Metformin abuse and weight loss: A case report

Abstract

BACKGROUND

Metformin is generally safe but can cause lactic acidosis and rarely organ dysfunction during overdose. Misuse for weight loss, especially in undiagnosed eating disorder, is concerning. In stigmatized settings such conditions may go unrecognized This case illustrated severe complications from chronic metformin abuse in a young female with suspected anorexia nervosa, highlighting the need for integrated medical and psychiatric care. To the best of our knowledge, this is only the second case report of multiple organ dysfunction syndrome (MODS) due to metformin toxicity.

CASE SUMMARY

Here, we reported a rare case of MODS involving four organs due to metformin abuse. A 22-year-old female located in Syria with a history suspicious of anorexia nervosa presented with dehydration, diarrhea, and altered consciousness. Labs revealed mixed high and normal anion gap metabolic acidosis from starvation ketosis and bicarbonate loss. She recovered with supportive care but returned 3 months later in shock with severe acidemia, kidney injury, pancreatitis, and liver dysfunction, consistent with MODS. Further history revealed chronic metformin abuse (up to 3000 mg/day) for weight loss. She recovered fully and began cognitive behavioral therapy. This case underscored the dangers of metformin misuse in eating disorders.

CONCLUSION

This case highlighted the potentially life-threatening consequences of surreptitious metformin abuse in the context of an underlying eating disorder. Early recognition, thorough history-taking, and multidisciplinary management, including psychiatric support, are essential for recovery and prevention of recurrence.

Key Words: Metformin; Metformin abuse; Multiple organ dysfunction syndrome; Metformin and weight loss; Anorexia nervosa; Metformin and eating disorder, Lactic acidosis; Case report

Core Tip: This report described a rare case of multiple organ dysfunction syndrome triggered by chronic metformin abuse in a young female with suspected anorexia nervosa. The patient survived two distinct episodes of metformin toxicity with the second requiring mechanical ventilation, vasopressors, and renal replacement therapy. The case highlighted the growing misuse of metformin for weight loss.

INTRODUCTION

Metformin is a widely prescribed oral hypoglycemic agent with a well-established safety profile. However, in cases of overdose or impaired clearance, it can lead to lactic acidosis and in rare instances multiple organ dysfunction syndrome (MODS)[1]. Misuse of metformin for weight loss has been increasingly reported, particularly among individuals with disordered eating behaviors. Anorexia nervosa, a psychiatric condition marked by distorted body image and weight control behaviors, may go unrecognized and untreated[2], especially in cultures where mental health remains stigmatized[3]. This case highlighted the life-threatening consequences of metformin abuse in a young female with suspected anorexia nervosa, underscoring the importance of integrated medical and psychiatric care.

CASE PRESENTATION

Chief complaints

A 22-year-old Syrian female with a prior history of a suspected eating disorder presented to the emergency department with acute-onset, severe epigastric abdominal pain worsened by food intake and accompanied by nausea, persistent vomiting, and low-grade fever. The severity of her symptoms prompted immediate medical evaluation.

History of present illness

Our patient presented to the emergency department with a sudden and intense episode of severe epigastric abdominal pain. The pain was worsened by food intake and accompanied by persistent nausea, repeated vomiting, and a low-grade fever. Her appearance was markedly ill with a noticeably low body mass index, and her respiratory effort appeared labored on arrival.

History of past illness

Her past medical history was notable for a prior hospitalization at another medical facility in late spring (May 2022) during which she presented to the emergency department with a 3-day history of watery diarrhea (occurring three times daily in moderate volumes), decreased oral intake, profound fatigue, dizziness, and a reduced level of consciousness. At that time she was found to have lost 17 kg over the preceding year, resulting in a body mass index of 17.2 kg/m², suggestive of undernutrition. On examination, she appeared clinically dehydrated with dry mucous membranes, delayed capillary refill, and mild orthostatic hypotension.

Initial laboratory investigations revealed a mixed metabolic acidosis with both high anion gap metabolic acidosis and normal anion gap metabolic acidosis; the delta-delta ratio was 0.17, indicating a complex, concurrent acid-base disturbance. Bedside abdominal ultrasonography at that time revealed gallbladder stasis. A provisional diagnosis of anorexia nervosa was made, and she was admitted to the intensive care unit (ICU) for management. Treatment included aggressive intravenous (IV) fluid resuscitation, IV thiamine supplementation, and oral nutritional support. She showed clinical improvement and normalization of laboratory values.

The underlying cause of the initial acid-base disturbance remained unclear as the patient did not disclose any relevant history at the time. Unfortunately, she was lost to follow-up regarding her suspected eating disorder and did not pursue further psychiatric or nutritional evaluation.

Personal and family history

There was no significant personal or family history of hereditary metabolic or endocrine disorders. The patient denied any history of chronic illnesses or regular use of prescribed medications prior to her current presentation (Augst 2022).

Physical examination

On initial examination, she was tachypneic and in visible respiratory distress with a respiratory rate of 35 breaths per minute. Arterial blood gas analysis revealed a profound metabolic acidosis with a critically low pH of 6.97 (Tables 1 and 2). Her blood pressure was significantly decreased at 75/43 mmHg.

Table 1 Patient’s laboratory findings.

	May 26, 2022 (initial presentation)	Day 1 (August 24, 2022)	Day 2 (August 25, 2022)	Day 3 (August 26, 2022)	Day 4 (August 27, 2022)	Day 5 (August 28, 2022)
Hemoglobin (Reference: 12-16 g/dL)				10.6	10.0	10.5
Mean corpuscular volume (Reference: 78-96 fL)				93	92	91
Sodium (Reference: 135-145 mmol/L)	138	135	132		135	134
Potassium (Reference: 3.5-5.0 mmol/L)	3.5	4.9	3.5		3.2	3.4
Chloride (Reference: 98-107 mmol/L)	112
Potential of hydrogen	7.28	6.97	7.21	7.36	7.42
Bicarbonate (Reference 22-28 mEq/L)	12.0	2.0	5.1	12.8	20.3
Partial pressure of carbon dioxide (Reference: 35-45 mmHg)	30.0	8.9	12.7	22.3	31.1
Partial pressure of oxygen (Reference: 75 to 100 mmHg)					43
Creatinine (Reference: 0.6-1.2 mg/dL)	1.00	6.02		3.21	4.15	4.92
Urea (Reference: 7-20 mg/dL)	33	109		62	79	93
Serum ketones (Reference: Negative)	Positive
C-reactive protein (Reference: < 0.5 mg/dL)		0.43	1.21	4.54	4.59	5.18
Procalcitonin (Reference: Up to 0.5 ng/dL)			1.03		0.34
Lactate dehydrogenase (Reference: 60-248 U/L)			327	309	358
Venous lactic acid (Reference: 4.5-19.8 mg/dL)			27
Amylase (Reference: 0-120 U/L)		412		1377	986
Lipase (Reference: 10-55 U/L)				3360
Alanine aminotransferase (Reference: 0-40 U/L)		25	23
Aspartate aminotransferase (Reference: 0-40 U/L)			27		35
Albumin (Reference: 3.2-5.0 g/dL)			3.4	2.9	2.8
Globulin (Reference: 2.7-3.3 g/dL)			2.5	1.7	1.9
Total proteins (Reference: 6.4-8.3 g/dL)			5.9	4.6	4.7
Prothrombin time (Reference: 11-15 Seconds)			17.8
Partial thromboplastin time (Reference: 25-40 Seconds)
International normalized ratio (Reference: 0.8-1.2)		3.4	1.53
Lactate level (Reference: 0.5-2.2 mmol/L)		9.5

Table 2 Patient’s laboratory findings.

	Day 6 (August 29, 2022)	Day 7 (August 30, 2022)	Day 8 (August 31, 2022)	Day 11 (September 3, 2022)	Day 19 (September 11, 2022)
Amylase (Reference: 0-104 U/L)	410		342		228
Creatinine (Reference: 0.6-1.2 mg/dL)	5.32	5.53	5.77	2.99	0.75
Urea (Reference: 7-20 mg/dL)	96	90	91	63	17
Alanine transaminase (Reference: 0-40 U/L)	753	1186	775	204	35
Aspartate aminotransferase (Reference: 0-40 U/L)			297		17
Bilirubin (Total, direct) (Reference: Total 2.0-1.2 mg/dL, direct 0-0.3 mg/dL)		Total: 1.16; Direct: 0.94
Albumin (Reference: 3.2-5.0 g/dL)	135.0				3.6
Globulin (Reference: 2.7-3.3 g/dL)	3.6
Total proteins (Reference: 6.4-8.3 g/dL)	4.6
Prothrombin time (Reference: 11-15 Seconds)	34.9	19.7	17.7
Partial thromboplastin time (Reference: 25-40 Seconds)	39	37	32
International normalized ratio (Reference: 0.8-1.2)	3.40	1.73	1.52
Bicarbonate (Reference 22-28 mEq/L)
Partial pressure of oxygen (Reference: 75-100 mmHg)
C-reactive protein (Reference: < 0.5 mg/dL)		4.52	4.49		1.13
Procalcitonin (Reference: Up to 0.5 ng/dL)		71.2	33.6
Sodium (Reference: 135-145 mmol/L)		135.0	133.0	133.0	146.6
Potassium (Reference: 3.5-5.0 mmol/L)		3.90	3.70	2.64	4.57

Laboratory examinations

Serial laboratory evaluations revealed severe acidemia, acute kidney injury, markedly elevated pancreatic enzymes (indicative of acute pancreatitis), and elevated liver transaminases suggestive of shock liver. Furthermore, evidence of synthetic liver dysfunction was present with a low serum albumin and elevated international normalized ratio (INR) (Tables 1 and 2). Unfortunately, due to limited resources and testing availability in our local setting in Syria, serial lactate measurements were not performed. Additionally, metformin measurements were not conducted (Tables 1 and 2).

Imaging examinations

Abdominal magnetic resonance imaging revealed gallbladder dilation with ascites, bilateral renal enlargement, moderate hepatomegaly, and bilateral moderate pleural effusions. These findings were consistent with systemic involvement and evolving organ dysfunction.

MULTIDISCIPLINARY EXPERT CONSULTATION

The management of this patient with MODS secondary to metformin abuse required a multidisciplinary approach. Gastroenterology was consulted for evaluation and management of pancreatitis and hepatic dysfunction. Nephrology provided guidance on acute kidney injury and the initiation of dialysis. Pulmonology and the ICU team managed respiratory failure, including intubation and critical care support. Psychiatry was involved due to concerns for an underlying eating disorder, and a dietitian was consulted to optimize nutritional intake and feeding recommendations during recovery.

FINAL DIAGNOSIS

After a retrospective evaluation of the current admission (Augst 2022), the patient was found to have developed metformin-associated lactic acidosis (MALA), a life-threatening complication characterized by profound metabolic acidosis in the setting of metformin accumulation. The diagnosis was supported by the presence of severe acidemia (pH 6.97), elevated lactate levels (9.5 mmol/L), and acute kidney injury (serum creatinine 6.02 mg/dL), all of which are hallmark features of MALA.

This was further complicated by the development of MODS as defined by the Sequential Organ Failure Assessment (SOFA) criteria. At peak illness severity the patient demonstrated involvement of at least four major organ systems: Respiratory, requiring mechanical ventilation; cardiovascular, hypotension requiring vasopressor support (norepinephrine); renal, marked azotemia (serum creatinine 6.02 mg/dL); and hepatic, synthetic dysfunction (INR 3.4) and elevated liver transaminases.

The calculated SOFA score exceeded 13, a level associated with high mortality and consistent with advanced multiorgan failure.

Importantly, these events occurred in the context of an underlying eating disorder, presumptively anorexia nervosa and provided the behavioral substrate for the surreptitious and prolonged misuse of metformin. The patient later disclosed consuming doses as high as 3000 mg daily over the course of a year in an effort to induce weight loss. This behavior not only precipitated MALA but also masked the etiology during her first presentation (May 2022), delaying the identification of the underlying psychiatric condition.

TREATMENT

Upon presentation (Augst 2022) the patient was emergently intubated due to deteriorating consciousness and respiratory distress, placed on mechanical ventilation, and immediately administered 2 L of IV normal saline. She was then transferred to the ICU for advanced supportive care. Despite initial fluid resuscitation her hypotension persisted, necessitating the initiation of norepinephrine infusion to maintain an adequate mean arterial pressure, particularly to support renal perfusion in the setting of acute kidney injury.

Her management included complete bowel rest (NPO), two sessions of intermittent hemodialysis, and aggressive IV fluid therapy. IV thiamine was also administered prophylactically, given the high suspicion of underlying nutritional deficiencies associated with a restrictive eating pattern. By day 3 of admission, her condition began to stabilize, allowing for the gradual reintroduction of oral nutrition. She was successfully extubated on day 4.

Throughout her ICU stay, close hemodynamic monitoring and a multidisciplinary supportive approach were pivotal to her recovery.

It is important to note that metformin abuse was not known at the time of admission; therefore, its discontinuation occurred as part of the inpatient care process. Once her critical condition stabilized, the history of surreptitious metformin use emerged, reinforcing the need for discontinuation and counseling.

OUTCOME AND FOLLOW-UP

She was followed up at 2-week and 8-week intervals post-discharge and demonstrated complete clinical recovery (September and October 2022). She has since initiated cognitive behavioral therapy for her presumptive underlying eating disorder and has remained adherent to medical advice to discontinue metformin. However, she continues to show reluctance in discussing her case in detail, often appearing embarrassed and emotionally distressed when the topic is brought up. Her case highlighted the complex psychosocial factors that may accompany self-medication practices, especially in the Middle East, and underscored the importance of longitudinal psychiatric support.

DISCUSSION

Our patient experienced a rare and complex clinical course culminating in MODS, triggered by MALA in the context of likely undiagnosed anorexia nervosa. This case illustrated how isolated metabolic abnormalities can reflect deeper systemic and psychosocial processes and how early recognition and aggressive intervention can enable survival, even in near-fatal situations.

MODS is defined as the progressive dysfunction of two or more organ systems such that homeostasis cannot be maintained without intensive medical support[4]. It frequently follows systemic insults like sepsis, trauma, or toxic exposures and evolves through a biphasic model: An initial systemic inflammatory response syndrome followed by secondary endothelial injury, mitochondrial dysfunction, and oxidative stress. Inflammatory mediators such as tumor necrosis factor alpha and interleukin-1 beta activate leukocytes and endothelial cells, leading to capillary leak, microvascular thrombosis, and impaired perfusion. Mitochondrial failure, a hallmark of MODS, disrupts oxidative phosphorylation, causing cytopathic hypoxia and energy failure. Ultimately, interorgan communication is disrupted, driving the progression to multiorgan failure[5].

Mortality in MODS increases with the number of systems affected. Two-organ dysfunction carries an approximately 30% mortality risk while dysfunction of four or more organs exceeds 70%[6]. Based on the SOFA criteria, our patient had at least four organ systems affected: Respiratory (mechanical ventilation); cardiovascular (vasopressors); renal (creatinine 6.02 mg/dL); and hepatic (INR 3.4, elevated transaminases). Her SOFA score exceeded 13, correlating with an estimated mortality above 70%[7].

A key driver of MODS in our patient was MALA, a rare but life-threatening complication of metformin toxicity. MALA is defined by high-anion gap metabolic acidosis (pH < 7.35, bicarbonate < 22 mmol/L), elevated serum lactate (> 5 mmol/L), and recent or ongoing metformin use. Though uncommon its course can be rapidly fatal if not recognized and treated promptly. A recent meta-summary of 242 cases found MALA in 92.6% of metformin toxicity presentations with a mortality rate of 19.8%[8]. Other reports echo this, including mortality rates of 10.8% in the United Kingdom poison center data, 16.2% in a systematic review, 17% in a Taiwanese ICU cohort, and up to 36.2% at 30 days in a Thai study[9].

Our patient’s nadir pH of 6.9 and lactate peak of 27 mg/dL were strongly consistent with severe MALA, a profile associated with a mortality rate as high as 83%[10]. Her survival, therefore, represents a rare and extraordinary outcome, underscoring the importance of rapid diagnosis and aggressive management.

While the exact causality between MALA and MODS is complex and not fully delineated, several mechanisms plausibly link them. MALA contributes to systemic hypoperfusion and profound metabolic acidosis, impairing mitochondrial respiration and oxygen utilization, factors that can precipitate widespread cellular injury and multiorgan dysfunction[8].

Treatment of MALA centers on rapid correction of acid-base imbalance and elimination of the offending agent. In our case renal replacement therapy (RRT) played a pivotal role. RRT is a cornerstone in managing severe MALA, especially in patients with profound acidemia or impaired metformin clearance. It has been shown to improve survival even in those with extremely low pH (as low as 6.9) and elevated lactate[8,10]. Discontinuation of metformin is equally critical as it halts ongoing lactic acid generation and interrupts the feedback loop perpetuating the acidosis and organ injury. In our patient prompt initiation of RRT, mechanical ventilation, cessation of metformin, and intensive supportive care led to a marked and rapid recovery, validating these therapeutic principles.

Her clinical trajectory featured two distinct hospitalizations within 3 months, both marked by episodes of acidosis. The first, in late spring (May 2022), was relatively mild and resolved with fluids and nutritional support. The second, occurring in mid-summer (August 2022), however, led to catastrophic deterioration, including respiratory failure, circulatory collapse, acute pancreatitis, hepatic dysfunction, and profound metabolic acidosis, within 72 h. This biphasic course prompted deeper investigation, particularly given her previously unremarkable medical history, ultimately revealing chronic surreptitious use of metformin (up to 3000 mg daily for 1 year) likely in the context of an undiagnosed eating disorder.

Although approved for type 2 diabetes, metformin is increasingly used off-label for weight loss, and reports of its abuse in individuals with disordered eating are growing[11]. In this case, covert metformin ingestion without medical indication was eventually disclosed, raising suspicion for anorexia nervosa. The presumptive diagnosis was first considered due to severe malnutrition and weight loss, but no psychiatric assessment was performed during the first hospitalization (May 2022). Only after stabilization and repeated inquiry in the second hospitalization (Augst 2022) did the patient admit to intentional metformin use, reinforcing concerns about body image distortion and reluctance to seek help in such population.

Anorexia nervosa has a lifetime prevalence of 0.8%-6.3% in females and 0.1%-0.3% in males, yet lots of patients remains underdiagnosed, especially in culturally conservative settings such as the Middle East[12]. In Syria and other Middle Eastern countries, psychiatric illness is often heavily stigmatized. Patients may hide symptoms, avoid treatment, and delay disclosure out of fear of social judgment[3]. In our patient’s case this sociocultural stigma likely contributed to the delayed recognition of her eating disorder and the covert behavior that led to her critical illness.

This case underscored a crucial yet often overlooked dimension of modern medicine: The intersection of psychiatric illness with severe medical deterioration. The artificial divide between “medical” and “psychiatric” domains can obscure the root cause of disease, particularly when psychological disorders manifest somatically or covertly. Clinicians must be equipped to recognize behavioral cues, ask sensitive yet direct questions, and maintain a high index of suspicion for psychiatric pathology in unexplained or atypical presentations. In societies where discussing mental health remains taboo, a stigma-conscious and integrated approach is not only beneficial: It can be lifesaving.

CONCLUSION

This case underscored the severe and potentially fatal complications that can arise from covert metformin misuse, particularly in patients with underlying eating disorders such as anorexia nervosa. Prolonged and excessive metformin use may precipitate profound metabolic disturbances, including mixed metabolic acidosis and progression to MODS. Timely diagnosis, careful elicitation of a detailed history, and a multidisciplinary approach that integrates both medical stabilization and psychiatric intervention are critical to improving outcomes and preventing relapse. Raising awareness about this dangerous practice is vital, especially in regions where mental health stigma may delay recognition and treatment.

ACKNOWLEDGEMENTS

We thank the patient for allowing us to share her case details and being cooperative with us.