This document is a Direct Healthcare Professional Communication (DHPC) issued in August 2025 by a Marketing Authorization Holder (MAH) in agreement with the Egyptian Drug Authority. Its primary purpose is to communicate a critical safety warning regarding the use of the diabetes medication Metformin in patients with specific mitochondrial diseases.
Here is a detailed breakdown of the key points:
1. Core Safety Warning and Recommendations
The document strongly advises against using Metformin in patients with known mitochondrial diseases, specifically:
- MELAS Syndrome (Mitochondrial Encephalopathy with Lactic Acidosis, and Stroke-like episodes)
- MIDD (Maternally Inherited Diabetes and Deafness)
The reasons for this warning are:
- Risk of Lactic Acidosis Exacerbation: Metformin can worsen the build-up of lactic acid in the blood, a condition these patients are already prone to.
- Risk of Neurologic Complications: It may trigger or worsen serious neurological problems, such as the stroke-like episodes seen in MELAS, leading to a deterioration of the disease.
2. Key Recommendations for Healthcare Professionals
- Before Prescribing: Clinicians should meticulously ask about a family history of diabetes, deafness, neurological disorders, or other symptoms that might suggest an underlying mitochondrial disease.
- High Suspicion: Maintain a high level of suspicion for mitochondrial disease in patients with atypical diabetes (e.g., lean patients, early-onset diabetes with hearing loss, or a family history of maternally inherited diabetes).
- If Symptoms Appear: If a patient shows signs of MELAS or MIDD after starting Metformin, the treatment should be stopped immediately, and a prompt diagnostic evaluation should be performed.
- Alternative Treatments: For managing diabetes in these specific patients, alternative glucose-lowering agents that do not interfere with mitochondrial function should be considered and prioritized.
3. Background and Scientific Rationale
- Metformin’s Mechanism: The document explains that Metformin’s primary action involves inhibiting mitochondrial respiration (specifically Complex I). In patients with pre-existing mitochondrial defects (like MELAS and MIDD), this action can dangerously increase lactate production and worsen their underlying mitochondrial dysfunction.
- General Consensus: It states that, based on conclusions from the European Medicines Agency (EMA), the general medical consensus is to avoid Metformin in these patient groups due to the high risk of adverse effects.
4. Descriptions of the Diseases
- MELAS Syndrome: A mitochondrial disorder characterized by stroke-like episodes, lactic acidosis, and encephalopathy. It is often caused by a specific mutation in mitochondrial DNA (m.3243A>G).
- MIDD: Another mitochondrial disorder that presents with diabetes and sensorineural hearing loss, also frequently linked to the same m.3243A>G mutation.
5. Regulatory Actions and Reporting
- Label Update: A new warning about this risk will be added to the local Summary of Product Characteristics (SMPCs) for Metformin in Egypt.
- Call for Reporting: Healthcare professionals are urged to report any suspected adverse reactions through the Egyptian pharmacovigilance system via email, an online portal (VigiFlow), or a hotline (15301).
In summary, this DHPC is an important safety alert informing Egyptian healthcare professionals that Metformin is contraindicated in patients with mitochondrial diseases like MELAS and MIDD due to the serious risks of worsening lactic acidosis and causing severe neurological complications. It provides clear guidance on patient assessment, alternative treatments, and the need for immediate action if problems arise.
