Type 2 DiabetesPhase 4NCT01729156

Effects of Metformin on Hepatic FFA Metabolism

A Phase 4 study testing Metformin in people with Type 2 Diabetes and Dyslipidemia, run by Lars Christian Gormsen.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 50 to 70 yearsHealthy volunteers can take part
Conditions the study is for: Type 2 Diabetes, Dyslipidemia
What is being tested?: Metformin
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 36 participants
Where: No sites listed yet
Study dates: Jan 2013to 5 May 2017
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 50 to 70 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

Recently diagnosed type 2 diabetes
Age 50-70 years
BMI<40

Who cannot join

Insulin treatment
NASH (non alcoholic steatohepatitis)
Cancer
Anemia
HbA1C>8.5 %
Chronic or acute pancreatitis

Show all 10Show fewer

Alcohol or medicine abuse
Allergy towards metformin
Claustrophobia
Severe obesity (weight >130 kilogram)

About this study

Official title: Effects of Metformin on Hepatic Free Fatty Acid Metabolism in Patients Diagnosed With Type 2 Diabetes: A C11 PET Study

Background: Metformin treatment has beneficial effects on both glucose and lipid metabolism. Whereas there is general agreement that the blood glucose lowering effect of metformin results from inhibition of hepatic gluconeogenesis, it is less clear exactly how the drug lowers blood triglyceride concentration. There are indications that it enhances hepatic free fatty acid (FFA) oxidation thus diminishing substrate for reesterification and resecretion as very-low-density-lipoprotein (VLDL) triglycerides (TG). However, the liver is not easily accessible for sampling in humans and data on the clinical effects of metformin in the liver are therefore lacking. This may change due to the increasing use of the positron emission tomography (PET) technique. Using PET isotopes (11C or 18F) coupled to either palmitate or a fatty acid analogue, it is possible to non-invasively measure hepatic fatty acid handling.

Aim: To determine how 3 months metformin treatment (1000 mg twice daily) affects hepatic lipid and glucose metabolism in patients with newly diagnosed type 2 diabetes.

Design: Randomized, placebo controlled, double-blind parallel study with patients receiving either metformin or placebo. A control group of BMI and age-matched non-diabetic individuals will receive metformin for 3 months.

Hypothesis: Metformin lowers VLDL-TG secretion and circulating triglycerides by increasing hepatic fatty acid oxidation

Conditions: Type 2 Diabetes, Dyslipidemia
Being tested: Metformin, Placebo
Keywords: Type 2 diabetes, Hepatic fatty acid oxidation, Dyslipidemia, Metformin
Medical subject headings: Diabetes Mellitus, Type 2, Dyslipidemias

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MetforminDrug
Also called Metformin "Sandoz" 500 mg
1000 mg metformin twice daily in 3 months
PlaceboDrug
2 tablets twice daily in 3 months

Study groups in NCT01729156
Study group	Role	What they receive
Healthy controls	Other	Healthy controls receiving 1000 mg metformin twice daily for 3 months Receives: Drug: Metformin
Placebo	Placebo comparator	Placebo Receives: Drug: Placebo
Metformin	Active comparator	Metformin "Sandoz", 1000 mg twice daily for 3 months Receives: Drug: Metformin

What is being measured

The primary outcome is the main question the study is designed to answer.

Hepatic Fatty Acid Oxidation
Hepatic fatty acid oxidation assessed by dynamic C11-palmitate PET
Measured: 90 days
Hepatic Fatty Acid Reesterification
Hepatic fatty acid reesterification assessed by C11-palmitate PET
Measured: 90 days
Hepatic Fatty Acid Uptake
Hepatic fatty acid uptake assessed by C11-palmitate PET
Measured: 90 days
VLDL-TG Secretion
Hepatic VLDL-TG secretion assessed by [1-14C] VLDL tracer
Measured: 90 days
Whole Body Glucose Rd
Whole body basal glucose metabolism assessed by [3-3H]glucose tracer kinetics
Measured: 90 days

Secondary outcomes (2)

Fatty Acid Turnover
Fatty acid turnover assessed as whole body C11-palmitate turnover
Measured: 90 days
VLDL-TG Oxidation
VLDL-TG oxidation assessed by 14C carbon dioxide (CO2) in exhaled breath
Measured: 90 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 20135 May 2017

First posted20 Nov 2012 (estimated)
Study startJan 2013
Primary completion5 May 2017
Study completion5 May 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 36 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01729156
Sponsor's protocol ID: C11palmitatMetformin
Status last verified: Sep 2019
First submitted: 13 Nov 2012
Last updated: 15 Oct 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Pedersen AKN, Gormsen LC, Nielsen S, Jessen N, Bjerre M. Metformin Improves the Prerequisites for FGF21 Signaling in Patients With Type 2 Diabetes. J Clin Endocrinol Metab. 2024 Jan 18;109(2):e552-e561. doi: 10.1210/clinem/dgad583.
PubMed 37776319
Gormsen LC, Sondergaard E, Christensen NL, Brosen K, Jessen N, Nielsen S. Metformin increases endogenous glucose production in non-diabetic individuals and individuals with recent-onset type 2 diabetes. Diabetologia. 2019 Jul;62(7):1251-1256. doi: 10.1007/s00125-019-4872-7. Epub 2019 Apr 11.
PubMed 30976851

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

Not yet recruitingPhase 3
Efficacy and Safety of Once-Weekly SHR-3167 Compared With Once-Daily Insulin Glargine in Adults With Insulin-Naive Type 2 Diabetes
Type 2 Diabetes
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Not yet recruitingPhase 3
A Study to Evaluate the Effectiveness and Safety of the Drug AZD6234 for Managing Weight in Adults Who Are Obese or Overweight. These Participants May or May Not Also Have Type 2 Diabetes
Obesity, Overweight
Not yet recruiting
Impact of Endoscopic Sleeve Gastroplasty (ESG) in Obese Adults With Type 2 Diabetes (T2D)
Type 2 Diabetes Mellitus (T2D), Obesity (BMI>30)

All Type 2 Diabetes trials

Study at a glance

From the registry record, last updated by the sponsor on 15 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Effects of Metformin on Hepatic Free Fatty Acid Metabolism in Patients Diagnosed With Type 2 Diabetes: A C11 PET Study
ClinicalTrials.gov ID: NCT01729156
Acronym / sponsor ID: C11palmitatMetformin
Conditions: Type 2 Diabetes, Dyslipidemia
Keywords: Type 2 diabetes, Hepatic fatty acid oxidation, Dyslipidemia, Metformin
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 36 participants (actual)
Lead sponsor: Lars Christian GormsenUniversity, hospital or other
Study start: Jan 2013
Primary completion: 5 May 2017 (actual)
Study completion: 5 May 2017 (actual)
First posted: 20 Nov 2012 (estimated)
Results: Posted 15 Oct 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Aim: To determine how 3 months metformin treatment (1000 mg twice daily) affects hepatic lipid and glucose metabolism in patients with newly diagnosed type 2 diabetes.

Hypothesis: Metformin lowers VLDL-TG secretion and circulating triglycerides by increasing hepatic fatty acid oxidation

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 3

Arm	Type	Receives
Healthy controls	Other	Drug: MetforminHealthy controls receiving 1000 mg metformin twice daily for 3 months
Placebo	Placebo comparator	Drug: PlaceboPlacebo
Metformin	Active comparator	Drug: MetforminMetformin "Sandoz", 1000 mg twice daily for 3 months

Who may qualify

Ages: 50 to 70 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Recently diagnosed type 2 diabetes
Age 50-70 years
BMI<40

Key exclusion criteria (10 listed)

Insulin treatment
NASH (non alcoholic steatohepatitis)
Cancer
Anemia
HbA1C>8.5 %

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
MetforminAlso: Metformin "Sandoz" 500 mg1000 mg metformin twice daily in 3 months	Drug	Healthy controls, Metformin
Placebo2 tablets twice daily in 3 months	Drug	Placebo

Primary outcome

Hepatic Fatty Acid Oxidation
Time frame: 90 days
Hepatic fatty acid oxidation assessed by dynamic C11-palmitate PET
Hepatic Fatty Acid Reesterification
Time frame: 90 days
Hepatic fatty acid reesterification assessed by C11-palmitate PET
Hepatic Fatty Acid Uptake
Time frame: 90 days
Hepatic fatty acid uptake assessed by C11-palmitate PET
VLDL-TG Secretion
Time frame: 90 days
Hepatic VLDL-TG secretion assessed by [1-14C] VLDL tracer
Whole Body Glucose Rd
Time frame: 90 days
Whole body basal glucose metabolism assessed by [3-3H]glucose tracer kinetics

2 secondary outcomes

Fatty Acid Turnover
Time frame: 90 days
VLDL-TG Oxidation
Time frame: 90 days

Results and safety

Results posted to the registry on 15 Oct 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Healthy Controls	12	11
Placebo	12	12
Metformin	12	12

Primary outcome: Hepatic Fatty Acid Oxidation

Time frame: 90 days. Mean (Standard Deviation). Unit: micromol/ml/min

Measure	Healthy Controls n = 10	Placebo n = 11	Metformin n = 10
Value	0.052 (0.024)	0.045 (0.024)	0.042 (0.017)

Primary outcome: Hepatic Fatty Acid Reesterification

Time frame: 90 days. Mean (Standard Deviation). Unit: micromol/ml/min

Measure	Healthy Controls n = 10	Placebo n = 11	Metformin n = 10
Value	0.134 (0.056)	0.091 (0.035)	0.113 (0.025)

Primary outcome: Hepatic Fatty Acid Uptake

Time frame: 90 days. Mean (Standard Deviation). Unit: micromol/ml/min

Measure	Healthy Controls n = 10	Placebo n = 11	Metformin n = 10
Value	0.186 (0.067)	0.137 (0.051)	0.155 (0.029)

Primary outcome: VLDL-TG Secretion

Time frame: 90 days. Mean (Standard Deviation). Unit: micromol/min

Measure	Healthy Controls n = 11	Placebo n = 11	Metformin n = 11
Value	48 (30)	83 (49)	71 (31)

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: During the 90 days trial. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Healthy Controls	0 of 12 (0%)	1 of 12 (8.3%)	0 of 12
Placebo	0 of 12 (0%)	1 of 12 (8.3%)	0 of 12
Metformin	0 of 12 (0%)	0 of 12 (0%)	0 of 12

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 37776319Pedersen AKN, Gormsen LC, Nielsen S, Jessen N, Bjerre M. Metformin Improves the Prerequisites for FGF21 Signaling in Patients With Type 2 Diabetes. J Clin Endocrinol Metab. 2024 Jan 18;109(2):e552-e561. doi: 10.1210/clinem/dgad583.
Derived from this study: PubMed 30976851Gormsen LC, Sondergaard E, Christensen NL, Brosen K, Jessen N, Nielsen S. Metformin increases endogenous glucose production in non-diabetic individuals and individuals with recent-onset type 2 diabetes. Diabetologia. 2019 Jul;62(7):1251-1256. doi: 10.1007/s00125-019-4872-7. Epub 2019 Apr 11.

Related trials for Type 2 Diabetes

Not yet recruitingPhase 3
Efficacy and Safety of Once-Weekly SHR-3167 Compared With Once-Daily Insulin Glargine in Adults With Insulin-Naive Type 2 Diabetes
Type 2 Diabetes
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Not yet recruitingPhase 3
A Study to Evaluate the Effectiveness and Safety of the Drug AZD6234 for Managing Weight in Adults Who Are Obese or Overweight. These Participants May or May Not Also Have Type 2 Diabetes
Obesity, Overweight
Not yet recruiting
Impact of Endoscopic Sleeve Gastroplasty (ESG) in Obese Adults With Type 2 Diabetes (T2D)
Type 2 Diabetes Mellitus (T2D), Obesity (BMI>30)

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Lars C Gormsen, MD PhD principal investigator

Aarhus University Hospital

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Metformin in people with Type 2 Diabetes and Dyslipidemia, run by Lars Christian Gormsen.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Hepatic Fatty Acid Oxidation (time frame: 90 days). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01729156, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2019.