Clinical trial NCT03233178: Measurement of Alanine Aminotransaminase (ALT) Following Initiation of Antidiabetic Agents in Patients With Type 2 Diabetes in a Real-world Clinical Setting: a Retrospective Cohort Study
Official title: Measurement of Alanine Aminotransaminase (ALT) Following Initiation of Antidiabetic Agents in Patients With Type 2 Diabetes in a Real-world Clinical Setting: a Retrospective Cohort Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: T2DM (Type 2 Diabetes Mellitus)
Fatty Liver
NAFLD
Lead sponsor: LMC Diabetes & Endocrinology Ltd.
Sponsor class: OTHER
First posted: 2017-07-28
Enrollment: 4000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: 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.

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of T2DM based upon historical clinical diagnosis
* Patients who initiated canagliflozin, dapagliflozin, liraglutide or sitagliptin by an LMC physician between January 2011 and December 2015, or patients who did not initiate a new diabetes therapy between June 2014 and June 2015.

Exclusion Criteria:

* Diagnosis of type 1 diabetes
* Patients who switched to one of the study treatments from another medication of the same medication class

Primary outcomes:
measure: Change in ALT in patients with T2DM initiating SGLT2 inhibitors, Liraglutide or Sitagliptin compared to control
timeFrame: 1 year
Secondary outcomes:
measure: Change in Hemoglobin A1c from baseline to follow-up
timeFrame: 1 year
measure: Change in Fasting Plasma Glucose from baseline to follow-up
timeFrame: 1 year
measure: Change in body weight from baseline to follow-up
timeFrame: 1 year
measure: Change in Body Mass Index (BMI) from baseline to follow-up
timeFrame: 1 year
measure: Change in Waist Circumference (WC) from baseline to follow-up
timeFrame: 1 year
measure: Change in triglycerides from baseline to follow-up
timeFrame: 1 year
Other outcomes:
Locations:
city: Brampton
country: Canada
facility: LMC Brampton
state: Ontario
Study officials:
References:
citation: 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.