Contact information
Type
Scientific
Primary contact
Dr Joy Cuthbertson
ORCID ID
Contact details
11 Village Green
Doagh
Ballyclare
Northern Ireland
BT39 0UD
United Kingdom
+44 (0)77614 01203
joycuthbertson@msn.com
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
RGHT000140
Study information
Scientific title
Acronym
Study hypothesis
Metformin inhibits dipeptidyl peptidase IV (DPPIV) degradation and increases physiological effects of glucagon-like peptide-1 (GLP-1).
Ethics approval
Health and Personal Social Services (HPSS) Research Ethics Committee 3, approved on 29th November 2005 (ref: HPSSREC 05/NIR03/181)
Study design
Ramdomised cross-over controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Condition
Type 2 diabetes
Intervention
Drugs/placebo administered in Study A and B:
A/B 1: one placebo tablet (oral) stat dose
A/B 2: 1 g metformin (oral) stat dose
A/B 3: 120 mg nateglinide (oral) stat dose
In Study A and B all subjects received the two drugs and placebo, one at a time in different orders as single doses, at each visit one week apart. The subjects were given a standard mixed meal. Study B was extended with subjects returning; this time they were kept fasting. In Study A subjects were not on any oral hypoglycaemic agents. In Study B if any of the subjects were on an oral hypoglycaemic agent this was stopped for a 3-week washout period prior to starting the study.
In Study C and D the subjects received all three combinations below, one combination as a single dose at a time, one week apart:
Cross-over combinations for study C:
C1: placebo (oral) and 1.5 nmol/kg body weight GLP-1 subcutaneous (sc) stat dose
C2: 120 mg nateglinide (oral) and 1.5 nmol/kg body weight GLP-1 sc stat dose
C3: 120 mg nateglinide (oral) and 1 ml normal saline sc stat dose
Cross-over combinations for Study D:
D1: placebo (oral) and 1.5 nmol/kg body weight GLP-1 sc stat dose
D2: 1 g metformin (oral) and 1.5 nmol/kg body weight GLP-1 sc stat dose
D3: 1 g metformin (oral) and 1 ml normal saline sc stat dose
Intervention type
Drug
Phase
Not Specified
Drug names
Metformin, nateglinide, glucagon-like peptide-1 (GLP-1)
Primary outcome measures
Blood samples were collected from the participants at -5, 0, 30, 60, 120, 180 and 240 minutes for the measurements of the following:
1. Glucose
2. Insulin
3. C-peptide
4. DPPIV activity
5. GLP-1
Secondary outcome measures
Serum metformin levels, measured by high performance liquid chromatography on blood samples collected at 0, 60, 120 and 240 minutes.
Overall trial start date
03/08/2005
Overall trial end date
01/08/2007
Reason abandoned
Eligibility
Participant inclusion criteria
1. Both males and females, aged greater than 18 years
2. Type 2 diabetes controlled by diet or a single oral hypoglycaemic agent
3. HbA1c less than 7.5%
4. No significant liver, cardiac or renal problems (creatinine greater than 150 mmol/l)
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
40
Participant exclusion criteria
Type 2 diabetes on two or more hypoglycaemic agents or requiring insulin.
Recruitment start date
03/08/2005
Recruitment end date
01/08/2007
Locations
Countries of recruitment
United Kingdom
Trial participating centre
11 Village Green
Northern Ireland
BT39 0UD
United Kingdom
Sponsor information
Organisation
Royal Victoria Hospital (UK)
Sponsor details
274 Grosvenor Road
Belfast
Northern Ireland
BT12 6BA
United Kingdom
Sponsor type
Other
Website
Funders
Funder type
Government
Funder name
Northern Ireland Health and Social Services Central Services Agency (UK) - Research and Development Fellowship (ref: EAT/2955/04)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary
2009 results in: http://www.ncbi.nlm.nih.gov/pubmed/19538242
2011 results in: http://www.ncbi.nlm.nih.gov/pubmed/20152998
2011 results in: http://www.ncbi.nlm.nih.gov/pubmed/21194775
Publication citations
-
Results
Cuthbertson J, Patterson S, O'Harte FP, Bell PM, Investigation of the effect of oral metformin on dipeptidylpeptidase-4 (DPP-4) activity in Type 2 diabetes., Diabet. Med., 2009, 26, 6, 649-654, doi: 10.1111/j.1464-5491.2009.02748.x.
-
Results
Cuthbertson J, Patterson S, O'Harte FP, Bell PM, Addition of metformin to exogenous glucagon-like peptide-1 results in increased serum glucagon-like peptide-1 concentrations and greater glucose lowering in type 2 diabetes mellitus., Metab. Clin. Exp., 2011, 60, 1, 52-56, doi: 10.1016/j.metabol.2010.01.001.
-
Results
Bell PM, Cuthbertson J, Patterson S, O'Harte FP, Additive hypoglycaemic effect of nateglinide and exogenous glucagon-like peptide-1 in type 2 diabetes., Diabetes Res. Clin. Pract., 2011, 91, 3, e68-70, doi: 10.1016/j.diabres.2010.11.033.