Condition category
Nutritional, Metabolic, Endocrine
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information



Primary contact

Dr Joy Cuthbertson


Contact details

11 Village Green
Northern Ireland
BT39 0UD
United Kingdom
+44 (0)77614 01203

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

Scientific title


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


Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type


Patient information sheet


Type 2 diabetes


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



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


Overall trial end date


Reason abandoned


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


Age group




Target number of participants


Participant exclusion criteria

Type 2 diabetes on two or more hypoglycaemic agents or requiring insulin.

Recruitment start date


Recruitment end date



Countries of recruitment

United Kingdom

Trial participating centre

11 Village Green
Northern Ireland
BT39 0UD
United Kingdom

Sponsor information


Royal Victoria Hospital (UK)

Sponsor details

274 Grosvenor Road
Northern Ireland
BT12 6BA
United Kingdom

Sponsor type




Funder type


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


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:
2011 results in:
2011 results in:

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