Alogliptin Tablets Specified Drug-use Survey "Type 2 Diabetic Patients Receiving Combination Therapy With a Hypoglycemic Agent (e.g., Insulin Preparations or Rapid-acting Insulin Secretagogues)"

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02221284
• Collaborator: (none)
• Enrollment: 964
• Locations: 2
• Actual Duration (Months): 36
• Patients Per Site: 482
• Patients Per Site Per Month: 13.4

Study Details

Study Description

Brief Summary

The purpose of this survey is to evaluate the safety and efficacy of long-term use of alogliptin tablets (Nesina Tablets) in type 2 diabetic patients who have had an inadequate response to hypoglycemic agents (e.g., insulin preparations or rapid-acting insulin secretagogues)* in addition to dietary/exercise therapy. Participants will receive alogliptin as part of routine medical care.

• Patients receiving these hypoglycemic agents (excluding α-glucosidase inhibitors, thiazolidines, sulfonylureas, and biguanides) were excluded from existing specified drug-use surveys for alogliptin tablets.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus	Drug: Alogliptin

Detailed Description

This survey was designed to evaluate the safety and efficacy of long-term use of alogliptin tablets (Nesina Tablets) in type 2 diabetic patients who have had an inadequate response to hypoglycemic agents (e.g., insulin preparations or rapid-acting insulin secretagogues) in addition to dietary/exercise therapy. Participants will receive alogliptin as part of routine medical care.

For adults, 25 mg of alogliptin is usually administered orally once daily.

Study Design

• Study Type: Observational
• Actual Enrollment: 964 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Alogliptin (Nesina) Tablets Specified Drug-use Survey "Type 2 Diabetes Mellitus: Combination Therapy With Hypoglycemic Drug (Insulin Preparation or Rapid-acting Insulin Secretagogues, Etc)"
• Actual Study Start Date: Jun 30, 2014
• Actual Primary Completion Date: Jun 30, 2017
• Actual Study Completion Date: Jun 30, 2017

Arms and Interventions

Arm	Intervention/Treatment
Alogliptin Alogliptin 25 milligram (mg), tablets, orally, once daily, up to 12 months, along with an insulin preparations, with a rapid-acting insulin secretagogue (Glinide), with a SGLT-2 inhibitor, or the other diabetic drugs within 3 months prior to the start of alogliptin treatment or during the alogliptin treatment period in routine medical care.	Drug: Alogliptin; Alogliptin tablets; Other Names: Nesina Tablets

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Who Had One or More Adverse Reactions [Up to Month 12]

   Adverse drug reactions are defined as adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms or diseases temporally associated with the use of a medicinal product reported from the first dose of study drug to the last dose of study drug.

Secondary Outcome Measures

1. Change From Baseline in Glycosylated Hemoglobin (HbA1c) [Baseline, and final assessment point (up to Month 12)]

   The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at final assessment point (up to Month 12) relative to baseline.

2. Number of Participants Achieving Specified HbA1c Level (< 7.0% and <6.0%) [Baseline, and final assessment point (up to Month 12)]

   The reported data were number of participants who achieved specified HbA1c Level (< 7.0% and <6.0%) during this study.

3. Change From Baseline in Laboratory Test Values (Fasting Blood Glucose Level) [Baseline, and final assessment point (up to Month 12)]

   The reported data were change from baseline in fasting blood glucose level.

4. Change From Baseline in Laboratory Test Values (Fasting Insulin Level) [Baseline, and final assessment point (up to Month 12)]

   The reported data were change from baseline in fasting insulin level.

5. Change From Baseline in Laboratory Test Values (Homeostasis Model Assessment Ratio [HOMA-R]) [Baseline, and final assessment point (up to Month 12)]

   The reported data were change from baseline in HOMA-R. HOMA-R measures insulin resistance, calculated by fasting insulin (μU/mL) multiplied by fasting glucose (mg/dL), and divided by a constant (405). A higher score indicates higher insulin resistance.

6. Change From Baseline in Laboratory Test Values (Homeostasis Model Assessment of Beta-cell Function [HOMA-β]) [Baseline, and final assessment point (up to Month 12)]

   The reported data were change from baseline in HOMA-β. HOMA-β measures as following; HOMA-β = fasting insulin (μU/mL) ×360/{fasting glucose (mg/dL) - 63}.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

-Type 2 diabetic patients meeting the following criteria are included in this survey:

Patients who have had an inadequate response to the following medications/therapies:

• Use of one hypoglycemic agent such as insulin preparations and rapid-acting insulin secretagogues, excluding other types of hypoglycemic agents (e.g., α-glucosidase inhibitors, thiazolidines, sulfonylureas, and biguanides)*, in addition to dietary/exercise therapy

• For use of alogliptin tablets in combination with these agents, a specified drug-use survey is currently ongoing.

Exclusion Criteria:

-Type 2 diabetic patients who meet any of the following criteria are excluded from this survey: Patients with contraindications for alogliptin tablets

1. Those with severe ketosis, in a state of diabetic coma or precoma, or with type 1 diabetes mellitus [Quickly rectifying hyperglycemia with administration of intravenous fluid or insulin is essential in these patients; therefore, administration of alogliptin tablets is not appropriate.]

2. Those with severe infections, before or after surgery, or with serious trauma [Controlling blood glucose with an injection of insulin is desirable for these patients; therefore, administration of alogliptin tablets is not appropriate.]

3. Those with a history of hypersensitivity to any of the ingredients of alogliptin tablets

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Osaka		Japan
2		Tokyo		Japan

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Study Director, Takeda

Study Documents (Full-Text)

• Study Protocol - Jun 2, 2017
• Statistical Analysis Plan - Apr 11, 2018

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT02221284
• Other Study ID Numbers: 121-016; JapicCTI-142609
• First Posted: Aug 20, 2014
• Last Update Posted: Nov 6, 2019
• Last Verified: Oct 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Takeda: Pharmacological therapy
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Alogliptin

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 196 investigative sites in Japan, from 30 June 2014 to 30 June 2017. Data reports overall population, since data not collected separately per arm as specified in protocol.
Pre-assignment Detail	Enrolled participants had a diagnosis of type 2 diabetic mellitus and an inadequate response to hypoglycemic agents in addition to dietary/exercise therapy. Participants received interventions as part of routine medical care. Data reports overall population, since data not collected separately per arm as specified in protocol.

Arm/Group Title	Overall Population
Arm/Group Description	Alogliptin 25 milligram (mg), tablets, orally, once daily, up to 12 months, along with an insulin preparations, with a rapid-acting insulin secretagogue (Glinide), with a SGLT-2 inhibitor, or the other diabetic drugs within 3 months prior to the start of alogliptin treatment or during the alogliptin treatment period in routine medical care.
Period Title: Overall Study
STARTED	964
COMPLETED	903
NOT COMPLETED	61

Baseline Characteristics

Arm/Group Title	Alogliptin + Insulin	Alogliptin + Glinide	Alogliptin + SGLT-2 Inhibitor	Alogliptin + Other	Total
Arm/Group Description	Alogliptin 25 mg, tablets, orally, once daily for up to 12 months, along with insulin preparation within 3 months prior to the start of alogliptin treatment or during the alogliptin treatment period. Participants received interventions as part of routine medical care.	Alogliptin 25 mg, tablets, orally, once daily for up to 12 months, along with rapid-acting insulin secretagogue (Glinide) within 3 months prior to the start of alogliptin treatment or during the alogliptin treatment period. Participants received interventions as part of routine medical care.	Alogliptin 25 mg, tablets, orally, once daily for up to 12 months, along with SGLT-2 inhibitor within 3 months prior to the start of alogliptin treatment or during the alogliptin treatment period. Participants received interventions as part of routine medical care.	Alogliptin 25 mg, tablets, orally, once daily for up to 12 months, along without insulin preparations, glinide, or SGLT-2 inhibitor within 3 months prior to the start of alogliptin treatment or during the alogliptin treatment period. Participants received interventions as part of routine medical care.	Total of all reporting groups
Overall Participants	573	166	102	62	903
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	65.6 (12.27)	67.9 (11.71)	61.0 (13.72)	61.2 (14.31)	65.2 (12.65)
Sex: Female, Male (Count of Participants)
Female	257 44.9%	67 40.4%	35 34.3%	26 41.9%	385 42.6%
Male	316 55.1%	99 59.6%	67 65.7%	36 58.1%	518 57.4%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (Number) [Number]
Japan	573 100%	166 100%	102 100%	62 100%	903 100%
Duration of Diagnosis of Type-2 Diabetes Mellitus (Years) (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	14.24 (10.858)	9.03 (9.058)	6.57 (6.911)	7.45 (6.831)	12.26 (10.458)
Height (Centimeters (cm)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Centimeters (cm)]	160.0 (9.70)	160.2 (10.12)	164.3 (9.38)	162.4 (9.02)	160.6 (9.78)
Weight (Kilograms (kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Kilograms (kg)]	62.57 (12.910)	62.45 (13.141)	72.37 (14.654)	68.32 (14.248)	64.11 (13.667)
BMI (kg/meter (m)^2) [Median (Standard Deviation) ]
Median (Standard Deviation) [kg/meter (m)^2]	24.40 (4.037)	24.22 (3.515)	26.71 (4.380)	25.90 (4.312)	24.69 (4.065)
Waist Circumference (Male) (Count of Participants)
< 85 cm	15 2.6%	12 7.2%	2 2%	1 1.6%	30 3.3%
>= 85 cm	22 3.8%	17 10.2%	9 8.8%	5 8.1%	53 5.9%
Unknown	279 48.7%	70 42.2%	56 54.9%	30 48.4%	435 48.2%
Waist Circumference (Female) (Count of Participants)
< 90 cm	25 4.4%	13 7.8%	2 2%	1 1.6%	41 4.5%
>= 90 cm	15 2.6%	3 1.8%	2 2%	1 1.6%	21 2.3%
Unknown	217 37.9%	51 30.7%	31 30.4%	24 38.7%	323 35.8%
Healthcare Category (Count of Participants)
Outpatient	539 94.1%	161 97%	101 99%	57 91.9%	858 95%
Inpatient	34 5.9%	5 3%	1 1%	5 8.1%	45 5%
Medical Complications (Count of Participants)
Had No Medical Complications	69 12%	18 10.8%	21 20.6%	14 22.6%	122 13.5%
Had Medical Complications	504 88%	148 89.2%	81 79.4%	48 77.4%	781 86.5%
Concomitant Diabetes Mellitus (Count of Participants)
Had No Concomitant Diabetes Mellitus	324 56.5%	123 74.1%	65 63.7%	44 71%	556 61.6%
Had Concomitant Diabetes Mellitus	249 43.5%	43 25.9%	37 36.3%	18 29%	347 38.4%
Concomitant Hypertension (Count of Participants)
Had No Concomitant Hypertension	247 43.1%	63 38%	41 40.2%	26 41.9%	377 41.7%
Had Concomitant Hypertension	326 56.9%	103 62%	61 59.8%	36 58.1%	526 58.3%
Concomitant Hyperlipidemia (Count of Participants)
Had No Concomitant Hyperlipidemia	261 45.5%	68 41%	38 37.3%	29 46.8%	396 43.9%
Had Concomitant Hyperlipidemia	312 54.5%	98 59%	64 62.7%	33 53.2%	507 56.1%
Concomitant Hyperuricaemia (Count of Participants)
Had No Concomitant Hyperuricaemia	522 91.1%	145 87.3%	93 91.2%	60 96.8%	820 90.8%
Had Concomitant Hyperuricaemia	51 8.9%	21 12.7%	9 8.8%	2 3.2%	83 9.2%
Concomitant Hepatic Disorder (Count of Participants)
Had No Concomitant Hepatic Disorder	467 81.5%	147 88.6%	84 82.4%	51 82.3%	749 82.9%
Had Concomitant Hepatic Disorder	106 18.5%	19 11.4%	18 17.6%	11 17.7%	154 17.1%
Degree of Hepatic Dysfunction (Count of Participants)
Normal	404 70.5%	94 56.6%	63 61.8%	36 58.1%	597 66.1%
Grade 1	25 4.4%	7 4.2%	5 4.9%	4 6.5%	41 4.5%
Grade 2	4 0.7%	3 1.8%	5 4.9%	1 1.6%	13 1.4%
Unknown	140 24.4%	62 37.3%	29 28.4%	21 33.9%	252 27.9%
Concomitant Renal Disorder (Count of Participants)
Had No Concomitant Renal Disorder	412 71.9%	139 83.7%	73 71.6%	49 79%	673 74.5%
Had Concomitant Renal Disorder	161 28.1%	27 16.3%	29 28.4%	13 21%	230 25.5%
Degree of Renal Dysfunction (eGFR) (Count of Participants)
Normal	85 14.8%	30 18.1%	23 22.5%	16 25.8%	154 17.1%
Mild	235 41%	38 22.9%	38 37.3%	22 35.5%	333 36.9%
Moderate	118 20.6%	28 16.9%	18 17.6%	4 6.5%	168 18.6%
Severe	12 2.1%	1 0.6%	0 0%	0 0%	13 1.4%
Normal or Mild	320 55.8%	68 41%	61 59.8%	38 61.3%	487 53.9%
Moderate or Severe	130 22.7%	29 17.5%	18 17.6%	4 6.5%	181 20%
Unknown	123 21.5%	69 41.6%	23 22.5%	20 32.3%	235 26%
Degree of Renal Dysfunction (Cr) (Count of Participants)
Normal or Mild	431 75.2%	94 56.6%	78 76.5%	42 67.7%	645 71.4%
Moderate	17 3%	3 1.8%	1 1%	0 0%	21 2.3%
Severe	2 0.3%	0 0%	0 0%	0 0%	2 0.2%
Moderate or Severe	19 3.3%	3 1.8%	1 1%	0 0%	23 2.5%
Unknown	123 21.5%	69 41.6%	23 22.5%	20 32.3%	235 26%
Concomitant Cardiac Disease (Count of Participants)
Had No Concomitant Cardiac Disease	467 81.5%	154 92.8%	96 94.1%	54 87.1%	771 85.4%
Had Concomitant Cardiac Disease	106 18.5%	12 7.2%	6 5.9%	8 12.9%	132 14.6%
Concomitant Heart Failure (Count of Participants)
Had No Concomitant Heart Failure	546 95.3%	166 100%	101 99%	61 98.4%	874 96.8%
Had Concomitant Heart Failure	27 4.7%	0 0%	1 1%	1 1.6%	29 3.2%
New York Heart Association (NYHA) Heart Failure Classification (Count of Participants)
Class I	15 2.6%	0 0%	0 0%	1 1.6%	16 1.8%
Class II	9 1.6%	0 0%	1 1%	0 0%	10 1.1%
Unknown	3 0.5%	0 0%	0 0%	0 0%	3 0.3%
Concomitant Stroke-Related Disease (Count of Participants)
Had No Concomitant Stroke-Related Disease	520 90.8%	157 94.6%	99 97.1%	61 98.4%	837 92.7%
Had Concomitant Stroke-Related Disease	53 9.2%	9 5.4%	3 2.9%	1 1.6%	66 7.3%
Concomitant Allergic Condition (Count of Participants)
Had No Concomitant Allergic Condition	553 96.5%	161 97%	99 97.1%	59 95.2%	872 96.6%
Had Concomitant Allergic Condition	20 3.5%	5 3%	3 2.9%	3 4.8%	31 3.4%
Concomitant Malignant Tumor (Count of Participants)
Had No Concomitant Malignant Tumor	548 95.6%	160 96.4%	102 100%	59 95.2%	869 96.2%
Had Concomitant Malignant Tumor	25 4.4%	6 3.6%	0 0%	3 4.8%	34 3.8%
Medical History (Count of Participants)
Had No Medical History	411 71.7%	123 74.1%	95 93.1%	47 75.8%	676 74.9%
Had Medical History	125 21.8%	28 16.9%	5 4.9%	12 19.4%	170 18.8%
Unknown	37 6.5%	15 9%	2 2%	3 4.8%	57 6.3%
Predisposition to Hypersensitivity (Count of Participants)
Had No Predisposition to Hypersensitivity	508 88.7%	141 84.9%	98 96.1%	56 90.3%	803 88.9%
Had Predisposition to Hypersensitivity	33 5.8%	11 6.6%	3 2.9%	4 6.5%	51 5.6%
Unknown	32 5.6%	14 8.4%	1 1%	2 3.2%	49 5.4%
Drinking Habits (Count of Participants)
Yes	110 19.2%	49 29.5%	23 22.5%	14 22.6%	196 21.7%
No	377 65.8%	92 55.4%	57 55.9%	39 62.9%	565 62.6%
Unknown	86 15%	25 15.1%	22 21.6%	9 14.5%	142 15.7%
Smoking Classification (Count of Participants)
Never Smoked	289 50.4%	65 39.2%	43 42.2%	25 40.3%	422 46.7%
Current Smoker	64 11.2%	31 18.7%	15 14.7%	16 25.8%	126 14%
Ex-Smoker	103 18%	45 27.1%	19 18.6%	10 16.1%	177 19.6%
Unknown	117 20.4%	25 15.1%	25 24.5%	11 17.7%	178 19.7%
Hemoglobin A1c (HbA1c) (Percent) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percent]	8.44 (1.662)	7.60 (1.051)	7.66 (1.379)	8.78 (2.053)	8.21 (1.612)

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Who Had One or More Adverse Reactions
Description	Adverse drug reactions are defined as adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms or diseases temporally associated with the use of a medicinal product reported from the first dose of study drug to the last dose of study drug.
Time Frame	Up to Month 12

Outcome Measure Data

Analysis Population Description

Safety Analysis Set; The safety analysis set was defined as all participants who completed the study.

Arm/Group Title	Alogliptin + Insulin	Alogliptin + Glinide	Alogliptin + SGLT-2 Inhibitor	Alogliptin + Other
Arm/Group Description	Alogliptin 25 mg, tablets, orally, once daily for up to 12 months, along with insulin preparation within 3 months prior to the start of alogliptin treatment or during the alogliptin treatment period. Participants received interventions as part of routine medical care.	Alogliptin 25 mg, tablets, orally, once daily for up to 12 months, along with rapid-acting insulin secretagogue (Glinide) within 3 months prior to the start of alogliptin treatment or during the alogliptin treatment period. Participants received interventions as part of routine medical care.	Alogliptin 25 mg, tablets, orally, once daily for up to 12 months, along with SGLT-2 inhibitor within 3 months prior to the start of alogliptin treatment or during the alogliptin treatment period. Participants received interventions as part of routine medical care.	Alogliptin 25 mg, tablets, orally, once daily for up to 12 months, along without insulin preparations, glinide, or SGLT-2 inhibitor within 3 months prior to the start of alogliptin treatment or during the alogliptin treatment period. Participants received interventions as part of routine medical care.
Measure Participants	573	166	102	62
Number [Percentage of Participants]	5.41 0.9%	1.20 0.7%	0.98 1%	0.00 0%

2. Secondary Outcome

Title	Change From Baseline in Glycosylated Hemoglobin (HbA1c)
Description	The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at final assessment point (up to Month 12) relative to baseline.
Time Frame	Baseline, and final assessment point (up to Month 12)

Outcome Measure Data

Analysis Population Description

Efficacy assessment population was defined as participants who completed study and had available efficacy data at baseline and post baseline. Efficacy analysis was planned to be assessed in Alogliptin + Insulin, Alogliptin + Glinide and Alogliptin + SGLT-2 inhibitor groups and data for Alogliptin + Other were not collected as specified in protocol.

Arm/Group Title	Alogliptin + Insulin	Alogliptin + Glinide	Alogliptin + SGLT-2 Inhibitor
Arm/Group Description	Alogliptin 25 mg, tablets, orally, once daily for up to 12 months, along with insulin preparation within 3 months prior to the start of alogliptin treatment or during the alogliptin treatment period. Participants received interventions as part of routine medical care.	Alogliptin 25 mg, tablets, orally, once daily for up to 12 months, along with rapid-acting insulin secretagogue (Glinide) within 3 months prior to the start of alogliptin treatment or during the alogliptin treatment period. Participants received interventions as part of routine medical care.	Alogliptin 25 mg, tablets, orally, once daily for up to 12 months, along with SGLT-2 inhibitor within 3 months prior to the start of alogliptin treatment or during the alogliptin treatment period. Participants received interventions as part of routine medical care.
Measure Participants	546	158	96
Mean (Standard Deviation) [Percent]	-0.66 (1.622)	-0.49 (0.940)	-0.60 (1.102)

3. Secondary Outcome

Title	Number of Participants Achieving Specified HbA1c Level (< 7.0% and <6.0%)
Description	The reported data were number of participants who achieved specified HbA1c Level (< 7.0% and <6.0%) during this study.
Time Frame	Baseline, and final assessment point (up to Month 12)

Outcome Measure Data

Analysis Population Description

Efficacy assessment population was defined as participants who completed study and had available efficacy data at baseline and post baseline. Efficacy analysis was planned to be assessed in Alogliptin + Insulin, Alogliptin + Glinide and Alogliptin + SGLT-2 inhibitor groups and data for Alogliptin + Other were not collected as specified in protocol.

Arm/Group Title	Alogliptin + Insulin	Alogliptin + Glinide	Alogliptin + SGLT-2 Inhibitor
Arm/Group Description	Alogliptin 25 mg, tablets, orally, once daily for up to 12 months, along with insulin preparation within 3 months prior to the start of alogliptin treatment or during the alogliptin treatment period. Participants received interventions as part of routine medical care.	Alogliptin 25 mg, tablets, orally, once daily for up to 12 months, along with rapid-acting insulin secretagogue (Glinide) within 3 months prior to the start of alogliptin treatment or during the alogliptin treatment period. Participants received interventions as part of routine medical care.	Alogliptin 25 mg, tablets, orally, once daily for up to 12 months, along with SGLT-2 inhibitor within 3 months prior to the start of alogliptin treatment or during the alogliptin treatment period. Participants received interventions as part of routine medical care.
Measure Participants	557	162	101
HbA1c Level < 7.0%	161 28.1%	87 52.4%	55 53.9%
HbA1c Level < 6.0%	22 3.8%	10 6%	7 6.9%

4. Secondary Outcome

Title	Change From Baseline in Laboratory Test Values (Fasting Blood Glucose Level)
Description	The reported data were change from baseline in fasting blood glucose level.
Time Frame	Baseline, and final assessment point (up to Month 12)

Outcome Measure Data

Analysis Population Description

Efficacy assessment population was defined as participants who completed study and had available efficacy data at baseline and post baseline. Efficacy analysis was planned to be assessed in Alogliptin + Insulin, Alogliptin + Glinide and Alogliptin + SGLT-2 inhibitor groups and data for Alogliptin + Other were not collected as specified in protocol.

Arm/Group Title	Alogliptin + Insulin	Alogliptin + Glinide	Alogliptin + SGLT-2 Inhibitor
Arm/Group Description	Alogliptin 25 mg, tablets, orally, once daily for up to 12 months, along with insulin preparation within 3 months prior to the start of alogliptin treatment or during the alogliptin treatment period. Participants received interventions as part of routine medical care.	Alogliptin 25 mg, tablets, orally, once daily for up to 12 months, along with rapid-acting insulin secretagogue (Glinide) within 3 months prior to the start of alogliptin treatment or during the alogliptin treatment period. Participants received interventions as part of routine medical care.	Alogliptin 25 mg, tablets, orally, once daily for up to 12 months, along with SGLT-2 inhibitor within 3 months prior to the start of alogliptin treatment or during the alogliptin treatment period. Participants received interventions as part of routine medical care.
Measure Participants	87	33	21
Mean (Standard Deviation) [Milligram (mg)/deciliter (dL)]	-16.4 (65.96)	-32.0 (42.00)	-18.7 (35.86)

5. Secondary Outcome

Title	Change From Baseline in Laboratory Test Values (Fasting Insulin Level)
Description	The reported data were change from baseline in fasting insulin level.
Time Frame	Baseline, and final assessment point (up to Month 12)

Outcome Measure Data

Analysis Population Description

Efficacy assessment population was defined as participants who completed study and had available efficacy data at baseline and post baseline. Efficacy analysis was planned to be assessed in Alogliptin + Insulin, Alogliptin + Glinide and Alogliptin + SGLT-2 inhibitor groups and data for Alogliptin + Other were not collected as specified in protocol.

Arm/Group Title	Alogliptin + Insulin	Alogliptin + Glinide	Alogliptin + SGLT-2 Inhibitor
Arm/Group Description	Alogliptin 25 mg, tablets, orally, once daily for up to 12 months, along with insulin preparation within 3 months prior to the start of alogliptin treatment or during the alogliptin treatment period. Participants received interventions as part of routine medical care.	Alogliptin 25 mg, tablets, orally, once daily for up to 12 months, along with rapid-acting insulin secretagogue (Glinide) within 3 months prior to the start of alogliptin treatment or during the alogliptin treatment period. Participants received interventions as part of routine medical care.	Alogliptin 25 mg, tablets, orally, once daily for up to 12 months, along with SGLT-2 inhibitor within 3 months prior to the start of alogliptin treatment or during the alogliptin treatment period. Participants received interventions as part of routine medical care.
Measure Participants	5	10	1
Mean (Standard Deviation) [Micro Units per Milliliter (μU/mL)]	-3.08 (3.414)	2.26 (4.948)	0.40 (NA)

6. Secondary Outcome

Title	Change From Baseline in Laboratory Test Values (Homeostasis Model Assessment Ratio [HOMA-R])
Description	The reported data were change from baseline in HOMA-R. HOMA-R measures insulin resistance, calculated by fasting insulin (μU/mL) multiplied by fasting glucose (mg/dL), and divided by a constant (405). A higher score indicates higher insulin resistance.
Time Frame	Baseline, and final assessment point (up to Month 12)

Outcome Measure Data

Analysis Population Description

Efficacy assessment population was defined as participants who completed study and had available efficacy data at baseline and post baseline. Efficacy analysis was planned to be assessed in Alogliptin + Insulin, Alogliptin + Glinide and Alogliptin + SGLT-2 inhibitor groups and data for Alogliptin + Other were not collected as specified in protocol.

Arm/Group Title	Alogliptin + Insulin	Alogliptin + Glinide	Alogliptin + SGLT-2 Inhibitor
Arm/Group Description	Alogliptin 25 mg, tablets, orally, once daily for up to 12 months, along with insulin preparation within 3 months prior to the start of alogliptin treatment or during the alogliptin treatment period. Participants received interventions as part of routine medical care.	Alogliptin 25 mg, tablets, orally, once daily for up to 12 months, along with rapid-acting insulin secretagogue (Glinide) within 3 months prior to the start of alogliptin treatment or during the alogliptin treatment period. Participants received interventions as part of routine medical care.	Alogliptin 25 mg, tablets, orally, once daily for up to 12 months, along with SGLT-2 inhibitor within 3 months prior to the start of alogliptin treatment or during the alogliptin treatment period. Participants received interventions as part of routine medical care.
Measure Participants	5	10	1
Mean (Standard Deviation) [HOMA-R Score]	-2.58 (2.170)	-0.25 (2.094)	0.00 (NA)

7. Secondary Outcome

Title	Change From Baseline in Laboratory Test Values (Homeostasis Model Assessment of Beta-cell Function [HOMA-β])
Description	The reported data were change from baseline in HOMA-β. HOMA-β measures as following; HOMA-β = fasting insulin (μU/mL) ×360/{fasting glucose (mg/dL) - 63}.
Time Frame	Baseline, and final assessment point (up to Month 12)

Outcome Measure Data

Analysis Population Description

Efficacy assessment population was defined as participants who completed study and had available efficacy data at baseline and post baseline. Efficacy analysis was planned to be assessed in Alogliptin + Insulin, Alogliptin + Glinide and Alogliptin + SGLT-2 inhibitor groups and data for Alogliptin + Other were not collected as specified in protocol.

Arm/Group Title	Alogliptin + Insulin	Alogliptin + Glinide	Alogliptin + SGLT-2 Inhibitor
Arm/Group Description	Alogliptin 25 mg, tablets, orally, once daily for up to 12 months, along with insulin preparation within 3 months prior to the start of alogliptin treatment or during the alogliptin treatment period. Participants received interventions as part of routine medical care.	Alogliptin 25 mg, tablets, orally, once daily for up to 12 months, along with rapid-acting insulin secretagogue (Glinide) within 3 months prior to the start of alogliptin treatment or during the alogliptin treatment period. Participants received interventions as part of routine medical care.	Alogliptin 25 mg, tablets, orally, once daily for up to 12 months, along with SGLT-2 inhibitor within 3 months prior to the start of alogliptin treatment or during the alogliptin treatment period. Participants received interventions as part of routine medical care.
Measure Participants	5	10	1
Mean (Standard Deviation) [Percentage of beta cell function]	12.32 (17.286)	33.38 (19.851)	15.40 (NA)

Adverse Events

Time Frame	Up to Month 12
Adverse Event Reporting Description	At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Only adverse drug reactions (ADRs) were collected and reported on safety results sections here. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment.
Arm/Group Title	Alogliptin + Insulin		Alogliptin + Glinide		Alogliptin + SGLT-2 Inhibit		Alogliptin + Other
Arm/Group Description	Alogliptin 25 mg, tablets, orally, once daily for up to 12 months, along with insulin preparation within 3 months prior to the start of alogliptin treatment or during the alogliptin treatment period. Participants received interventions as part of routine medical care.		Alogliptin 25 mg, tablets, orally, once daily for up to 12 months, along with rapid-acting insulin secretagogue (Glinide) within 3 months prior to the start of alogliptin treatment or during the alogliptin treatment period. Participants received interventions as part of routine medical care.		Alogliptin 25 mg, tablets, orally, once daily for up to 12 months, along with SGLT-2 inhibitor within 3 months prior to the start of alogliptin treatment or during the alogliptin treatment period. Participants received interventions as part of routine medical care.		Alogliptin 25 mg, tablets, orally, once daily for up to 12 months, along without insulin preparations, glinide, or SGLT-2 inhibitor within 3 months prior to the start of alogliptin treatment or during the alogliptin treatment period. Participants received interventions as part of routine medical care.
All Cause Mortality
	Alogliptin + Insulin		Alogliptin + Glinide		Alogliptin + SGLT-2 Inhibit		Alogliptin + Other
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/573 (0.5%)		0/166 (0%)		0/102 (0%)		0/62 (0%)
Serious Adverse Events
	Alogliptin + Insulin		Alogliptin + Glinide		Alogliptin + SGLT-2 Inhibit		Alogliptin + Other
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/573 (0.5%)		0/166 (0%)		0/102 (0%)		0/62 (0%)
Cardiac disorders
Cardiac failure acut	1/573 (0.2%)		0/166 (0%)		0/102 (0%)		0/62 (0%)
Cardio-respiratory arrest	1/573 (0.2%)		0/166 (0%)		0/102 (0%)		0/62 (0%)
General disorders
Death	1/573 (0.2%)		0/166 (0%)		0/102 (0%)		0/62 (0%)
Other (Not Including Serious) Adverse Events
	Alogliptin + Insulin		Alogliptin + Glinide		Alogliptin + SGLT-2 Inhibit		Alogliptin + Other
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/573 (1.7%)		2/166 (1.2%)		0/102 (0%)		0/62 (0%)
Metabolism and nutrition disorders
Hypoglycaemia	7/573 (1.2%)		0/166 (0%)		0/102 (0%)		0/62 (0%)
Skin and subcutaneous tissue disorders
Rash	3/573 (0.5%)		2/166 (1.2%)		0/102 (0%)		0/62 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.