Condition category
Nutritional, Metabolic, Endocrine
Date applied
26/09/2007
Date assigned
28/11/2008
Last edited
25/09/2013
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

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

http://www.belfasttrust.hscni.net/hospitals/RVHIntro.htm

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

  1. 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.

  2. 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.

  3. 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.

Additional files

Editorial Notes