Type 2 Diabetes Mellitus
Conditions
Keywords
Diabetes, Insulin, Glargine, Metformin, Acarbose, Diet, Exercise, Lifestyle
Brief summary
The purpose of this pilot trial is to determine whether an intensive treatment with insulin glargine, metformin, acarbose and lifestyle can normalize blood glucose levels in patients with recently diagnosed type 2 diabetes mellitus when compared to standard diabetes care.
Detailed description
This is a pilot trial of 125 patients allocated to either usual care (1/3), 2 months or 4 months of intensive lifestyle and pharmacotherapy followed by cessation of all drug therapy.
Interventions
DRUGinsulin glargine
sc injection
DRUGmetformin
oral administration
DRUGacarbose
oral administration
BEHAVIORALlifestyle therapy
diet and exercise
OTHERStandard glycemic care
as informed by the current clinical practice guidelines
Sponsors
Hamilton Health Sciences Corporation
Population Health Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. men and women 30-80 years of age inclusive 2. type 2 diabetes mellitus diagnosed by a physician within 3 years prior to patient enrollment 3. anti-diabetic drug regimen (either drug or dose of drug) unchanged during 8 weeks prior to screening and randomization 4. HbA1C ≤ 8.5% on no oral hypoglycemic agents or HbA1C ≤ 7.5% on 1 agent or on half-maximal doses of 2 agents 5. body mass index ≥ 23 kg/m2 6. a negative pregnancy test and an agreement to use a reliable method of birth control for the duration of the trial in all females with childbearing potential 7. ability and willingness to perform self-monitoring of capillary blood glucose (SMBG) 8. ability and willingness to self-inject insulin 9. provision of informed consent.
Exclusion criteria
1. current use of insulin therapy 2. history of hypoglycemia unawareness, or severe hypoglycemia requiring assistance 3. renal dysfunction as evidenced by serum creatinine (Cr) ≥ 124 μmol/l 4. history of lactic acidosis or diabetic ketoacidosis 5. active liver disease or elevated alanine transferase (ALT) levels ≥ 2.5 times upper limit of normal at the time of enrollment 6. history of inflammatory bowel disease, colonic ulcers, recent or significant bowel surgery, or predisposition to bowel obstruction 7. cardiovascular disease including any of: * systolic blood pressure \>180 mmHg or diastolic blood pressure \>105 mmHg * peripheral vascular disease * left bundle branch block or third degree AV block * tachyarrhythmias or bradyarrhythmias with uncontrolled ventricular rate * stenotic valvular heart disease * cardiomyopathy * history of heart failure * history of aortic dissection * documented history of angina or coronary artery disease * history of stroke or transient ischemic attack 8. pulmonary disease with dependence on oxygen 9. history of any disease requiring intermittent or continuous systemic glucocorticoid treatment 10. history of any major illness with a life expectancy of \<3 years 11. history of injury or any other condition that significantly limits participant's ability to achieve moderate levels of physical activity 12. any history of excessive alcohol intake, acute or chronic 13. known hypersensitivity to metformin, acarbose, or insulin glargine.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Normoglycemia on Therapy | (1) 8 weeks and (2) 16 weeks | 1. Percentage of participants achieving normoglycemia on therapy in the experimental group 1 compared to the control group. 2. Percentage of participants achieving normoglycemia on therapy in the experimental group 2 compared to the control group. Normoglycemia on therapy is defined as a mean fasting capillary blood glucose \</=5.4 mmol/L and a mean 2-hour pc blood glucose \</=6.8 mmol/L on 2 seven-point glucose profiles. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Normal Fasting Plasma Glucose | 52 weeks | Normal fasting plasma glucose is defined as \<6.1 mmol/L. |
| Change in Fasting Plasma Glucose From Baseline | Baseline and 52 weeks | — |
| HbA1C | 8, 20, 28 and 52 weeks | — |
| 1) Percentage of Participants With Normal Glucose Tolerance in the Experimental Group 1 Compared to the Control Group. 2) Percentage of Participants With Normal Glucose Tolerance in the Experimental Group 2 Compared to the Control Group. | (1) 20 weeks and (2) 28 weeks | Normal glucose tolerance is defined as a fasting plasma glucose \<6.1 mmol/L and a 2-hour pc plasma glucose \<7.8 mmol/L on a 75 g oral glucose tolerance test off diabetes drugs. |
| Number of Participants With Symptomatic Hypoglycemic Episodes | 52 weeks | — |
| Number of Participants With Severe Hypoglycemic Episodes | 52 weeks | — |
| Change in Weight From Baseline | Baseline, 8, 20, 28 and 52 weeks | — |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1 (Short) insulin glargine: sc injection
metformin: oral administration
acarbose: oral administration
lifestyle therapy: diet and exercise | 28 |
| Group 2 (Long) insulin glargine: sc injection
metformin: oral administration
acarbose: oral administration
lifestyle therapy: diet and exercise | 27 |
| Standard Care Standard glycemic care: as informed by the current clinical practice guidelines | 28 |
| Total | 83 |
Baseline characteristics
| Characteristic | Group 1 (Short) | Group 2 (Long) | Standard Care | Total |
|---|---|---|---|---|
| Age, Continuous | 55.1 years STANDARD_DEVIATION 9.2 | 57.9 years STANDARD_DEVIATION 10.5 | 58.2 years STANDARD_DEVIATION 11.1 | 57.1 years STANDARD_DEVIATION 10.3 |
| Race/Ethnicity, Customized Caucasian | 25 Participants | 23 Participants | 25 Participants | 73 Participants |
| Race/Ethnicity, Customized Non-Caucasian | 3 Participants | 4 Participants | 3 Participants | 10 Participants |
| Region of Enrollment Canada | 28 participants | 27 participants | 28 participants | 83 participants |
| Sex: Female, Male Female | 14 Participants | 15 Participants | 14 Participants | 43 Participants |
| Sex: Female, Male Male | 14 Participants | 12 Participants | 14 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 28 | 0 / 27 | 0 / 28 |
| other Total, other adverse events | 3 / 28 | 1 / 27 | 3 / 28 |
| serious Total, serious adverse events | 0 / 28 | 0 / 27 | 0 / 28 |
Outcome results
Primary
Normoglycemia on Therapy
1. Percentage of participants achieving normoglycemia on therapy in the experimental group 1 compared to the control group. 2. Percentage of participants achieving normoglycemia on therapy in the experimental group 2 compared to the control group. Normoglycemia on therapy is defined as a mean fasting capillary blood glucose \</=5.4 mmol/L and a mean 2-hour pc blood glucose \</=6.8 mmol/L on 2 seven-point glucose profiles.
Time frame: (1) 8 weeks and (2) 16 weeks
Population: Primary outcome (1) is reported in Experimental Group 1 and Standard care at 8 weeks. Primary outcome (2) is reported in experimental Group 2 and Standard care at 16 weeks.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1 (Short) | Normoglycemia on Therapy | Group 1 and Standard care at 8 weeks | 14 Participants |
| Group 2 (Long) | Normoglycemia on Therapy | Group 2 and Standard care at 16 weeks | 19 Participants |
| Standard Care | Normoglycemia on Therapy | Group 1 and Standard care at 8 weeks | 1 Participants |
| Standard Care | Normoglycemia on Therapy | Group 2 and Standard care at 16 weeks | 1 Participants |
Secondary
1) Percentage of Participants With Normal Glucose Tolerance in the Experimental Group 1 Compared to the Control Group. 2) Percentage of Participants With Normal Glucose Tolerance in the Experimental Group 2 Compared to the Control Group.
Normal glucose tolerance is defined as a fasting plasma glucose \<6.1 mmol/L and a 2-hour pc plasma glucose \<7.8 mmol/L on a 75 g oral glucose tolerance test off diabetes drugs.
Time frame: (1) 20 weeks and (2) 28 weeks
Population: Outcome (1) is reported in Experimental Group 1 and Standard care at 20 weeks. Outcome (2) is reported in experimental Group 2 and Standard care at 28 weeks.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1 (Short) | 1) Percentage of Participants With Normal Glucose Tolerance in the Experimental Group 1 Compared to the Control Group. 2) Percentage of Participants With Normal Glucose Tolerance in the Experimental Group 2 Compared to the Control Group. | Group 1 and Standard care at 20 weeks | 2 Participants |
| Group 2 (Long) | 1) Percentage of Participants With Normal Glucose Tolerance in the Experimental Group 1 Compared to the Control Group. 2) Percentage of Participants With Normal Glucose Tolerance in the Experimental Group 2 Compared to the Control Group. | Group 2 and Standard care at 28 weeks | 2 Participants |
| Standard Care | 1) Percentage of Participants With Normal Glucose Tolerance in the Experimental Group 1 Compared to the Control Group. 2) Percentage of Participants With Normal Glucose Tolerance in the Experimental Group 2 Compared to the Control Group. | Group 1 and Standard care at 20 weeks | 2 Participants |
| Standard Care | 1) Percentage of Participants With Normal Glucose Tolerance in the Experimental Group 1 Compared to the Control Group. 2) Percentage of Participants With Normal Glucose Tolerance in the Experimental Group 2 Compared to the Control Group. | Group 2 and Standard care at 28 weeks | 1 Participants |
Secondary
Change in Fasting Plasma Glucose From Baseline
Time frame: Baseline and 52 weeks
Population: FPG was not available for some participants at 52 weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1 (Short) | Change in Fasting Plasma Glucose From Baseline | -0.23 mmol/L | Standard Deviation 0.96 |
| Group 2 (Long) | Change in Fasting Plasma Glucose From Baseline | -0.64 mmol/L | Standard Deviation 1.38 |
| Standard Care | Change in Fasting Plasma Glucose From Baseline | 0.05 mmol/L | Standard Deviation 1.02 |
Secondary
Change in Weight From Baseline
Time frame: Baseline, 8, 20, 28 and 52 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 (Short) | Change in Weight From Baseline | Baseline | 99.5 kg | Standard Deviation 23.3 |
| Group 1 (Short) | Change in Weight From Baseline | 28 weeks | 93.3 kg | Standard Deviation 20.6 |
| Group 1 (Short) | Change in Weight From Baseline | 20 weeks | 92.8 kg | Standard Deviation 21.1 |
| Group 1 (Short) | Change in Weight From Baseline | 52 weeks | 96.6 kg | Standard Deviation 21.7 |
| Group 1 (Short) | Change in Weight From Baseline | 8 weeks | 95.3 kg | Standard Deviation 21.8 |
| Group 2 (Long) | Change in Weight From Baseline | 52 weeks | 93.8 kg | Standard Deviation 16.4 |
| Group 2 (Long) | Change in Weight From Baseline | Baseline | 95.3 kg | Standard Deviation 15.2 |
| Group 2 (Long) | Change in Weight From Baseline | 8 weeks | 92.4 kg | Standard Deviation 15 |
| Group 2 (Long) | Change in Weight From Baseline | 20 weeks | 90.5 kg | Standard Deviation 14.8 |
| Group 2 (Long) | Change in Weight From Baseline | 28 weeks | 91.7 kg | Standard Deviation 15.2 |
| Standard Care | Change in Weight From Baseline | 8 weeks | 87.1 kg | Standard Deviation 14.1 |
| Standard Care | Change in Weight From Baseline | 52 weeks | 86.5 kg | Standard Deviation 14.6 |
| Standard Care | Change in Weight From Baseline | 28 weeks | 86.1 kg | Standard Deviation 13.5 |
| Standard Care | Change in Weight From Baseline | Baseline | 89.3 kg | Standard Deviation 14.6 |
| Standard Care | Change in Weight From Baseline | 20 weeks | 86.3 kg | Standard Deviation 13.5 |
Secondary
HbA1C
Time frame: 8, 20, 28 and 52 weeks
Population: Some participants did not provide HbA1C values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 (Short) | HbA1C | 8 weeks | 6.1 percent | Standard Deviation 0.5 |
| Group 1 (Short) | HbA1C | 20 weeks | 6.2 percent | Standard Deviation 0.4 |
| Group 1 (Short) | HbA1C | 28 weeks | 6.5 percent | Standard Deviation 0.8 |
| Group 1 (Short) | HbA1C | 52 weeks | 6.4 percent | Standard Deviation 0.8 |
| Group 2 (Long) | HbA1C | 52 weeks | 6.7 percent | Standard Deviation 0.7 |
| Group 2 (Long) | HbA1C | 8 weeks | 6.0 percent | Standard Deviation 0.4 |
| Group 2 (Long) | HbA1C | 28 weeks | 6.4 percent | Standard Deviation 0.5 |
| Group 2 (Long) | HbA1C | 20 weeks | 6.1 percent | Standard Deviation 0.3 |
| Standard Care | HbA1C | 52 weeks | 6.5 percent | Standard Deviation 0.7 |
| Standard Care | HbA1C | 20 weeks | 6.6 percent | Standard Deviation 0.7 |
| Standard Care | HbA1C | 28 weeks | 6.6 percent | Standard Deviation 0.7 |
| Standard Care | HbA1C | 8 weeks | 6.6 percent | Standard Deviation 0.7 |
Secondary
Number of Participants With Severe Hypoglycemic Episodes
Time frame: 52 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 (Short) | Number of Participants With Severe Hypoglycemic Episodes | 0 Participants |
| Group 2 (Long) | Number of Participants With Severe Hypoglycemic Episodes | 0 Participants |
| Standard Care | Number of Participants With Severe Hypoglycemic Episodes | 0 Participants |
Secondary
Number of Participants With Symptomatic Hypoglycemic Episodes
Time frame: 52 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 (Short) | Number of Participants With Symptomatic Hypoglycemic Episodes | 9 Participants |
| Group 2 (Long) | Number of Participants With Symptomatic Hypoglycemic Episodes | 10 Participants |
| Standard Care | Number of Participants With Symptomatic Hypoglycemic Episodes | 1 Participants |
Secondary
Percentage of Participants With Normal Fasting Plasma Glucose
Normal fasting plasma glucose is defined as \<6.1 mmol/L.
Time frame: 52 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 (Short) | Percentage of Participants With Normal Fasting Plasma Glucose | 5 Participants |
| Group 2 (Long) | Percentage of Participants With Normal Fasting Plasma Glucose | 5 Participants |
| Standard Care | Percentage of Participants With Normal Fasting Plasma Glucose | 3 Participants |