Liraglutide in Type 1 Diabetes
| Status: | Recruiting |
|---|---|
| Conditions: | Diabetes |
| Therapuetic Areas: | Endocrinology |
| Healthy: | No |
| Age Range: | 18 - 75 |
| Updated: | 11/8/2017 |
| Start Date: | November 2012 |
| End Date: | November 2019 |
| Contact: | Paresh Dandona, MD |
| Email: | pdandona@kaleidahealth.org |
| Phone: | 7168981940 |
The control of glucose homeostasis in subjects with type 1 diabetes is fragile since
exogenous insulin cannot compensate for changing requirements and is not precise either in
terms of the dose or the bio-availability of the insulin injected. Furthermore, in the near
total absence of insulin secretion, the physiological post prandial inhibition of glucagon
secretion by the α-cell is also probably deficient in all type 1 diabetics. Thus, there is a
need for therapies beyond insulin that can further improve glycemic control and reduce
fluctuations in glucose in these subjects. The investigators have recently shown that
Liraglutide, a glucagon like peptide (GLP)-1 analogue with duration of action of 24 hours,
when added to insulin in subjects with well controlled type 1 diabetes reduces mean and
standard deviation of blood glucose, HbA1c and insulin requirements. Since C-peptide
concentrations did not alter following Liraglutide, it is likely that the suppression of
glucagon may have contributed to this effect. The glucose lowering effects of GLP-1 agonists
are well established in subjects with type 2 diabetes, however, these have not been studied
prospectively in subjects with type 1 diabetes. The investigators have, therefore, designed
this study to investigate the central hypothesis that in patients with type 1 diabetes,
Liraglutide has a glucose lowering effect. A major secondary objective of this study is to
elucidate the mechanisms responsible for its glucose lowering effects and those involved in
reducing the insulin dose. The specific aims of this proposal are:
Hypothesis 1: Treatment with Liraglutide in patients with type 1 diabetes decreases HbA1c,
fasting, postprandial and the overall mean glucose concentrations while decreasing the dose
of insulin required.
Aim 1.1: To compare the HbA1c, mean fasting, glucose, mean weekly glucose, standard deviation
of weekly blood glucose concentrations as recorded by continuous glucose monitoring and the
dose of insulin required prior to and following 52 weeks of treatment with 1.8 mg of
liraglutide daily.
Aim 1.2: To compare the postprandial glucose concentrations following a test meal before and
after 52 weeks of treatment with 1.8 mg of liraglutide daily.
Hypothesis 2: Treatment with Liraglutide in patients with type 1 diabetes decreases basal and
postprandial glucagon concentrations and increases basal and postprandial C-peptide
concentrations.
Aim 2.1: To compare the basal and postprandial glucagon and C-peptide concentrations
following a test meal before and after 52 weeks of treatment with 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 treatment with 1.8 mg of daily subcutaneous liraglutide.
exogenous insulin cannot compensate for changing requirements and is not precise either in
terms of the dose or the bio-availability of the insulin injected. Furthermore, in the near
total absence of insulin secretion, the physiological post prandial inhibition of glucagon
secretion by the α-cell is also probably deficient in all type 1 diabetics. Thus, there is a
need for therapies beyond insulin that can further improve glycemic control and reduce
fluctuations in glucose in these subjects. The investigators have recently shown that
Liraglutide, a glucagon like peptide (GLP)-1 analogue with duration of action of 24 hours,
when added to insulin in subjects with well controlled type 1 diabetes reduces mean and
standard deviation of blood glucose, HbA1c and insulin requirements. Since C-peptide
concentrations did not alter following Liraglutide, it is likely that the suppression of
glucagon may have contributed to this effect. The glucose lowering effects of GLP-1 agonists
are well established in subjects with type 2 diabetes, however, these have not been studied
prospectively in subjects with type 1 diabetes. The investigators have, therefore, designed
this study to investigate the central hypothesis that in patients with type 1 diabetes,
Liraglutide has a glucose lowering effect. A major secondary objective of this study is to
elucidate the mechanisms responsible for its glucose lowering effects and those involved in
reducing the insulin dose. The specific aims of this proposal are:
Hypothesis 1: Treatment with Liraglutide in patients with type 1 diabetes decreases HbA1c,
fasting, postprandial and the overall mean glucose concentrations while decreasing the dose
of insulin required.
Aim 1.1: To compare the HbA1c, mean fasting, glucose, mean weekly glucose, standard deviation
of weekly blood glucose concentrations as recorded by continuous glucose monitoring and the
dose of insulin required prior to and following 52 weeks of treatment with 1.8 mg of
liraglutide daily.
Aim 1.2: To compare the postprandial glucose concentrations following a test meal before and
after 52 weeks of treatment with 1.8 mg of liraglutide daily.
Hypothesis 2: Treatment with Liraglutide in patients with type 1 diabetes decreases basal and
postprandial glucagon concentrations and increases basal and postprandial C-peptide
concentrations.
Aim 2.1: To compare the basal and postprandial glucagon and C-peptide concentrations
following a test meal before and after 52 weeks of treatment with 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 treatment with 1.8 mg of daily subcutaneous liraglutide.
Inclusion Criteria:
1. Type 1 Diabetes on continuous subcutaneous insulin infusion (CSII; also known as
insulin pump) or multiple (four or more) injections of insulin per day.
2. Regularly measuring blood sugars four times daily.
3. HbA1c of less than 8.5%.
4. Well versed with carbohydrate counting.
5. Age 18-75 years.
6. BMI 20-40 kg/m2
Exclusion Criteria:
1. Type 1 diabetes for less than 6 months;
2. Coronary event or procedure (myocardial infarction, unstable angina, coronary artery
bypass, surgery or coronary angioplasty) in the previous four weeks;
3. Hepatic disease (transaminase > 3 times normal) or cirrhosis;
4. Renal impairment (serum eGFR < 30ml/min/1.73m2);
5. HIV or Hepatitis B or C positive status;
6. Participation in any other concurrent clinical trial;
7. Any other life-threatening, non-cardiac disease;
8. Use of an investigational agent or therapeutic regimen within 30 days of study.
9. history of pancreatitis
10. pregnancy
11. inability to give informed consent
12. history of gastroparesis
13. history of medullary thyroid carcinoma or MEN 2 syndrome.
We found this trial at
1
site
Buffalo, New York 14209
Principal Investigator: Paresh Dandona, MBBS,PhD
Phone: 716-898-1950
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