Kidney Week

Abstract: TH-PO0435

Metformin-Associated Lactic Acidosis Triggered by Combined Use of Metformin and a GLP-1 Receptor Agonist: A Report of Two Cases

Session Information

• Fluid, Electrolyte, and Acid-Base Disorders: Clinical - 1
  November 06, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Fluid, Electrolytes, and Acid-Base Disorders

• 1102 Fluid, Electrolyte, and Acid-Base Disorders: Clinical

Authors

• Hussain, Hamed Shaik Mohammad Shoukat, St Elizabeth's Medical Center, Brighton, Massachusetts, United States

Hamed Shaik Mohammad Shoukat Hussain, MD

• Lorlowhakarn, Koravich, St Elizabeth's Medical Center, Brighton, Massachusetts, United States

Koravich Lorlowhakarn, MD

• Ali, Mustafa, St Elizabeth's Medical Center, Brighton, Massachusetts, United States

Mustafa Ali, MD

• Alhaddad, Juliano, St Elizabeth's Medical Center, Brighton, Massachusetts, United States

Juliano Alhaddad, MD

• Jaber, Bertrand L., St Elizabeth's Medical Center, Brighton, Massachusetts, United States

Bertrand L. Jaber, MD, MS, FASN

Introduction

Metformin-associated lactic acidosis [MALA] is a rare manifestation of metformin toxicity that occurs due to impaired elimination or following an acute overdose. It is associated with a high case-fatality rate. We present two patients with type 2 diabetes mellitus [T2DM] who developed MALA after co-prescription of metformin and semaglutide, a glucagon-like peptide-1 receptor agonist [GLP-1 RA].

Case Description

The first patient is a 67-year-old man who presented with 1 month of poor appetite, nausea, and vomiting after starting semaglutide while on metformin and lisinopril. He had severe acute kidney injury [AKI] with a serum creatinine [SCr] of 8.2 mg/dL and severe lactic acidosis (serum pH of <6.80, bicarbonate [HCO₃] of 3 mEq/L, anion gap [AG] of 40 mmol/L, lactic acid [LA] of 21.2 mmol/L). Serum metformin level was 31 mcg/mL (therapeutic range 1-2 mcg/mL). The second patient is a 69-year-old woman who presented with nausea, vomiting, and diarrhea 2 weeks after a semaglutide dose increase, while on metformin, lisinopril, linagliptin, and glyburide. She had severe AKI with a SCr of 8.7 mg/dL and severe lactic acidosis (pH <6.82, HCO₃ of 4 mEq/L, AG of 39 mmol/L, LA of 14.5 mmol/L). Serum metformin level was 23 mcg/mL. Both patients received emergent continuous veno-venous hemodialysis due to vasopressor requirement and had full renal recovery, and both had metformin, semaglutide, and lisinopril discontinued on discharge.

Discussion

MALA is a life-threatening manifestation of metformin toxicity. Drug-drug interactions should be considered as a cause. GLP-1 RAs have multiple and expanding indications, and their prescription rates are rising rapidly. Semaglutide prescriptions, specifically, increased by 411% from 2021 to 2023. These agents are associated with significant gastrointestinal side effects, notably loss of appetite, nausea, and vomiting. We propose possible side-effect synergism when metformin and a GLP-1 RA are co-prescribed, with a heightened risk of renal dysfunction and unintentional metformin toxicity, specifically MALA. Prudence should be exercised when co-prescribing these 2 classes with close monitoring of kidney function and possibly reducing the dose of metformin, and there should be emphasis on sick day rule teaching.

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025796yzg54