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The primary objective of this study is to investigate the change in Alanine Aminotransaminase (ALT) in patients with Type 2 Diabetes Mellitus (T2DM) initiating Sodium Glucose Cotransporter 2 (SGLT2) inhibitors, liraglutide, or sitagliptin, compared to a control group of patients who did not initiate a new antihyperglycemic therapy. The hypothesis is that patients using Sodium Glucose Cotransporter 2 inhibitors (SGLT2i) will achieve a greater reduction in ALT compared to the control group.
Non-alcoholic fatty liver disease (NAFLD) is very commonly associated with type 2 diabetes mellitus (T2DM) 1. Alanine aminotransferase (ALT) is a common biomarker used to predict levels of NAFLD. The only class of antidiabetic agents thought to be protective of NAFLD are thiazolidinedione's. Few studies have investigated the effect of other antidiabetic agents on bio markers of fatty liver disease 2. A recent pooled analysis of randomized controlled trials that compared canagliflozin to either placebo or sitagliptin showed significant reductions in ALT in the canagliflozin cohorts, which were fully explained by HbA1c and body weight reductions 3. As well, a study that compared ALT change in patients initiating liraglutide found significant reductions in ALT, which was strongly correlated to reduction in body weight 4. However, the effect of different antidiabetic agents on bio markers of fatty liver disease is not well characterized.
The primary objective of this study is to investigate the change in ALT in patients with T2DM initiating SGLT2 inhibitors, liraglutide, or sitagliptin, compared to a control group of patients who did not initiate a new antihyperglycemic therapy. The hypothesis is that patients using SGLT2i will achieve a greater reduction in ALT compared to the control group.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| SGLT2 | Patients initiating SGLT2 inhibitors |
| |
| Liraglutide | Patients initiation liraglutide |
| |
| Sitagliptin | Patients initiating sitagliptin |
| |
| Control Group | Patients who did not initiate any new anti-hyperglycemic treatment |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Non-interventional | Other |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in ALT in patients with T2DM initiating SGLT2 inhibitors, Liraglutide or Sitagliptin compared to control | Change in ALT in patients with T2DM initiating SGLT2 inhibitors, Liraglutide or Sitagliptin compared to control | 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Hemoglobin A1c from baseline to follow-up | Change in HbA1c from baseline to follow-up | 1 year |
| Change in Fasting Plasma Glucose from baseline to follow-up | Change in Fasting Plasma Glucose from baseline to follow-up |
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Inclusion Criteria:
Exclusion Criteria:
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This study will include patients with T2DM who are patients at LMC Diabetes & Endocrinology. Patients will be included in the treatment cohorts if they initiated canagliflozin, dapagliflozin, liraglutide or sitagliptin, between January 2011 and December 2015, and did not discontinue the treatment prior to 6 weeks of being on the medication. The control group will include patients with T2DM who are patients at LMC Diabetes & Endocrinology, and who did not initiate any new diabetes treatment between June 2014 and June 2015.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| LMC Brampton | Brampton | Ontario | L6S 0C9 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30149145 | Derived | Bajaj HS, Brown RE, Bhullar L, Sohi N, Kalra S, Aronson R. SGLT2 inhibitors and incretin agents: Associations with alanine aminotransferase activity in type 2 diabetes. Diabetes Metab. 2018 Dec;44(6):493-499. doi: 10.1016/j.diabet.2018.08.001. Epub 2018 Aug 24. |
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| 1 year |
| Change in body weight from baseline to follow-up | Change in body weight from baseline to follow-up | 1 year |
| Change in Body Mass Index (BMI) from baseline to follow-up | Change in BMI from baseline to follow-up | 1 year |
| Change in Waist Circumference (WC) from baseline to follow-up | Change in WC from baseline to follow-up | 1 year |
| Change in triglycerides from baseline to follow-up | Change in triglycerides from baseline to follow-up | 1 year |
| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| D005234 | Fatty Liver |
| D065626 | Non-alcoholic Fatty Liver Disease |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
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