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| Name | Class |
|---|---|
| AstraZeneca | INDUSTRY |
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The purpose of the study is to determine whether in patients with early type 2 diabetes, a short-term intensive metabolic intervention comprising Forxiga, metformin, basal insulin glargine and lifestyle approaches will be superior to standard diabetes therapy in achieving sustained diabetes remission.
This is a multicentre, open-label, randomized controlled trial in 152 patients with recently-diagnosed T2DM. Participants will be randomized to 2 treatment groups: (a) a 12-week course of treatment with Forxiga, metformin, insulin glargine and lifestyle therapy, and (b) standard diabetes therapy, and followed for a total of 64 weeks (1 year and 3 months). In all participants with HbA1C<7.3% at the 12 week visit, glucose-lowering medications will be discontinued and participants will be encouraged to continue with lifestyle modifications and regular glucose monitoring. Participants with HbA1C ≥ 7.3% at this visit or who experience hyperglycemia relapse after stopping drugs will receive standard glycemic management as informed by the current Canadian Diabetes Association clinical practice guidelines.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intervention | Experimental | Drug: insulin glargine - sc injection; Drug: metformin, oral administration; Drug: forxiga, oral administration; Behavioral: lifestyle therapy, diet and exercise |
|
| Standard Care | No Intervention | Standard glycemic care as informed by the current clinical practice guidelines |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| insulin glargine | Drug | Dose is titrated to achieve fasting normoglycemia |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Achieving Drug-free Diabetes Remission in the Experimental Group Compared to the Control Group | Drug-free diabetes remission is defined as HbA1C < 6.5 % off glucose-lowering agents for at least 12 weeks. | 24 weeks after randomization |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Achieving Drug-free Diabetes Remission | Drug-free diabetes remission is defined as HbA1C < 6.5 % off glucose-lowering agents for at least 12 weeks. | 64 weeks after randomization |
| Number of Participants Achieving Drug-free HbA1C < 6.0% |
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Inclusion Criteria:
Exclusion Criteria:
current use of insulin therapy;
history of hypoglycemia unawareness, or severe hypoglycemia requiring assistance;
history of end-stage renal disease or renal dysfunction as evidenced by eGFR<60 mL/min/1.73 m2 by MDRD formula;
history of lactic acidosis or diabetic ketoacidosis;
active liver disease or elevated alanine transferase (ALT) levels ≥ 2.5 times upper limit of normal at the time of enrollment;
history of bladder cancer or undiagnosed hematuria;
history of breast cancer;
history of polycythemia;
evidence of volume depletion or hypotension (systolic blood pressure < 90 mmHg);
systolic blood pressure > 180 mmHg or diastolic blood pressure > 105 mmHg;
diagnosed cardiovascular disease (unless cleared for a moderate intensity exercise program by a specialist) including:
dependence on oxygen;
history of any disease requiring frequent intermittent or continuous systemic glucocorticoid treatment;
history of bariatric surgery, or planned bariatric surgery in the next 1.5 years;
history of any major illness with a life expectancy of < 3 years;
history of injury or any other condition that significantly limits participant's ability to achieve moderate levels of physical activity;
any history of excessive alcohol intake, acute or chronic;
currently pregnant, or breastfeeding, or not using a reliable method of birth control for the duration of the trial in all females with childbearing potential; reliable methods of birth control include oral contraceptive (birth control pill), hormonal injection, implant, patch, or vaginal ring, intrauterine device, barrier method (condom and spermicide), tubal ligation, partner vasectomy or abstinence;
known hypersensitivity to metformin, Forxiga, or insulin glargine.
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| Name | Affiliation | Role |
|---|---|---|
| Natalia McInnes, MD | McMaster University | Principal Investigator |
| Hertzel C Gerstein, MD | Hamilton Health Sciences Corporation | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Calgary | Calgary | Alberta | T2T 5C7 | Canada | ||
| Health Science Centre |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32403130 | Derived | McInnes N, Hall S, Sultan F, Aronson R, Hramiak I, Harris S, Sigal RJ, Woo V, Liu YY, Gerstein HC. Remission of Type 2 Diabetes Following a Short-term Intervention With Insulin Glargine, Metformin, and Dapagliflozin. J Clin Endocrinol Metab. 2020 Aug 1;105(8):dgaa248. doi: 10.1210/clinem/dgaa248. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Intervention | Drug: insulin glargine - sc injection; Drug: metformin, oral administration; Drug: forxiga, oral administration; Behavioral: lifestyle therapy, diet and exercise insulin glargine: Dose is titrated to achieve fasting normoglycemia metformin: Dose is titrated to 1 g bid or maximal tolerated dose Forxiga: Dose is titrated to 10 mg po daily or maximal tolerated dose Lifestyle therapy: Lifestyle intervention includes individualized dietary and exercise advice and frequent visits for goal reinforcement, behavior modification and problem-solving |
| FG001 | Standard Care | Standard glycemic care as informed by the current clinical practice guidelines |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Intervention | Drug: insulin glargine - sc injection; Drug: metformin, oral administration; Drug: forxiga, oral administration; Behavioral: lifestyle therapy, diet and exercise insulin glargine: Dose is titrated to achieve fasting normoglycemia metformin: Dose is titrated to 1 g bid or maximal tolerated dose Forxiga: Dose is titrated to 10 mg po daily or maximal tolerated dose Lifestyle therapy: Lifestyle intervention includes individualized dietary and exercise advice and frequent visits for goal reinforcement, behavior modification and problem-solving |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Number of Participants Achieving Drug-free Diabetes Remission in the Experimental Group Compared to the Control Group | Drug-free diabetes remission is defined as HbA1C < 6.5 % off glucose-lowering agents for at least 12 weeks. | Posted | Count of Participants | Participants | 24 weeks after randomization |
|
64 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Intervention | Drug: insulin glargine - sc injection; Drug: metformin, oral administration; Drug: forxiga, oral administration; Behavioral: lifestyle therapy, diet and exercise insulin glargine: Dose is titrated to achieve fasting normoglycemia metformin: Dose is titrated to 1 g bid or maximal tolerated dose Forxiga: Dose is titrated to 10 mg po daily or maximal tolerated dose Lifestyle therapy: Lifestyle intervention includes individualized dietary and exercise advice and frequent visits for goal reinforcement, behavior modification and problem-solving |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cholecystitis | Hepatobiliary disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Genitourinary infection | Infections and infestations | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Natalia McInnes | McMaster University | 905-521-2100 | natalia.mcinnes@mcmaster.ca |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 15, 2015 | Aug 12, 2020 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| D003920 | Diabetes Mellitus |
| D007333 | Insulin Resistance |
| D009043 | Motor Activity |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| D000069036 | Insulin Glargine |
| D008687 | Metformin |
| C529054 | dapagliflozin |
| D004032 | Diet |
| D015444 | Exercise |
| ID | Term |
|---|---|
| D049528 | Insulin, Long-Acting |
| D061385 | Insulins |
| D010187 | Pancreatic Hormones |
| D036361 | Peptide Hormones |
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| metformin | Drug | Dose is titrated to 1 g bid or maximal tolerated dose |
|
| Forxiga | Drug | Dose is titrated to 10 mg po daily or maximal tolerated dose |
|
|
| Lifestyle therapy | Behavioral | Lifestyle intervention includes individualized dietary and exercise advice and frequent visits for goal reinforcement, behavior modification and problem-solving |
|
|
Drug-free complete diabetes remission is defined as HbA1C < 6.0 % off glucose-lowering agents for at least 12 weeks. |
| 24 weeks after randomization |
| Number of Participants Achieving Diabetes Relapse Without Overt Hyperglycemia Off Diabetes Drugs | Diabetes relapse without overt hyperglycemia is defined as HbA1C 6.5-6.9% off glucose-lowering agents for at least 12 weeks. | 24 weeks |
| Glycated Hemoglobin (HbA1C) | Expressed in Diabetes Control and Complications Trial (DCCT) units | 12 weeks after randomization |
| Number of Participants With Non-severe Symptomatic Hypoglycemic Episodes | Symptomatic hypoglycemic episode is defined as an event with clinical symptoms consistent with hypoglycemia. | During 64 weeks of follow-up |
| Percentage of Weight Loss From Baseline | (Weight at randomization - weight at 12 weeks)/(weight at randomization) | 12 weeks after randomization |
| Change in Waist Circumference From Baseline | (Waist circumference at 12 weeks - waist circumference at randomization) | 12 weeks after randomization |
| Number of Participants With Severe Hypoglycemic Episodes | Severe hypoglycemic episode is defined as an event with clinical symptoms consistent with hypoglycemia in which the participant required the assistance of another person, and one of the following: (i) the event was associated with a documented self-measured or laboratory plasma glucose level \ | During 64 weeks of follow-up |
| Winnipeg |
| Manitoba |
| R3E 3P4 |
| Canada |
| McMaster University | Hamilton | Ontario | L8N 3Z5 | Canada |
| St. Joseph's Hospital | London | Ontario | N6A 4V2 | Canada |
| Western University | London | Ontario | N6G 2M1 | Canada |
| LMC | Toronto | Ontario | M4G 3E8 | Canada |
| St. Michaels's Hospital | Toronto | Ontario | M5C 2T2 | Canada |
| BG001 | Standard Care | Standard glycemic care as informed by the current clinical practice guidelines |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Duration of diabetes | Mean | Standard Deviation | months |
|
| Glycated hemoglobin (HbA1C) | Expressed in Diabetes Control and Complications Trial (DCCT) units | Mean | Standard Deviation | percentage of glycated hemoglobin |
|
| Body Mass Index (BMI) | Mean | Standard Deviation | kg/m^2 |
|
| OG001 |
| Standard Care |
Standard glycemic care as informed by the current clinical practice guidelines |
|
|
| Secondary | Number of Participants Achieving Drug-free Diabetes Remission | Drug-free diabetes remission is defined as HbA1C < 6.5 % off glucose-lowering agents for at least 12 weeks. | Posted | Count of Participants | Participants | 64 weeks after randomization |
|
|
|
| Secondary | Number of Participants Achieving Drug-free HbA1C < 6.0% | Drug-free complete diabetes remission is defined as HbA1C < 6.0 % off glucose-lowering agents for at least 12 weeks. | Posted | Count of Participants | Participants | 24 weeks after randomization |
|
|
|
| Secondary | Number of Participants Achieving Diabetes Relapse Without Overt Hyperglycemia Off Diabetes Drugs | Diabetes relapse without overt hyperglycemia is defined as HbA1C 6.5-6.9% off glucose-lowering agents for at least 12 weeks. | Posted | Count of Participants | Participants | 24 weeks |
|
|
|
| Secondary | Glycated Hemoglobin (HbA1C) | Expressed in Diabetes Control and Complications Trial (DCCT) units | Posted | Mean | Standard Deviation | percentage of glycated hemoglobin | 12 weeks after randomization |
|
|
|
| Secondary | Number of Participants With Non-severe Symptomatic Hypoglycemic Episodes | Symptomatic hypoglycemic episode is defined as an event with clinical symptoms consistent with hypoglycemia. | Posted | Count of Participants | Participants | During 64 weeks of follow-up |
|
|
|
| Secondary | Percentage of Weight Loss From Baseline | (Weight at randomization - weight at 12 weeks)/(weight at randomization) | Posted | Mean | Standard Deviation | percentage of weight loss | 12 weeks after randomization |
|
|
|
| Secondary | Change in Waist Circumference From Baseline | (Waist circumference at 12 weeks - waist circumference at randomization) | Posted | Mean | Standard Deviation | cm | 12 weeks after randomization |
|
|
|
| Secondary | Number of Participants With Severe Hypoglycemic Episodes | Severe hypoglycemic episode is defined as an event with clinical symptoms consistent with hypoglycemia in which the participant required the assistance of another person, and one of the following: (i) the event was associated with a documented self-measured or laboratory plasma glucose level \ | Posted | Count of Participants | Participants | During 64 weeks of follow-up |
|
|
|
| 0 |
| 77 |
| 3 |
| 77 |
| 12 |
| 77 |
| EG001 | Standard Care | Standard glycemic care as informed by the current clinical practice guidelines | 0 | 77 | 0 | 77 | 10 | 77 |
| Viral gastroenteritis | Gastrointestinal disorders | Non-systematic Assessment |
|
| Resection of liver metastases from colorectal cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Non-systematic Assessment |
|
| Other infections | Infections and infestations | Non-systematic Assessment |
|
| Abscess drainage | Infections and infestations | Non-systematic Assessment |
|
| Injury | Injury, poisoning and procedural complications | Non-systematic Assessment |
|
| Abdominal pain | General disorders | Non-systematic Assessment |
|
| Moderate renal dysfunction defined as GFR 30-60 ml/min/1.73m2 | Renal and urinary disorders | Systematic Assessment |
|
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| D006946 | Hyperinsulinism |
| D001519 | Behavior |
| D006728 |
| Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
| D009747 | Nutritional Physiological Phenomena |
| D000066888 | Diet, Food, and Nutrition |
| D010829 | Physiological Phenomena |
| D009043 | Motor Activity |
| D009068 | Movement |
| D009142 | Musculoskeletal Physiological Phenomena |
| D055687 | Musculoskeletal and Neural Physiological Phenomena |