Type 2 DiabetesIMPACTNCT04088851
"Hepatic Substrate Flux Rates in Type 2 Diabetes"
A study testing On Metformin and Off Metformin in people with Type 2 Diabetes, run by German Diabetes Center at 1 site in Germany.
Trial summary
Investigation of the effects of redox shuttle inhibition by metformin on gluconeogenic flux rates of lactate and glycerol in humans with type 2 diabetes Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Type 2 Diabetes
- What is being tested?
- On Metformin and Off Metformin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 23 participants
- Where
- 1 siteGermany
- Study dates
- 11 Sep 2019to 31 Dec 2025
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- type 2 diabetes (duration <7 years),
- age (18-75 years)
- BMI <40 kg/m2
- HbA1c 6-15%
Who cannot join
- uncontrolled hyperglycaemia (>340 mg/dl)
- diabetes types other than type 2 diabetes (ADA criteria)
- thiazolidinedione use during the preceding 6 months
- clinically relevant angiopathy, restrictive or obstructive lung diseases
- other acute or chronic diseases including wounds and the use of pharmacological agents known to affect insulin sensitivity, lipid metabolism or immunological function.
Trial locations and contacts
1 site in 1 country.
Germany1 site
German Diabetes Center
Düsseldorf, North Rhine-Westphalia, 40225
About this study
Official title: "Non-invasive Measurement of Hepatic Substrate Flux Rates in People with Diabetes Mellitus Type 2"
Investigation of the effects of redox shuttle inhibition by metformin on gluconeogenic flux rates of lactate and glycerol in humans with type 2 diabetes
Read the detailed description
Type 2 diabetes (T2D) is characterized by insulin resistance and relative insulin deficiency leading to hyperglycemia. Enhanced endogenous glucose production during fasting is a key feature of hepatic insulin resistance and a major contributor to deterioration of glycemia. Metformin reduces fasting gluconeogenesis (GNG); the underlying mechanisms are still not fully understood, but involve the inhibition of complexes of the electron transport chain and thus the redox shuttle.
The investigators have previously provided evidence for abnormal hepatic ATP synthesis and mitochondrial efficiency in T2D, but it remains unknown, how and which substrate fluxes account for excessive GNG in T2D. For this reason, this proposal aims at investigating hepatic glucose and energy fluxes in T2D with focus on gluconeogenic contribution of lactate and glycerol to hepatic mitochondrial substrate flux, mitochondrial ATP synthase flux and the activity of the redox shuttle, also after metformin intake, by using a novel combination of positional isotopomer nuclear magnetic resonance (NMR) analysis (PINTA) with multinuclei magnetic resonance spectroscopy (MRS).
- Conditions
- Type 2 Diabetes
- Being tested
- On Metformin, Off Metformin
- Keywords
- type 2 diabetes, redox shuttle, gluconeogenesis
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
On MetforminDrug
Oral intake of Metformin (1 g / day) for 2 weeks
Off MetforminDrug
No oral intake of Metformin (1 g / day) for 2 weeks
| Study group | Role | What they receive |
|---|---|---|
| Metformin - T2D | Experimental | Participants with type-2 diabetes will intake metformin 1 g daily for 2 weeks Receives: Drug: On Metformin |
| No Metformin - T2D | Placebo comparator | Participants with type-2 diabetes will pause metformin 1 g daily for 2 weeks Receives: Drug: Off Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hepatic gluconeogenic flux (U-13C-lactate tracer) (mg/min)
Hepatic gluconeogenic flux rates from lactate [mg/min] in humans with T2D w/wo metformin treatment will be measured by specific tracer metabolism and turnover of the substrates.
Measured: 2 weeks
Hepatic gluconeogenic flux (glycerol tracer) (mg/min)
Hepatic gluconeogenic flux rates from glycerol [mg/min] in humans with T2D w/wo metformin treatment will be measured by specific tracer metabolism and turnover of the substrates.
Measured: 2 weeks
Secondary outcomes (4)
Endogenous glucose production (mg/min/kg BW)
Endogenous glucose production (mg/min/kg BW) in humans with T2D w/wo metformin treatment will be measured by specific tracer metabolism and turnover of the substrates.
Measured: 2 weeks
Hepatic mitochondrial oxidative flux (mg/min)
Hepatic mitochondrial oxidative flux (mg/min) in humans with T2D w/wo metformin treatment will be measured by specific tracer metabolism and turnover of the substrates.
Measured: 2 weeks
Hepatic gammaATP (mmol/L)
Hepatic energy [ATP mmol/l] content will be assessed in people with T2D with and without metformin treatment by employing specific 31P- magnetic resonance spectroscopy.
Measured: 2 weeks
Hepatic lipid content (%)
Hepatic fat [%] content will be assessed in people with T2D with and without metformin treatment by employing specific 1H- magnetic resonance spectroscopy.
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2019
- Study start11 Sep 2019
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)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 N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 23 participants (estimated)
Sponsor and investigators
- Lead sponsor
- German Diabetes Center
- Sponsor type
- University, hospital or other
- Collaborators
- Yale University
- Responsible party
- Sponsor
- Investigators
- Michael Roden, Prof., MD, Principal investigator, German Diabetes Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04088851
- Sponsor's protocol ID
- IMPACT
- Acronym
- IMPACT
- Status last verified
- Dec 2024
- First submitted
- 11 Sep 2019
- Last updated
- 13 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kahl S, LaMoia TE, Jonuscheit M, Heilmann G, Rohrer S, Bobrov P, Dewidar B, Pafili K, Sarabhai T, Schrauwen-Hinderling V, Shulman GI, Petersen KF, Roden M. Metformin Lowers Fasting Hyperglycemia by Increasing Glucose Clearance in People with Moderately Controlled Type 2 Diabetes. Drugs. 2026 Oct 15. doi: 10.1007/s40265-026-02370-6. Online ahead of print.
PubMed 42875657
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- "Non-invasive Measurement of Hepatic Substrate Flux Rates in People with Diabetes Mellitus Type 2"
- ClinicalTrials.gov ID
- NCT04088851
- Acronym / sponsor ID
- IMPACT / IMPACT
- Conditions
- Type 2 Diabetes
- Keywords
- type 2 diabetes, redox shuttle, gluconeogenesis
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 23 participants (estimated)
- Lead sponsor
- German Diabetes CenterUniversity, hospital or other
- Collaborators
- Yale University
- Study start
- 11 Sep 2019 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 13 Sep 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Investigation of the effects of redox shuttle inhibition by metformin on gluconeogenic flux rates of lactate and glycerol in humans with type 2 diabetes
Detailed description
Type 2 diabetes (T2D) is characterized by insulin resistance and relative insulin deficiency leading to hyperglycemia. Enhanced endogenous glucose production during fasting is a key feature of hepatic insulin resistance and a major contributor to deterioration of glycemia. Metformin reduces fasting gluconeogenesis (GNG); the underlying mechanisms are still not fully understood, but involve the inhibition of complexes of the electron transport chain and thus the redox shuttle.
The investigators have previously provided evidence for abnormal hepatic ATP synthesis and mitochondrial efficiency in T2D, but it remains unknown, how and which substrate fluxes account for excessive GNG in T2D. For this reason, this proposal aims at investigating hepatic glucose and energy fluxes in T2D with focus on gluconeogenic contribution of lactate and glycerol to hepatic mitochondrial substrate flux, mitochondrial ATP synthase flux and the activity of the redox shuttle, also after metformin intake, by using a novel combination of positional isotopomer nuclear magnetic resonance (NMR) analysis (PINTA) with multinuclei magnetic resonance spectroscopy (MRS).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Metformin - T2D | Experimental | Drug: On MetforminParticipants with type-2 diabetes will intake metformin 1 g daily for 2 weeks |
| No Metformin - T2D | Placebo comparator | Drug: Off MetforminParticipants with type-2 diabetes will pause metformin 1 g daily for 2 weeks |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- type 2 diabetes (duration <7 years),
- age (18-75 years)
- BMI <40 kg/m2
- HbA1c 6-15%
Key exclusion criteria (5 listed)
- uncontrolled hyperglycaemia (>340 mg/dl)
- diabetes types other than type 2 diabetes (ADA criteria)
- thiazolidinedione use during the preceding 6 months
- clinically relevant angiopathy, restrictive or obstructive lung diseases
- other acute or chronic diseases including wounds and the use of pharmacological agents known to affect insulin sensitivity, lipid metabolism or immunological function.
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 |
|---|---|---|
| On MetforminOral intake of Metformin (1 g / day) for 2 weeks | Drug | Metformin - T2D |
| Off MetforminNo oral intake of Metformin (1 g / day) for 2 weeks | Drug | No Metformin - T2D |
Primary outcome
Hepatic gluconeogenic flux (U-13C-lactate tracer) (mg/min)
Time frame: 2 weeks
Hepatic gluconeogenic flux rates from lactate [mg/min] in humans with T2D w/wo metformin treatment will be measured by specific tracer metabolism and turnover of the substrates.
Hepatic gluconeogenic flux (glycerol tracer) (mg/min)
Time frame: 2 weeks
Hepatic gluconeogenic flux rates from glycerol [mg/min] in humans with T2D w/wo metformin treatment will be measured by specific tracer metabolism and turnover of the substrates.
4 secondary outcomes
Endogenous glucose production (mg/min/kg BW)
Time frame: 2 weeks
Hepatic mitochondrial oxidative flux (mg/min)
Time frame: 2 weeks
Hepatic gammaATP (mmol/L)
Time frame: 2 weeks
Hepatic lipid content (%)
Time frame: 2 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2025.
- Derived from this study: PubMed 42875657Kahl S, LaMoia TE, Jonuscheit M, Heilmann G, Rohrer S, Bobrov P, Dewidar B, Pafili K, Sarabhai T, Schrauwen-Hinderling V, Shulman GI, Petersen KF, Roden M. Metformin Lowers Fasting Hyperglycemia by Increasing Glucose Clearance in People with Moderately Controlled Type 2 Diabetes. Drugs. 2026 Oct 15. doi: 10.1007/s40265-026-02370-6. Online ahead of print.
- Individual participant dataSharing planned: No
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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.
Michael Roden, Prof., MD principal investigator
German Diabetes Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing On Metformin and Off Metformin in people with Type 2 Diabetes, run by German Diabetes Center at 1 site in Germany.
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 4 inclusion and 5 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: under way, not looking for participants, as of the sponsor's last update on 13 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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 gluconeogenic flux (U-13C-lactate tracer) (mg/min) (time frame: 2 weeks). The study lists 2 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 NCT04088851, which also lists 1 linked publication.
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 13 Jan 2025.