D012139SEPSMETNCT07591402
Metformine as a Protective Factor of Mortality in Type 2 Diabetic Patients Admitted to the ICU for Septic Shock.
An observational study of D012139 and D003924, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Septic shock is a major complication of sepsis and is one of the leading causes of admission to intensive care unit (ICU) as well as a major contributor to global mortality, accounting for one in five deaths worldwide and approximately 11 million deaths annually. Read more about this study
- Who is it for?
- Ages 18 years and older
- How many people
- 2,740 participants
- Where
- 1 siteFrance
- Study dates
- 15 Oct 2019to 15 Dec 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Adults patients with type 2 diabete admitted for septic shock to one of the 30 ICU across18 parisians hospitals (APHP) , from July 2017 to September 2022
Who may be able to join
- Patients with type 2 diabete
- admitted for septic shock to ICU (APHP) , from July 2017 to September 2022.
Who cannot join
- Patients under the age of 18,
- without electronical medical record,
- whithout any information about their antidiabetic treatment and those with multiple ICU hospitalization.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Metformine as a Protective Factor of Mortality in Type 2 Diabetic Patients Admitted to the ICU for Septic Shock: a Multicentre Retrospective Cohort Study.
Septic shock is a major complication of sepsis and is one of the leading causes of admission to intensive care unit (ICU) as well as a major contributor to global mortality, accounting for one in five deaths worldwide and approximately 11 million deaths annually. There is around 530 millions of people living with diabetes, with type 2 diabetes accounting for 96% of these population. Among these patients, septic shock is a major concern, as they are more susceptible to developing infections and have more associated comorbidities. Metformin is the first line oral treatment for type 2 diabete. Beyond its metabolic effects, metformin has pleitropic effects exerting actions on mitochondrial metabolism and immune-inflammatory pathway that could potentially be benefit in septic shock. Several observational studies, converge on a reduction in mortality among patients treated with long-term metformin prior to their admission to the ICU for sepsis or septic shock as well as a reduction in renal dysfunction. Despite these results, the current literature remains highly heterogeneous in its methodology. Most studies focused on patients with sepsis rather than targetting specifically most severe patients with septic shock. Study designs vary widely, most of them are monocentric, some included patients in the emergency departments and others compared type 2 diabetic patients to patients without any history of diabetes making comparisons and generalisation of findings difficult. The main objective of this study was to evaluate the effect of pre-admission metformin exposure in type 2 diabetic patients admitted to the ICU for septic shock on 30-day mortality and on organ failures.
Read the detailed description
Septic shock is one of the leading causes of admission to intensive care units (ICU), with an incidence of approximately 19 million patients per year worldwide. Despite progress made in the management of patients suffering from this condition, mortality and morbidity remain high and show little improvement. Indeed, according to studies, the mortality rate of septic shock ranges from 25 to 30%. Diabetic patients, due to their susceptibility to infections and greater vulnerability, represent a significant proportion of patient cohorts in septic shock. Moreover, diabetes is a factor of poor prognosis during septic shock.
Metformin, an oral anti-diabetic treatment, is currently considered the first-line therapy for type 2 diabetes. It modifies glucose metabolism by inhibiting, notably at the mitochondrial level, the electron transport chain through the inhibition of complex I. This inhibition of complex I decreases mitochondrial production of Adenosine Triphosphate (ATP) and induces activation of AMPK, a key enzyme in energy metabolism. Thus, metformin is responsible for an increase in glycolysis and an inhibition of gluconeogenesis in the liver.
During septic shock, mitochondrial ATP production is limited due to decreased arterial oxygen transport, leading to tissue hypoxia and mitochondrial dysfunction. This results in increased anaerobic energy production through activation of glycolysis, and consequently, increased lactate production responsible for metabolic acidosis. Several studies focusing on septic shock have observed that hyperlactatemia during the initial hours of management is a factor of poor prognosis.
Given the alterations in mitochondrial metabolism caused by metformin, which may exacerbate hyperlactatemia, its potential accumulation in cases of acute renal failure, the hepatic metabolism of lactate, and the deleterious consequences of lactic metabolic acidosis, it is recommended to discontinue metformin during septic shock. However, despite these recommendations, some studies suggest a lower mortality rate in septic shock patients treated with metformin, despite older age, higher rates of cardiovascular disease, and renal failure.
The first hypothesis is that patients on metformin may have better adaptation of their energy metabolism during a significant drop in oxygen supply (a mitochondrial adaptive mechanism reducing energy needs), which limits oxidative stress and its harmful effects. The second hypothesis is that metformin has an immunomodulatory role, resulting in a more moderate inflammatory response in case of infection, and thus less endothelial and visceral dysfunction. Thus, metformin, through modification of mitochondrial metabolism, appears to have pleiotropic, anti-inflammatory, antithrombotic, and vasoactive effects that could be beneficial in septic shock. The benefit of metformin in patients with septic shock therefore needs to be clarified through well-conducted large cohort studies.
- Keywords
- type 2 diabete, septic shock
- Medical subject headings
- Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Patients who receiving metformin before the inclusion | Patients with type 2 diabete admitted to ICU for septic shock who receiving metformin before the inclusion | |
| Patients who receiving other antidiabetic drugs before the inclusion | Patients with type 2 diabete admitted to ICU for septic shock who receiving other antidiabetic drugs before the inclusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
30-day mortality
The primary objective of this study is to evaluate the effect of metformin treatment on mortality in septic shock among type II diabetics patients.
The primary endpoint is mortality within a 30-day time frame following admission to the intensive care unit.
Measured: 30 days
Secondary outcomes (5)
90-day mortality
Evaluate the effect of metformin treatment on mortality at 90 days after ICU admission.
Measured: 90 days after ICU admission.
Multiorgan failures
Number of patients with at least one organ failure, defined by the presence of ≥1 ICD-10 diagnosis code for renal, hemodynamic, cardiac, respiratory, or hepatic failure.
Measured: From ICU admission to ICU discharge (up to 30 days)
Duration of vasopressor use
Duration of vasopressor use, defined as the cumulative number of days with administration of vasopressors based on repeated CCAM code EQLF003 (each code corresponding to 24 hours of therapy)
Measured: From ICU admission to ICU discharge (up to 30 days)
Mechanical ventilation
Number of patients with mechanical ventilation, defined by the presence of ≥1 CCAM procedure code for mechanical ventilation
Measured: From hospital admission to hospital discharge (up to 30 days)
Acute Kidney Injury (AKI)
Number of participants with acute kidney injury (AKI), defined according to the Kidney Disease Improving Global Outcomes (KDIGO)
Measured: From ICU admission to ICU discharge (up to 30 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2026
- Study start15 Oct 2019
- Primary completion1 Dec 2022
- Study completion15 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for D012139Studies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 2,740 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Marie Werner, MD, Principal investigator, Service d'Anesthésie Réanimation Chirurgicale, DMU 12 Anesthésie Réanimation Chirurgicale Médecine Péri-opératoire et Douleur, Hôpital Bicêtre, AP-HP, Université Paris-Saclay, Le Kremlin-Bicêtre, France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07591402
- Sponsor's protocol ID
- APHP240993
- Other IDs
- CSE 19-0019
- Acronym
- SEPSMET
- Status last verified
- Nov 2025
- First submitted
- 19 Nov 2025
- Last updated
- 15 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metformine as a Protective Factor of Mortality in Type 2 Diabetic Patients Admitted to the ICU for Septic Shock: a Multicentre Retrospective Cohort Study.
- ClinicalTrials.gov ID
- NCT07591402
- Acronym / sponsor ID
- SEPSMET / APHP240993
- Keywords
- type 2 diabete, septic shock
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 2,740 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 15 Oct 2019 (actual)
- Primary completion
- 1 Dec 2022 (actual)
- Study completion
- 15 Dec 2024 (actual)
- First posted
- 15 May 2026 (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.
Septic shock is a major complication of sepsis and is one of the leading causes of admission to intensive care unit (ICU) as well as a major contributor to global mortality, accounting for one in five deaths worldwide and approximately 11 million deaths annually. There is around 530 millions of people living with diabetes, with type 2 diabetes accounting for 96% of these population. Among these patients, septic shock is a major concern, as they are more susceptible to developing infections and have more associated comorbidities. Metformin is the first line oral treatment for type 2 diabete. Beyond its metabolic effects, metformin has pleitropic effects exerting actions on mitochondrial metabolism and immune-inflammatory pathway that could potentially be benefit in septic shock. Several observational studies, converge on a reduction in mortality among patients treated with long-term metformin prior to their admission to the ICU for sepsis or septic shock as well as a reduction in renal dysfunction. Despite these results, the current literature remains highly heterogeneous in its methodology. Most studies focused on patients with sepsis rather than targetting specifically most severe patients with septic shock. Study designs vary widely, most of them are monocentric, some included patients in the emergency departments and others compared type 2 diabetic patients to patients without any history of diabetes making comparisons and generalisation of findings difficult. The main objective of this study was to evaluate the effect of pre-admission metformin exposure in type 2 diabetic patients admitted to the ICU for septic shock on 30-day mortality and on organ failures.
Detailed description
Septic shock is one of the leading causes of admission to intensive care units (ICU), with an incidence of approximately 19 million patients per year worldwide. Despite progress made in the management of patients suffering from this condition, mortality and morbidity remain high and show little improvement. Indeed, according to studies, the mortality rate of septic shock ranges from 25 to 30%. Diabetic patients, due to their susceptibility to infections and greater vulnerability, represent a significant proportion of patient cohorts in septic shock. Moreover, diabetes is a factor of poor prognosis during septic shock.
Metformin, an oral anti-diabetic treatment, is currently considered the first-line therapy for type 2 diabetes. It modifies glucose metabolism by inhibiting, notably at the mitochondrial level, the electron transport chain through the inhibition of complex I. This inhibition of complex I decreases mitochondrial production of Adenosine Triphosphate (ATP) and induces activation of AMPK, a key enzyme in energy metabolism. Thus, metformin is responsible for an increase in glycolysis and an inhibition of gluconeogenesis in the liver.
During septic shock, mitochondrial ATP production is limited due to decreased arterial oxygen transport, leading to tissue hypoxia and mitochondrial dysfunction. This results in increased anaerobic energy production through activation of glycolysis, and consequently, increased lactate production responsible for metabolic acidosis. Several studies focusing on septic shock have observed that hyperlactatemia during the initial hours of management is a factor of poor prognosis.
Given the alterations in mitochondrial metabolism caused by metformin, which may exacerbate hyperlactatemia, its potential accumulation in cases of acute renal failure, the hepatic metabolism of lactate, and the deleterious consequences of lactic metabolic acidosis, it is recommended to discontinue metformin during septic shock. However, despite these recommendations, some studies suggest a lower mortality rate in septic shock patients treated with metformin, despite older age, higher rates of cardiovascular disease, and renal failure.
The first hypothesis is that patients on metformin may have better adaptation of their energy metabolism during a significant drop in oxygen supply (a mitochondrial adaptive mechanism reducing energy needs), which limits oxidative stress and its harmful effects. The second hypothesis is that metformin has an immunomodulatory role, resulting in a more moderate inflammatory response in case of infection, and thus less endothelial and visceral dysfunction. Thus, metformin, through modification of mitochondrial metabolism, appears to have pleiotropic, anti-inflammatory, antithrombotic, and vasoactive effects that could be beneficial in septic shock. The benefit of metformin in patients with septic shock therefore needs to be clarified through well-conducted large cohort studies.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients who receiving metformin before the inclusion | – | –Patients with type 2 diabete admitted to ICU for septic shock who receiving metformin before the inclusion |
| Patients who receiving other antidiabetic drugs before the inclusion | – | –Patients with type 2 diabete admitted to ICU for septic shock who receiving other antidiabetic drugs before the inclusion |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Adults patients with type 2 diabete admitted for septic shock to one of the 30 ICU across18 parisians hospitals (APHP) , from July 2017 to September 2022
Key inclusion criteria (2 listed)
- Patients with type 2 diabete
- admitted for septic shock to ICU (APHP) , from July 2017 to September 2022.
Key exclusion criteria (3 listed)
- Patients under the age of 18,
- without electronical medical record,
- whithout any information about their antidiabetic treatment and those with multiple ICU hospitalization.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
30-day mortality
Time frame: 30 days
The primary objective of this study is to evaluate the effect of metformin treatment on mortality in septic shock among type II diabetics patients. The primary endpoint is mortality within a 30-day time frame following admission to the intensive care unit.
5 secondary outcomes
90-day mortality
Time frame: 90 days after ICU admission.
Multiorgan failures
Time frame: From ICU admission to ICU discharge (up to 30 days)
Duration of vasopressor use
Time frame: From ICU admission to ICU discharge (up to 30 days)
Mechanical ventilation
Time frame: From hospital admission to hospital discharge (up to 30 days)
Acute Kidney Injury (AKI)
Time frame: From ICU admission to ICU discharge (up to 30 days)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2026.
- Individual participant dataSharing planned: No
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.
Marie Werner, MD principal investigator
Service d'Anesthésie Réanimation Chirurgicale, DMU 12 Anesthésie Réanimation Chirurgicale Médecine Péri-opératoire et Douleur, Hôpital Bicêtre, AP-HP, Université Paris-Saclay, Le Kremlin-Bicêtre, France
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of D012139 and D003924, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 2 inclusion and 3 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 May 2026. 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 France. 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. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
30-day mortality (time frame: 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 May 2026.