The loss of beta-cell function in type 1 diabetes necessitates the use of insulin in these patients. However, a majority of such patients are not well controlled in spite of clever insulin delivering devices and continuous glucose monitoring. We, therefore, investigated the effect of liraglutide, a GLP-1 analog in combination with insulin given as a continuous subcutaneous infusion of insulin (CSII) in such patients. These patients were monitored continuously for glucose concentrations (CGM). The combination of insulin and liraglutide resulted in the reduction of fasting and mean blood glucose concentrations within 2 to 3 days with a concomitant reduction in the dose of insulin by 40%. There was a marked reduction in both hyperglycemic and hypoglycemic excursions. There was a fall in body weight, BMI, HbA1c and CRP concentrations within 9 weeks. This persisted over a period of 24 weeks. We now propose the first placebo controlled prospective, randomized study to compare the beneficial effect of liraglutide in type 1 diabetics on treatment with insulin for 56 weeks. This study will also assess whether liraglutide exerts a glucagon suppressive action post- prandially. If indeed, this study confirms a beneficial effect of liraglutide in these patients, it could becom a routine part of the treatment of type 1diabetes with marked improvements in glucose homeostasis and, therefore, a potential reduction in microvascular complications of diabetes.

Public Health Relevance

In view of the total dependence and the relative inadequacy of therapy based on insulin alone in patients with type 1 diabetes, we have investigated the effect of liraglutide as an addition to insulin in these patients. The dramatic and rapid improvement in glycemic control, glycemic excursions, HbA1c, body weight and CRP concentrations has led us to propose this prospective, randomized study on the effect of liraglutide in type 1 diabetics. If confirmed, liraglutide and other GLP-1 agonists may become routine in the treatment of this condition.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK092653-03
Application #
8728834
Study Section
Clinical and Integrative Diabetes and Obesity Study Section (CIDO)
Program Officer
Linder, Barbara
Project Start
2012-09-04
Project End
2017-08-31
Budget Start
2014-09-01
Budget End
2015-08-31
Support Year
3
Fiscal Year
2014
Total Cost
Indirect Cost
Name
State University of New York at Buffalo
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Buffalo
State
NY
Country
United States
Zip Code
14260
Ghanim, Husam; Green, Kelly; Abuaysheh, Sanaa et al. (2015) Suppressive effect of insulin on the gene expression and plasma concentrations of mediators of asthmatic inflammation. J Diabetes Res 2015:202406
Dhindsa, Sandeep; Reddy, Anand; Karam, Jyotheen Sukhmoy et al. (2015) Prevalence of subnormal testosterone concentrations in men with type 2 diabetes and chronic kidney disease. Eur J Endocrinol 173:359-66