Remission Evaluation of Metabolic Interventions in Type 2 Diabetes (REMIT Pilot Trial)

• Sponsor: Population Health Research Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT01181674
• Collaborator: Hamilton Health Sciences Corporation (Other)
• Enrollment: 83
• Location: 1
• Arms: 3
• Duration (Months): 56
• Patients Per Site Per Month: 1.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus	Drug: insulin glargine; Drug: metformin; Drug: acarbose; Behavioral: lifestyle therapy; Drug: insulin glargine; Drug: metformin; Drug: acarbose; Behavioral: lifestyle therapy; Other: Standard glycemic care	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 83 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Remission Evaluation of Metabolic Interventions in Type 2 Diabetes (REMIT): A Randomized Controlled Pilot Trial
• Study Start Date: Jan 1, 2011
• Actual Primary Completion Date: Feb 1, 2015
• Actual Study Completion Date: Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1 (short)	Drug: insulin glargine; sc injection; Drug: metformin; oral administration; Drug: acarbose; oral administration; Behavioral: lifestyle therapy; diet and exercise
Experimental: Group 2 (long)	Drug: insulin glargine; sc injection; Drug: metformin; oral administration; Drug: acarbose; oral administration; Behavioral: lifestyle therapy; diet and exercise
Other: Standard care	Other: Standard glycemic care; as informed by the current clinical practice guidelines

Outcome Measures

Primary Outcome Measures

1. Normoglycemia on Therapy [(1) 8 weeks and (2) 16 weeks]

   Percentage of participants achieving normoglycemia on therapy in the experimental group 1 compared to the control group. 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 Outcome Measures

1. 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.

2. Percentage of Participants With Normal Fasting Plasma Glucose [52 weeks]

   Normal fasting plasma glucose is defined as <6.1 mmol/L.

3. Change in Fasting Plasma Glucose From Baseline [Baseline and 52 weeks]

4. HbA1C [8, 20, 28 and 52 weeks]

5. Change in Weight From Baseline [Baseline, 8, 20, 28 and 52 weeks]

6. Number of Participants With Symptomatic Hypoglycemic Episodes [52 weeks]

7. Number of Participants With Severe Hypoglycemic Episodes [52 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts 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

1. pulmonary disease with dependence on oxygen

2. history of any disease requiring intermittent or continuous systemic glucocorticoid treatment

3. history of any major illness with a life expectancy of <3 years

4. history of injury or any other condition that significantly limits participant's ability to achieve moderate levels of physical activity

5. any history of excessive alcohol intake, acute or chronic

6. known hypersensitivity to metformin, acarbose, or insulin glargine.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	McMaster University Medical Centre, Diabetes Care and Research Program	Hamilton	Ontario	Canada	L8N 3Z5

Sponsors and Collaborators

• Population Health Research Institute
• Hamilton Health Sciences Corporation

Investigators

• Principal Investigator: Hertzel Gerstein, MD, Population Health Research Institute
• Principal Investigator: Natalia McInnes (nee Yakubovich), MD, Population Health Research Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Dr. Hertzel Gerstein, Director, Division of Endocrinology and Metabolism, McMaster University, Population Health Research Institute
• ClinicalTrials.gov Identifier: NCT01181674
• Other Study ID Numbers: REMIT Pilot; Control # 139433, 143584; 10-346
• First Posted: Aug 13, 2010
• Last Update Posted: May 21, 2020
• Last Verified: May 1, 2020

• Keywords provided by Dr. Hertzel Gerstein, Director, Division of Endocrinology and Metabolism, McMaster University, Population Health Research Institute: Diabetes; Insulin; Glargine; Metformin; Acarbose; Diet; Exercise; Lifestyle
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Insulin; Insulin, Globin Zinc; Metformin; Insulin Glargine; Acarbose

Study Results

Participant Flow

Arm/Group Title	Group 1 (Short)	Group 2 (Long)	Standard Care
Arm/Group Description	insulin glargine: sc injection metformin: oral administration acarbose: oral administration lifestyle therapy: diet and exercise	insulin glargine: sc injection metformin: oral administration acarbose: oral administration lifestyle therapy: diet and exercise	Standard glycemic care: as informed by the current clinical practice guidelines
Period Title: Overall Study
STARTED	28	27	28
COMPLETED	28	27	26
NOT COMPLETED	0	0	2

Baseline Characteristics

Arm/Group Title	Group 1 (Short)	Group 2 (Long)	Standard Care	Total
Arm/Group Description	insulin glargine: sc injection metformin: oral administration acarbose: oral administration lifestyle therapy: diet and exercise	insulin glargine: sc injection metformin: oral administration acarbose: oral administration lifestyle therapy: diet and exercise	Standard glycemic care: as informed by the current clinical practice guidelines	Total of all reporting groups
Overall Participants	28	27	28	83
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.1 (9.2)	57.9 (10.5)	58.2 (11.1)	57.1 (10.3)
Sex: Female, Male (Count of Participants)
Female	14 50%	15 55.6%	14 50%	43 51.8%
Male	14 50%	12 44.4%	14 50%	40 48.2%
Race/Ethnicity, Customized (Count of Participants)
Caucasian	25 89.3%	23 85.2%	25 89.3%	73 88%
Non-Caucasian	3 10.7%	4 14.8%	3 10.7%	10 12%
Region of Enrollment (participants) [Number]
Canada	28 100%	27 100%	28 100%	83 100%

Outcome Measures

1. Primary Outcome

Title	Normoglycemia on Therapy
Description	Percentage of participants achieving normoglycemia on therapy in the experimental group 1 compared to the control group. 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

Outcome Measure Data

Analysis Population Description

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/Group Title	Group 1 (Short)	Group 2 (Long)	Standard Care
Arm/Group Description	insulin glargine: sc injection metformin: oral administration acarbose: oral administration lifestyle therapy: diet and exercise	insulin glargine: sc injection metformin: oral administration acarbose: oral administration lifestyle therapy: diet and exercise	Standard glycemic care: as informed by the current clinical practice guidelines
Measure Participants	28	27	28
Group 1 and Standard care at 8 weeks	14 50%	1 3.7%
Group 2 and Standard care at 16 weeks	19 67.9%	1 3.7%

2. Secondary Outcome

Title	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.
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Group 1 (Short)	Group 2 (Long)	Standard Care
Arm/Group Description	insulin glargine: sc injection metformin: oral administration acarbose: oral administration lifestyle therapy: diet and exercise	insulin glargine: sc injection metformin: oral administration acarbose: oral administration lifestyle therapy: diet and exercise	Standard glycemic care: as informed by the current clinical practice guidelines
Measure Participants	28	27	28
Group 1 and Standard care at 20 weeks	2 7.1%	2 7.4%
Group 2 and Standard care at 28 weeks	2 7.1%	1 3.7%

3. Secondary Outcome

Title	Percentage of Participants With Normal Fasting Plasma Glucose
Description	Normal fasting plasma glucose is defined as <6.1 mmol/L.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1 (Short)	Group 2 (Long)	Standard Care
Arm/Group Description	insulin glargine: sc injection metformin: oral administration acarbose: oral administration lifestyle therapy: diet and exercise	insulin glargine: sc injection metformin: oral administration acarbose: oral administration lifestyle therapy: diet and exercise	Standard glycemic care: as informed by the current clinical practice guidelines
Measure Participants	23	23	25
Count of Participants [Participants]	5 17.9%	5 18.5%	3 10.7%

4. Secondary Outcome

Title	Change in Fasting Plasma Glucose From Baseline
Time Frame	Baseline and 52 weeks

Outcome Measure Data

Analysis Population Description

FPG was not available for some participants at 52 weeks.

Arm/Group Title	Group 1 (Short)	Group 2 (Long)	Standard Care
Arm/Group Description	insulin glargine: sc injection metformin: oral administration acarbose: oral administration lifestyle therapy: diet and exercise	insulin glargine: sc injection metformin: oral administration acarbose: oral administration lifestyle therapy: diet and exercise	Standard glycemic care: as informed by the current clinical practice guidelines
Measure Participants	23	23	25
Mean (Standard Deviation) [mmol/L]	-0.23 (0.96)	-0.64 (1.38)	0.05 (1.02)

5. Secondary Outcome

Title	HbA1C
Time Frame	8, 20, 28 and 52 weeks

Outcome Measure Data

Analysis Population Description

Some participants did not provide HbA1C values.

Arm/Group Title	Group 1 (Short)	Group 2 (Long)	Standard Care
Arm/Group Description	insulin glargine: sc injection metformin: oral administration acarbose: oral administration lifestyle therapy: diet and exercise	insulin glargine: sc injection metformin: oral administration acarbose: oral administration lifestyle therapy: diet and exercise	Standard glycemic care: as informed by the current clinical practice guidelines
Measure Participants	24	23	25
8 weeks	6.1 (0.5)	6.0 (0.4)	6.6 (0.7)
20 weeks	6.2 (0.4)	6.1 (0.3)	6.6 (0.7)
28 weeks	6.5 (0.8)	6.4 (0.5)	6.6 (0.7)
52 weeks	6.4 (0.8)	6.7 (0.7)	6.5 (0.7)

6. Secondary Outcome

Title	Change in Weight From Baseline
Time Frame	Baseline, 8, 20, 28 and 52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1 (Short)	Group 2 (Long)	Standard Care
Arm/Group Description	insulin glargine: sc injection metformin: oral administration acarbose: oral administration lifestyle therapy: diet and exercise	insulin glargine: sc injection metformin: oral administration acarbose: oral administration lifestyle therapy: diet and exercise	Standard glycemic care: as informed by the current clinical practice guidelines
Measure Participants	23	22	25
Baseline	99.5 (23.3)	95.3 (15.2)	89.3 (14.6)
8 weeks	95.3 (21.8)	92.4 (15.0)	87.1 (14.1)
20 weeks	92.8 (21.1)	90.5 (14.8)	86.3 (13.5)
28 weeks	93.3 (20.6)	91.7 (15.2)	86.1 (13.5)
52 weeks	96.6 (21.7)	93.8 (16.4)	86.5 (14.6)

7. Secondary Outcome

Title	Number of Participants With Symptomatic Hypoglycemic Episodes
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1 (Short)	Group 2 (Long)	Standard Care
Arm/Group Description	insulin glargine: sc injection metformin: oral administration acarbose: oral administration lifestyle therapy: diet and exercise	insulin glargine: sc injection metformin: oral administration acarbose: oral administration lifestyle therapy: diet and exercise	Standard glycemic care: as informed by the current clinical practice guidelines
Measure Participants	28	27	28
Count of Participants [Participants]	9 32.1%	10 37%	1 3.6%

8. Secondary Outcome

Title	Number of Participants With Severe Hypoglycemic Episodes
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1 (Short)	Group 2 (Long)	Standard Care
Arm/Group Description	insulin glargine: sc injection metformin: oral administration acarbose: oral administration lifestyle therapy: diet and exercise	insulin glargine: sc injection metformin: oral administration acarbose: oral administration lifestyle therapy: diet and exercise	Standard glycemic care: as informed by the current clinical practice guidelines
Measure Participants	28	27	28
Count of Participants [Participants]	0 0%	0 0%	0 0%

Adverse Events

Time Frame	52 weeks
Arm/Group Title	Group 1 (Short)		Group 2 (Long)		Standard Care
Arm/Group Description	insulin glargine: sc injection metformin: oral administration acarbose: oral administration lifestyle therapy: diet and exercise		insulin glargine: sc injection metformin: oral administration acarbose: oral administration lifestyle therapy: diet and exercise		Standard glycemic care: as informed by the current clinical practice guidelines
All Cause Mortality
	Group 1 (Short)		Group 2 (Long)		Standard Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/28 (0%)		0/27 (0%)		0/28 (0%)
Serious Adverse Events
	Group 1 (Short)		Group 2 (Long)		Standard Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/28 (0%)		0/27 (0%)		0/28 (0%)
Other (Not Including Serious) Adverse Events
	Group 1 (Short)		Group 2 (Long)		Standard Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/28 (10.7%)		1/27 (3.7%)		3/28 (10.7%)
General disorders
Chest pain	2/28 (7.1%)	2	1/27 (3.7%)	1	0/28 (0%)	0
Injury, poisoning and procedural complications
Fracture	1/28 (3.6%)	1	1/27 (3.7%)	1	3/28 (10.7%)	3
Motor vehicle accident	0/28 (0%)	0	0/27 (0%)	0	2/28 (7.1%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.