Liraglutide in the Treatment of Type 1 Diabetes Mellitus

NCT01722266 | Completed Phase 3 Results FDA Drug

• 1 other identifier: NN1962
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

Hypothesis 1: Treatment with Liraglutide in patients with type 1 diabetes decreases fasting, postprandial and the overall mean glucose concentrations. Aim 1.1: To compare the mean fasting, the mean weekly glucose and the standard deviation of weekly blood glucose concentrations as recorded by continuous glucose monitoring prior to and following 6 weeks and 12 weeks of treatment with 0.6, 1.2 and 1.8 mg of liraglutide daily. In addition, the time spent at glucose concentrations \>150 and 200mg/dl and \<70 and \<40 mg/dl will also be compared. Aim 1.2: To compare the postprandial glucose concentrations following a test meal before and after 12 weeks of treatment with 0.6, 1.2 and 1.8 mg of liraglutide daily. Glucose concentrations will be measured as areas under the curve for the data obtained from the meal challenge. Aim 1.3: To compare HbA1c levels(glycated hemoglobin) before and after 12 weeks of treatment with 0.6, 1.2 and 1.8 mg of liraglutide daily Hypothesis 2: Treatment with Liraglutide in patients with type 1 diabetes decreases postprandial glucagon concentrations and increases postprandial C-peptide concentrations. Aim 2.1: To compare fasting and postprandial glucagon and C-peptide concentrations following a test meal before and after 12 weeks of treatment with 0.6, 1.2 and 1.8 mg of liraglutide daily. Hypothesis 3: Treatment with Liraglutide in patients with type 1 diabetes delays gastric emptying. Aim 3.1: To compare the gastric emptying as measured by acetaminophen absorption before and after 12 weeks of treatment with 0.6, 1.2 and 1.8 mg of liraglutide daily.

Conditions

Type 1 Diabetes

Keywords

Liraglutide; Glucagon; Systolic blood pressure; Weight; Carbohydrate intake; Insulin dose; HbA1c; Post-prandial glucagon

Outcome Measures

Primary Outcomes (1)

• Change in Mean Weekly Glucose Concentrations

  The primary endpoint of the study is to detect a difference from baseline in mean weekly blood glucose concentrations before and after 12 weeks of treatment in each of the Liraglutide groups.

  12 Weeks

Secondary Outcomes (6)

• Change in HbA1c

  12 Weeks

• Change in Body Weight From Baseline

  12 weeks

• Change in Total Insulin Dose From Baseline

  12 weeks

• Change in the Area Under Curve (AUC) of Glucose Following the Meal

  12 weeks

• Change in Carbohydrate Intake

  12 weeks

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Daily Injection

Drug: Placebo

Liraglutide 1.8mg

ACTIVE COMPARATOR

Daily Injection

Drug: Liraglutide

Liraglutide 1.2mg

ACTIVE COMPARATOR

Daily injections

Drug: Liraglutide

Liraglutide 0.6 mg

ACTIVE COMPARATOR

Daily injection

Drug: Liraglutide

Interventions

Liraglutide DRUG

Patients randomized to 1.2 mg of liraglutide : They will start liraglutide 0.6 mg sc once daily for one week and will increase the dose to 1.2 mg sc once daily thereafter. Patients randomized to 1.8 mg of liraglutide: They will start liraglutide 0.6 mg sc once daily for one week; will increase to 1.2 mg sc once daily for second week and will stay on 1.8 mg of liraglutide from third week onwards.

Also known as: Victoza

Liraglutide 0.6 mg; Liraglutide 1.2mg; Liraglutide 1.8mg

Placebo DRUG

Patients randomized to 1.2 mg of placebo: They will start placebo 0.6 mg sc once daily for one week and then increase to 1.2 mg once daily thereafter. Patients randomized to 1.8 mg of placebo: They will start placebo 0.6 mg sc once daily for one week; increase to 1.2 mg sc once daily for second week and then to 1.8 mg sc once daily from third week onwards.

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with type 1 diabetes mellitus: Fasting c-peptide \< 0.1nmol/l on insulin therapy for more than 12 months with or without history of diabetic ketoacidosis.
• Using a continuous glucose monitoring device (CGM) and regularly measuring their blood sugars four times daily
• HbA1c of less than 8.5%.
• Well versed with carbohydrate counting
• Age 18-75 years

You may not qualify if:

• Type 1 diabetes for less than 12 months;
• Coronary event or procedure (myocardial infarction, unstable angina, coronary artery bypass, surgery or coronary angioplasty) in the previous four weeks;
• Hepatic disease (transaminase \> 3 times normal) or cirrhosis;
• Renal impairment (serum creatinine \> 1.5);
• HIV or Hepatitis C positive status;
• Participation in any other concurrent clinical trial;
• Any other life-threatening, non-cardiac disease;
• Use of an investigational agent or therapeutic regimen within 30 days of study.
• history of pancreatitis
• pregnancy
• inability to give informed consent
• history of gastroparesis
• history of medullary thyroid carcinoma or MEN 2 syndrome.
• Family history of MEN 2, Family history of medullary thyroid cancer, or familial medullary thyroid cancer
• Women of childbearing potential who are not using adequate contraception 16) Women who are pregnant

Sponsors & Collaborators

• University at Buffalo: lead
• Novo Nordisk A/S: collaborator

Study Sites (1)

Diabetes-Endocrinology Center of Western NY

Williamsville, New York, 14221, United States

Location

Related Publications (13)

• Kuhadiya ND, Malik R, Bellini NJ, Patterson JL, Traina A, Makdissi A, Dandona P. Liraglutide as additional treatment to insulin in obese patients with type 1 diabetes mellitus. Endocr Pract. 2013 Nov-Dec;19(6):963-7. doi: 10.4158/EP13065.OR.

  PMID: 23807520 BACKGROUND

• Varanasi A, Bellini N, Rawal D, Vora M, Makdissi A, Dhindsa S, Chaudhuri A, Dandona P. Liraglutide as additional treatment for type 1 diabetes. Eur J Endocrinol. 2011 Jul;165(1):77-84. doi: 10.1530/EJE-11-0330. Epub 2011 Jun 6.

  PMID: 21646283 BACKGROUND

• Kielgast U, Asmar M, Madsbad S, Holst JJ. Effect of glucagon-like peptide-1 on alpha- and beta-cell function in C-peptide-negative type 1 diabetic patients. J Clin Endocrinol Metab. 2010 May;95(5):2492-6. doi: 10.1210/jc.2009-2440. Epub 2010 Mar 5.

  PMID: 20207828 BACKGROUND

• Rother KI, Spain LM, Wesley RA, Digon BJ 3rd, Baron A, Chen K, Nelson P, Dosch HM, Palmer JP, Brooks-Worrell B, Ring M, Harlan DM. Effects of exenatide alone and in combination with daclizumab on beta-cell function in long-standing type 1 diabetes. Diabetes Care. 2009 Dec;32(12):2251-7. doi: 10.2337/dc09-0773. Epub 2009 Oct 6.

  PMID: 19808924 BACKGROUND

• Ghanim H, Aljada A, Daoud N, Deopurkar R, Chaudhuri A, Dandona P. Role of inflammatory mediators in the suppression of insulin receptor phosphorylation in circulating mononuclear cells of obese subjects. Diabetologia. 2007 Feb;50(2):278-85. doi: 10.1007/s00125-006-0508-9. Epub 2006 Dec 16.

  PMID: 17180352 BACKGROUND

• Wajchenberg BL, Feitosa AC, Rassi N, Lerario AC, Betti RT. Glycemia and cardiovascular disease in type 1 diabetes mellitus. Endocr Pract. 2008 Oct;14(7):912-23. doi: 10.4158/EP.14.7.912.

  PMID: 18996824 BACKGROUND

• Buse JB, Klonoff DC, Nielsen LL, Guan X, Bowlus CL, Holcombe JH, Maggs DG, Wintle ME. Metabolic effects of two years of exenatide treatment on diabetes, obesity, and hepatic biomarkers in patients with type 2 diabetes: an interim analysis of data from the open-label, uncontrolled extension of three double-blind, placebo-controlled trials. Clin Ther. 2007 Jan;29(1):139-53. doi: 10.1016/j.clinthera.2007.01.015.

  PMID: 17379054 BACKGROUND

• Montanya E, Sesti G. A review of efficacy and safety data regarding the use of liraglutide, a once-daily human glucagon-like peptide 1 analogue, in the treatment of type 2 diabetes mellitus. Clin Ther. 2009 Nov;31(11):2472-88. doi: 10.1016/j.clinthera.2009.11.034.

  PMID: 20109994 BACKGROUND

• Varanasi A, Patel P, Makdissi A, Dhindsa S, Chaudhuri A, Dandona P. Clinical use of liraglutide in type 2 diabetes and its effects on cardiovascular risk factors. Endocr Pract. 2012 Mar-Apr;18(2):140-5. doi: 10.4158/EP11169.OR.

  PMID: 21856595 BACKGROUND

• Varanasi A, Chaudhuri A, Dhindsa S, Arora A, Lohano T, Vora MR, Dandona P. Durability of effects of exenatide treatment on glycemic control, body weight, systolic blood pressure, C-reactive protein, and triglyceride concentrations. Endocr Pract. 2011 Mar-Apr;17(2):192-200. doi: 10.4158/EP10199.OR.

  PMID: 20841306 BACKGROUND

• Okerson T, Yan P, Stonehouse A, Brodows R. Effects of exenatide on systolic blood pressure in subjects with type 2 diabetes. Am J Hypertens. 2010 Mar;23(3):334-9. doi: 10.1038/ajh.2009.245. Epub 2009 Dec 17.

  PMID: 20019672 BACKGROUND

• Lebovitz HE. Adjunct therapy for type 1 diabetes mellitus. Nat Rev Endocrinol. 2010 Jun;6(6):326-34. doi: 10.1038/nrendo.2010.49. Epub 2010 Apr 20.

  PMID: 20404854 BACKGROUND

• Kuhadiya ND, Dhindsa S, Ghanim H, Mehta A, Makdissi A, Batra M, Sandhu S, Hejna J, Green K, Bellini N, Yang M, Chaudhuri A, Dandona P. Addition of Liraglutide to Insulin in Patients With Type 1 Diabetes: A Randomized Placebo-Controlled Clinical Trial of 12 Weeks. Diabetes Care. 2016 Jun;39(6):1027-35. doi: 10.2337/dc15-1136. Epub 2016 Apr 5.

  PMID: 27208343 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Body Weight

Interventions

Liraglutide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; 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

Limitations and Caveats

Three subjects randomized to 1.2 mg group and one subject randomized to 1.8 mg group tolerated only 0.6 mg. These 4 subjects were included in the 0.6 mg group for analysis.

Results Point of Contact

• Title: Nitesh D Kuhadiya,MD,MPH ;Co-Investigator;Assistant Professor of Medicine, Section of Endocrinology
• Organization: University at Buffalo

niteshku@buffalo.edu

716-626-7998

Study Officials

• Paresh Dandona, MBBS, PhD

  Kaleida Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Distinguished Professor of Medicine

Study Record Dates

• First Submitted: November 2, 2012
• First Posted: November 6, 2012
• Study Start: November 1, 2012
• Primary Completion: April 1, 2014
• Study Completion: December 1, 2014
• Last Updated: January 5, 2024
• Results First Posted: March 13, 2015

Record last verified: 2024-01

Locations

US (1)