Beyond diabetes: harnessing the power of metformin in burn care

Critical Care volume 29, Article number: 423 (2025) Published: 07 October 2025

Abstract

Burn injuries are complex and devastating traumas that trigger a profound systemic metabolic response, characterized by hyperglycemia, insulin resistance, and a hypermetabolic state. Notably, hyperglycemia is a critical determinant of worse prognoses in burn patients. While insulin has long been the gold standard for managing post-burn hyperglycemia, its therapy is associated with a risk of hypoglycemic events, which can exacerbate morbidity and compromise patient outcomes. As such, investigation of alternative therapeutics is warranted to improve glycemic control while mitigating associated risks. Recently, metformin, a first-line therapy for the treatment of type II diabetes, has emerged as a potential therapeutic agent for the management of post-burn hyperglycemia as well as other burn injury sequelae. This review examines the mechanistic underpinnings of metformin, its potential application in managing post-burn hyperglycemia, and its comparative advantages over other hypoglycemic agents. Additionally, we examine the broad spectrum of metformin’s pleiotropic effects in the context of burn injury–extending beyond glycemic control to include attenuation of muscle catabolism, suppression of lipolysis, regulation of non-shivering thermogenesis, support of mitochondrial and immune function, enhanced wound healing, and its potential role in addressing burn-induced acceleration of biological aging. Taken together, we discuss how metformin represents a paradigm shift in burn care, with the potential to substantially improve patient outcomes.

 

Comparison of all-cause mortality with different blood glucose control strategies in patients with diabetes in the ICU: a network meta-analysis of randomized controlled trials

Annals of Intensive Care volume 15, Article number: 51 (2025) Published: 09 April 2025

Background

The optimal glucose control strategy for intensive care unit (ICU) patients with diabetes remains a topic of debate. This study aimed to compare the effects of strict glucose control, intermediate strict glucose control, liberal glucose control, and very liberal glucose control on reducing all-cause mortality in ICU patients with diabetes through a network meta-analysis.

Methods

We conducted a search in PubMed, Cochrane Library, Embase, and Web of Science for randomized controlled trials comparing different glucose control strategies in ICU patients with diabetes up to October 1, 2024. The primary outcome was all-cause 90-day mortality. The Risk of Bias 2 tool was used to assess bias in the included studies. Data analysis was performed using Stata (version 17).

Results

A total of 12 randomized controlled trials involving 5,297 participants were included in the final analysis. The results showed that there was no statistically significant difference between the four glucose control strategies in reducing all-cause 90-day mortality. The surface under the cumulative ranking (SUCRA), which was used to rank the strategies and display the probability of each strategy being ranked first, showed the following: intermediate strict control (SUCRA 88%), liberal control (SUCRA 55.3%), very liberal control (SUCRA 40.3%), and strict control (SUCRA 16.5%). The cumulative probability of each strategy’s rank in reducing all-cause mortality, from best to worst, showed that the most likely ranking was intermediate strict control, liberal control, very liberal control, and strict control.

Conclusions

In ICU patients with diabetes, no significant statistical difference was observed among the four glucose control strategies in reducing all-cause 90-day mortality. The SUCRA rankings are hypothesis-generating and require further validation. Therefore, the current evidence is insufficient to definitively conclude that any one strategy is superior to the others in reducing mortality.

Association between metformin use prior to admission and lower mortality in septic adult patients with diabetes mellitus: beware of potential confounders

Association between metformin use prior to admission and lower mortality in septic adult patients with diabetes mellitus: beware of potential confounders

by Patrick M. Honore, Aude Mugisha, Luc Kugener, Sebastien Redant, Rachid Attou, Andrea Gallerani and David De Bels

Critical Care volume 24, Article number: 183 (2020) Published: 28 April 2020

We read with great interest the recent paper by Liang et al. who conclude that their meta-analysis indicated an association between metformin (MET) use prior to admission and lower mortality in septic adult patients with diabetes mellitus [1]. We would like to make some comments. Nearly half of critically ill patients, especially those with septic shock, have or develop acute kidney injury (AKI), and 20–25% need renal replacement therapy (RRT) within the first week of their admission [2]. Because of its low molecular weight and minimal protein binding, metformin is equally (highly) eliminated by ultrafiltration (convection) and dialysis (diffusion). Furthermore, its large volume of distribution within a two-compartment pharmacokinetic model implies that metformin may be more effectively cleared by prolonged RRT. This was corroborated by Keller et al., who showed a dramatic reduction of metabolic acidosis and metformin plasma concentrations within the first 24 h after initiating CRRT in patients with MET-induced lactic acidosis, followed by normalization on the second day in all subjects [3]. Although we do not know the exact rate of CRRT in both arms [1], it may well be that one group had more CRRT than the other, particularly the metformin group. For instance, in the study of Doenyas-Barak et al., which had a huge impact on the conclusions of this meta-analysis, the use of RRT was higher in the MET-treated population (38.6 vs. 21.2%, p = 0.13) [1, 4]. Accordingly, we suspect that the observed difference in mortality rate may be due to the more frequent use of RRT in the MET-treated population. A protective effect of RRT has already been suggested by Peters et al., who found that despite higher illness severity, the mortality rate in patients with MET-associated lactic acidosis treated with intermittent hemodialysis (IHD) was no different to that of non-dialyzed subjects [5].

Diabetes and Glucose Dysregulation and Transition to Delirium in ICU Patients

Diabetes and Glucose Dysregulation and Transition to Delirium in ICU Patients

van Keulen, Kris; Knol, Wilma; Belitser, Svetlana V.; van der Linden, Paul D.; Heerdink, Eibert R.; Egberts, Toine C. G.; Slooter, Arjen J. C.

Critical Care Medicine: September 2018 - Volume 46 - Issue 9 - p 1444–1449

Objectives: To investigate whether diabetes and glucose dysregulation (hyperglycemia and/or hypoglycemia) are associated with ICU delirium.

Design: Prospective cohort study. Setting: Thirty-two–bed mixed intensive care in a tertiary care center. Patients: Critically ill patients admitted to the ICU with transitions of mental status from awake and nondelirious to delirious or remaining awake and nondelirious on the next day. Patients admitted because of a neurologic illness were excluded. Interventions: None.

Measurements and Main Results: The study population consisted of 2,745 patients with 1,720 transitions from awake and nondelirious to delirious and 11,421 nontransitions remaining awake and nondelirious. Generalized mixed effects models with logit link function were performed to study the association between diabetes mellitus, glucose dysregulation, and delirium, adjusting for potential confounders. Diabetes was not associated with delirium (odds ratio adjusted, 0.93; 95% CI, 0.73–1.18). In all patients, the occurrence of hyperglycemia (odds ratio adjusted, 1.35; 95% CI, 1.15–1.59) and the occurrence of both hyperglycemia and hypoglycemia on the same day (odds ratio adjusted, 1.65; 95% CI, 1.12–2.28) compared with normoglycemia were associated with transition to delirium. Hypoglycemia was not associated with transition to delirium (odds ratio adjusted, 1.86; 95% CI, 0.73–3.71). In patients without diabetes, the occurrence of hyperglycemia (odds ratio adjusted, 1.41; 95% CI, 1.16–1.68) and the occurrence of both hyperglycemia and hypoglycemia on the same day (odds ratio adjusted, 1.87; 95% CI, 1.07–2.89) were associated with transition to delirium. In patients with diabetes, glucose dysregulation was not associated with ICU delirium.

Conclusions: Diabetes mellitus was not associated with the development of ICU delirium. For hypoglycemia, only a nonsignificant odds ratio for ICU delirium could be noted. Hyperglycemia and the occurrence of hyperglycemia and hypoglycemia on the same day were associated with ICU delirium but only in patients without diabetes. Our study supports the institution of measures to prevent glucose dysregulation in nondiabetic ICU patients and contributes to the understanding of the determinants of delirium.

Liberal Glycemic Control in Critically Ill Patients With Type 2 Diabetes: An Exploratory Study

Liberal Glycemic Control in Critically Ill Patients With Type 2 Diabetes: An Exploratory Study

Critical Care Medicine:

September 2016 - Volume 44 - Issue 9 - p 1695–1703

Kar, Palash

Objectives: The optimal blood glucose target in critically ill patients with preexisting diabetes and chronic hyperglycemia is unknown. In such patients, we aimed to determine whether a “ liberal” approach to glycemic control would reduce hypoglycemia and glycemic variability and appear safe. Design: Prospective, open-label, sequential-period exploratory study. Setting: Medical-surgical ICU. Patients: During sequential 6-month periods, we studied 83 patients with preexisting type 2 diabetes and chronic hyperglycemia (glycated hemoglobin, ≥ 7.0% at ICU admission). Intervention: During the “standard care” period, 52 patients received insulin to treat blood glucose concentrations greater than 10 mmol/L whereas during the “liberal” period, 31 patients received insulin to treat blood glucose concentrations greater than 14 mmol/L. Measurements and Main Results: Time-weighted mean glucose concentrations and the number and duration of moderate (< 4.0 mmol/L) and severe (≤ 2.2 mmol/L) hypoglycemic episodes were recorded, with moderate and severe hypoglycemic episodes grouped together. Glycemic variability was assessed by calculating the coefficient of variability for each patient. Safety was evaluated using clinical outcomes and plasma concentrations of markers of inflammation, glucose-turnover, and oxidative stress. Mean glucose (TWglucoseday 0–7, standard care: 9.3 [1.8] vs liberal: 10.3 [2.1] mmol/L; p = 0.02) and nadir blood glucose (4.4 [1.5] vs 5.5 [1.6] mmol/L; p < 0.01) were increased during the liberal period. There was a signal toward reduced risk of moderate-severe hypoglycemia (relative risk: liberal compared with standard care: 0.47 [95% CI, 0.19–1.13]; p = 0.09). Ten patients (19%) during the standard period and one patient (3%) during the liberal period had recurrent episodes of moderate-severe hypoglycemia. Liberal therapy reduced glycemic variability (coefficient of variability, 33.2% [12.9%] vs 23.8% [7.7%]; p < 0.01). Biomarker data and clinical outcomes were similar. Conclusions: In critically ill patients with type 2 diabetes and chronic hyperglycaemia, liberal glycemic control appears to attenuate glycemic variability and may reduce the prevalence of moderate-severe hypoglycemia.

Blood glucose concentration and outcome of critical illness : The impact of diabetes

Egi , M . ; Bellomo , R . ; Stachowski , E . ; French , C . J . ; Hart , G . K . ; et al
http://ovidsp.ovid.com/athens/ovidweb.cgi?T=JS&MODE=ovid&NEWS=n&PAGE=toc&D=ovft&AN=00003246-000000000-00000 Full Text (01/1995 - /)

Page: 2249-2255 Vol/Issue: 2008 ; VOL 36 ; PART 8
ISSN Print: 0090-3493 E-ISSN: 1530-0293 Print Holdings: Yes
Search Google: Article Author(s)