
Group B (Phase 1 RA Insulin)2.17

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Percentage of Patients Achieving HbA1c <=7% at Week 24

This is a component of the primary endpoint (NCT00467649)
Timeframe: 24 Weeks

InterventionPercent (Number)
Group A (Phase 1 SYMLIN)44.6
Group B (Phase 1 RA Insulin)55.4

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Percentage of Patients With a Severe Hypoglycemia Adverse Event

This is a component of the primary endpoint. (NCT00467649)
Timeframe: 24 Weeks

InterventionPercent (Number)
Group A (Phase 1 SYMLIN)0.0
Group B (Phase 1 RA Insulin)0.0

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Percentage of Patients With no Weight Gain at Week 24

This is a component of the primary endpoint (NCT00467649)
Timeframe: 24 Weeks

InterventionPercent (Number)
Group A (Phase 1 SYMLIN)46.4
Group B (Phase 1 RA Insulin)14.3

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The Percentage of Patients Achieving HbA1c <=7% at Week 24 With no Gain in Body Weight From Baseline and no Incidence of Severe Hypoglycemia

A severe hypoglycemia is defined as an event during which the patient required the assistance of another individual (including aid in ingestion of oral carbohydrate); and/or required the administration of glucagon injection, intravenous glucose, or other medical intervention. (NCT00467649)
Timeframe: 24 Weeks

InterventionPercent (Number)
Group A (Phase 1 SYMLIN)30.4
Group B (Phase 1 RA Insulin)10.7

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Fasting Serum Lipids Change From Baseline to Week 24

(NCT00467649)
Timeframe: Baseline, week 24

,
Interventionmg/dL (Mean)
Total CholesterolHDLLDLTriglycerides
Group A (Phase 1 SYMLIN)-1.811.112.36-28.96
Group B (Phase 1 RA Insulin)5.271.659.12-31.98

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Hypoglycemia Adverse Events

"MILD: patient reported symptoms consistent with hypoglycemia that may or may not have been documented by glucose monitoring at the time of symptoms. Symptoms did not greatly interrupt or interfere with the patients daily activities. Symptoms dissipated spontaneously or upon eating.~MODERATE: Patient reported symptoms consistent with hypoglycemia that may or may not have been documented by glucose monitoring at the time of symptoms. Symptoms interrupted or interfered with the patients daily activities and required immediate self treatment (e.g. carbohydrate ingestion).~SEVERE: Patient required the assistance of another individual (including aid in ingestion of oral carbohydrate): and/or required the administration of glucagon injection, intravenous glucose, or other medical intervention." (NCT00467649)
Timeframe: 36 weeks

,,,,,
Interventionparticipants (Number)
MildModerateSevere
Group A (Phase 1 SYMLIN)31120
Group B (Phase 1 RA Insulin)46130
Group C (Phase 2 SYMLIN)700
Group D (Phase 2 SYMLIN+RA)1810
Group E (Phase 2 RA Insulin)920
Group F (Phase 2 RA Insulin + SYMLIN)1930

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Phase 2: Change in Body Weight at Week 36

Two changes are calculated, the first by subtracting Week 36 value from the Phase 1 Baseline value (total change over 36 weeks), the second by subtracting the Week 36 value from the Phase 2 Baseline value (change from week 24 to week 36 only). (NCT00467649)
Timeframe: Phase 1 Baseline, Phase 2 Baseline at Week 24, Week 36

,,,
Interventionkg (Mean)
Phase 1 BaselineChange From Phase 1 Baseline to Week 36Phase 2 Baseline at Week 24Change From Phase 2 Baseline to Week 36
Group C (Phase 2 SYMLIN)109.98-0.80108.500.69
Group D (Phase 2 SYMLIN+RA)104.831.34105.670.50
Group E (Phase 2 RA Insulin)104.423.90107.870.44
Group F (Phase 2 RA Insulin + SYMLIN)105.304.51110.68-0.86

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Phase 2: Change in HbA1c at Week 36

Two changes are calculated, the first by subtracting Week 36 value from the Phase 1 Baseline value (total change over 36 weeks), the second by subtracting the Week 36 value from the Phase 2 Baseline value (change from week 24 to week 36 only). (NCT00467649)
Timeframe: Phase 1 Baseline, Phase 2 Baseline at Week 24, Week 36

,,,
InterventionPercent (Mean)
Phase 1 BaselineChange From Phase 1 Baseline to Week 36Phase 2 Baseline at Week 24Change From Phase 2 Baseline to Week 36
Group C (Phase 2 SYMLIN)8.35-1.966.260.14
Group D (Phase 2 SYMLIN+RA)8.03-0.687.57-0.23
Group E (Phase 2 RA Insulin)7.85-1.496.140.22
Group F (Phase 2 RA Insulin + SYMLIN)8.38-0.997.320.07

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Change in Body Weight From Baseline at Week 24

Baseline values are presented in the Baseline Characteristics section (NCT00467649)
Timeframe: From Baseline to Week 24

Interventionkg (Least Squares Mean)
Group A (Phase 1 SYMLIN)0.02
Group B (Phase 1 RA Insulin)4.65

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# Participants With Hypoglycemic Events

number of participants in the treatment arms with of hypoglycemic events (< 70 mg/dl) (NCT00596687)
Timeframe: hospital stay days 2-10

Interventionparticipants (Number)
Basal Bolus24
SSRI5

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Mean Blood Glucose Concentration

blood glucose concentration in the intervention groups after second day of treatment to up to 10 days of treatment (NCT00596687)
Timeframe: hospital stay days 2-10

Interventionmg/dl (Mean)
Basal Bolus145
SSRI172

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Monthly Rate of Unexplained Hyperglycemia and/ or Confirmed Infusion Set Occlusion

"Unexplained hyperglycemia defined as blood glucose value above 300 mg/dL (16.7 mmol/L) with no apparent medical dietary, insulin dosage or pump failure reason.~Pump infusion set occlusion defined by at least one of the following items:~pump occlusion alarm,~patient observation of an occlusion, spontaneously or because of elevated blood glucose value." (NCT00607087)
Timeframe: over 13 weeks of each treatment period

Interventionevents per patient per month (Mean)
Insulin Glulisine2.02
Insulin Aspart1.32
Insulin Lispro1.54

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Patients With at Least One Site Infection, Site Inflammation/Erythema, Pruritus or Isolated Pain at Injection Site

"Infection: local reaction at the infusion site requiring local or systemic antibiotherapy, or local drainage as per Investigator judgment.~Site inflammation or erythema: local reaction at the infusion site with no need for local or systemic antibiotherapy as per Investigator judgment.~Pruritis at injection site: presence of pruritis at the infusion site without any symptom of inflammation or erythema and/or infection.~Isolated pain at injection site: presence of pain at the infusion site without any symptom of inflammation or erythema and/or infection." (NCT00607087)
Timeframe: over 13 weeks of each treatment period

Interventionpatients (Number)
Insulin Glulisine110
Insulin Aspart110
Insulin Lispro107

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Glycosylated Hemoglobin: HbA1c

Glycolysated Haemoglobin (HbA1c) is a biological parameter that reflects the blood glucose concentration over a long period of time. It is the standard parameter for glycemic control follow-up in diabetic patients. This parameter is expressed in percentage (%) and the target in diabetes management is to reach a HbA1c <7% (NCT00607087)
Timeframe: over 13 weeks of each treatment period

,,
Interventionpercentage (Mean)
First week (week 1) (n=253, n=254, n=255)Last week (week 13) (n=252, n=255, n=251)
Insulin Aspart7.337.25
Insulin Glulisine7.317.32
Insulin Lispro7.287.33

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Percentage of Patients With at Least One Episode of Significant Ketosis and/ or Risk Level for Impending Diabetic Ketoacidosis

"Diabetic ketoacidosis (DKA) is preceded by an increase in ketone production, resulting in blood ketone value increase (hyperketonemia) and later in ketone urine value (hyperketonuria).~Significant hyperketonemia and risk level for impending diabetic ketoacidosis (DKA) are reported respectively as a blood ketone value from 0.6 to 1.5 mmol/L and >1.5 mmol/l" (NCT00607087)
Timeframe: over 13 weeks of each treatment period

Interventionpercentage of patients (Number)
Insulin Glulisine17.6
Insulin Aspart10.9
Insulin Lispro11.7

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Percentage of Patients With at Least One Unexplained Hyperglycemia

Unexplained hyperglycemia defined as blood glucose value above 300 mg/dL (16.7 mmol/L) with no apparent medical dietary, insulin dosage or pump failure reason. (NCT00607087)
Timeframe: over 13 weeks of each treatment period

Interventionpercentage of patients (Number)
Insulin Glulisine61.3
Insulin Aspart55.9
Insulin Lispro56.3

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Percentage of Patients With at Least One Unexplained Hyperglycemia and/ or Confirmed Infusion Set Occlusion

"Unexplained hyperglycemia defined as blood glucose value above 300 mg/dL (16.7 mmol/L) with no apparent medical dietary, insulin dosage or pump failure reason.~Pump infusion set occlusion defined by at least one of the following items:~pump occlusion alarm,~patient observation of an occlusion, spontaneously or because of elevated blood glucose value." (NCT00607087)
Timeframe: over 13 weeks of each treatment period

Interventionpercentage of patients (Number)
Insulin Glulisine68.4
Insulin Aspart62.1
Insulin Lispro61.3

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Rate of Nocturnal Symptomatic Hypoglycemia With a Plasma Glucose (PG) ≤70 mg/dL Per Patient-year

Nocturnal Symptomatic hypoglycemia was defined as an event with clinical symptoms that are considered to result from hypoglycemia (confirmed or not by a glucose measurement) and associated with prompt recovery after oral carbohydrate administration which occurs while the patient is asleep, after bedtime and before getting up in the morning. (NCT00607087)
Timeframe: over 13 weeks of each treatment period

Interventionevents in patient-year (Mean)
Insulin Glulisine12.80
Insulin Aspart9.66
Insulin Lispro9.48

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Rate of Severe Symptomatic Hypoglycemia Per Patient-year

"Severe symptomatic hypoglycemia is defined as an event with clinical symptoms that are considered to results from hypoglycemia in which the patient required assistance of another person and one of the following:~the event was associated with a measured blood glucose level below 36 mg/dL~or event was associated with prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration." (NCT00607087)
Timeframe: over 13 weeks of each treatment period

Interventionevents in patient-year (Mean)
Insulin Glulisine1.63
Insulin Aspart1.39
Insulin Lispro1.07

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Rate of Symptomatic Hypoglycemia With a Plasma Glucose (PG) ≤ 70 mg/dL Per Patient-year

Symptomatic hypoglycemia is defined as an event with clinical symptoms that are considered to results from hypoglycemia (confirmed or not by a glucose measurement) and associated with prompt recovery after oral carbohydrate administration. (NCT00607087)
Timeframe: over 13 weeks of each treatment period

Interventionevents in patient-year (Mean)
Insulin Glulisine73.88
Insulin Aspart65.06
Insulin Lispro62.74

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Time Interval Between Infusion Set Changes in Routine

"Patients treated with insulin pump have to change their infusion set regularly (i.e.change was recommended every 48h). The patients were asked to report any change of their infusion set and the reason for change (routine basis or because of occurrence of a specific event such as occlusion, unexplained hyperglycemia or adverse event).~Changes in routine correspond to interval between changes according to patient use." (NCT00607087)
Timeframe: over 13 weeks of each treatment period

Interventionhours (Mean)
Insulin Glulisine70.72
Insulin Aspart71.00
Insulin Lispro71.07

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Time Interval Between Infusion Set Changes: All Changes

"Patients treated with insulin pump have to change their infusion set regularly (i.e.change was recommended every 48h). The patients were asked to report any change of their infusion set and the reason for change (routine basis or because of occurrence of a specific event such as occlusion, unexplained hyperglycemia or adverse event).~All changes include all the changes whatever the reason such as routine or requested by occurrence of events." (NCT00607087)
Timeframe: over 13 weeks of each treatment period

Interventionhours (Mean)
Insulin Glulisine69.1
Insulin Aspart69.44
Insulin Lispro69.98

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Total Daily Basal Insulin Infusion

dose of the basal insulin regimen administered throughout the 24-hour period (NCT00607087)
Timeframe: over 13 weeks of each treatment period

,,
InterventionUnits (Mean)
First week (week 1) (n=251, n=249, n=250)Last week (week 13) (n=251, n=249, n=251)
Insulin Aspart20.9320.81
Insulin Glulisine20.8320.86
Insulin Lispro20.8521.11

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Total Daily Bolus Insulin Dose

dose of every increment administered for example before meals (NCT00607087)
Timeframe: over 13 weeks of each treatment period

,,
InterventionUnits (Mean)
First week (week 1) (n=249, n=247, n=250)Last week (week 13) (n=248, n=244, n=249)
Insulin Aspart18.4918.64
Insulin Glulisine18.6318.58
Insulin Lispro18.4019.19

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Percentage of Patients With at Least One Confirmed Infusion Set Occlusion

"Pump infusion set occlusion defined by at least one of the following items:~pump occlusion alarm,~patient observation of an occlusion, spontaneously or because of elevated blood glucose value." (NCT00607087)
Timeframe: over 13 weeks of each treatment period

Interventionpercentage of patients (Number)
Insulin Glulisine32.8
Insulin Aspart27.0
Insulin Lispro27.0

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Monthly Rate of Confirmed Infusion Set Occlusion

(NCT00607087)
Timeframe: over 13 weeks of each treatment period

Interventionevents per patient per month (Mean)
Insulin Glulisine0.41
Insulin Aspart0.28
Insulin Lispro0.31

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Monthly Rate of Episode of Significant Ketosis and/ or Risk Level for Impending Diabetic Ketoacidosis

"Diabetic ketoacidosis (DKA) is preceded by an increase in ketone production, resulting in blood ketone value increase (hyperketonemia) and later in ketone urine value (hyperketonuria).~Significant hyperketonemia and risk level for impending diabetic ketoacidosis (DKA) are reported respectively as a blood ketone value from 0.6 to 1.5 mmol/L and >1.5 mmol/l" (NCT00607087)
Timeframe: over 13 weeks of each treatment period

Interventionevents per patient per month (Mean)
Insulin Glulisine0.14
Insulin Aspart0.06
Insulin Lispro0.06

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Monthly Rate of Unexplained Hyperglycemia

(NCT00607087)
Timeframe: over 13 weeks of each treatment period

Interventionevents per patient per month (Mean)
Insulin Glulisine1.61
Insulin Aspart1.04
Insulin Lispro1.23

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Infarct Size Absolute Change From Baseline at Day 60

Infarct size is measured by cardiac Magnetic Resonance Imaging (MRI) as the percentage of Left Ventricular (LV) mass. (NCT00670228)
Timeframe: From baseline at Day 60

Interventionpercentage of LV mass change (Mean)
Intensive Insulin Therapy (IIT)-7.84
Standard Glycemic Care (SGC)-15.72

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Left Ventricular (LV) Function Evaluated by Cardiac Magnetic Resonance Imaging (MRI)

Due to study early termination and the limited number of randomized subjects, descriptive statistics for the Day 3 Ejection Fraction were selected for presentation instead of for Day 60 as initially planned. (NCT00670228)
Timeframe: At Day 3

Interventionpercentage of Ejection Fraction (Mean)
Intensive Insulin Therapy (IIT)43.08
Standard Glycemic Care (SGC)43.43

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Occurrence of the Major Adverse Cardiovascular Events (MACE)

"MACE:~Cardiac death, New onset or worsening congestive heart failure (>24 h post-admission) event evaluating using New York Heart Association (NYHA) Class II or greater Non-fatal Myocardial Infarction, Severe arrhythmia, Stroke/TIA (Transient Ischemic Attack), Cardiogenic shock, Catheterization/revascularization, Unstable angina leading to hospitalisation" (NCT00670228)
Timeframe: At Day 60

,
Interventionevents (Number)
Severe arrhythmiaShockRevascularizationNew onset or worsening of congestive heart failureMyocardial Infarction (MI)Death
Intensive Insulin Therapy (IIT)701111
Standard Glycemic Care (SGC)210001

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Biomarkers of Inflammation Measurement: CRP (C-Reactive Protein)

(NCT00670228)
Timeframe: At Day 60

Interventionmg/L (Mean)
Intensive Insulin Therapy (IIT)2.52
Standard Glycemic Care (SGC)2.96

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Average Blood Glucose Over 6 Days

Participants have their blood glucose measured daily for six days. The average blood glucose measure over all six days is compared between the two treatment cohorts. (NCT00911625)
Timeframe: 6 Days

Interventionmilligrams per deciliter (Mean)
0.5 Units/kg174
0.25 Units/kg174.5

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Difference in the Two Hour and Four Hour Post Prandial Blood Glucose Levels Following Administration of Insulin Glulisine Versus Insulin Aspart at the End of the Twenty Study Days

Compare average blood glucose at 2 and 4 hours post prandial minus blood glucose at baseline (prior to eating) (NCT00913497)
Timeframe: measured daily at baseline, 2 and 4 hours post prandial for 20 days

,
Interventionmg/dL (Mean)
Baseline blood sugar (prior to eating)2 hour postprandial Blood Glucose excursion (2h measurement minus baseline)4 hour postprandial blood glucose excursion (4h measurement minus baseline)
Insulin Aspart133.498.64.4
Insulin Glulisine136.4113.55.5

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Occurrence of Hypoglycemia;

(NCT00913497)
Timeframe: measured daily at 2 and 4 hours postprandial for 20 days

,
Interventionnumber of events (Number)
2 hour post prandial hypoglycemia4 hour post prandial hypoglycemia
Insulin Aspart926
Insulin Glulisine819

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Number of Patients With Hypoglycemia Events (Blood Glucose Levels < 70 mg/dL) During Their Hospital Stay That Are Treated With Basal Plus, Basal-bolus and SSRI Treatments

Effective Glycemic control is also assessed by number of hypoglycemia events among the patients treated with Basal plus, basal-bolus and SSRI treatments. Hypoglycemia event is defined as blood glucose levels <70 mg/dL. Number of patients with hypoglycemia episodes that are treated with Basal plus, basal-bolus and SSRI treatment regimens during their hospital stay are examined and compared. (NCT00979628)
Timeframe: During hospital stay, up to 12 days

Interventionparticipants (Number)
Basal Bolus23
Basal Plus Regimen17
Sliding Scale Regular Insulin (SSRI)2

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Mean Blood Glucose Levels (Measured in mg/dL) at Randomization Are Compared to Mean Blood Glucose Levels After First Day of Treatment Among Subjects Treated With Basal Plus, Basal -Bolus and SSRI Treatments

The primary outcome is to determine the effective glycemic control among the subjects that received Basal Plus (glargine once daily plus corrective doses of glulisine before meals and bedtime as needed), Basal Bolus approach of glargine once daily plus corrective doses of glulisine before meals and Sliding Scale Regular Insulin (SSRI). Glycemic control is measured by mean blood glucose(BG) levels in mg/dL after first day of treatment and are compared to mean BG levels at randomization among subjects treated with Basal Plus, Basal -bolus and SSRI treatments. The optimal glycemic control is achieved when BG levels are between 70 mg/dL -140 mg/dL. The BG levels levels below 70 mg/dL are regarded as hypoglycemic events. The BG levels levels above 140 mg/dl are considered elevated and Hyperglycemia defined as a fasting BG >126 mg/dl or random BG >200 mg/dl on two or more occasions). (NCT00979628)
Timeframe: Randomization and 24 hrs after treatment

,,
Interventionmg/dL (Mean)
RandomizationAfter first day of therapy
Basal Bolus200156
Basal Plus Regimen194163
Sliding Scale Regular Insulin (SSRI)187172

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Area Under the Concentration-time Curve for Serum Insulin From Time 0 to 60 Minutes (AUC0-60)

Area under the concentration (AUC)-time curve was derived as the area under the serum insulin concentration profile from 0 to 60 minutes. Blood samples were taken 30, 20, and 10 minutes (mins) prior to each injection; every 3 mins (from 0 to 15 mins); and at 20, 25, 30, 45, and 60 mins after each injection. (NCT00979875)
Timeframe: Predose up to 60 minutes postdose

Interventionminutes*nanomolars (min*nM) (Mean)
Glulisine Alone11667.14
Glulisine + rHuPH2023807.14
Lispro Alone10687.14
Lispro + rHuPH2027850.00
Aspart Alone8065.00
Aspart + rHuPH2020778.57

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Time to Maximum Glucose Infusion Rate (tGIR[Max])

Blood samples were taken 30, 20, 10 minutes (mins) prior to each injection; every 3 mins (from 0 to 15 mins); every 5 mins (from 15 to 30 mins); every 15 mins (from 30 to 90 mins); every 30 mins (from 90 to 240 mins); and every 60 mins (from 240 to 480 mins) after each injection. (NCT00979875)
Timeframe: Predose up to 480 minutes postdose

Interventionminutes (Mean)
Glulisine Alone141.93
Glulisine + rHuPH20113.36
Lispro Alone160.14
Lispro + rHuPH20103.57
Aspart Alone158.79
Aspart + rHuPH2096.93

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Time to Maximum Serum Insulin Concentration (Tmax)

Tmax was determined as the timepoint where the maximum of all valid concentration measurements for each measurement series was observed. Samples were taken 30, 20, 10 minutes (mins) prior to each injection; every 3 mins (from 0 to 15 mins); every 5 mins (from 15 to 30 mins); every 15 mins (from 30 to 90 mins); every 30 mins (from 90 to 240 mins); and every 60 mins (from 240 to 480 mins) after each injection. (NCT00979875)
Timeframe: Predose up to 480 minutes postdose

Interventionminutes (Mean)
Glulisine Alone80.36
Glulisine + rHuPH2041.43
Lispro Alone67.50
Lispro + rHuPH2041.07
Aspart Alone85.71
Aspart + rHuPH2043.57

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Percentage of Total Area Under the Concentration-time Curve for Serum Insulin Attained by Time t (AUC0-t)

Percentage of total area under the concentration (AUC)-time curve at 15, 30, 60, 120 minutes after injection was measured. Blood samples were taken 30, 20, 10 minutes (mins) prior to each injection; every 3 mins (from 0 to 15 mins); every 5 mins (from 15 to 30 mins); every 15 mins (from 30 to 90 mins); and at 90 and 120 mins after each injection. (NCT00979875)
Timeframe: Predose up to 120 minutes postdose

,,,,,
Interventionpercentage of total AUC (Mean)
AUC0-15AUC0-30AUC0-60AUC0-120
Aspart + rHuPH202.9213.6641.5177.37
Aspart Alone0.563.5416.8547.97
Glulisine + rHuPH205.2915.8239.4571.70
Glulisine Alone2.027.0920.6850.35
Lispro + rHuPH202.3813.8142.8877.00
Lispro Alone0.683.8818.7250.14

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Time to Early and Late 50% Maximum Serum Insulin Concentration (t[50%Max])

Blood samples were taken 30, 20, 10 minutes (mins) prior to each injection; every 3 mins (from 0 to 15 mins); every 5 mins (from 15 to 30 mins); every 15 mins (from 30 to 90 mins); every 30 mins (from 90 to 240 mins); and every 60 mins (from 240 to 480 mins) after each injection. (NCT00979875)
Timeframe: Predose up to 480 minutes postdose

,,,,,
Interventionminutes (Mean)
early t(50%max)late t(50%max)
Aspart + rHuPH2017.98102.82
Aspart Alone31.93193.50
Glulisine + rHuPH2010.16118.92
Glulisine Alone21.06195.43
Lispro + rHuPH2018.9689.59
Lispro Alone30.69176.79

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Time to Percentage of Total Insulin Exposure

Time to 10% and 50% of total insulin exposure was measured. Samples were taken 30, 20, 10 minutes (mins) prior to each injection; every 3 mins (from 0 to 15 mins); every 5 mins (from 15 to 30 mins); every 15 mins (from 30 to 90 mins); every 30 mins (from 90 to 240 mins); and every 60 mins (from 240 to 480 mins) after each injection. (NCT00979875)
Timeframe: Predose up to 480 minutes postdose

,,,,,
Interventionminutes (Mean)
Time to 10% of total insulin exposureTime to 50% of total insulin exposure
Aspart + rHuPH2026.9972.53
Aspart Alone48.42130.86
Glulisine + rHuPH2023.3978.64
Glulisine Alone39.59123.65
Lispro + rHuPH2026.3570.97
Lispro Alone46.56123.39

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Mean Blood Glucose Concentration

Mean blood glucose concentration at baseline (NCT01131052)
Timeframe: Baseline

Interventionmg/dL (Mean)
Basal Plus198.2
Sliding Scale Regular Insulin (SSRI)191.8

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Mean of Daily Blood Glucose Concentration

Mean of daily blood glucose concentration at baseline (NCT01131052)
Timeframe: Baseline

Interventionmg/dL (Mean)
Basal Plus163.0
Sliding Scale Regular Insulin (SSRI)137.7

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Mean of Glycosylated Hemoglobin (hbA1c)

Mean glycosylated hemoglobin (hbA1c) at baseline. The A1C test result is reported as a percentage. The higher the percentage, the higher a person's blood glucose levels have been. A normal A1C level is below 5.7 percent. (NCT01131052)
Timeframe: 3 months

Interventionpercent of glycosylated hemoglobin (Mean)
Basal Plus7.0
Sliding Scale Regular Insulin (SSRI)6.3

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Mean of Glycosylated Hemoglobin (hbA1c)

Mean glycosylated hemoglobin (hbA1c) at baseline. The A1C test result is reported as a percentage. The higher the percentage, the higher a person's blood glucose levels have been. A normal A1C level is below 5.7 percent. (NCT01131052)
Timeframe: 6 months

Interventionpercent of glycosylated hemoglobin (Mean)
Basal Plus6.7
Sliding Scale Regular Insulin (SSRI)6.3

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Mean of Glycosylated Hemoglobin (hbA1c)

Mean glycosylated hemoglobin (hbA1c) at baseline. The A1C test result is reported as a percentage. The higher the percentage, the higher a person's blood glucose levels have been. A normal A1C level is below 5.7 percent. (NCT01131052)
Timeframe: Baseline

Interventionpercent of glycosylated hemoglobin (Mean)
Basal Plus6.8
Sliding Scale Regular Insulin (SSRI)6.5

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Mean of Weekly Fasting Blood Glucose Concentration

Mean weekly blood glucose concentration at 3 months (NCT01131052)
Timeframe: 3 months

Interventionmg/dL (Mean)
Basal Plus130
Sliding Scale Regular Insulin (SSRI)123

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Percent of Participants With a Mean Blood Glucose Concentration of Less Than 40 mg/dL

Mean weekly blood glucose concentration less than 40 mg/dL at 3 months (NCT01131052)
Timeframe: 3 months

Interventionpercentage of participants (Number)
Basal Plus0
Sliding Scale Regular Insulin (SSRI)1

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Percent of Participants With a Mean Blood Glucose Concentration of Less Than 70 mg/dL

Mean weekly blood glucose concentration less than 70 mg/dL at 3 months (NCT01131052)
Timeframe: 3 months

Interventionpercentage of participants (Number)
Basal Plus28
Sliding Scale Regular Insulin (SSRI)31

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Mean Daily Insulin Dose

Prandial insulin doses were recorded during 10-point glucose monitoring for a total of 3 days during each treatment period (3 days during Week 10 of Treatment Period 1 and 3 days during Week 22 of Treatment Period 2). The mean daily insulin dose over the 3 days during each treatment period is presented. Data is presented by combined treatment group (Lispro-PH20 + Aspart-PH20 = Analog-PH20) and combined comparator drug (Insulin Lispro from both cohorts). (NCT01194245)
Timeframe: Week 10 and Week 22

Interventionunits (U) (Mean)
Analog-PH2054.28
Insulin Lispro56.05

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Mean Daily Postprandial Glucose (PPG) Excursions

Participants performed 10-point glucose monitoring for a total of 3 days during each treatment period (3 days during Week 10 of Treatment Period 1 and 3 days during Week 22 of Treatment Period 2). Mean daily postprandial plasma glucose (PPG) excursions (referring to the change in blood glucose levels from before to after a meal) during 10-point glucose monitoring for breakfast, lunch, and dinner are presented. Data were collected 1 and 2 hours (hr) after each meal for 3 days and the means of each excursion are presented. (NCT01194245)
Timeframe: Week 10 and Week 22

,
Interventionmilligrams per deciliter (mg/dL) (Mean)
1-hr breakfast excursion2-hr breakfast excursion1-hr lunch excursion2-hr lunch excursion1-hr dinner excursion2-hr dinner excursion
Analog-PH2018.85-5.6316.2610.68-0.31-5.13
Insulin Lispro27.467.0826.2520.774.47-5.16

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Rates of Hypoglycemia at the End of Each Treatment Period

Overall rates of hypoglycemia (blood glucose ≤70 milligrams per deciliter [mg/dL] and <56 mg/dL) were calculated based on 4 weeks of observation for each treatment period. Data is presented by combined treatment group (Lispro-PH20 + Aspart-PH20 = Analog-PH20) and combined comparator drug (Insulin Lispro from both cohorts). A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. (NCT01194245)
Timeframe: Week 12 and Week 24

,
Interventionevents per participant per month (Number)
≤70 mg/dL<56 mg/dL
Analog-PH2018.967.50
Insulin Lispro19.918.05

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Percentage of Participants Meeting Glucose Targets

Participants were instructed to monitor their blood glucose levels a minimum of 4 times per day on all non-10-point glucose monitoring days. The number of participants meeting 90-minute postprandial plasma glucose (PPG) targets of <140 and <180 milligrams per deciliter (mg/dL) for at least 2/3 of values during non-10-point glucose monitoring days was recorded. The percentage was calculated by dividing the number of participants with values meeting the specified target at least 2/3 of the time by the total number of participants analyzed, multiplied by 100. Data is presented by combined treatment group (Lispro-PH20 + Aspart-PH20 = Analog-PH20) and combined comparator drug (Insulin Lispro from both cohorts). (NCT01194245)
Timeframe: Baseline through Week 24, excluding 10-point glucose monitoring days

,
Interventionpercentage of participants (Number)
PPG <140 mg/dL for all mealsPPG <140 mg/dL for breakfastPPG <180 mg/dL for all mealsPPG <180 mg/dL for breakfast
Analog-PH2015.021.469.970.5
Insulin Lispro8.810.659.354.0

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Change From Baseline in Body Weight at the End of Each Treatment Period

Body weight was measured at baseline (Week 0) and at the end of each treatment period (Week 12 and Week 24). Data is presented by combined treatment group (Lispro-PH20 + Aspart-PH20 = Analog-PH20) and combined comparator drug (Insulin Lispro from both cohorts). (NCT01194245)
Timeframe: Baseline, Week 12 and Week 24

Interventionpounds (lbs) (Mean)
Analog-PH20-0.25
Insulin Lispro0.10

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Change From Baseline in Glycosylated Hemoglobin A1C (HbA1c) at the End of Each Treatment Period

Glycosylated hemoglobin A1C (HBA1c) levels were measured at baseline (Week 0) and at the end of each treatment period (Week 12 and Week 24). Data are presented by combined treatment group (Lispro-PH20 + Aspart-PH20 = Analog-PH20) and combined comparator drug (Insulin Lispro from both cohorts). Least Squares (LS) means were calculated from mixed effects linear models with treatment (Lispro, Aspart), recombinant human hyaluronidase PH20 (rHuPH20; yes, no), and treatment sequence as fixed effects and participant within treatment sequence as a random effect. (NCT01194245)
Timeframe: Baseline, Week 12 and Week 24

Interventionpercentage of hemoglobin A1C (Mean)
Analog-PH20-0.14
Insulin Lispro-0.19

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Change From Baseline in Body Weight at the End of Each Treatment Period

Change from baseline in body weight at the end of each treatment period (Week 12 and Week 24) is presented. Data are presented by combined treatment group (Lispro-PH20 + Aspart-PH20 = Analog-PH20) and combined comparator drug (Insulin lispro from both cohorts). (NCT01194258)
Timeframe: Baseline, Week 12 and Week 24

Interventionpounds (Mean)
Analog-PH203.35
Insulin-lispro3.44

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Change From Baseline in Glycosylated Hemoglobin A1C (HbA1C) at the End of Each Treatment Period

Change in glycosylated hemoglobin A1C (HbA1C) from baseline (Week 0) to end of treatment period (Week 12 and Week 24) is presented. Data are presented by combined treatment group (Lispro-recombinant human hyaluronidase PH20 (PH20) + Aspart-PH20 = Analog-PH20) and combined comparator drug (Insulin lispro from both groups). Least squares (LS) means were calculated from linear contrasts of mixed effects linear models with treatment (Lispro, Aspart), PH20 (yes, no), and treatment sequence as fixed effects and participant within treatment sequence as a random effect. (NCT01194258)
Timeframe: Baseline, Week 12 and Week 24

Interventionpercentage of HbA1C (Mean)
Analog-PH20-0.48
Insulin Lispro-0.46

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Mean Daily Insulin Dose as Recorded During 10-Point Glucose Monitoring

Mean daily insulin dose as recorded during 10-point glucose monitoring is reported. Blood glucose values were obtained during a total of 3 days during each treatment period (3 days during Week 10 of Treatment Period 1 and 3 days during Week 22 of Treatment Period 2) at the following timepoints: immediately prior to breakfast (fasting), 1 hour (hr) after breakfast, 2 hr after breakfast, immediately prior to lunch, 1 hr after lunch, 2 hr after lunch, immediately prior to dinner, 1 hr after dinner, 2 hr after dinner, and at 03:00. A minimum of 7 determinations were required for each day during the 3 days of 10-point glucose profiles. Prandial insulin doses were also recorded during the 10-point glucose monitoring and the mean daily insulin dose over the 3 days was calculated. Data are presented by combined treatment group (Lispro-PH20 + Aspart-PH20 = Analog-PH20) and combined comparator drug (Insulin Lispro from both cohorts). (NCT01194258)
Timeframe: Week 10 and Week 22

Interventionunits of Insulin (Mean)
Analog-PH20122.99
Insulin Lispro127.47

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Mean Daily PPG Excursions

Participants performed 10-point glucose monitoring for a total of 3 days during each treatment period (3 days during Week 10 of Treatment Period 1 and 3 days during Week 22 of Treatment Period 2). Mean daily PPG excursions during 10-point glucose monitoring for breakfast, lunch, and dinner from Treatment Period 1 or Treatment Period 2 are presented. PPG refers to the change in glucose concentration before to after a meal. Data were collected 1 and 2 hours (hr) after each meal. Data are presented by combined treatment group (Lispro-PH20 + Aspart-PH20 = Analog-PH20) and combined comparator drug (insulin lispro from both cohorts). (NCT01194258)
Timeframe: Week 10 and Week 22

,
Interventionmg/dL (Mean)
1 hr after breakfast excursion (n=105, n=107)2 hr after breakfast excursion (n=105, n=107)1 hr after lunch excursion (n=105, n=106)2 hr after lunch excursion (n=104, n=106)1 hr after dinner excursion (n=104, n=107)2 hr after dinner excursion (n=104, n=107)
Analog-PH2033.6716.6418.4720.7621.2412.72
Insulin Lispro40.3822.9427.2825.2718.0915.75

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Percentage of Participants Meeting Glucose Targets at Least 2/3 of the Time

Participants were instructed to monitor their blood glucose levels a minimum of 4 times per day on all non-10-point glucose monitoring days. The number of participants meeting 90-minute postprandial plasma glucose (PPG) targets of <140 and <180 milligrams per deciliter (mg/dL) for at least 2/3 of values was recorded during non-10-point glucose monitoring was recorded. The number of participants was recorded, and the percentage of participants meeting glucose targets was calculated by the number of participants with values meeting the specified target at least 2/3 of the time by the total number of participants analyzed, multiplied by 100. Data is presented by combined treatment group (Lispro-PH20 + Aspart-PH20 = Analog-PH20) and combined comparator drug (Insulin Lispro from both cohorts). (NCT01194258)
Timeframe: Baseline through Week 24, excluding 10-point glucose monitoring days

,
InterventionPercentage of participants (Number)
Overall 90-minute PPG <140 mg/dLPPG <140 mg/dL for breakfastPPG <140 mg/dL for lunchPPG <140 mg/dL for dinnerOverall 90 minute PPG <180 mg/dLPPG <180 mg/dL for breakfastPPG <180 mg/dL for lunchPPG <180 mg/dL for dinner
Analog-PH2013.924.328.713.071.370.483.567.0
Insulin Lispro14.817.426.115.774.865.280.070.4

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Rates of Hypoglycemia at the End of Each Treatment Period

The rate of hypoglycemia, defined as blood glucose levels ≤70 mg/dL and <56 mg/dL, was calculated based on 4 weeks of observation prior to the end of treatment period (that is, Week 12 and Week 24). Data are presented by combined treatment group (Lispro-PH20 + Aspart-PH20 = Analog-PH20) and combined comparator drug (Insulin lispro from both groups). A summary of serious and other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module. (NCT01194258)
Timeframe: Week 12 and Week 24

,
InterventionEvents per participant per month (Number)
Blood glucose <70 mg/dL (n=111, n=113)Blood glucose <56 mg/dL (n=91, n=86)
Analog-PH207.921.99
Insulin Lispro7.661.78

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Olfactory Function

"The Sniff Magnitude Test (SMT) measures olfactory function not influenced by cognitive problems (minimal dependence on language, cognitive ability, memory, and odor naming ability). Sniff magnitude ratios are calculated as a ratio of sniff magnitudes (area under the sniff curve). Lower sniff magnitude ratios indicate more impairment.~[average sniff magnitude of malodor/average sniff magnitude to a null odor]" (NCT01436045)
Timeframe: 60 minute post intranasal administration

Interventionratio of area under the sniff curve (Mean)
Post-Insulin Glulisine2.5
Post Placebo2.33

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Cognitive Performance

"The results are presented as a mean number of correct responses for each cognitive assessment.~For each of these, a lower number correct is indicative of a higher cognitive deficit.~Ranges are as follows: RBANS List Learning (0-40), RBANS Story Memory (0-24), RBANS Figure Copy (0-20), RBANSLine Orientation (0-20), RBANS Semantic Fluency (0-unlimited), RBANS List Recall (0-10), RBANS List Recognition (0-20), RBANS Story Recall (0-12), RBANS Figure Recall (0-20), Digit Span Forward (0-16), Digit Span Backward (0-16), Boston Naming (0-15)." (NCT01436045)
Timeframe: 20 minutes post-intranasal administration

,
Interventionmean total correct responses (Mean)
RBANS List LearningRBANS Story MemoryRBANS Figure CopyRBANS Line OrientationRBANS Semantic FluencyRBANS List RecallRBANS List RecognitionRBANS Story RecallRBANS Figure RecallDigit Span ForwardDigit Span BackwardBoston Naming Test
Post-Insulin Glulisine15.928.5816.5814.2512.250.8314.922.124.839.425.5811.75
Post-Placebo16.678.4116.9212.2512.51.014.752.334.929.05.7511.75

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Trails B - Errors

The results are presented as the mean sum of the errors during the Trails B assessment For each of these, a higher number of errors is indicative of a higher cognitive deficit. (NCT01436045)
Timeframe: 20 minutes post-intranasal administration

Interventionmean number of errors (Mean)
Post-Insulin Glulisine1.17
Post-Placebo2.08

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Trails B - Seconds

The results are presented as the number of seconds to complete Trails B. For each of these, a higher number of seconds is indicative of a higher cognitive deficit. (NCT01436045)
Timeframe: 20 minutes post-intranasal administration

Interventionmean seconds (Mean)
Post-Insulin Glulisine166.83
Post-Placebo177.25

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Difference Between Pre- and 120 Minute Post-prandial Blood Glucose Concentrations at Dinner

Blood glucose concentrations were measured prior to and 120 minutes following dinner. Analysis was based on intention to treat. While missing data was imputed, it was known that this data was 'not missing at random' thus violating standard statistical assumptions with imputation. Therefore imputed data was not included in the final model. (NCT01621776)
Timeframe: averaged over 5 days

Interventionmg/dl (Mean)
Humalog170.57
Apidra160.96
Novolog153.46

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The Difference Between Pre- and 120 Minute Post-prandial Blood Glucose Concentrations at Lunch.

"Blood glucose concentrations were measured prior to and 90 minutes following lunch. Analysis was based on intention to treat. While missing data was imputed, it was known that this data was 'not missing at random' thus violating standard statistical assumptions with imputation. Therefore imputed data was not included in the final model.~The number of participants for analysis was based upon a convenience sample of individuals attending Florida Camp for Children and Youth with Diabetes at Camp Winona." (NCT01621776)
Timeframe: averaged over 5 days

Interventionmg/dl (Mean)
Humalog146.69
Apidra143.68
Novolog149.02

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Difference Between Pre- and 120 Minute Post-prandial Blood Glucose Concentrations at Breakfast

Blood glucose concentrations were measured prior to and 120 minutes following breakfast. Analysis was based on intention to treat. While missing data was imputed, it was known that this data was 'not missing at random' thus violating standard statistical assumptions with imputation. Therefore imputed data was not included in the final model. (NCT01621776)
Timeframe: averaged over 5 days

Interventionmg/dl (Mean)
Humalog225.62
Apidra225.46
Novolog208.64

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Change in Insulin Glargine Dose From Baseline to Week 26

Change in Insulin glargine dose was calculated by subtracting the baseline value from Week 26 value. Missing data was imputed using LOCF. The on-treatment period for this efficacy variable was the time from the first dose of study drug up to the day of last dose of study drug. (NCT01768559)
Timeframe: Baseline, Week 26

InterventionU (Least Squares Mean)
Lixisenatide0.7
Insulin Glulisine QD-0.06
Insulin Glulisine TID-3.13

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Change in Average 7-point SMPG Profiles From Baseline to Week 26

Participants recorded a 7-point plasma glucose profile measured before and 2 hours after each meal and at bedtime three times in a week before baseline, before visit Week 12 and before visit week 26 and the average value across the profiles performed in the week a visit for the 7-time points was calculated. Change in average 7-point SMPG was calculated by subtracting baseline value from Week 26 value. Missing data was imputed using LOCF. The on-treatment period for this efficacy variable was defined as the time from the first dose of study drug up to the day of last dose of study drug. (NCT01768559)
Timeframe: Baseline, Week 26

Interventionmmol/L (Least Squares Mean)
Lixisenatide-0.784
Insulin Glulisine QD-0.782
Insulin Glulisine TID-1.053

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Change in PPG From Baseline to Week 26 (in Participants Who Had an Injection of Investigational Medicinal Product [IMP] Before Breakfast)

The 2-hour PPG test measured blood glucose 2 hours after eating a standardized meal. Change in PPG was calculated by subtracting baseline value from Week 26 value. Missing data was imputed using LOCF. The on-treatment period for this efficacy variable was the time from the first dose of study drug up to the day of last dose of study drug. (NCT01768559)
Timeframe: Baseline, Week 26

Interventionmmol/L (Mean)
Lixisenatide-3.93
Insulin Glulisine QD-1.62
Insulin Glulisine TID-1.87

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Insulin Glulisine Dose at Week 26

The on-treatment period for this efficacy variable was the time from the first dose of study drug up to the day of last dose of study drug. Missing data was imputed using LOCF. (NCT01768559)
Timeframe: Week 26

InterventionU (Mean)
Insulin Glulisine QD9.97
Insulin Glulisine TID20.24

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Percentage of Participants Who Reached the Target of HbA1c <7% and Had no Weight Gain at Week 26

The on-treatment period for HbA1c assessment was defined as the time from the first dose of study drug up to 14 days after the last dose of study drug. The on-treatment period for body weight assessment was defined as the time from the first dose of study drug up to 3 days after the last dose of study drug. (NCT01768559)
Timeframe: Week 26

Interventionpercentage of participants (Number)
Lixisenatide31.2
Insulin Glulisine QD16.7
Insulin Glulisine TID17.6

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Percentage of Participants Who Reached the Target of HbA1c <7% at Week 26 and Did Not Experienced Documented (Plasma Glucose <60 mg/dL) Symptomatic Hypoglycemia During 26 Week Treatment Period

The on-treatment period for HbA1c assessment was defined as the time from the first dose of study drug up to 14 days after the last dose of study drug. The on-treatment period for symptomatic hypoglycemia assessment was defined as the time from the first dose of study drug up to 1 day after the last dose of study drug. (NCT01768559)
Timeframe: Week 26

Interventionpercentage of participants (Number)
Lixisenatide29.4
Insulin Glulisine QD24.2
Insulin Glulisine TID26.1

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Percentage of Participants With no Weight Gain at Week 26

The on-treatment period for this efficacy variable was the time from the first dose of study drug up to 3 days after the last dose of study drug. (NCT01768559)
Timeframe: Week 26

Interventionpercentage of participants (Number)
Lixisenatide64.7
Insulin Glulisine QD36.6
Insulin Glulisine TID30.5

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Total Insulin Dose at Week 26

"The on-treatment period for this efficacy variable was the time from the first dose of study drug up to the day of last dose of study drug. Missing data was imputed using LOCF.~The outcome is reporting results of total insulin (amounts of Insulin Glargine plus Insulin Glulisine ) only for the arms in which Insulin Glulisine was administered and is not applicable for the lixisenatide arm in which only Insulin Glargine is administered. Change in dose of the insulin used by patients in the Lixisenatide arm (i.e. Insulin Glargine) is reported in the secondary Outcome Measure 9." (NCT01768559)
Timeframe: Week 26

InterventionU (Mean)
Insulin Glulisine QD73.61
Insulin Glulisine TID81.05

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Percentage of Participants With Documented Symptomatic and Severe Symptomatic Hypoglycemia

Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of <60 mg/dL (3.3 mmol/L). Severe symptomatic hypoglycemia was symptomatic hypoglycemia event in which the participant required the assistance of another person and was associated with either a plasma glucose level below 36 mg/dL (2.0 mmol/L) or prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration, if no plasma glucose measurement was available. (NCT01768559)
Timeframe: First dose of study drug up to 3 days after the last dose administration (maximum of 185 days)

,,
Interventionpercentage of participants (Number)
Documented symptomatic hypoglycemiaSevere symptomatic hypoglycemia
Insulin Glulisine QD37.50.7
Insulin Glulisine TID44.60
Lixisenatide31.50

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Percentage of Participants With HbA1c Level <7% and ≤6.5% at Week 26

The on-treatment period for this efficacy variable was defined as the time from the first dose of study drug up to 14 days after the last dose of study drug. Missing data was imputed using LOCF. (NCT01768559)
Timeframe: Week 26

,,
Interventionpercentage of participants (Number)
HbA1c ≤6.5%HbA1c <7.0%
Insulin Glulisine QD17.838.4
Insulin Glulisine TID30.849.2
Lixisenatide20.542.1

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Percentage of Participants Who Reached the Target of HbA1c <7%, Had no Weight Gain at Week 26, and Did Not Experience Documented (Plasma Glucose <60 mg/dL) Symptomatic Hypoglycemia During 26-Week Treatment Period

The on-treatment period for HbA1c assessment was defined as the time from the first dose of study drug up to 14 days after the last dose of study drug. The on-treatment period for body weight assessment was defined as the time from the first dose of study drug up to 3 days after the last dose of study drug. The on-treatment period for symptomatic hypoglycemia assessment was defined as the time from the first dose of study drug up to 1 day after the last dose of study drug. Participants without post-baseline on-treatment values (HbA1c and body weight) that were no more than 30 days apart were counted as non-responders if at least one of the components (HbA1c and/or body weight) was available and showed non-response, or if they experienced at least one documented symptomatic hypoglycemia during the on-treatment period. Otherwise, they were counted as missing data. (NCT01768559)
Timeframe: Week 26

Interventionpercentage of participants (Number)
Lixisenatide22.2
Insulin Glulisine QD9.2
Insulin Glulisine TID10.8

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Change in Body Weight From Baseline to Week 26

"Primary outcome was the comparison between Lixisenatide versus Insulin Glulisine TID.~Change in body weight was calculated by subtracting baseline value from Week 26 value. Missing data was imputed using LOCF. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug up to 3 days after the last dose of study drug." (NCT01768559)
Timeframe: Baseline, Week 26

Interventionkg (Least Squares Mean)
Lixisenatide-0.63
Insulin Glulisine QD1.03
Insulin Glulisine TID1.37

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Change in FPG From Baseline to Week 26

Change in FPG was calculated by subtracting baseline value from Week 26 value. Missing data was imputed using LOCF. The on-treatment period for this efficacy variable was the time from the first dose of study drug up to 1 day after the last dose of study drug. (NCT01768559)
Timeframe: Baseline, Week 26

Interventionmmol/L (Least Squares Mean)
Lixisenatide-0.23
Insulin Glulisine QD-0.21
Insulin Glulisine TID-0.06

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Change in Glucose Excursions From Baseline to Week 26 (in Participants Who Had an Injection of IMP Before Breakfast)

Glucose excursion = 2-hour PPG minus plasma glucose 30 minutes prior to the standardized meal test, before study drug administration. Change in glucose excursions was calculated by subtracting baseline value from Week 26 value. Missing data was imputed using LOCF. The on-treatment period for this efficacy variable was the time from the first dose of study drug up to the day of last dose of study drug. (NCT01768559)
Timeframe: Baseline, Week 26

Interventionmmol/L (Mean)
Lixisenatide-3.42
Insulin Glulisine QD-1.59
Insulin Glulisine TID-1.56

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Change in HbA1c From Baseline to Week 26

Change in HbA1C was calculated by subtracting baseline value from Week 26 value. Missing data was imputed using last on-treatment observation carried forward (LOCF). On-treatment period for this efficacy variable was defined as the time from the first dose of study drug up to 14 days after the last dose of study drug. Here, number of participants analyzed = participants with baseline and at least one post-baseline HbA1c assessment during on-treatment period. (NCT01768559)
Timeframe: Baseline, Week 26

Interventionpercentage of hemoglobin (Least Squares Mean)
Lixisenatide-0.63
Insulin Glulisine QD-0.58
Insulin Glulisine TID-0.84

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Time Per Day <56 Milligrams Per Deciliter (mg/dL), ≤70 mg/dL, >70 mg/dL, <140 mg/dL, ≥140 mg/dL, Outside of 71 to 180 mg/dL, and Outside of 71 to 139 mg/dL

For each participant, the following CGM parameters were calculated using CGM values recorded after Randomization up to Month 12: time per day spent in the pre-defined glucose classes. (NCT01848990)
Timeframe: Randomization to Month 12

,
Interventionminutes (Least Squares Mean)
Time per day <56 mg/dLTime per day ≤70 mg/dLTime per day >70 mg/dLTime per day <140 mg/dLTime per day ≥140 mg/dLTime per day outside of 71 to 180 mg/dLTime per day outside of 71 to139 mg/dL
Hylenex Recombinant18.163.01358.8660.3756.4464.4819.4
Standard Rapid-Acting Insulin CSII20.368.51351.9683.7732.5461.7801.0

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Number of Participants With the Indicated Responses to the Device Handling Questions

Participants were asked device handling questions to provide information about the impact of the Hylenex administration procedure on everyday life and to investigate perceptions of the overall efficacy and responsiveness of their insulin program. Question 1: Achieve excellent post meal glucose control; Question 2: Insulin responds quickly when basal rate is changed; Question 3: Insulin responds quickly when correction bolus is given. (NCT01848990)
Timeframe: Month 12

InterventionParticipants (Count of Participants)
Question 172221138Question 172221139Question 272221138Question 272221139Question 372221139Question 372221138
Neither agree or disagreeDisagreeCompletely agreeAgreeCompletely disagree
Standard Rapid-Acting Insulin CSII0
Hylenex Recombinant110
Standard Rapid-Acting Insulin CSII28
Hylenex Recombinant97
Standard Rapid-Acting Insulin CSII44
Hylenex Recombinant59
Standard Rapid-Acting Insulin CSII22
Hylenex Recombinant5
Standard Rapid-Acting Insulin CSII3
Hylenex Recombinant31
Standard Rapid-Acting Insulin CSII8
Hylenex Recombinant146
Standard Rapid-Acting Insulin CSII48
Hylenex Recombinant71
Hylenex Recombinant25
Standard Rapid-Acting Insulin CSII12
Hylenex Recombinant3
Standard Rapid-Acting Insulin CSII1
Hylenex Recombinant36
Standard Rapid-Acting Insulin CSII14
Hylenex Recombinant165
Standard Rapid-Acting Insulin CSII39
Hylenex Recombinant34
Hylenex Recombinant38
Standard Rapid-Acting Insulin CSII20
Standard Rapid-Acting Insulin CSII2

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Standard Deviation of Self-Monitoring Blood Glucose Values at 12 Months

Standard deviation of self-monitoring blood glucose values was calculated based on measurements taken within 15 minutes before a meal, 1 month and up to 12 months after study drug administration. LS means were calculated from ANOVA with treatment (Hylenex, standard rapid-acting insulin CSII) as a fixed effect. Comparisons were made by pooling all of the rHuPH20 pretreatment participants (including both Formulations 1 and 2) and comparing against the standard CSII treatment arm. Formulation 1 versus Formulation 2 was compared as a supportive analysis. (NCT01848990)
Timeframe: After Month 1 up to Month 12

Interventionmg/dL (Least Squares Mean)
Hylenex Recombinant72.9
Standard Rapid-acting Insulin CSII72.4

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Standard Deviation of Self-Monitoring Blood Glucose Values at 6 Months

Standard deviation of self-monitoring blood glucose values was calculated based on measurements taken within 15 minutes before a meal, 1 month and up to 6 months after study drug administration. LS means were calculated from ANOVA with treatment (Hylenex, standard rapid-acting insulin CSII) as a fixed effect. Comparisons were made by pooling all of the rHuPH20 pretreatment participants (including both Formulations 1 and 2) and comparing against the standard CSII treatment arm. Formulation 1 versus Formulation 2 was compared as a supportive analysis. (NCT01848990)
Timeframe: After Month 1 up to Month 6

Interventionmg/dL (Least Squares Mean)
Hylenex Recombinant70.9
Standard Rapid-acting Insulin CSII72.2

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Area Per Day <56 mg/dL, ≤70 mg/dL, ≥140 mg/dL, Outside of 71 to 180 mg/dL, and Outside of 71 to 139 mg/dL

For each participant, the following continuous glucose monitoring (CGM) parameters were calculated using CGM values recorded after Randomization up to Month 12: area per day spent in the pre-defined glucose classes. The area per day for a specific glucose concentration range (e.g., <56 mg/dL) is the sum of the area under the curve with glucose concentration falling in the specific glucose concentration range (e.g., <56 mg/dL). For example, if the glucose stays constant at 50 mg/dL for the whole day (1,440 minutes), the area per day for glucose < 56 mg/dL equals: 50*1440 = 72,000 mg*minutes/dL. (NCT01848990)
Timeframe: Randomization to Month 12

,
Interventionmg*minutes/deciliter (Least Squares Mean)
Area per day <56 mg/dLArea per day ≤70 mg/dLArea per day ≥140 mg/dLArea per day outside of 71 to 180 mg/dLArea per day outside of 71 to 139 mg/dL
Hylenex Recombinant129.7687.042660.220033.843347.2
Standard Rapid-Acting Insulin CSII163.2771.742317.220411.243089.0

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Average Glucose, Median Glucose, and Average Daily Standard Deviation

For each participant, the following continuous glucose monitoring (CGM) parameters were calculated using CGM values recorded after Randomization up to Month 12: average glucose, median glucose, and average daily standard deviation. (NCT01848990)
Timeframe: Randomization to Month 12

,
Interventionmilliliters per deciliter (Least Squares Mean)
Average glucoseMedian glucoseAverage daily standard deviation
Hylenex Recombinant152.9145.248.9
Standard Rapid-Acting Insulin CSII151.9143.449.7

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Rates of Hyperglycemia Events to Month 12

Overall rates of hyperglycemia (defined as blood glucose >240 mg/dL and >300 mg/dL) were based on measurements after 1 month up to 12 months. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. Comparisons were made by pooling all of the rHuPH20 pretreatment participants (including both Formulations 1 and 2) and comparing against the standard CSII treatment arm. Formulation 1 versus Formulation 2 was compared as a supportive analysis. (NCT01848990)
Timeframe: After Month 1 up to Month 12

,
Interventionevents per participant per month (Number)
>240 mg/dL>300 mg/dL
Hylenex Recombinant18.97847.1138
Standard Rapid-acting Insulin CSII18.27856.8900

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Average of Bolus Times Relative to Meal Times

The average meal bolus timing relative to meal time is defined as the minutes between the start time of a meal bolus and the start time of a meal. (NCT01848990)
Timeframe: Month 1 to Month 12

,
Interventionminutes (Mean)
BreakfastLunchDinnerOverall
Hylenex Recombinant-2.3-1.8-1.7-1.9
Standard Rapid-Acting Insulin CSII-3.9-1.6-1.7-2.4

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Average of Daily Insulin Doses (Bolus, Basal, and Total)

The daily bolus insulin dose is calculated as the daily prandial (occurring before a meal) insulin dose plus the daily corrective insulin dose. Cumulative basal dosage is to generally be within 40% to 60% of the total daily dose. (NCT01848990)
Timeframe: from Randomization up to Month 12

,
InterventionInternational units (Least Squares Mean)
Daily bolus doseDaily basal doseDaily total dose
Hylenex Recombinant21.928.049.9
Standard Rapid-Acting Insulin CSII22.925.748.5

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Change From Baseline in Body Weight to Month 12

Baseline is defined as the last measurement prior to randomization. (NCT01848990)
Timeframe: Baseline; Week 2; Months 1, 2, 3, 4, 6, 9, and 12

,
Interventionkilograms (Mean)
Week 2Month 1Month 2Month 3Month 4Month 6Month 9Month 12
Hylenex Recombinant-0.10-0.11-0.030.160.040.600.910.61
Standard Rapid-Acting Insulin CSII0.190.200.480.370.370.830.920.48

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Change From Baseline in DTSQs and DTSQc at Month 12

The Diabetes Treatment Satisfaction Questionnaire-status version (DTSQs) and DTSQ-change version (DTSQc) are validated tools to assess treatment satisfaction and change in treatment satisfaction after therapy changes have occurred. The scale total was computed by adding the 6 items (1, 4, 5, 6, 7, and 8) to produce the Treatment Satisfaction scale total, which has a minimum of 0 and a maximum of 36 on the DTSQs and a minimum of -18 and a maximum of 18 on the DTSQc. Higher scores represent greater satisfaction. If any of the 6 item scores were missing and the numbers of missing scores were less than the number of non-missing scores, the Treatment Satisfaction scale score was to be computed by taking the average of the existing scores and multiplying the average by 6. If there were less than 4 non-missing item scores, the Treatment Satisfaction scale score was not to be calculated. Baseline is defined as the last measurement prior to randomization. (NCT01848990)
Timeframe: Baseline; Month 12

,
Interventionscore on a scale (Least Squares Mean)
DTSQsDTSQc
Hylenex Recombinant0.09.4
Standard Rapid-Acting Insulin CSII0.09.4

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Change From Baseline in Weighted Impact ADDQoL Values at Month 12

The Audit of Diabetes Dependent Quality of Life (ADDQoL) is a validated, diabetes-specific questionnaire to evaluate the participant's assessment of quality of life (QoL). Participants rated the impact of diabetes on 19 applicable domains on a scale from -3 (maximum negative impact) to +3 (maximum positive impact) and then rated the importance of those domains for their QoL on a scale from 3 (very important) to 0 (not at all important). Impact ratings were multiplied by the corresponding importance ratings to provide a weighted-impact score for each domain from -9 (maximum negative impact) to +9 (maximum positive impact). (NCT01848990)
Timeframe: Baseline; Month 12

,
Interventionscore on a scale (Least Squares Mean)
Leisure activitiesWork lifeLocal or long distance travelVacationsDo physicallyFamily lifeFriendships and social lifeClose personal relationshipSex lifePhysical appearanceSelf-confidenceMotivationThe way people in general reactFeelings about the futureFinancial situationLiving situation and conditionsDepend on othersFreedom to eatFreedom to drink
Hylenex Recombinant-0.2-0.1-0.40.0-0.10.20.30.10.00.10.00.00.2-0.10.10.0-0.10.0-0.2
Standard Rapid-Acting Insulin CSII0.00.0-0.20.2-0.20.10.10.1-0.3-0.2-0.10.3-0.10.30.0-0.10.4-0.3-0.3

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Mean Glucose Excursions at 12 Months

A 4-hour postprandial glucose excursion was measured for 3 meals after 1 month up to 12 months. For each of the 3 meals, the mealtime (breakfast, lunch, and dinner) excursions were calculated as the post-meal glucose value minus the pre-meal (for measurements taken within 15 minutes before a meal). The average of all excursions is presented. LS means were calculated from ANOVA with treatment (Hylenex, standard rapid-acting insulin CSII) as a fixed effect. Comparisons were made by pooling all of the rHuPH20 pretreatment participants (including both Formulations 1 and 2) and comparing against the standard CSII treatment arm. Formulation 1 versus Formulation 2 was compared as a supportive analysis. (NCT01848990)
Timeframe: After Month 1 up to Month 12

,
Interventionmilligrams per deciliter (mg/dL) (Least Squares Mean)
BreakfastLunchDinnerOverall
Hylenex Recombinant20.122.412.717.1
Standard Rapid-acting Insulin CSII24.921.013.819.7

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Mean Glucose Excursions at 6 Months

A 4-hour postprandial glucose excursion was measured for 3 meals after 1 month up to 6 months. For each of the 3 meals, the mealtime (breakfast, lunch, and dinner) excursions were calculated as the post-meal glucose value minus the pre-meal (for measurements taken within 15 minutes before a meal). The average of all excursions is presented. Least Squares (LS) means were calculated from ANOVA with treatment (Hylenex, standard rapid-acting insulin CSII) as a fixed effect. Comparisons were made by pooling all of the rHuPH20 pretreatment participants (including both Formulations 1 and 2) and comparing against the standard CSII treatment arm. Formulation 1 versus Formulation 2 was compared as a supportive analysis. (NCT01848990)
Timeframe: After Month 1 up to Month 6

,
Interventionmilligrams per deciliter (mg/dL) (Least Squares Mean)
BreakfastLunchDinnerOverall
Hylenex Recombinant17.322.212.617.1
Standard Rapid-acting Insulin CSII20.717.912.516.9

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Number of Participants Achieving HbA1c <7.0% and HbA1c ≤6.5% at Month 12

The number of participants achieving HbA1c goals of <7% and ≤6.5% was calculated. (NCT01848990)
Timeframe: Month 12

,
InterventionParticipants (Count of Participants)
HbA1c <7.0%HbA1c ≤6.5%
Hylenex Recombinant6118
Standard Rapid-Acting Insulin CSII216

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Rates of HEs to Month 12

Overall rates of hypoglycemia (defined as blood glucose ≤70 milligrams per deciliter [mg/dL] and <56 mg/dL) were based on measurements after 1 month up to 12 months. A severe HE was classified as an event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. A nocturnal HE was classified as an event with a blood glucose of ≤70 mg/dL with start time between 2300 and 0600, inclusive. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. Comparisons were made by pooling all of the rHuPH20 pretreatment participants (including both Formulations 1 and 2) and comparing against the standard CSII treatment arm. Formulation 1 versus Formulation 2 was compared as a supportive analysis. (NCT01848990)
Timeframe: After Month 1 up to Month 12

,
Interventionevents per participant per month (Number)
<56 mg/dL≤70 mg/dLNocturnal HEsSevere HEs
Hylenex Recombinant2.679211.38031.67540.0091
Standard Rapid-acting Insulin CSII3.302212.35911.92030.0085

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Average Carbohydrate Factor (CarbF) Values

CarbF is calculated as 2.6 * weight (pounds) / total daily dose of insulin (grams per unit). (NCT01848990)
Timeframe: Month 1 to Month 12

Interventiongrams per unit (Least Squares Mean)
Hylenex Recombinant11.1
Standard Rapid-Acting Insulin CSII11.0

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Average Correction Factor (CorrF) Values

CorrF is calculated as 1960 / total daily dose of insulin (milligrams/[deciliter*unit]). (NCT01848990)
Timeframe: Month 1 to Month 12

Interventionmilligrams/(deciliter*unit) (Least Squares Mean)
Hylenex Recombinant43.2
Standard Rapid-Acting Insulin CSII45.3

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Change From Baseline in Average Weighted Impact ADDQoL Values at Month 12

The ADDQoL is a validated, diabetes-specific questionnaire to evaluate the participant's assessment of QoL. Participants rated the impact of diabetes on 19 applicable domains on a scale from -3 (maximum negative impact) to +3 (maximum positive impact) and then rated the importance of those domains for their QoL on a scale from 3 (very important) to 0 (not at all important). Impact ratings were multiplied by the corresponding importance ratings to provide a weighted-impact score for each domain from -9 (maximum negative impact) to +9 (maximum positive impact). Weighted impact scores were summed and divided by the number of applicable domains to give an overall Average Weighted Impact (AWI) score (higher values represent more positive impact). If there were less than 13 non-missing weighted-impact values, AWI was not to be calculated. Baseline is defined as the last measurement prior to randomization. (NCT01848990)
Timeframe: Baseline; Month 12

Interventionscore on a scale (Least Squares Mean)
Hylenex Recombinant0.0
Standard Rapid-Acting Insulin CSII0.0

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Change From Baseline to 12 Months in HbA1c

Change from Baseline was calculated as the post-Baseline value minus the Baseline value. (NCT01848990)
Timeframe: Baseline; 12 Months

Interventionpercentage of HbA1c (Mean)
Hylenex Recombinant-0.13
Standard Rapid-Acting Insulin CSII-0.26

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Change From Baseline to 6 Months in Glycosylated Hemoglobin (HbA1c)

Change from Baseline was calculated as the post-Baseline value minus the Baseline value. (NCT01848990)
Timeframe: Baseline; 6 Months

Interventionpercentage of HbA1c (Mean)
Hylenex Recombinant-0.14
Standard Rapid-Acting Insulin CSII-0.18

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Mean Additional Time for Hylenex Pre-administration

Participants were asked device handling questions to provide information about the impact of the Hylenex administration procedure on everyday life and to investigate perceptions of the overall efficacy and responsiveness of their insulin program. (NCT01848990)
Timeframe: Month 12

Interventionminutes (Mean)
Hylenex Recombinant2.9
Standard Rapid-Acting Insulin CSII3.8

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Mean Time to Change Infusion Site

Participants were asked device handling questions to provide information about the impact of the Hylenex administration procedure on everyday life and to investigate perceptions of the overall efficacy and responsiveness of their insulin program. (NCT01848990)
Timeframe: Month 12

Interventionminutes (Mean)
Hylenex Recombinant5.7
Standard Rapid-Acting Insulin CSII4.7

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Mean Times Per Week Participants Said They Were Eating to Avoid Going Low Due to Late Insulin Action

Participants were asked device handling questions to provide information about the impact of the Hylenex administration procedure on everyday life and to investigate perceptions of the overall efficacy and responsiveness of their insulin program. (NCT01848990)
Timeframe: Month 12

Interventionoccurrences per week (Mean)
Hylenex Recombinant2.1
Standard Rapid-Acting Insulin CSII2.5

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Number of Participants With the Indicated Responses to the Question Regarding the Difficulty of Infusion Site Change

Participants were asked device handling questions to provide information about the impact of the Hylenex administration procedure on everyday life and to investigate perceptions of the overall efficacy and responsiveness of their insulin program. (NCT01848990)
Timeframe: Month 12

,
InterventionParticipants (Count of Participants)
Very easyEasyDifficultVery difficult
Hylenex Recombinant14313030
Standard Rapid-Acting Insulin CSII494611

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Rates of Hyperglycemia Events to Month 6

Overall rates of hyperglycemia (defined as blood glucose >240 mg/dL and >300 mg/dL) were based on measurements after 1 month up to 6 months. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. Comparisons were made by pooling all of the rHuPH20 pretreatment participants (including both Formulations 1 and 2) and comparing against the standard CSII treatment arm. Formulation 1 versus Formulation 2 was compared as a supportive analysis. (NCT01848990)
Timeframe: After Month 1 up to Month 6

,
Interventionevents per participant per month (Number)
>240 mg/dL>300 mg/dL
Hylenex Recombinant18.04226.4768
Standard Rapid-acting Insulin CSII18.46966.8155

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Rates of Hypoglycemia Events (HE) to Month 6

Overall rates of hypoglycemia (defined as blood glucose ≤70 milligrams per deciliter [mg/dL] and <56 mg/dL) were based on measurements after 1 month up to 6 months. A severe HE was classified as an event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. A nocturnal HE was classified as an event with a blood glucose of ≤70 mg/dL with start time between 2300 and 0600, inclusive. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. Comparisons were made by pooling all of the rHuPH20 pretreatment participants (including both Formulations 1 and 2) and comparing against the standard CSII treatment arm. Formulation 1 versus Formulation 2 was compared as a supportive analysis. (NCT01848990)
Timeframe: After Month 1 up to Month 6

,
Interventionevents per participant per month (Number)
<56 mg/dL≤70 mg/dLNocturnal HEsSevere HEs
Hylenex Recombinant2.910311.62191.62240.0055
Standard Rapid-acting Insulin CSII4.197014.71122.07270.0160

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Memory Retention Measured by Fuld Object-Memory Evaluation (FOME)

Memory retention is the percentage of items correctly identify during the delayed recall trial compared storage trial 5. Range: 0-100 percent. A higher percentage indicates a better outcome. (NCT02432716)
Timeframe: 20 minutes

Interventionpercentage of items correctly identified (Mean)
Post- Placebo72.3
Post-Insulin (Glulisine)68.7

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Memory Retention Measured by Rivermead Behavioral Memory Test (RBMT-C).

The RBMT-C provides an objective measure of everyday memory problems reported and observed in subjects with memory difficulties. The test is standardized for use with children ranging in age from 5 to 10 years. Here, we used it for evaluation of Down Syndrome subjects. The story recall subtests involves immediate free recall, cued recall, and delayed recall of short story material which is presented orally to subjects by the examiner. The RBMT-C is appealing for use in this population because the task is engaging, simple, and has been shown in other studies to be an effective measure of memory functions. Memory retention is the percentage of story elements recalled after a delay compared to right after the story is complete. Range: 0-100. A higher score means a better outcome. (NCT02432716)
Timeframe: 20 minutes

Interventionpercentage of story elements recalled (Mean)
Post- Placebo9.7
Post-Insulin (Glulisine)16.9

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Safety Measured by Adverse Events

Number of adverse and/or serious events (NCT02432716)
Timeframe: 1 year

InterventionParticipants (Count of Participants)
Insulin (Glulisine), Then Placebo0
Placebo, Then Insulin (Glulisine)0

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Cognitive Change Measured by Fuld Object-Memory Evaluation (FOME)

"During the examination, a patient is presented with ten common objects they are asked to identify by touch. The test uses distraction to test recall. For all, a higher score indicates a better outcome.~Learning curve is the number of objects the difference in the number of items they are able to correctly identify from the greater of trials 4 or 5 compared to trial 1. Range: 0-10~Total immediate recall is the number of objects recalled over all of the trials. Range: 0-50~Total delayed recall is the number of objects recalled after 5 minutes. Range: 0-10~Recognition memory is the number of items correct from a multiple choice list of three when unable to correctly identify items from delayed recall. Range: 0-10~Retention estimate is the number of items recalled after 5 minutes or being reminded with multiple choice. Range: 0-10" (NCT02432716)
Timeframe: 20 minutes

,
Interventionscore on a scale (Mean)
Learning CurveTotal Immediate RecallTotal Delayed RecallRecognition MemoryRetention Estimate
Post- Placebo2.333.86.12.38.3
Post-Insulin (Glulisine)2.036.86.41.98.3

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Cognitive Change Measured by Rivermead Behavioral Memory Test (RBMT-C)

"The RBMT-C provides an objective measure of everyday memory problems reported and observed in subjects with memory difficulties. The test is standardized for use with children ranging in age from 5 to 10 years. Here, we used it for evaluation of Down Syndrome subjects. The story recall subtests involves immediate free recall, cued recall, and delayed recall of short story material which is presented orally to subjects by the examiner. The RBMT-C is appealing for use in this population because the task is engaging, simple, and has been shown in other studies to be an effective measure of memory functions. For all, a higher score means a better outcome.~Immediate Recall is the number of story elements recalled right after the story is complete. Range: 0-31~Delayed Recall is the number of story elements recalled after a delay. Range: 0-31" (NCT02432716)
Timeframe: 20 minutes

,
Interventionscore on a scale (Mean)
Immediate RecallDelayed Recall
Post- Placebo6.66.6
Post-Insulin (Glulisine)5.47.2

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Change in Cognition as Measured by the Alzheimer's Disease Assessment Scale - Cognitive 13 (ADAS-Cog 13)

The ADAS-Cog was developed as an outcome measure for global cognition in clinical trials for Alzheimer's disease. The ADAS-Cog assesses multiple cognitive domains including memory, language, praxis, and orientation. The modified ADAS-Cog 13-item scale includes all original ADAS-Cog items with the addition of a number cancellation task and a delayed free recall task, for a total of 85 points (0: no cognitive impairment; 85: severe impairment). (NCT02503501)
Timeframe: Baseline and 6 months

Interventionscore on a scale (Mean)
Insulin Glulisine1.56
Placebo0.81

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Change in Functional Performance as Measured by the Clinical Dementia Rating (CDR) Scale

The CDR is a 5-point scale used to characterize six domains of cognitive and functional performance applicable to Alzheimer disease and related dementias: Memory, Orientation, Judgment & Problem Solving, Community Affairs, Home & Hobbies, and Personal Care. Possible scores on the CDR are 0 (no impairment), 0.5 (very mild), 1 (mild), 2 (moderate), and 3 (severe). The total CDR ratings for each of the six cognitive/functional domains can be added to create a CDR sum of boxes (SOB). The overall SOB score ranges from 0 to 18; with 18 indicating severe impairment and 0 indicating no impairment. (NCT02503501)
Timeframe: Baseline and 6 months

Interventionscore on a scale (Mean)
Insulin Glulisine0.53
Placebo-0.08

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Change in Functional Performance as Measured by the Functional Activities Questionnaire (FAQ)

The FAQ measures instrumental activities of daily living (IADLs), such as preparing balanced meals and managing personal finances. The FAQ is a sum of scores ranging from 0 (normal) to 30 (complete dependence on others). (NCT02503501)
Timeframe: Baseline and 6 months

Interventionscore on a scale (Mean)
Insulin Glulisine2.5
Placebo0.92

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Percent of Blood Glucose 70-180 Measured by Point of Care Test

Percent of Blood Glucose Readings in the 70-180 mg/dL Range Measured by Point of Care Test (NCT03013985)
Timeframe: 3 months post enrollment

Interventionpercentage of BG readings (Mean)
Basal Bolus Insulin With Glargine U300 and Glulisine Insulin50.3
Basal Bolus Insulin With Glargine U100 and Glulisine Insulin54.9

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Number Subjects With Cardiac Complications

The number of subjects experiencing cardiac cardiac complications will be recorded. (NCT03013985)
Timeframe: 3 months post enrollment

InterventionParticipants (Count of Participants)
Basal Bolus Insulin With Glargine U300 and Glulisine Insulin5
Basal Bolus Insulin With Glargine U100 and Glulisine Insulin11

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Number of Patients With Acute Renal Failure

The number of subjects with a clinical diagnosis with documented new-onset abnormal renal function (increment in serum creatinine > 0.5 mg/dL from baseline). (NCT03013985)
Timeframe: 3 months post enrollment

InterventionParticipants (Count of Participants)
Basal Bolus Insulin With Glargine U300 and Glulisine Insulin1
Basal Bolus Insulin With Glargine U100 and Glulisine Insulin1

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Mean Daily Glucose in Patients With Length of Stay Shorter Than 5 Days

Glycemic control will be conducted by measuring mean daily blood glucose concentration for subjects with length of hospital stay shorter than 5 days (NCT03013985)
Timeframe: Up to 5 days

Interventionmg/dL (Mean)
Basal Bolus Insulin With Glargine U300 and Glulisine Insulin193.53
Basal Bolus Insulin With Glargine U100 and Glulisine Insulin193.64

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Mean Daily Glucose in Patients With Length of Stay Shorter Than 3 Days

Glycemic control will be conducted by measuring mean daily blood glucose concentration for subjects with length of hospital stay shorter than 3 days (NCT03013985)
Timeframe: Up to 3 days

Interventionmg/dL (Mean)
Basal Bolus Insulin With Glargine U300 and Glulisine Insulin169.71
Basal Bolus Insulin With Glargine U100 and Glulisine Insulin196.72

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Number of Days of Hospital Stay

The number of days of hospital stay for each subject will be recorded. (NCT03013985)
Timeframe: Up to 10 days

Interventiondays (Median)
Basal Bolus Insulin With Glargine U300 and Glulisine Insulin6
Basal Bolus Insulin With Glargine U100 and Glulisine Insulin4

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Mean Daily Glucose in Patients With Admission HbA1c Lower Than 8%

Glycemic control will be measured by mean daily blood glucose concentration for subjects with HbA1c lower than 8% at admission. The average of all pre-meal and bedtime glucose values will be calculated. (NCT03013985)
Timeframe: up to 3 months post enrollment

Interventionmg/dL (Mean)
Basal Bolus Insulin With Glargine U300 and Glulisine Insulin150
Basal Bolus Insulin With Glargine U100 and Glulisine Insulin134.4

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Mean Daily Glucose in Patients With Admission HbA1c Higher Than 8%

Mean daily blood glucose concentration for subjects with HbA1c higher than 8% at admission will be recorded (NCT03013985)
Timeframe: up to 3 months post enrollment

Interventionmg/dL (Mean)
Basal Bolus Insulin With Glargine U300 and Glulisine Insulin152.3
Basal Bolus Insulin With Glargine U100 and Glulisine Insulin155.6

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Mean Daily Blood Glucose Concentration Inpatient

The mean daily blood glucose concentration for all participants will be calculated by taking the average of all pre-meal and bedtime glucose values collected each day after the first day of therapy during the hospital stay. (NCT03013985)
Timeframe: up to 10 days (day of hospital discharge)

Interventionmg/dL (Mean)
Basal Bolus Insulin With Glargine U300 and Glulisine Insulin186
Basal Bolus Insulin With Glargine U100 and Glulisine Insulin184

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Mean Daily Blood Glucose Concentration After Hospital Discharge

Subjects will measure their blood sugar levels at home by finger stick before meals two or three times per day and record the readings in a diary. The readings will be averaged for each day and the mean daily blood glucose concentration will be calculated. (NCT03013985)
Timeframe: assessed from day 11 (day after hospital discharge) up to 3 months

Interventionmg/dL (Mean)
Basal Bolus Insulin With Glargine U300 and Glulisine Insulin171.6
Basal Bolus Insulin With Glargine U100 and Glulisine Insulin164.5

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Hospital Mortality

Number of hospital deaths that occur. (NCT03013985)
Timeframe: During hospital stay - up to 10 days

Interventionevents (Number)
Basal Bolus Insulin With Glargine U300 and Glulisine Insulin0
Basal Bolus Insulin With Glargine U100 and Glulisine Insulin2

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Percent of Subjects With Severe Hypoglycemia

Percent of subjects experiencing severe hypoglycemia (BG <54 mg/dl) will be recorded. (NCT03013985)
Timeframe: 3 months post enrollment

Interventionpercentage of subjects (Number)
Basal Bolus Insulin With Glargine U300 and Glulisine Insulin0
Basal Bolus Insulin With Glargine U100 and Glulisine Insulin6

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Percent of Subjects With Hypoglycemic Events

Percent of of subjects with hypoglycemic events (BG < 70 mg/dl) will be recorded. (NCT03013985)
Timeframe: 3 months post enrollment

Interventionpercentage of subjects (Number)
Basal Bolus Insulin With Glargine U300 and Glulisine Insulin8.7
Basal Bolus Insulin With Glargine U100 and Glulisine Insulin9.5

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Mean Daily Glucose in Patients With Length of Stay Longer Than 5 Days

Glycemic control will be measured by mean daily blood glucose concentration for subjects with length of hospital stay longer than 5 days. The average of daily pre-meal and bedtime glucose values will be calculated. (NCT03013985)
Timeframe: Up to 10 days

Interventionmg/dL (Mean)
Basal Bolus Insulin With Glargine U300 and Glulisine Insulin188.46
Basal Bolus Insulin With Glargine U100 and Glulisine Insulin174.55

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SubstanceRelationship StrengthStudiesTrialsClassesRoles
3-cresol
3-cresol: RN given refers to parent cpd. m-cresol : A cresol with the methyl substituent at position 3. It is a minor urinary metabolite of toluene.		2.110cresolhuman xenobiotic metabolite
lactic acid
Lactic Acid: A normal intermediate in the fermentation (oxidation, metabolism) of sugar. The concentrated form is used internally to prevent gastrointestinal fermentation. (From Stedman, 26th ed). 2-hydroxypropanoic acid : A 2-hydroxy monocarboxylic acid that is propanoic acid in which one of the alpha-hydrogens is replaced by a hydroxy group.		3.43112-hydroxy monocarboxylic acidalgal metabolite;
Daphnia magna metabolite
glycerol
Moon: The natural satellite of the planet Earth. It includes the lunar cycles or phases, the lunar month, lunar landscapes, geography, and soil.		3.4311alditol;
triol		algal metabolite;
detergent;
Escherichia coli metabolite;
geroprotector;
human metabolite;
mouse metabolite;
osmolyte;
Saccharomyces cerevisiae metabolite;
solvent
niacinamide
nicotinamide : A pyridinecarboxamide that is pyridine in which the hydrogen at position 3 is replaced by a carboxamide group.		2.0310pyridine alkaloid;
pyridinecarboxamide;
vitamin B3		anti-inflammatory agent;
antioxidant;
cofactor;
EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor;
EC 3.5.1.98 (histone deacetylase) inhibitor;
Escherichia coli metabolite;
geroprotector;
human urinary metabolite;
metabolite;
mouse metabolite;
neuroprotective agent;
Saccharomyces cerevisiae metabolite;
Sir2 inhibitor
palmitic acid
Palmitic Acid: A common saturated fatty acid found in fats and waxes including olive oil, palm oil, and body lipids.. hexadecanoic acid : A straight-chain, sixteen-carbon, saturated long-chain fatty acid.		2.0110long-chain fatty acid;
straight-chain saturated fatty acid		algal metabolite;
Daphnia magna metabolite;
EC 1.1.1.189 (prostaglandin-E2 9-reductase) inhibitor;
plant metabolite
phenol
[no description available]		2.110phenolsantiseptic drug;
disinfectant;
human xenobiotic metabolite;
mouse metabolite
lauric acid
dodecanoic acid : A straight-chain, twelve-carbon medium-chain saturated fatty acid with strong bactericidal properties; the main fatty acid in coconut oil and palm kernel oil.		2.1710medium-chain fatty acid;
straight-chain saturated fatty acid		algal metabolite;
antibacterial agent;
plant metabolite
metformin
Metformin: A biguanide hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. Metformin improves glycemic control by improving insulin sensitivity and decreasing intestinal absorption of glucose. (From Martindale, The Extra Pharmacopoeia, 30th ed, p289). metformin : A member of the class of guanidines that is biguanide the carrying two methyl substituents at position 1.		8.4686guanidinesenvironmental contaminant;
geroprotector;
hypoglycemic agent;
xenobiotic
pioglitazone
Pioglitazone: A thiazolidinedione and PPAR GAMMA agonist that is used in the treatment of TYPE 2 DIABETES MELLITUS.. pioglitazone : A member of the class of thiazolidenediones that is 1,3-thiazolidine-2,4-dione substituted by a benzyl group at position 5 which in turn is substituted by a 2-(5-ethylpyridin-2-yl)ethoxy group at position 4 of the phenyl ring. It exhibits hypoglycemic activity.		3.4511aromatic ether;
pyridines;
thiazolidinediones		antidepressant;
cardioprotective agent;
EC 2.7.1.33 (pantothenate kinase) inhibitor;
EC 6.2.1.3 (long-chain-fatty-acid--CoA ligase) inhibitor;
ferroptosis inhibitor;
geroprotector;
hypoglycemic agent;
insulin-sensitizing drug;
PPARgamma agonist;
xenobiotic
thalidomide
Thalidomide: A piperidinyl isoindole originally introduced as a non-barbiturate hypnotic, but withdrawn from the market due to teratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppressive and anti-angiogenic activity. It inhibits release of TUMOR NECROSIS FACTOR-ALPHA from monocytes, and modulates other cytokine action.. thalidomide : A racemate comprising equimolar amounts of R- and S-thalidomide.. 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione : A dicarboximide that is isoindole-1,3(2H)-dione in which the hydrogen attached to the nitrogen is substituted by a 2,6-dioxopiperidin-3-yl group.		2.0310phthalimides;
piperidones
thymidine
[no description available]		2.0210pyrimidine 2'-deoxyribonucleosideEscherichia coli metabolite;
human metabolite;
metabolite;
mouse metabolite
biguanides
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.. biguanides : A class of oral hypoglycemic drugs used for diabetes mellitus or prediabetes treatment. They have a structure based on the 2-carbamimidoylguanidine skeleton.		4.3511guanidines
lysine
Lysine: An essential amino acid. It is often added to animal feed.. lysine : A diamino acid that is caproic (hexanoic) acid bearing two amino substituents at positions 2 and 6.. L-lysine : An L-alpha-amino acid; the L-isomer of lysine.		2.0110aspartate family amino acid;
L-alpha-amino acid zwitterion;
L-alpha-amino acid;
lysine;
organic molecular entity;
proteinogenic amino acid		algal metabolite;
anticonvulsant;
Escherichia coli metabolite;
human metabolite;
micronutrient;
mouse metabolite;
nutraceutical;
plant metabolite;
Saccharomyces cerevisiae metabolite
tyrosine
Tyrosine: A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.. tyrosine : An alpha-amino acid that is phenylalanine bearing a hydroxy substituent at position 4 on the phenyl ring.		3.8221amino acid zwitterion;
erythrose 4-phosphate/phosphoenolpyruvate family amino acid;
L-alpha-amino acid;
proteinogenic amino acid;
tyrosine		EC 1.3.1.43 (arogenate dehydrogenase) inhibitor;
fundamental metabolite;
micronutrient;
nutraceutical
pyrroles
1H-pyrrole : A tautomer of pyrrole that has the double bonds at positions 2 and 4.. pyrrole : A five-membered monocyclic heteroarene comprising one NH and four CH units which forms the parent compound of the pyrrole group of compounds. Its five-membered ring structure has three tautomers. A 'closed class'.. azole : Any monocyclic heteroarene consisting of a five-membered ring containing nitrogen. Azoles can also contain one or more other non-carbon atoms, such as nitrogen, sulfur or oxygen.		2.0310pyrrole;
secondary amine
pyrazines
Pyrazines: A heterocyclic aromatic organic compound with the chemical formula C4H4N2.. pyrazine : A diazine that is benzene in which the carbon atoms at positions 1 and 4 have been replaced by nitrogen atoms.		3.4811diazine;
pyrazines		Daphnia magna metabolite
glutamic acid
Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.. glutamic acid : An alpha-amino acid that is glutaric acid bearing a single amino substituent at position 2.		2.0110glutamic acid;
glutamine family amino acid;
L-alpha-amino acid;
proteinogenic amino acid		Escherichia coli metabolite;
ferroptosis inducer;
micronutrient;
mouse metabolite;
neurotransmitter;
nutraceutical
ranolazine
Ranolazine: An acetanilide and piperazine derivative that functions as a SODIUM CHANNEL BLOCKER and prevents the release of enzymes during MYOCARDIAL ISCHEMIA. It is used in the treatment of ANGINA PECTORIS.. N-(2,6-dimethylphenyl)-2-{4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]piperazin-1-yl}acetamide : An aromatic amide obtained by formal condensation of the carboxy group of 2-{4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]piperazin-1-yl}acetic acid with the amino group of 2,6-dimethylaniline.. ranolazine : A racemate comprising equal amounts of (R)- and (S)-ranolazine. Used for treatment of chronic angina.		2.0310aromatic amide;
monocarboxylic acid amide;
monomethoxybenzene;
N-alkylpiperazine;
secondary alcohol
triazoles
Triazoles: Heterocyclic compounds containing a five-membered ring with two carbon atoms and three nitrogen atoms with the molecular formula C2H3N3.. triazoles : An azole in which the five-membered heterocyclic aromatic skeleton contains three N atoms and two C atoms.		3.48111,2,3-triazole
conivaptan
conivaptan : The amide resulting from the formal condensation of 4-[(biphenyl-2-ylcarbonyl)amino]benzoic acid with the benzazepine nitrogen of 2-methyl-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzazepine. It is an antagonist for two of the three types of arginine vasopressin (AVP) receptors, V1a and V2. It is used as its hydrochloride salt for the treatment of hyponatraemia (low blood sodium levels) caused by syndrome of inappropriate antidiuretic hormone (SIADH).		2.0310benzazepineaquaretic;
vasopressin receptor antagonist
lubiprostone
[no description available]		2.0310
anidulafungin
Anidulafungin: Echinocandin antifungal agent that is used in the treatment of CANDIDEMIA and CANDIDIASIS.. anidulafungin : A semisynthetic echinocandin anti-fungal drug. It is active against Aspergillus and Candida species and is used for the treatment of invasive candidiasis.		2.0310antibiotic antifungal drug;
azamacrocycle;
echinocandin;
heterodetic cyclic peptide;
semisynthetic derivative
sorafenib
[no description available]		2.0310(trifluoromethyl)benzenes;
aromatic ether;
monochlorobenzenes;
phenylureas;
pyridinecarboxamide		angiogenesis inhibitor;
anticoronaviral agent;
antineoplastic agent;
EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor;
ferroptosis inducer;
tyrosine kinase inhibitor
lenalidomide
[no description available]		2.0310aromatic amine;
dicarboximide;
isoindoles;
piperidones		angiogenesis inhibitor;
antineoplastic agent;
immunomodulator
3-nitrotyrosine
3-nitrotyrosine: RN given refers to parent cpd without isomeric designation. 3-nitrotyrosine : A nitrotyrosine comprising tyrosine having a nitro group at the 3-position on the phenyl ring.		3.43112-nitrophenols;
C-nitro compound;
nitrotyrosine;
non-proteinogenic alpha-amino acid
glycogen
glycogen : A polydisperse, highly branched glucan composed of chains of D-glucopyranose residues in alpha(1->4) glycosidic linkage, joined together by alpha(1->6) glycosidic linkages. A small number of alpha(1->3) glycosidic linkages and some cumulative alpha(1->6) links also may occur. The branches in glycogen typically contain 8 to 12 glucose residues.		2.2110
nelarabine
nelarabine: prodrug of ara-G. nelarabine : A purine nucleoside in which O-methylguanine is attached to arabinofuranose via a beta-N(9)-glycosidic bond. Inhibits DNA synthesis and causes cell death; a prodrug of 9-beta-D-arabinofuranosylguanine (ara-G).		2.0310beta-D-arabinoside;
monosaccharide derivative;
purine nucleoside		antineoplastic agent;
DNA synthesis inhibitor;
prodrug
alprostadil
[no description available]		2.0310prostaglandins Eanticoagulant;
human metabolite;
platelet aggregation inhibitor;
vasodilator agent
su 11248
[no description available]		2.0310monocarboxylic acid amide;
pyrroles		angiogenesis inhibitor;
antineoplastic agent;
EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor;
immunomodulator;
neuroprotective agent;
vascular endothelial growth factor receptor antagonist
sitagliptin phosphate
Sitagliptin Phosphate: A pyrazine-derived DIPEPTIDYL-PEPTIDASE IV INHIBITOR and HYPOGLYCEMIC AGENT that increases the levels of the INCRETIN hormones GLUCAGON-LIKE PEPTIDE-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). It is used in the treatment of TYPE 2 DIABETES.		3.4811
insulin detemir
Insulin Detemir: A recombinant long-acting insulin and hypoglycemic agent in which a MYRISTIC ACID is conjugated to a LYSINE at position B29. It is used to manage BLOOD GLUCOSE levels in patients with DIABETES MELLITUS.		7.05130
c-peptide
C-Peptide: The middle segment of proinsulin that is between the N-terminal B-chain and the C-terminal A-chain. It is a pancreatic peptide of about 31 residues, depending on the species. Upon proteolytic cleavage of proinsulin, equimolar INSULIN and C-peptide are released. C-peptide immunoassay has been used to assess pancreatic beta cell function in diabetic patients with circulating insulin antibodies or exogenous insulin. Half-life of C-peptide is 30 min, almost 8 times that of insulin.		4.422
insulin, isophane
Insulin, Isophane: An intermediate-acting INSULIN preparation with onset time of 2 hours and duration of 24 hours. It is produced by crystallizing ZINC-insulin-PROTAMINES at neutral pH 7. Thus it is called neutral protamine Hagedorn for inventor Hans Christian Hagedorn.		11.2136
humulin s
Insulin, Regular, Human: Regular insulin preparations that contain the HUMAN insulin peptide sequence.. insulin (human) : An insulin that is produced in the pancreas and involved in regulating the metabolism of carbohydrates (particularly glucose) and fats. Commonly thought of as a protein, it consists of two peptide chains, one containing 21 amino acid residues and the other containing 30; the chains are joined together by 2 disulfide bonds. Recombinant insulin is identical to human insulin, but is synthesised by inserting the human insulin gene into E. coli, which then produces insulin for human use. It is used in the treatment of type I and type II diabetes.		6.7243
insulin glargine
Insulin Glargine: A recombinant LONG ACTING INSULIN and HYPOGLYCEMIC AGENT that is used to manage BLOOD GLUCOSE in patients with DIABETES MELLITUS.		17.437242
insulin degludec
[no description available]		5.6441
ConditionIndicatedRelationship StrengthStudiesTrials
Chronic Illness
[description not available]		02.4110
Extrasystole, Ventricular
[description not available]		02.4110
Autoimmune Diabetes
[description not available]		014.554315
Cardiac Failure
[description not available]		02.4110
Fasting Hypoglycemia
HYPOGLYCEMIA expressed in the postabsorptive state, after prolonged FASTING, or an overnight fast.		015.644632
Chronic Disease
Diseases which have one or more of the following characteristics: they are permanent, leave residual disability, are caused by nonreversible pathological alteration, require special training of the patient for rehabilitation, or may be expected to require a long period of supervision, observation, or care (Dictionary of Health Services Management, 2d ed). For epidemiological studies chronic disease often includes HEART DISEASES; STROKE; CANCER; and diabetes (DIABETES MELLITUS, TYPE 2).		02.4110
Diabetes Mellitus, Type 1
A subtype of DIABETES MELLITUS that is characterized by INSULIN deficiency. It is manifested by the sudden onset of severe HYPERGLYCEMIA, rapid progression to DIABETIC KETOACIDOSIS, and DEATH unless treated with insulin. The disease may occur at any age, but is most common in childhood or adolescence.		014.554315
Heart Failure
A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION.		07.4110
Hypoglycemia
A syndrome of abnormally low BLOOD GLUCOSE level. Clinical hypoglycemia has diverse etiologies. Severe hypoglycemia eventually lead to glucose deprivation of the CENTRAL NERVOUS SYSTEM resulting in HUNGER; SWEATING; PARESTHESIA; impaired mental function; SEIZURES; COMA; and even DEATH.		015.644632
Diabetes Mellitus, Adult-Onset
[description not available]		020.0113691
Diabetes Mellitus, Type 2
A subclass of DIABETES MELLITUS that is not INSULIN-responsive or dependent (NIDDM). It is characterized initially by INSULIN RESISTANCE and HYPERINSULINEMIA; and eventually by GLUCOSE INTOLERANCE; HYPERGLYCEMIA; and overt diabetes. Type II diabetes mellitus is no longer considered a disease exclusively found in adults. Patients seldom develop KETOSIS but often exhibit OBESITY.		020.0113691
Weight Gain
Increase in BODY WEIGHT over existing weight.		07.3353
Lipodystrophy
A collection of heterogenous conditions resulting from defective LIPID METABOLISM and characterized by ADIPOSE TISSUE atrophy. Often there is redistribution of body fat resulting in peripheral fat wasting and central adiposity. They include generalized, localized, congenital, and acquired lipodystrophy.		04.8321
Cognitive Decline
[description not available]		04.6211
Acute Confusional Senile Dementia
[description not available]		04.6211
Alzheimer Disease
A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57)		04.6211
Cognitive Dysfunction
Diminished or impaired mental and/or intellectual function.		04.6211
Hyperglycemia, Postprandial
Abnormally high BLOOD GLUCOSE level after a meal.		09.411310
Insulin Sensitivity
[description not available]		04.9342
Hyperglycemia
Abnormally high BLOOD GLUCOSE level.		09.411310
Insulin Resistance
Diminished effectiveness of INSULIN in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent HYPERGLYCEMIA or KETOSIS.		04.9342
Anaphylactic Reaction
[description not available]		03.0910
Allergy, Drug
[description not available]		06.1862
Anaphylaxis
An acute hypersensitivity reaction due to exposure to a previously encountered ANTIGEN. The reaction may include rapidly progressing URTICARIA, respiratory distress, vascular collapse, systemic SHOCK, and death.		03.0910
Drug Hypersensitivity
Immunologically mediated adverse reactions to medicinal substances used legally or illegally.		06.1862
Alloxan Diabetes
[description not available]		02.1710
Diabetes Mellitus
A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.		07.68131
Enlarged Liver
[description not available]		02.2110
Drug Overdose
Accidental or deliberate use of a medication or street drug in excess of normal dosage.		02.2110
Pregnancy in Diabetes
[description not available]		03.8520
Diabetes Mellitus, Gestational
[description not available]		03.8520
Pregnancy
The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.		03.8520
Diabetes, Gestational
Diabetes mellitus induced by PREGNANCY but resolved at the end of pregnancy. It does not include previously diagnosed diabetics who become pregnant (PREGNANCY IN DIABETICS). Gestational diabetes usually develops in late pregnancy when insulin antagonistic hormones peaks leading to INSULIN RESISTANCE; GLUCOSE INTOLERANCE; and HYPERGLYCEMIA.		03.8520
Autoimmune Disease
[description not available]		02.0810
Compensatory Hyperinsulinemia
A GLUCOSE-induced HYPERINSULINEMIA, a marker of insulin-resistant state. It is a mechanism to compensate for reduced sensitivity to insulin.		03.8621
Symptom Cluster
[description not available]		02.0810
AIRE Deficiency
[description not available]		02.0810
Autoimmune Diseases
Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.		02.0810
Hyperinsulinism
A syndrome with excessively high INSULIN levels in the BLOOD. It may cause HYPOGLYCEMIA. Etiology of hyperinsulinism varies, including hypersecretion of a beta cell tumor (INSULINOMA); autoantibodies against insulin (INSULIN ANTIBODIES); defective insulin receptor (INSULIN RESISTANCE); or overuse of exogenous insulin or HYPOGLYCEMIC AGENTS.		03.8621
Syndrome
A characteristic symptom complex.		07.0810
Diabetic Angiopathies
VASCULAR DISEASES that are associated with DIABETES MELLITUS.		06.7642
Disease Exacerbation
[description not available]		02.110
Anxiety
Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with ANXIETY DISORDERS.		04.411
Body Weight
The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.		05.8542
Overweight
A status with BODY WEIGHT that is above certain standards. In the scale of BODY MASS INDEX, overweight is defined as having a BMI of 25.0-29.9 kg/m2. Overweight may or may not be due to increases in body fat (ADIPOSE TISSUE), hence overweight does not equal over fat.		02.110
Obesity
A status with BODY WEIGHT that is grossly above the recommended standards, usually due to accumulation of excess FATS in the body. The standards may vary with age, sex, genetic or cultural background. In the BODY MASS INDEX, a BMI greater than 30.0 kg/m2 is considered obese, and a BMI greater than 40.0 kg/m2 is considered morbidly obese (MORBID OBESITY).		05.4453
Kidney Failure
A severe irreversible decline in the ability of kidneys to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism.		04.821
Renal Insufficiency
Conditions in which the KIDNEYS perform below the normal level in the ability to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of PROTEINURIA) and reduction in GLOMERULAR FILTRATION RATE.		09.821
Complications of Diabetes Mellitus
[description not available]		04.3841
Acidosis, Diabetic
[description not available]		08.2265
Diabetic Ketoacidosis
A life-threatening complication of diabetes mellitus, primarily of TYPE 1 DIABETES MELLITUS with severe INSULIN deficiency and extreme HYPERGLYCEMIA. It is characterized by KETOSIS; DEHYDRATION; and depressed consciousness leading to COMA.		08.2265
Complication, Postoperative
[description not available]		012.612525
Postoperative Complications
Pathologic processes that affect patients after a surgical procedure. They may or may not be related to the disease for which the surgery was done, and they may or may not be direct results of the surgery.		012.612525
Arterial Diseases, Carotid
[description not available]		03.4511
Idiopathic Inflammatory Myopathies
[description not available]		03.4511
Carotid Artery Diseases
Pathological conditions involving the CAROTID ARTERIES, including the common, internal, and external carotid arteries. ATHEROSCLEROSIS and TRAUMA are relatively frequent causes of carotid artery pathology.		03.4511
Myositis
Inflammation of a muscle or muscle tissue.		03.4511
Cardiovascular Stroke
[description not available]		03.4611
Myocardial Infarction
NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).		03.4611
Critical Illness
A disease or state in which death is possible or imminent.		02.9910
Weight Reduction
[description not available]		02.0210
Weight Loss
Decrease in existing BODY WEIGHT.		02.0210