The Effect of Simple Basal Insulin Titration, Metformin Plus Liraglutide for Type 2 Diabetes With Very Elevated HbA1c - The SIMPLE Study

NCT01966978 | Completed Phase 4 Results

• 1 other identifier: STU 072013-030
• Study Type: interventional
• Target: 157
• Locations: 1 country
• Sites: 1

Brief Summary

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%).

Conditions

Diabetes Mellitus, Type 2; Diabetes

Keywords

Diabetes Mellitus, Type 2; Insulin; Insulin, Long-Acting; Insulin, Short Acting; Detemir; Liraglutide; GLP-1; Glucagon Like Peptide; Metformin; Uncontrolled Diabetes; Elevated A1c; Incretins

Outcome Measures

Primary Outcomes (1)

• Mean Change From Randomization in A1c at Week 26

  Change in glycosylated Hemoglobin A1c (A1c) from randomization to 26 weeks of therapy

  Baseline and Week 26

Secondary Outcomes (7)

• Composite End-point

  Week 0 (Randomization) , Week 26

• Percentage of Participants Reaching Target A1c of <7% at Week 26

  Week 26

• Percentage of Participants Reaching Pre-specified "Treatment Failure" Outcome

  week 13

• Mean Change From Randomization in Body Weight

  Week 0 (Randomization) , Week 26

• Hypoglycemic Episodes

  Week 0 (Randomization) , Week 2, week 4, week 13, Week 26

Study Arms (2)

Control: Metformin, Insulin Detemir, Insulin Aspart

ACTIVE COMPARATOR

Metformin titrated to max tolerated dose (at least 1000 mg/day); Insulin detemir titrated based on the study protocol; Insulin Aspart titrated by the physician

Drug: Metformin; Drug: Detemir; Drug: Insulin Aspart

Metformin, insulin determir, Liraglutide

ACTIVE COMPARATOR

Metformin 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)

Drug: Metformin; Drug: Detemir; Drug: Liraglutide

Interventions

Metformin DRUG

Metformin 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)

Also known as: Metformin tablets

Control: Metformin, Insulin Detemir, Insulin Aspart; Metformin, insulin determir, Liraglutide

Detemir DRUG

Insulin 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.

Also known as: Insulin Detemir subcutaneous once or twice daily

Control: Metformin, Insulin Detemir, Insulin Aspart; Metformin, insulin determir, Liraglutide

Liraglutide DRUG

Initial 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

Also known as: Liraglutide 6 mg/mL Subcutaneously

Metformin, insulin determir, Liraglutide

Insulin Aspart DRUG

Insulin 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

Also known as: Insulin Aspart Subcutaneous injection one to three times daily

Control: Metformin, Insulin Detemir, Insulin Aspart

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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.

You may not qualify if:

• 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;
• Type 1 diabetes as purposefully withholding meal-time insulin is contraindicated;
• Clinical state requiring inpatient admission/treatment;
• Contraindication or strong cautions to any of the study medications:
• Creatinine above 1.4 mg/dl for women and 1.5 mg/dl for men (per metformin label)
• History of lactic acidosis (per metformin label)
• Advanced hepatic or cardiac disease (per metformin label)
• Age \>80 years (per metformin label)
• Chronic alcohol use (\>14 drinks/week)
• History of pancreatitis (per liraglutide label)
• Personal or family history of medullary thyroid cancer or MEN syndrome (per liraglutide label)
• Pregnancy and lactation (per liraglutide label)
• Any serious or unstable medical condition as it would interfere with treatment assignment as well as outcome measurement;
• Any scheduled elective procedures/surgeries;
• Active infections, including osteomyelitis;

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

Study Sites (1)

UT Southwestern Medical Center

Dallas, Texas, 02720, United States

Location

Related Publications (1)

• Patel S, Abreu M, Tumyan A, Adams-Huet B, Li X, Lingvay I. Effect of medication adherence on clinical outcomes in type 2 diabetes: analysis of the SIMPLE study. BMJ Open Diabetes Res Care. 2019 Nov 18;7(1):e000761. doi: 10.1136/bmjdrc-2019-000761. eCollection 2019.

  PMID: 31803482 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus; Insulin Resistance

Interventions

Metformin; Insulin Detemir; Liraglutide; Insulin Aspart

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Insulin, Long-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Insulin, Short-Acting

Results Point of Contact

• Title: Dr. Ildiko Lingvay
• Organization: UT Southwestern Medical Center

ildiko.lingvay@utsouthwestern.edu

214-648-2779

Study Officials

• Ildiko Lingvay

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: October 17, 2013
• First Posted: October 22, 2013
• Study Start: November 1, 2014
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: October 22, 2019
• Results First Posted: October 22, 2019

Record last verified: 2019-10

Locations

US (1)