SUN-164 Use of Metformin, Premixed Insulin, and Glucagon-Like Peptide-1 Receptor Agonist as a Therapeutic Approach for Uncontrolled Type 2 Diabetes Mellitus

Background: Large doses of basal insulin may do little to improve glycemic. Adding pre-prandial insulin increases the number of injections and complicates treatment. Simplifying medication regimen by decreasing injections may improve compliance and lead to improved Hemoglobin A1c (HbA1c). Traditionally once prandial insulin is added, oral medications and other injectable insulin sparing agents are stopped except metformin. There are no published studies on use of Glucagon-like peptide-1 receptor agonists (GLP-1 RA) with prandial insulin or premixed insulin. The purpose of this retrospective review was to assess if changing patients with long history of poorly controlled diabetes on large doses of basal insulin with or without pre-prandial insulin to premixed insulin, GLP-1 RA and metformin improved glycemic control over 12 months. Methods: We conducted a retrospective cohort study of adult patients with Type 2 Diabetes (T2DM) who presented to our outpatient medical center between January 1, 2000 and November 1, 2017. We selected all patients who were given premixed insulin and a form of GLP-1 RA simultaneously with or without metformin with no other diabetic medication and had at least a 3 month follow-up HbA1c. We reviewed HbA1c, weight and cumulative daily insulin dose over 12 months. We collected all demographic data as well as adverse events. Results: 32 patients met inclusion criteria with 31 of the 32 patients having 12 month HbA1c data. Average duration of T2DM was 14.2 (SD 7.1) years. Mean HbA1c at baseline was 10.5% (SD 2.1). By 6 months mean HbA1c had declined to 8.6% (SD 2.1). At 12 months mean HbA1c change was -2.3 (SD 2.38, [95% CI: -3.183 to -1.437]; p = < 0.0001). At 12 months cumulative insulin dose was -34.9 units less than total initial insulin (SD 58.9 [95% CI: -56.55 to -13.32]; P = 0.0025). Average weight loss was -3.3 LBS (SD 20.1 [95% CI: -10.73 to 4.151]; p= 0.373). After 12 months 23% (7/31) of patients had HbA1c ≤ 7% and 61% (19/31) had HbA1c ≤ 8%. Of note 5 additional patients stopped regimen after <3 months, 3 for nausea, 1 for pancreatitis and 1 for skin reaction. Conclusion: Despite cumulative daily dose of insulin decreasing, using metformin, premixed insulin and GLP-1 RA in a historically difficult to control population with T2DM, improved glycemic over duration of 12 months. Prospective randomized studies need to be done to assess the benefit of this unique combination of available medication therapy.