Efficacy and Safety of FIAsp Compared to Insulin Aspart B... | NCT01831765

ID	Type	Description	Link
2010-024049-53	EudraCT Number
U1111-1118-2442	Other Identifier	WHO

Label	Type	Intervention Names
Meal time FIAsp and insulin detemir	Experimental	Drug: Faster-acting insulin aspart Drug: insulin detemir
Meal time insulin aspart and insulin detemir	Active Comparator	Drug: insulin detemir Drug: insulin aspart
Post meal FIAsp and insulin detemir	Experimental	Drug: insulin detemir Drug: Faster-acting insulin aspart

Name	Type	Description	Arm Group Labels	Other Names
Faster-acting insulin aspart	Drug	Injected subcutaneously (s.c., under the skin), dose individually adjusted. Meal time dosing is defined as injecting 0-2 minutes before the meal.

Measure	Description	Time Frame
Change From Baseline in HbA1c (Glycosylated Haemoglobin)	Change from baseline in HbA1c after 26 weeks of randomised treatment.	Week 0, week 26

Measure	Description	Time Frame
Change From Baseline in 2-hour PPG (Postprandial Glucose) Increment (Meal Test)	Change from baseline in 2-hour PPG increments after 26 weeks of randomised treatment (meal test).	Week 0, week 26
Change From Baseline in HbA1c (Post Meal Arm)

Name	Affiliation	Role
Global Clinical Registry (GCR, 1452)	Novo Nordisk A/S	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Novo Nordisk Investigational Site		Mobile	Alabama	36608	United States
Novo Nordisk Investigational Site

PubMed Identifier	Type	Citation	Retractions
30949906	Background	Rose L, Kadowaki T, Pieber TR, Buchholtz K, Ekelund M, Gorst-Rasmussen A, Philis-Tsimikas A. Efficacy and Safety of Fast-Acting Insulin Aspart in People with Type 1 Diabetes Using Carbohydrate Counting: A Post Hoc Analysis of Two Randomised Controlled Trials. Diabetes Ther. 2019 Jun;10(3):1029-1041. doi: 10.1007/s13300-019-0608-4. Epub 2019 Apr 4.
28356319

Label	URL
Clinical Trials at Novo Nordisk	View source

ID	Title	Description
FG000	Faster Aspart (Meal)	The subjects in this arm were administered mealtime faster aspart (100 U/mL) in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period + a 26-week additional treatment period. Mealtime faster aspart was administered subcutaneously (s.c., under the skin) 0-2 minutes before each main meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.

Arm/Group Information

ID	Title	Description
BG000	Faster Aspart (Meal)	The subjects in this arm were administered mealtime faster aspart (100 U/mL) in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period + a 26-week additional treatment period. Mealtime faster aspart was administered subcutaneously (s.c., under the skin) 0-2 minutes before each main meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.
BG001	Faster Aspart (Post)	The subjects in this arm were administered postmeal faster aspart (100 U/mL) in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period. Postmeal faster aspart was administered subcutaneously (s.c., under the skin) 20 minutes after the start of the meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.
BG002	NovoRapid (Meal)	The subjects in this arm were administered mealtime NovoRapid®/NovoLog®, 100 U/mL in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period + a 26-week additional treatment period. Mealtime NovoRapid®/NovoLog® was administered subcutaneously (s.c., under the skin) 0-2 minutes before each main meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.
BG003	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in HbA1c (Glycosylated Haemoglobin)

Change from baseline in HbA1c after 26 weeks of randomised treatment.

The FAS included all randomised subjects. For this endpoint, baseline and week 26 have been presented, where week 26 data is end of trial containing last available measurement.

Posted

Mean

Standard Deviation

Percentage of glycosylated haemoglobin

Week 0, week 26

ID	Title	Description
OG000	Faster Aspart (Meal)	The subjects in this arm were administered mealtime faster aspart (100 U/mL) in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period + a 26-week additional treatment period. Mealtime faster aspart was administered subcutaneously (s.c., under the skin) 0-2 minutes before each main meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.
OG001	Faster Aspart (Post)	The subjects in this arm were administered postmeal faster aspart (100 U/mL) in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period. Postmeal faster aspart was administered subcutaneously (s.c., under the skin) 20 minutes after the start of the meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.
OG002	NovoRapid (Meal)	The subjects in this arm were administered mealtime NovoRapid®/NovoLog®, 100 U/mL in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period + a 26-week additional treatment period. Mealtime NovoRapid®/NovoLog® was administered subcutaneously (s.c., under the skin) 0-2 minutes before each main meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.

Units	Counts
Participants	OG000381 OG001382 OG002380

Title

Denominators

Categories

Week 0 (Baseline)

Title	Measurements
	OG0007.62± 0.71 OG0017.63± 0.72 OG0027.58± 0.68

Week 26

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG002	Change from baseline in HbA1c analysed using a mixed effect model for repeated measurements including visit 14, 18, 22, 26, 30, 34 and 36. The model included treatment, region and strata (combination of bolus adjusting method, basal treatment regimen and continuous glucose monitoring (CGM) and frequently sampled meal test subgroup) as fixed effects, subject as random effect, baseline HbA1c as covariate and interaction between all fixed effects and visit, and between the covariate and visit.					Mean Difference (Net)	-0.15			2-Sided	95	-0.23	-0.07					Non-Inferiority or Equivalence

Secondary

Change From Baseline in 2-hour PPG (Postprandial Glucose) Increment (Meal Test)

Change from baseline in 2-hour PPG increments after 26 weeks of randomised treatment (meal test).

The FAS included all randomised subjects. For this endpoint, baseline and week 26 have been presented, where week 26 data is end of trial containing last available measurement. At baseline (week 0) 379, 377, 375 and 381, 382, 380 subjects at week 26 were analysed for faster aspart (meal), faster aspart (post) and Novorapid (meal) arms respectively.

Posted

Mean

Standard Deviation

mmol/L

Week 0, week 26

ID	Title	Description
OG000	Faster Aspart (Meal)	The subjects in this arm were administered mealtime faster aspart (100 U/mL) in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period + a 26-week additional treatment period. Mealtime faster aspart was administered subcutaneously (s.c., under the skin) 0-2 minutes before each main meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.
OG001	Faster Aspart (Post)

Secondary

Change From Baseline in HbA1c (Post Meal Arm)

Change from baseline in HbA1c (post meal arm) after 26 weeks of randomised treatment.

This endpoint was summarised using the FAS, which included all randomised subjects. For this endpoint, baseline and week 26 have been presented, where week 26 data is end of trial containing last available measurement.

Posted

Mean

Standard Deviation

Percentage of glycosylated haemoglobin

Week 0, week 26

ID	Title	Description
OG000	Faster Aspart (Post)	The subjects in this arm were administered postmeal faster aspart (100 U/mL) in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period. Postmeal faster aspart was administered subcutaneously (s.c., under the skin) 20 minutes after the start of the meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.
OG001	NovoRapid (Meal)	The subjects in this arm were administered mealtime NovoRapid®/NovoLog®, 100 U/mL in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period + a 26-week additional treatment period. Mealtime NovoRapid®/NovoLog® was administered subcutaneously (s.c., under the skin) 0-2 minutes before each main meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.

Secondary

Number of Treatment Emergent Confirmed Hypoglycaemic Episodes

Observed rate of treatment emergent severe or BG confirmed hypoglycaemic events per 100 patient years of exposure (PYE) from baseline until week 26. A hypoglycaemic episode was defined as treatment emergent if the onset of the episode was on or after the first day of exposure to randomised treatment and no later than 1 day after the last day of randomised treatment. Severe or BG confirmed is an episode that is severe according to the American Diabetes Association (ADA) classification (an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) or BG confirmed by a PG value <3.1 mmol/L (56 mg/dL) with or without symptoms consistent with hypoglycaemia.

The safety analysis set included all subjects receiving at least one dose of trial product/its comparator and contributed to the evaluation "as treated". Five (5) subjects randomised to the faster aspart (post) group have consistently taken their bolus insulin before meals throughout the trial and are handled as treated with faster aspart (meal).

Posted

Number

event rate/100 patient yrs of exposure

From baseline until week 26

ID	Title	Description
OG000	Faster Aspart (Meal)	The subjects in this arm were administered mealtime faster aspart (100 U/mL) in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period + a 26-week additional treatment period. Mealtime faster aspart was administered subcutaneously (s.c., under the skin) 0-2 minutes before each main meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.

Secondary

Change From Baseline in Body Weight

Change from baseline in body weight after 26 weeks of randomised treatment.

The FAS included all randomised subjects. For this endpoint baseline, and week 26 have been presented, where week 26 data is end of trial containing last available measurement. At baseline (week 0) 381, 382, 378 and 381, 382, 380 subjects at week 26 were analysed for faster aspart (meal), faster aspart (post) and Novorapid (meal) arms respectively.

Posted

Mean

Standard Deviation

Week 0, week 26

ID	Title	Description
OG000	Faster Aspart (Meal)	The subjects in this arm were administered mealtime faster aspart (100 U/mL) in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period + a 26-week additional treatment period. Mealtime faster aspart was administered subcutaneously (s.c., under the skin) 0-2 minutes before each main meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.
OG001	Faster Aspart (Post)	The subjects in this arm were administered postmeal faster aspart (100 U/mL) in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period. Postmeal faster aspart was administered subcutaneously (s.c., under the skin) 20 minutes after the start of the meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.

Secondary

Frequency of Adverse Events

All treatment emergent adverse events (TEAEs) from baseline until 52 weeks of randomised treatment. A TEAE was defined as an event that had an onset date on or after the first day of exposure to randomised treatment, and no later than 7 days after the last day of randomised treatment.

Posted

Number

event /100 patient yrs of exposure

After 52 weeks of randomised treatment

ID	Title	Description
OG000	Faster Aspart (Meal)	The subjects in this arm were administered mealtime faster aspart (100 U/mL) in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period + a 26-week additional treatment period. Mealtime faster aspart was administered subcutaneously (s.c., under the skin) 0-2 minutes before each main meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.

Secondary

Change in HbA1c

Change from baseline in HbA1c (%) after 52 weeks of randomised treatment.

The FAS included all randomised subjects. The statistical evaluation of the FAS was to follow the ITT principle and subjects contributed to the evaluation 'as randomised'. For this endpoint, baseline and week 52 have been presented, where week 52 data is the end of trial containing last available measurement.

Posted

Mean

Standard Deviation

Percentage of glycosylated haemoglobin

Week 0, week 52

ID	Title	Description
OG000	Faster Aspart (Meal)	The subjects in this arm were administered mealtime faster aspart (100 U/mL) in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period + a 26-week additional treatment period. Mealtime faster aspart was administered subcutaneously (s.c., under the skin) 0-2 minutes before each main meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.
OG001	NovoRapid (Meal)	The subjects in this arm were administered mealtime NovoRapid®/NovoLog®, 100 U/mL in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period + a 26-week additional treatment period. Mealtime NovoRapid®/NovoLog® was administered subcutaneously (s.c., under the skin) 0-2 minutes before each main meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.

Secondary

Change in PPG (Postprandial Glucose)

Change from baseline in PPG and PPG increment (meal test) after 52 weeks of randomised treatment.

The FAS included all randomised subjects. The number of subjects with data available for PPG at 120 mins at baseline were 379, 379 and 380, 380 at week 52 and for PPG increment (120 mins) at baseline were 379, 375 and 381, 380 at week 26 for faster aspart (meal) and Novorapid (meal) respectively.

Posted

Mean

Standard Deviation

mmol/L

Week 0, week 52

ID	Title	Description
OG000	Faster Aspart (Meal)	The subjects in this arm were administered mealtime faster aspart (100 U/mL) in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period + a 26-week additional treatment period. Mealtime faster aspart was administered subcutaneously (s.c., under the skin) 0-2 minutes before each main meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.
OG001	NovoRapid (Meal)	The subjects in this arm were administered mealtime NovoRapid®/NovoLog®, 100 U/mL in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period + a 26-week additional treatment period. Mealtime NovoRapid®/NovoLog® was administered subcutaneously (s.c., under the skin) 0-2 minutes before each main meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Faster Aspart (Meal)	The subjects in this arm were administered mealtime faster aspart (100 U/mL) in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period + a 26-week additional treatment period. Mealtime faster aspart was administered subcutaneously (s.c., under the skin) 0-2 minutes before each main meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.	35	386	252	386
EG001	Faster Aspart (Post)	The subjects in this arm were administered postmeal faster aspart (100 U/mL) in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period. Postmeal faster aspart was administered subcutaneously (s.c., under the skin) 20 minutes after the start of the meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.	28	377	189	377
EG002	NovoRapid (Meal)	The subjects in this arm were administered mealtime NovoRapid®/NovoLog®, 100 U/mL in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period + a 26-week additional treatment period. Mealtime NovoRapid®/NovoLog® was administered subcutaneously (s.c., under the skin) 0-2 minutes before each main meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.	33	380	236	380

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 events0 affected386 at risk EG0010 events0 affected377 at risk EG0021 events1 affected380 at risk
Adenocarcinoma of colon	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 events0 affected386 at risk EG0011 events1 affected377 at risk EG0020 events0 affected380 at risk
Anal fistula	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 events0 affected386 at risk EG0010 events0 affected377 at risk EG0021 events1 affected380 at risk
Aneurysm	Vascular disorders	MedDRA	Systematic Assessment	EG0001 events1 affected386 at risk EG0010 events0 affected377 at risk EG0020 events0 affected380 at risk
Angina pectoris	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 events0 affected386 at risk EG0011 events1 affected377 at risk EG0020 events0 affected380 at risk
Ankle fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 events1 affected386 at risk EG0011 events1 affected377 at risk EG0020 events0 affected380 at risk
Appendicitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 events1 affected386 at risk EG0010 events0 affected377 at risk EG0020 events0 affected380 at risk
Arrhythmia	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 events0 affected386 at risk EG0011 events1 affected377 at risk EG0020 events0 affected380 at risk
Arteriosclerosis coronary artery	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 events0 affected386 at risk EG0011 events1 affected377 at risk EG0020 events0 affected380 at risk
Blood glucose decreased	Investigations	MedDRA	Systematic Assessment	EG0000 events0 affected386 at risk EG0010 events0 affected377 at risk EG0022 events1 affected380 at risk
Bronchitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 events0 affected386 at risk EG0010 events0 affected377 at risk EG0021 events1 affected380 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 events1 affected386 at risk EG0010 events0 affected377 at risk EG0020 events0 affected380 at risk
Cardiac ventricular thrombosis	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 events1 affected386 at risk EG0010 events0 affected377 at risk EG0020 events0 affected380 at risk
Cardiovascular evaluation	Investigations	MedDRA	Systematic Assessment	EG0000 events0 affected386 at risk EG0010 events0 affected377 at risk EG0021 events1 affected380 at risk
Carotid artery stenosis	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 events0 affected386 at risk EG0011 events1 affected377 at risk EG0020 events0 affected380 at risk
Cellulitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 events0 affected386 at risk EG0010 events0 affected377 at risk EG0021 events1 affected380 at risk
Colitis microscopic	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 events0 affected386 at risk EG0010 events0 affected377 at risk EG0021 events1 affected380 at risk
Compartment syndrome	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 events0 affected386 at risk EG0010 events0 affected377 at risk EG0021 events1 affected380 at risk
Coronary arterial stent insertion	Surgical and medical procedures	MedDRA	Systematic Assessment	EG0001 events1 affected386 at risk EG0010 events0 affected377 at risk EG0020 events0 affected380 at risk
Coronary artery disease	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 events1 affected386 at risk EG0011 events1 affected377 at risk EG0020 events0 affected380 at risk
Coronary revascularisation	Surgical and medical procedures	MedDRA	Systematic Assessment	EG0000 events0 affected386 at risk EG0011 events1 affected377 at risk EG0020 events0 affected380 at risk
Diabetic ketoacidosis	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 events1 affected386 at risk EG0010 events0 affected377 at risk EG0022 events2 affected380 at risk
Diabetic retinopathy	Eye disorders	MedDRA	Systematic Assessment	EG0000 events0 affected386 at risk EG0010 events0 affected377 at risk EG0021 events1 affected380 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 events0 affected386 at risk EG0011 events1 affected377 at risk EG0020 events0 affected380 at risk
Fall	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0002 events2 affected386 at risk EG0010 events0 affected377 at risk EG0020 events0 affected380 at risk
Gastroenteritis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 events1 affected386 at risk EG0010 events0 affected377 at risk EG0020 events0 affected380 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG00016 events12 affected386 at risk EG00111 events11 affected377 at risk EG00210 events10 affected380 at risk
Hypoglycaemic seizure	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 events0 affected386 at risk EG0011 events1 affected377 at risk EG0020 events0 affected380 at risk
Hypoglycaemic unconsciousness	Nervous system disorders	MedDRA	Systematic Assessment	EG0008 events5 affected386 at risk EG0013 events3 affected377 at risk EG0025 events4 affected380 at risk
Ischaemic stroke	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 events0 affected386 at risk EG0010 events0 affected377 at risk EG0021 events1 affected380 at risk
Joint stiffness	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 events0 affected386 at risk EG0010 events0 affected377 at risk EG0021 events1 affected380 at risk
Lactic acidosis	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 events0 affected386 at risk EG0011 events1 affected377 at risk EG0020 events0 affected380 at risk
Lower limb fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 events0 affected386 at risk EG0011 events1 affected377 at risk EG0020 events0 affected380 at risk
Lumbar vertebral fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 events1 affected386 at risk EG0010 events0 affected377 at risk EG0021 events1 affected380 at risk
Lung neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 events1 affected386 at risk EG0010 events0 affected377 at risk EG0020 events0 affected380 at risk
Meniscal degeneration	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 events0 affected386 at risk EG0010 events0 affected377 at risk EG0021 events1 affected380 at risk
Mental status changes	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 events0 affected386 at risk EG0010 events0 affected377 at risk EG0021 events1 affected380 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 events0 affected386 at risk EG0010 events0 affected377 at risk EG0021 events1 affected380 at risk
Myocardial infarction	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 events0 affected386 at risk EG0010 events0 affected377 at risk EG0021 events1 affected380 at risk
Nasal septum deviation	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 events1 affected386 at risk EG0010 events0 affected377 at risk EG0020 events0 affected380 at risk
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 events0 affected386 at risk EG0011 events1 affected377 at risk EG0020 events0 affected380 at risk
Osteomyelitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 events0 affected386 at risk EG0011 events1 affected377 at risk EG0020 events0 affected380 at risk
Overdose	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 events0 affected386 at risk EG0011 events1 affected377 at risk EG0020 events0 affected380 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 events1 affected386 at risk EG0010 events0 affected377 at risk EG0021 events1 affected380 at risk
Papillary thyroid cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 events0 affected386 at risk EG0010 events0 affected377 at risk EG0021 events1 affected380 at risk
Peripheral arterial occlusive disease	Vascular disorders	MedDRA	Systematic Assessment	EG0001 events1 affected386 at risk EG0010 events0 affected377 at risk EG0020 events0 affected380 at risk
Peritoneal fibrosis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 events0 affected386 at risk EG0011 events1 affected377 at risk EG0020 events0 affected380 at risk
Peritonsillar abscess	Infections and infestations	MedDRA	Systematic Assessment	EG0000 events0 affected386 at risk EG0010 events0 affected377 at risk EG0021 events1 affected380 at risk
Pharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 events0 affected386 at risk EG0010 events0 affected377 at risk EG0021 events1 affected380 at risk
Pilonidal cyst	Infections and infestations	MedDRA	Systematic Assessment	EG0000 events0 affected386 at risk EG0011 events1 affected377 at risk EG0020 events0 affected380 at risk
Pneumonia staphylococcal	Infections and infestations	MedDRA	Systematic Assessment	EG0000 events0 affected386 at risk EG0011 events1 affected377 at risk EG0020 events0 affected380 at risk
Pyelonephritis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 events1 affected386 at risk EG0011 events1 affected377 at risk EG0020 events0 affected380 at risk
Radius fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 events1 affected386 at risk EG0010 events0 affected377 at risk EG0020 events0 affected380 at risk
Road traffic accident	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 events0 affected386 at risk EG0011 events1 affected377 at risk EG0020 events0 affected380 at risk
Subarachnoid haemorrhage	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 events1 affected386 at risk EG0010 events0 affected377 at risk EG0020 events0 affected380 at risk
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 events1 affected386 at risk EG0010 events0 affected377 at risk EG0020 events0 affected380 at risk
Tendon rupture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 events1 affected386 at risk EG0010 events0 affected377 at risk EG0020 events0 affected380 at risk
Thrombosis	Vascular disorders	MedDRA	Systematic Assessment	EG0001 events1 affected386 at risk EG0010 events0 affected377 at risk EG0020 events0 affected380 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 events1 affected386 at risk EG0010 events0 affected377 at risk EG0020 events0 affected380 at risk
Uterine polyp	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0001 events1 affected386 at risk EG0010 events0 affected377 at risk EG0020 events0 affected380 at risk
Vestibular neuronitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 events1 affected386 at risk EG0010 events0 affected377 at risk EG0020 events0 affected380 at risk
Viral infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 events0 affected386 at risk EG0010 events0 affected377 at risk EG0021 events1 affected380 at risk
Vomiting	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 events0 affected386 at risk EG0011 events1 affected377 at risk EG0020 events0 affected380 at risk
Wrong drug administered	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 events1 affected386 at risk EG0011 events1 affected377 at risk EG0020 events0 affected380 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Back pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG00036 events28 affected386 at risk EG00117 events15 affected377 at risk EG00222 events20 affected380 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG00021 events17 affected386 at risk EG00113 events12 affected377 at risk EG00221 events20 affected380 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00034 events27 affected386 at risk EG00111 events11 affected377 at risk EG00233 events27 affected380 at risk
Gastroenteritis	Infections and infestations	MedDRA	Systematic Assessment	EG00025 events20 affected386 at risk EG0018 events8 affected377 at risk EG00221 events17 affected380 at risk
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG00070 events37 affected386 at risk EG00141 events26 affected377 at risk EG00279 events45 affected380 at risk
Influenza	Infections and infestations	MedDRA	Systematic Assessment	EG00030 events22 affected386 at risk EG00112 events11 affected377 at risk EG00254 events37 affected380 at risk
Nasopharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG000214 events128 affected386 at risk EG001111 events90 affected377 at risk EG002174 events120 affected380 at risk
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00036 events28 affected386 at risk EG00129 events18 affected377 at risk EG00234 events23 affected380 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG00022 events17 affected386 at risk EG00121 events16 affected377 at risk EG00230 events23 affected380 at risk
Sinusitis	Infections and infestations	MedDRA	Systematic Assessment	EG00021 events19 affected386 at risk EG0017 events7 affected377 at risk EG00237 events28 affected380 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG00075 events56 affected386 at risk EG00131 events28 affected377 at risk EG00261 events40 affected380 at risk
Urinary tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG00025 events20 affected386 at risk EG00120 events15 affected377 at risk EG00229 events18 affected380 at risk
Vomiting	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00023 events19 affected386 at risk EG00116 events15 affected377 at risk EG00230 events25 affected380 at risk
Wrong drug administered	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG00031 events22 affected386 at risk EG00120 events18 affected377 at risk EG00228 events23 affected380 at risk

ID	Term
D003920	Diabetes Mellitus
D003922	Diabetes Mellitus, Type 1

ID	Term
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases
D001327	Autoimmune Diseases
D007154	Immune System Diseases

ID	Term
D049528	Insulin, Long-Acting
D061385	Insulins
D010187	Pancreatic Hormones
D036361	Peptide Hormones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins
D061266	Insulin, Short-Acting