Addition of Liraglutide to Patients With Type 2 Diabetes Treated With Multiple Daily Insulin Injections

NCT02113332 | Completed Phase 2 DMC

• 2 other identifiers: MDILiraglutide2012-001941-42
• Study Type: interventional
• Target: 124
• Locations: 1 country
• Sites: 14

Brief Summary

Liraglutide, a GLP-1-analogue has been shown to be an effective treatment option in patients on oral anti-diabetes therapy with beneficial effects on both glycaemic control and weight. However, to date there are no clinical trials of liraglutide added to insulin therapy, a population of patients generally having worse glycaemic control and weight gain. In clinical guidelines, use of multiple daily insulin injections (MDI) is usually the final therapeutic option for type 2 diabetic patients. The primary study aim is to evaluate whether the addition of liraglutide, compared to placebo, reduces the HbA1c level for overweight and obese type 2 diabetes patients with inadequate glycaemic control treated with multiple daily insulin injections (MDI). MDI is defined as treatment with any basal insulin combined with separate meal time insulin injections before the main meals, i.e. an insulin regimen with premixed insulin is not considered as MDI. The planned study duration is 24 weeks and includes 120 patients at 15 centers in Sweden.

Conditions

Type 2 Diabetes Mellitus

Keywords

Insulin injections; Overweight; Inadequate glycaemic control

Outcome Measures

Primary Outcomes (1)

• Change in HbA1c from baseline to week 24.

  Baseline, week 24

Secondary Outcomes (18)

• Change in weight from baseline to week 24

  Baseline, week 24

• Change in fasting glucose from baseline to week 24

  Baseline, week 24

• Change in the standard deviation of CGM from the run-in period to week 23-24

  Run-in period, week 23-24

• Change in mean glucose levels on CGM from the run-in period to week 23-24

  Run-in period, week 23-24

• Change in 1.5 hour postprandial glucose levels on capillary glucose measurements from the run-in period to week 23-24

  Run-in period, week 23-24

Study Arms (2)

Liraglutide

EXPERIMENTAL

Liraglutide injected once per day for 24 weeks. Dose is 1,8 mg or highest tolerable dose.

Drug: Liraglutide

Placebo

PLACEBO COMPARATOR

Placebo injected once per day for 24 weeks. Dose is 1,8 or highest tolerable dose.

Drug: Placebo

Interventions

Liraglutide DRUG

Also known as: Victoza

Liraglutide

Placebo DRUG

Placebo

Eligibility Criteria

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

You may qualify if:

• Informed consent obtained before trial-related activities (i.e., any activity that would not have been performed during routine patient management)
• Type 2 diabetes
• Adult patients over 18 years of age and less than or equal to 80 years of age
• HbA1c greater than or equal to 7.5% (NGSP standard=DCCT standard)=58 mmol/mol (IFCC standard) and less than or equal to 11.5%=102 mmol/mol
• Treated with MDI for at least the last 6 months
• Treated with/without metformin as only diabetes therapy apart from insulin
• Fasting C-peptide of 0.10 nmol/l or greater (ref. 0.25-1.0 nmol/l)
• BMI greater than 27,5 kg/m2 and less than 45 kg/m2

You may not qualify if:

• Type 1 diabetes
• Fasting glucose less than 6.0 mmol/l or greater than 15.0 mmol/l
• Unstable cardiovascular disease, NYHA Class II or greater heart failure , new symptoms of cardiovascular disease)
• Proliferative diabetic retinopathy or clinically significant macula oedema. Retinal photograph should not be older than 3 years.
• Systemic glucocorticoid treatment during the last 3 months, however, patients using systemic corticoid treatment only for substitution of cortisol deficiency (physiologic doses) such as Addisons Disease, do not need to be excluded
• Acute coronary syndrome, stroke, coronary artery intervention or myocardial infarction during the previous 6 months
• Creatinine greater than 150 micromol/l
• Liver transaminases greater than double of the normal reference interval
• Treatment with other oral antidiabetic agents than metformin during the previous 3 months
• Treatment with GLP-1 receptor agonists within 90 days of screening
• Severe psychiatric disorder (untreated severe depression, schizophrenia, dementia or severe alcohol or drug abuse)
• Frequent non-severe hypoglycaemia (greater than 2 times per week) or any severe hypoglycaemia during the previous month.
• Hypoglycaemic unawareness
• Current cancer or diagnosis of cancer in the previous 5 years (except basal cell skin cancer or squamous cell skin cancer).
• Personal history of non-familial thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 (MEN2)

Sponsors & Collaborators

• Vastra Gotaland Region: lead
• Novo Nordisk A/S: collaborator

Study Sites (14)

Ängelholm Hospital

Ängelholm, Sweden

Location

Falu Hospital

Falun, Sweden

Location

Clicical Trial Center Sahlgrenska

Gothenburg, Sweden

Location

Halmstad Hospital

Halmstad, Sweden

Location

Öbacka Clinic

Härnösand, Sweden

Location

Helsingborg Hospital

Helsingborg, Sweden

Location

Lindsdals Health Center

Kalmar, Sweden

Location

Karlskoga Hospital

Karlskoga, Sweden

Location

Kristianstad Hospital

Kristianstad, Sweden

Location

Kungsbacka Hospital

Kungsbacka, Sweden

Location

Malmö University Hospital

Malmo, Sweden

Location

CityDiabetes Clinic

Stockholm, Sweden

Location

NU-Hospital Organization

Uddevalla, Sweden

Location

Värnamo Hospital

Värnamo, Sweden

Location

Related Publications (10)

• American Diabetes Association. Standards of medical care in diabetes--2010. Diabetes Care. 2010 Jan;33 Suppl 1(Suppl 1):S11-61. doi: 10.2337/dc10-S011. No abstract available.

  PMID: 20042772 BACKGROUND

• National Board of Health and Welfare Sweden, (2010), Nationella Riktlinjer för diabetesvården, http://www.socialstyrelsen.se/nationellariktlinjerfordiabetesvarden

  BACKGROUND

• Pi-Sunyer FX. The impact of weight gain on motivation, compliance, and metabolic control in patients with type 2 diabetes mellitus. Postgrad Med. 2009 Sep;121(5):94-107. doi: 10.3810/pgm.2009.09.2056.

  PMID: 19820278 BACKGROUND

• Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998 Sep 12;352(9131):837-53.

  PMID: 9742976 BACKGROUND

• Vilsboll T, Rosenstock J, Yki-Jarvinen H, Cefalu WT, Chen Y, Luo E, Musser B, Andryuk PJ, Ling Y, Kaufman KD, Amatruda JM, Engel SS, Katz L. Efficacy and safety of sitagliptin when added to insulin therapy in patients with type 2 diabetes. Diabetes Obes Metab. 2010 Feb;12(2):167-77. doi: 10.1111/j.1463-1326.2009.01173.x.

  PMID: 20092585 BACKGROUND

• Pratley RE, Nauck M, Bailey T, Montanya E, Cuddihy R, Filetti S, Thomsen AB, Sondergaard RE, Davies M; 1860-LIRA-DPP-4 Study Group. Liraglutide versus sitagliptin for patients with type 2 diabetes who did not have adequate glycaemic control with metformin: a 26-week, randomised, parallel-group, open-label trial. Lancet. 2010 Apr 24;375(9724):1447-56. doi: 10.1016/S0140-6736(10)60307-8.

  PMID: 20417856 BACKGROUND

• Lind M, Jendle J, Torffvit O, Lager I. Glucagon-like peptide 1 (GLP-1) analogue combined with insulin reduces HbA1c and weight with low risk of hypoglycemia and high treatment satisfaction. Prim Care Diabetes. 2012 Apr;6(1):41-6. doi: 10.1016/j.pcd.2011.09.002. Epub 2011 Oct 19.

  PMID: 22015237 BACKGROUND

• Lind M. Incretin therapy and its effect on body weight in patients with diabetes. Prim Care Diabetes. 2012 Oct;6(3):187-91. doi: 10.1016/j.pcd.2012.04.006. Epub 2012 May 19.

  PMID: 22613745 BACKGROUND

• Workgroup on Hypoglycemia, American Diabetes Association. Defining and reporting hypoglycemia in diabetes: a report from the American Diabetes Association Workgroup on Hypoglycemia. Diabetes Care. 2005 May;28(5):1245-9. doi: 10.2337/diacare.28.5.1245. No abstract available.

  PMID: 15855602 BACKGROUND

• Lind M, Hirsch IB, Tuomilehto J, Dahlqvist S, Torffvit O, Pehrsson NG. Design and methods of a randomised double-blind trial of adding liraglutide to control HbA1c in patients with type 2 diabetes with impaired glycaemic control treated with multiple daily insulin injections (MDI-Liraglutide trial). Prim Care Diabetes. 2015 Feb;9(1):15-22. doi: 10.1016/j.pcd.2014.07.010. Epub 2014 Aug 28.

  PMID: 25175385 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Overweight

Interventions

Liraglutide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Marcus Lind, MD, PhD

  NU-Hospital Organization

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2014
• First Posted: April 14, 2014
• Study Start: January 1, 2013
• Primary Completion: August 1, 2014
• Study Completion: August 1, 2014
• Last Updated: February 3, 2015

Record last verified: 2014-12

Locations

SE (14)