Diabetes Mellitus, Type 2 | The Effect of Simple Basal Insulin Titration, Metformin Plus Liraglutide for Type 2 Diabetes With Very Elevated HbA1c - The SIMPLE Study
Diabetes Mellitus, Type 2 research study
What is the primary objective of this study?
The aim of this clinical trial is to assess and compare the effect of insulin detemir in combination with liraglutide and metformin versus insulin detemir in combination with insulin aspart and metformin in subjects with very uncontrolled Type 2 Diabetes (A1c > 10%).
Who is eligible to participate?
Inclusion Criteria: 1. Clinical diagnosis of type 2 diabetes with confirmed HbA1c level >10% at time of enrollment, regardless of prior or current treatment regimens, or time since diagnosis. Exclusion Criteria: 1. Age <18 as the feasibility and safety of this treatment regimen should be first established in the adult population; if successful, a subsequent pediatric study will be proposed; 2. Type 1 diabetes as purposefully withholding meal-time insulin is contraindicated; 3. Clinical state requiring inpatient admission/treatment; 4. Contraindication or strong cautions to any of the study medications: 1. Creatinine above 1.4 mg/dl for women and 1.5 mg/dl for men (per metformin label) 2. History of lactic acidosis (per metformin label) 3. Advanced hepatic or cardiac disease (per metformin label) 4. Age >80 years (per metformin label) 5. Chronic alcohol use (>14 drinks/week) 6. History of pancreatitis (per liraglutide label) 7. Personal or family history of medullary thyroid cancer or MEN syndrome (per liraglutide label) 8. Pregnancy and lactation (per liraglutide label) 5. Any serious or unstable medical condition as it would interfere with treatment assignment as well as outcome measurement; 6. Any scheduled elective procedures/surgeries; 7. Active infections, including osteomyelitis; 8. Not willing to participate, unable to keep projected appointments, unwillingness to receive injectable treatment; unwillingness to perform 7-point glucose profiles over 2 consecutive days the weeks prior to Randomization (visit 1)and the week prior to visit 6 9. Non English speaking.
Which medical condition, disease, disorder, syndrome, illness, or injury is researched?
Diabetes Mellitus, Type 2
Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.
Drug:MetforminMetformin will be started at 500 mg daily (or continued at current dose)and weekly titrated to 2000 mg or maximum tolerated dose (at least 1000 mg/day)
Drug:DetemirInsulin detemir will be started in both groups at 0.3 units/kg or conversion 1:1 from dose of basal insulin prior to randomization. The titration will be primarily patient-driven, based on our study protocol table. Additional physician driven titration will be allowed in both groups if patient fails to intensify basal insulin dose as directed.
Drug:LiraglutideInitial dose of 0.6 mg/day with weekly increments of 0.6 mg until dose of 1.8 mg/day or maximal tolerated dose (at least 1.2 mg/day)is reached
Drug:Insulin AspartInsulin aspart will be initiated at a dose of 0.3 units/kg/day divided among the number of meals taken daily and titrated based on physician clinical judgment with the goal of pre-prandial BG 70-130 mg/dL and post-prandial BG <180
Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.
Control: Metformin, Insulin Detemir, Insulin AspartMetformin titrated to max tolerated dose (at least 1000 mg/day); Insulin detemir titrated based on the study protocol; Insulin Aspart titrated by the physician
Metformin, insulin determir, LiraglutideMetformin titrated to max tolerated dose (at least 1000mg/day); Insulin detemir titrated based on the study protocol"; Liraglutide titrated to max tolerated dose (at least 1.2 mg/day)
Start Date: November 2014
Completed Date: December 2017
Phase: Phase 4
Primary Outcome: Composite end-point
Secondary Outcome: Mean change from randomization in A1c at week 26
Study sponsors, principal investigator, and references
Principal Investigator: Ildiko Lingvay
Lead Sponsor: University of Texas Southwestern Medical Center