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| Name | Class |
|---|---|
| Canadian Institutes of Health Research (CIHR) | OTHER_GOV |
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Type 2 diabetes mellitus is a chronic metabolic disorder characterized by progressive deterioration in the function of the pancreatic beta-cells, which are the cells that produce and secrete insulin (the hormone primarily responsible for the handling of glucose in the body). The investigators propose a randomized controlled trial to determine whether intermittent intensive insulin therapy is an effective therapeutic strategy that can preserve pancreatic beta-cell function and maintain glycemic control early in the course of type 2 diabetes.
In this study, eligible patients with type 2 diabetes will be randomized to either intermittent insulin therapy or not, on a background of metformin, after first undergoing a short course of intensive insulin therapy. The hypothesis under study is whether intermittent insulin therapy can preserve beta-cell function.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Metformin alone | Active Comparator | After a 3-week course of intensive insulin therapy, participants will be treated with ongoing metformin monotherapy. Metformin will be initiated at 500mg twice a day for the first 2 weeks, before progressing to 1000mg twice a day for the duration of the trial (24 months). |
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| Metformin + Intermittent Insulin Therapy | Experimental | After a 3-week course of intensive insulin therapy, participants will be treated with ongoing metformin monotherapy, initiated at 500mg twice a day for the first 2 weeks, before progressing to 1000mg twice a day for the duration of the trial (24 months). Participants will stop their metformin for 2 weeks every 3 months, during which time they will receive intermittent intensive insulin therapy for 2 weeks. The 2-week course of insulin therapy will be repeated at 3-, 6-, 9-, 12-, 15-,18- and 21-months, with final outcome measurement performed at 24-months. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Metformin alone | Drug |
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| Metformin + Intermittent Insulin Therapy |
| Measure | Description | Time Frame |
|---|---|---|
| Baseline-adjusted beta-cell function at 2 years, measured by Insulin Secretion-Sensitivity Index-2 (ISSI-2). | ISSI-2 is an established measure of beta-cell function. ISSI-2 is defined as the product of (i) insulin secretion measured by the ratio of the area-under-the-insulin-curve to the area-under-the-glucose curve and (ii) insulin sensitivity measured by the Matsuda index. | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Baseline-adjusted glycemic control at 2-years. | The secondary outcome of baseline-adjusted glycemic control at 2-years will be assessed by A1c (glycated hemoglobin) | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Achievement of target glycemic control | Achievement of target glycemic control will be assessed by the proportion of participants with A1c <7.0% | 2 years |
| achievement of glucose tolerance in the non-diabetic range |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ravi Retnakaran, MD | MOUNT SINAI HOSPITAL | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mount Sinai Hospital | Toronto | Ontario | M5G1X5 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37500612 | Derived | Retnakaran R, Pu J, Emery A, Harris SB, Reichert SM, Gerstein HC, McInnes N, Kramer CK, Zinman B. Determinants of sustained stabilization of beta-cell function following short-term insulin therapy in type 2 diabetes. Nat Commun. 2023 Jul 27;14(1):4514. doi: 10.1038/s41467-023-40287-w. |
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| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D008687 | Metformin |
| ID | Term |
|---|---|
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
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| Drug |
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The proportion of participants with glucose tolerance in the non-diabetic range will be determined on oral glucose tolerance test (OGTT) and defined based on current Canadian Diabetes Association classifications for glucose tolerance status on OGTT.
| 2 years |
| achievement of normal glucose tolerance | The proportion of participants with normal glucose tolerance will be determined on oral glucose tolerance test (OGTT) and defined based on current Canadian Diabetes Association classifications for glucose tolerance status on OGTT. | 2 years |
| insulin sensitivity | Insulin sensitivity will be measured by Matsuda index, a clamp-validated measure of whole-body insulin sensitivity that can be obtained from the oral glucose tolerance test | 2 years |
| D004700 | Endocrine System Diseases |