Diabetes Mellitus, Type 2
Conditions
Keywords
Drug Therapy
Brief summary
The purpose of this study is to observe alogliptin and alogliptin fixed-dose combinations (FDCs) utilization patterns, as well as clinical response to treatment with alogliptin or alogliptin FDCs, in standard clinical practice.
Detailed description
The drug being studied in this study is called alogliptin and alogliptin FDCs. Alogliptin and alogliptin FDCs is being researched to treat people who have diabetes mellitus type 2. This study will look at the glycosylated hemoglobin (HbA1c) level dynamics in participants with diabetes mellitus type 2. The study enrolled 593 patients. Alogliptin and alogliptin FDCs will be prescribed by the physician as part of participants' T2DM treatment program (independent of participation in this study). This multi-center study will be conducted in China. The overall duration of study for observation will be approximately 6 months, or up to loss to follow-up or death, whichever occurs first. Participants will make multiple visits to the clinic as per regular doctor's appointments.
Interventions
DRUGAlogliptin
Alogliptin tablets
DRUGAlogliptin FDC With Pioglitazone
Alogliptin FDC with pioglitazone tablets
DRUGAlogliptin FDC With Metformin
Alogliptin FDC with metformin tablets
Sponsors
Takeda
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Has a diagnosis of T2DM. 2. Has made the decision, along with his/her treating physician, to begin treatment with alogliptin or alogliptin fixed-dose combinations (FDCs). 3. Has an glycated hemoglobin (HbA1c) value recorded at most 3 months before initiation of treatment with alogliptin or alogliptin FDCs. 4. Alogliptin or alogliptin FDCs is prescribed according to the approved label for China and Hong Kong.
Exclusion criteria
1. Has gestational diabetes or type 1 diabetes mellitus. 2. Has used Dipeptidyl peptidase-4 inhibitors (DPP-IV inhibitors) or Glucagon like peptide-1 agonists (aGLP-1) within the 3 months prior to the start of alogliptin or alogliptin FDCs treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) Level at Month 6 | Baseline and Month 6 | 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 Month 6 relative to baseline. Glycosylated hemoglobin (HbA1c) as a diagnostic criteria of diabetes mellitus is ≥6.5%. A negative change from Baseline indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Decrease in HbA1c Level by <7.0% | Baseline and Month 6 | Percentage of participants with a decrease of \<7.0% from baseline in HbA1c were reported. |
| Percentage of Participants With a Decrease in HbA1c Level by >0.3% and No Tolerability Findings | Baseline and Month 6 | Percentage of participants with a decrease of \>0.3% from baseline in HbA1c along with no tolerability findings were reported. Tolerability findings included hypoglycemic event, or weight gain ≥5%. |
| Change From Baseline in Fasting Plasma Glucose (FPG) Level Over Time | Baseline and Months 3 and 6 | The change between the fasting plasma glucose value collected at Months 3 and 6 relative to baseline. A negative change from Baseline indicates improvement. |
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) Level at Month 6 in Subgroups of Participants With Different Clinical Characteristics | Baseline and Month 6 | 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 Month 6 relative to baseline. Glycosylated hemoglobin (HbA1c) as a diagnostic criteria of diabetes mellitus is ≥6.5%. Subgroups included participants with different baseline clinical characteristics with predictors such as prior therapy of diabetes mellitus, sex, age group, cardiovascular risk group, therapy type (monotherapy or combined therapy), baseline body mass index (BMI) and initial glycemic control. A negative change from Baseline indicates improvement. |
| Number of Participants With Adverse Drug Reactions (ADRs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) | Baseline up to Month 6 | An ADR is defined as any response to a medicinal product that is noxious and unintended and that occurs at doses normally used in humans for the prophylaxis, diagnosis, or therapy of diseases or for the restoration, correction, or modification of physiological function. An SAE is defined as any untoward medical occurrence or effect that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically important due to other reasons than the above mentioned criteria. Adverse events such as pancreatitis, hepatic disorders, and hypersensitivity reactions (including angioedema, anaphylaxis, and Stevens-Johnson syndrome) were considered as AESI. |
| Percentage of Participants Who Remain on Treatment With Alogliptin or Alogliptin FDCs | Months 3 and 6 | — |
| Time to Alogliptin or Alogliptin FDCs Dose Escalation or Dose Reduction | Months 3 and 6 | — |
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) Level Over Time | Baseline and Months 3 and 6 | 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 Months 3 and 6 relative to baseline. A negative change from Baseline indicates improvement. |
Countries
China, Hong Kong
Participant flow
Recruitment details
Participants took part in the study at 16 investigative sites in China from 22 Dec 2016 to 26 Jan 2018.
Pre-assignment details
Participants with a diagnosis of Type 2 Diabetes Mellitus (T2DM) prescribed alogliptin or alogliptin Fixed Dose Combinations (FDCs) with either metformin or pioglitazone were enrolled in this observational study.
Participants by arm
| Arm | Count |
|---|---|
| Alogliptin or Alogliptin Fixed Dose Combinations (FDCs) Participants with type 2 diabetes mellitus (T2DM) who received alogliptin or alogliptin FDCs, orally, prescribed by the physician as part of participants' T2DM treatment program (independent of participation in this study) were observed for approximately 6 months, or up to loss to follow-up or death, whichever occurred first. | 509 |
| Total | 509 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event/Adverse Drug Reaction | 1 |
| Overall Study | Lost For Observation During Study | 3 |
| Overall Study | Patient/Investigator's Decision to Stop | 403 |
| Overall Study | Reason Not Specified | 13 |
Baseline characteristics
| Characteristic | Alogliptin or Alogliptin Fixed Dose Combinations (FDCs) |
|---|---|
| Age, Continuous | 55.3 years STANDARD_DEVIATION 12.65 |
| Age, Customized >=45 to <65 years | 309 Participants |
| Age, Customized <45 years | 92 Participants |
| Age, Customized >=65 years | 108 Participants |
| Body Mass Index (BMI) | 25.86 kg/m^2 STANDARD_DEVIATION 3.5 |
| Body Mass Index, Customized <25 kg/m^2 | 193 Participants |
| Body Mass Index, Customized 25 to <30 kg/m^2 | 256 Participants |
| Body Mass Index, Customized >=30 kg/m^2 | 51 Participants |
| Body Mass Index, Customized Missing | 9 Participants |
| Glycosylated hemoglobin (HbA1c) Level | 8.690 percentage of glycosylated hemoglobin STANDARD_DEVIATION 1.8807 |
| Height | 167.37 cm STANDARD_DEVIATION 8.089 |
| Race/Ethnicity, Customized Asian | 508 Participants |
| Race/Ethnicity, Customized Han Nationality | 504 Participants |
| Race/Ethnicity, Customized Other | 5 Participants |
| Race/Ethnicity, Customized White | 1 Participants |
| Region of Enrollment China | 509 Participants |
| Sex: Female, Male Female | 207 Participants |
| Sex: Female, Male Male | 302 Participants |
| Weight | 72.66 kg STANDARD_DEVIATION 12.208 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 509 |
| other Total, other adverse events | 55 / 509 |
| serious Total, serious adverse events | 0 / 509 |
Outcome results
Primary
Change From Baseline in Glycosylated Hemoglobin (HbA1c) Level at Month 6
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 Month 6 relative to baseline. Glycosylated hemoglobin (HbA1c) as a diagnostic criteria of diabetes mellitus is ≥6.5%. A negative change from Baseline indicates improvement.
Time frame: Baseline and Month 6
Population: All participants dosed included participants with complete demographic information and eligible for the study and dosed at least once. Overall number of participants analyzed is the number of participants with evaluable data at the given time-point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alogliptin or Alogliptin Fixed Dose Combinations (FDCs) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) Level at Month 6 | -1.092 percentage of glycosylated hemoglobin | Standard Deviation 1.6803 |
Comparison: Statistical analysis for data at Baseline compared to the data at Month 6p-value: <0.00195% CI: [-1.44, -1.05]Regression, Linear
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) Level Over Time
The change between the fasting plasma glucose value collected at Months 3 and 6 relative to baseline. A negative change from Baseline indicates improvement.
Time frame: Baseline and Months 3 and 6
Population: All participants dosed included participants with complete demographic information and eligible for the study and dosed at least once. Number analyzed is the number of participants with evaluable data at the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin or Alogliptin Fixed Dose Combinations (FDCs) | Change From Baseline in Fasting Plasma Glucose (FPG) Level Over Time | Month 3 | -1.058 mg/dL | Standard Deviation 3.0026 |
| Alogliptin or Alogliptin Fixed Dose Combinations (FDCs) | Change From Baseline in Fasting Plasma Glucose (FPG) Level Over Time | Month 6 | -0.714 mg/dL | Standard Deviation 2.9802 |
Comparison: Statistical analysis for data at Baseline compared to the data at Month 395% CI: [-1.29, -0.62]
Comparison: Statistical analysis for data at Baseline compared to the data at Month 695% CI: [-1.36, -0.39]
Secondary
Change From Baseline in Glycosylated Hemoglobin (HbA1c) Level at Month 6 in Subgroups of Participants With Different Clinical Characteristics
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 Month 6 relative to baseline. Glycosylated hemoglobin (HbA1c) as a diagnostic criteria of diabetes mellitus is ≥6.5%. Subgroups included participants with different baseline clinical characteristics with predictors such as prior therapy of diabetes mellitus, sex, age group, cardiovascular risk group, therapy type (monotherapy or combined therapy), baseline body mass index (BMI) and initial glycemic control. A negative change from Baseline indicates improvement.
Time frame: Baseline and Month 6
Population: All participants dosed included participants with complete demographic information and eligible for the study and dosed at least once. Overall number of participants analyzed is the number of participants with evaluable data at the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin or Alogliptin Fixed Dose Combinations (FDCs) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) Level at Month 6 in Subgroups of Participants With Different Clinical Characteristics | Prior Therapy of Diabetes Mellitus, Ever Used | -1.154 percentage of glycosylated hemoglobin | Standard Deviation 1.7555 |
| Alogliptin or Alogliptin Fixed Dose Combinations (FDCs) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) Level at Month 6 in Subgroups of Participants With Different Clinical Characteristics | Prior Therapy of Diabetes Mellitus, Never Used | -0.882 percentage of glycosylated hemoglobin | Standard Deviation 1.4015 |
| Alogliptin or Alogliptin Fixed Dose Combinations (FDCs) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) Level at Month 6 in Subgroups of Participants With Different Clinical Characteristics | Sex, Male | -1.055 percentage of glycosylated hemoglobin | Standard Deviation 1.5898 |
| Alogliptin or Alogliptin Fixed Dose Combinations (FDCs) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) Level at Month 6 in Subgroups of Participants With Different Clinical Characteristics | Sex, Female | -1.150 percentage of glycosylated hemoglobin | Standard Deviation 1.8292 |
| Alogliptin or Alogliptin Fixed Dose Combinations (FDCs) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) Level at Month 6 in Subgroups of Participants With Different Clinical Characteristics | Age, <45 years | -1.658 percentage of glycosylated hemoglobin | Standard Deviation 1.8206 |
| Alogliptin or Alogliptin Fixed Dose Combinations (FDCs) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) Level at Month 6 in Subgroups of Participants With Different Clinical Characteristics | Age, >=45 to <65 years | -1.370 percentage of glycosylated hemoglobin | Standard Deviation 1.7121 |
| Alogliptin or Alogliptin Fixed Dose Combinations (FDCs) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) Level at Month 6 in Subgroups of Participants With Different Clinical Characteristics | Age,>=65 years | -0.203 percentage of glycosylated hemoglobin | Standard Deviation 1.1423 |
| Alogliptin or Alogliptin Fixed Dose Combinations (FDCs) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) Level at Month 6 in Subgroups of Participants With Different Clinical Characteristics | Cardiovascular Risk Group, Yes | -1.100 percentage of glycosylated hemoglobin | Standard Deviation 2.4973 |
| Alogliptin or Alogliptin Fixed Dose Combinations (FDCs) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) Level at Month 6 in Subgroups of Participants With Different Clinical Characteristics | Cardiovascular Risk Group, No | -1.092 percentage of glycosylated hemoglobin | Standard Deviation 1.64 |
| Alogliptin or Alogliptin Fixed Dose Combinations (FDCs) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) Level at Month 6 in Subgroups of Participants With Different Clinical Characteristics | Therapy Type, Monotherapy | -1.032 percentage of glycosylated hemoglobin | Standard Deviation 1.5122 |
| Alogliptin or Alogliptin Fixed Dose Combinations (FDCs) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) Level at Month 6 in Subgroups of Participants With Different Clinical Characteristics | Therapy Type, Combined Therapy | -1.106 percentage of glycosylated hemoglobin | Standard Deviation 1.7222 |
| Alogliptin or Alogliptin Fixed Dose Combinations (FDCs) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) Level at Month 6 in Subgroups of Participants With Different Clinical Characteristics | Baseline BMI, <25 kg/m^2 | -1.101 percentage of glycosylated hemoglobin | Standard Deviation 1.7339 |
| Alogliptin or Alogliptin Fixed Dose Combinations (FDCs) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) Level at Month 6 in Subgroups of Participants With Different Clinical Characteristics | Baseline BMI, 25 to <30 kg/m^2 | -1.037 percentage of glycosylated hemoglobin | Standard Deviation 1.6151 |
| Alogliptin or Alogliptin Fixed Dose Combinations (FDCs) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) Level at Month 6 in Subgroups of Participants With Different Clinical Characteristics | Baseline BMI, >=30 kg/m^2 | -1.342 percentage of glycosylated hemoglobin | Standard Deviation 1.853 |
| Alogliptin or Alogliptin Fixed Dose Combinations (FDCs) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) Level at Month 6 in Subgroups of Participants With Different Clinical Characteristics | Initial Glycemic Control, <7% | -0.046 percentage of glycosylated hemoglobin | Standard Deviation 0.7345 |
| Alogliptin or Alogliptin Fixed Dose Combinations (FDCs) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) Level at Month 6 in Subgroups of Participants With Different Clinical Characteristics | Initial Glycemic Control, >=7% | -1.525 percentage of glycosylated hemoglobin | Standard Deviation 1.7713 |
Comparison: Statistical analysis for subgroup: Prior therapy of diabetes mellitus, Ever used or Never usedp-value: 0.423Regression, Linear
Comparison: Statistical analysis for subgroup: Sex, Male or Femalep-value: 0.747Regression, Linear
Comparison: Statistical analysis for subgroup: Age, \<45 or \>=45 to \<65 years or \>=65 yearsp-value: <0.001Regression, Linear
Comparison: Statistical analysis for subgroup: Cardiovascular risk group, Yes or Nop-value: 0.99Regression, Linear
Comparison: Statistical analysis for subgroup: Therapy type, Monotherapy or Combined therapyp-value: 0.841Regression, Linear
Comparison: Statistical analysis for subgroup: Baseline BMI, \<25 or 25 to \<30 or \>=30 kg/m\^2p-value: 0.847Regression, Linear
Comparison: Statistical analysis for subgroup: Initial glycemic control, \<7% or \>=7%p-value: <0.001Regression, Linear
Secondary
Change From Baseline in Glycosylated Hemoglobin (HbA1c) Level Over Time
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 Months 3 and 6 relative to baseline. A negative change from Baseline indicates improvement.
Time frame: Baseline and Months 3 and 6
Population: All participants dosed included participants with complete demographic information and eligible for the study and dosed at least once. Number analyzed is the number of participants with evaluable data at the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin or Alogliptin Fixed Dose Combinations (FDCs) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) Level Over Time | Month 3 | -1.022 percentage of glycosylated hemoglobin | Standard Deviation 2.3669 |
| Alogliptin or Alogliptin Fixed Dose Combinations (FDCs) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) Level Over Time | Month 6 | -1.092 percentage of glycosylated hemoglobin | Standard Deviation 1.6803 |
Comparison: Statistical analysis for data at Baseline compared to the data at Month 395% CI: [-1.18, -0.72]
Comparison: Statistical analysis for data at Baseline compared to the data at Month 695% CI: [-1.44, -1.05]
Secondary
Number of Participants With Adverse Drug Reactions (ADRs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)
An ADR is defined as any response to a medicinal product that is noxious and unintended and that occurs at doses normally used in humans for the prophylaxis, diagnosis, or therapy of diseases or for the restoration, correction, or modification of physiological function. An SAE is defined as any untoward medical occurrence or effect that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically important due to other reasons than the above mentioned criteria. Adverse events such as pancreatitis, hepatic disorders, and hypersensitivity reactions (including angioedema, anaphylaxis, and Stevens-Johnson syndrome) were considered as AESI.
Time frame: Baseline up to Month 6
Population: All participants dosed included participants with complete demographic information and eligible for the study and dosed at least once.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Alogliptin or Alogliptin Fixed Dose Combinations (FDCs) | Number of Participants With Adverse Drug Reactions (ADRs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) | Adverse Drug Reaction (ADR) | 1 Participants |
| Alogliptin or Alogliptin Fixed Dose Combinations (FDCs) | Number of Participants With Adverse Drug Reactions (ADRs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) | Serious Adverse Event (SAE) | 0 Participants |
| Alogliptin or Alogliptin Fixed Dose Combinations (FDCs) | Number of Participants With Adverse Drug Reactions (ADRs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) | Adverse Event of Special Interest (AESI) | 0 Participants |
Secondary
Percentage of Participants Who Remain on Treatment With Alogliptin or Alogliptin FDCs
Time frame: Months 3 and 6
Population: All participants dosed included participants with complete demographic information and eligible for the study and dosed at least once. Number analyzed is the number of participants with evaluable data at the given time-point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alogliptin or Alogliptin Fixed Dose Combinations (FDCs) | Percentage of Participants Who Remain on Treatment With Alogliptin or Alogliptin FDCs | Month 3 | 100 percentage of participants |
| Alogliptin or Alogliptin Fixed Dose Combinations (FDCs) | Percentage of Participants Who Remain on Treatment With Alogliptin or Alogliptin FDCs | Month 6 | 100 percentage of participants |
Secondary
Percentage of Participants With a Decrease in HbA1c Level by >0.3% and No Tolerability Findings
Percentage of participants with a decrease of \>0.3% from baseline in HbA1c along with no tolerability findings were reported. Tolerability findings included hypoglycemic event, or weight gain ≥5%.
Time frame: Baseline and Month 6
Population: All participants dosed included participants with complete demographic information and eligible for the study and dosed at least once. Overall number of participants analyzed is the number of participants with evaluable data at the given time-point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alogliptin or Alogliptin Fixed Dose Combinations (FDCs) | Percentage of Participants With a Decrease in HbA1c Level by >0.3% and No Tolerability Findings | 64.3 percentage of participants |
Secondary
Percentage of Participants With a Decrease in HbA1c Level by <7.0%
Percentage of participants with a decrease of \<7.0% from baseline in HbA1c were reported.
Time frame: Baseline and Month 6
Population: All participants dosed included participants with complete demographic information and eligible for the study and dosed at least once. Overall number of participants analyzed is the number of participants with evaluable data at the given time-point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alogliptin or Alogliptin Fixed Dose Combinations (FDCs) | Percentage of Participants With a Decrease in HbA1c Level by <7.0% | 51.0 percentage of participants |
Secondary
Time to Alogliptin or Alogliptin FDCs Dose Escalation or Dose Reduction
Time frame: Months 3 and 6
Population: No participant was experienced the dose adjustment (dose escalation or dose reduction).