Metformin — Informed Consent (Off‑label Longevity / Metabolic Health)

INFORMED CONSENT FOR METFORMIN — OFF‑LABEL LONGEVITY / METABOLIC HEALTH USE

§1 PURPOSE, CONTEXT, AND SCOPE

§1.1 This document constitutes an informed consent agreement between the Patient identified herein (the "Patient") and the Prescribing Physician acting on behalf of the Clinic. It is intended to document that the Patient has received, understood, and accepted comprehensive information regarding the proposed pharmacological use of metformin for off‑label longevity/metabolic health purposes.

§1.3 Health optimization context: The Patient understands that the Clinic operates as a proactive health optimization / longevity practice. The Clinic is not an emergency provider. The Patient is responsible for maintaining an appropriate relationship with a primary care physician and/or relevant specialist(s) for diagnosis and management of disease, acute care, and emergencies.

§1.4 This consent is governed by the laws of Denmark and the European Union, including but not limited to the Danish Health Act (Sundhedsloven) and Regulation (EU) 2016/679 (General Data Protection Regulation).

§1.5 By signing this document, the Patient confirms they have had adequate time to read, consider, and ask questions, and that their questions have been answered to their satisfaction.

§3 MEDICATION, CLASS, AND DESCRIPTION OF TREATMENT

§3.1 Metformin is a biguanide medication that has been used for decades in the treatment of type 2 diabetes mellitus. It works primarily by reducing hepatic glucose production and improving insulin sensitivity.

§3.3 Intended use in this Clinic: The Patient understands that metformin is being prescribed for off‑label use related to longevity/metabolic health optimization. The Patient understands that this intended use is not an EMA‑authorised indication for non‑diabetic individuals and is based on preclinical research and emerging clinical evidence.

§3.4 Off‑label status: The Patient understands that:

  • Metformin is EMA‑authorised for the treatment of type 2 diabetes mellitus
  • Use for "longevity," "healthspan," "geroprotection," or metabolic health optimization in non‑diabetic individuals is off‑label
  • Clinical benefit for longevity/healthspan extension in humans is not proven
  • Evidence supporting longevity use is primarily from observational studies and preclinical research

§3.5 The treatment will be administered orally, typically once or twice daily, at a dose determined by the Prescribing Physician based on the Patient's clinical status, renal function, and treatment goals.

§4 REGULATORY STATUS AND APPROVED INDICATIONS

§4.1 Metformin has been authorised by the European Medicines Agency (EMA) for the treatment of type 2 diabetes mellitus, either as monotherapy or in combination with other glucose‑lowering agents.

§4.2 Off‑label longevity use: The Patient understands that prescribing metformin primarily for "longevity," "healthspan," "geroprotection," or proactive metabolic optimization in non‑diabetic individuals is off‑label and is not an EMA‑approved indication.

§4.3 The Patient understands that evidence supporting off‑label longevity use is derived from:

  • Observational studies suggesting potential associations with reduced cancer risk and improved outcomes
  • Preclinical research in model organisms
  • Ongoing research in the field of geroprotection
  • Large randomised controlled trials specific to longevity/healthspan in healthy individuals are not available

§4.4 The Patient understands that results observed in diabetic populations and preclinical models may not translate to comparable magnitude of benefit in healthy, non‑diabetic individuals, and that prevention of age‑related disease and extension of lifespan in an individual patient cannot be guaranteed.

§4.5 The Patient has been informed that the intended use in this Clinic is off‑label and accepts this information.

§5 PROPOSED BENEFITS OF TREATMENT

§5.1 The Patient understands that the potential benefits of metformin in the context of off‑label longevity/metabolic health use are hypothetical and not proven in healthy, non‑diabetic individuals. Proposed benefits may include, but are not limited to:

§5.1.1 Metabolic effects:

  • Improvement in insulin sensitivity
  • Modest effects on fasting glucose and HbA1c (in non‑diabetics, effects may be minimal)
  • Potential weight loss or weight maintenance

§5.1.2 Hypothetical longevity/healthspan effects: Based on observational and preclinical research, some authors propose that metformin may:

  • Influence cellular metabolism and energy sensing pathways
  • Potentially reduce risk of certain age‑related conditions
  • However, clinical benefit for longevity/healthspan extension in healthy individuals is not established

§5.2 No guarantee of benefit: The Patient acknowledges that:

  • No clinical benefit for longevity/healthspan extension in healthy, non‑diabetic individuals has been proven
  • Individual responses vary, and some patients may not experience any benefit
  • Metformin does not guarantee prevention of age‑related decline, extension of lifespan, or improvement in healthspan
  • Long‑term safety and efficacy for longevity use in healthy individuals are not established

§6 MATERIAL RISKS AND ADVERSE EFFECTS

§6.1 The Patient has been informed of the following risks and adverse effects associated with metformin therapy. The Patient understands that this list is not exhaustive and that other adverse effects may occur.

§6.2 Common adverse effects (occurring in ≥1% of patients):

  • Gastrointestinal intolerance: nausea, vomiting, diarrhoea, abdominal discomfort, metallic taste
  • These effects are often dose‑related and may improve with time or dose reduction
  • Taking metformin with food may reduce gastrointestinal side effects

§6.3 Uncommon adverse effects (occurring in 0.1–1% of patients):

  • Vitamin B12 deficiency (with long‑term use)
  • Lactic acidosis (rare but serious; see §6.4.1)
  • Hypoglycaemia (rare when used alone; more common when combined with other glucose‑lowering agents)

§6.4 Rare but serious adverse effects (occurring in <0.1% of patients or reported post‑marketing):

§6.4.1 Lactic acidosis (rare but potentially fatal):

Metformin can rarely cause lactic acidosis, a serious metabolic condition. The Patient understands that:

  • Lactic acidosis is rare but can be life‑threatening
  • Risk is increased in patients with:
  • Impaired renal function (eGFR <30 mL/min/1.73m² or as determined by clinician)
  • Impaired hepatic function
  • Severe heart failure
  • Acute illness or dehydration
  • Excessive alcohol consumption
  • Conditions causing tissue hypoxia
  • Symptoms of lactic acidosis include:
  • Muscle pain or weakness
  • Difficulty breathing
  • Abdominal pain
  • Nausea, vomiting
  • Dizziness, lightheadedness
  • Slow or irregular heartbeat
  • The Patient must seek emergency medical care immediately if these symptoms occur
  • The Patient must stop metformin and seek urgent care if they develop acute illness, severe dehydration, or conditions that may impair renal or hepatic function

§6.4.2 Vitamin B12 deficiency: Long‑term metformin use can cause vitamin B12 deficiency, which may lead to:

  • Anaemia
  • Neurological symptoms (numbness, tingling, cognitive changes)
  • The Patient understands that regular monitoring of vitamin B12 levels may be recommended

§6.4.3 Hypoglycaemia: Metformin alone rarely causes hypoglycaemia, but risk increases when combined with insulin, sulfonylureas, or other glucose‑lowering agents.

§6.4.4 Allergic reactions: Rare allergic reactions can occur. The Patient must seek urgent care for swelling of face/tongue/throat, difficulty breathing, or widespread rash.

§7 CONTRAINDICATIONS AND PRECAUTIONS

§7.1 The Patient confirms that they have disclosed all relevant medical history to the Prescribing Physician. Metformin is generally contraindicated or requires special caution in the following circumstances:

§7.2 Absolute contraindications:

  • Known hypersensitivity or allergy to metformin or any excipients
  • Severe renal impairment (eGFR <30 mL/min/1.73m² or as determined by clinician)
  • Acute or chronic conditions that may cause tissue hypoxia (e.g., severe heart failure, respiratory failure, recent myocardial infarction)
  • Severe hepatic impairment
  • Acute alcohol intoxication or chronic excessive alcohol consumption
  • Acute metabolic acidosis (including lactic acidosis)

§7.3 Relative contraindications and precautions:

  • Moderate renal impairment (eGFR 30–45 mL/min/1.73m²; requires dose adjustment and monitoring)
  • History of lactic acidosis
  • Conditions that may increase risk of lactic acidosis (e.g., dehydration, acute illness, surgery)
  • Vitamin B12 deficiency or risk factors for B12 deficiency
  • Use in children or adolescents (except under specialist supervision)

§8 DRUG INTERACTIONS

§8.1 The Patient has disclosed all current medications, including prescription drugs, over‑the‑counter medications, supplements, and herbal products. The following interactions are of clinical significance:

§8.2 Contrast media: Metformin should be temporarily discontinued before procedures involving iodinated contrast media (e.g., CT scans with contrast) to reduce the risk of contrast‑induced nephropathy and lactic acidosis. The Patient must inform the Clinic and other healthcare providers before any procedures involving contrast media.

§8.3 Alcohol: Excessive alcohol consumption increases the risk of lactic acidosis. The Patient agrees to limit alcohol consumption and to avoid excessive alcohol intake while taking metformin.

§8.4 Other glucose‑lowering agents: When combined with insulin, sulfonylureas, or other glucose‑lowering agents, the risk of hypoglycaemia increases.

§8.5 Cimetidine: May increase metformin levels; monitoring may be required.

§8.6 The Patient agrees to inform the Clinic before starting any new medication, especially before procedures involving contrast media.

§9 MONITORING REQUIREMENTS

§9.1 The Patient agrees to undergo monitoring as recommended by the Prescribing Physician, which may include:

§9.2 Baseline assessments (before starting metformin):

  • Renal function (serum creatinine, eGFR)
  • Liver function tests
  • Fasting glucose and HbA1c (if applicable)
  • Vitamin B12 level (baseline)
  • Complete blood count
  • Assessment of conditions that may increase risk of lactic acidosis

§9.3 Ongoing monitoring (typically every 6–12 months, or more frequently as clinically indicated):

  • Renal function (to ensure eGFR remains acceptable)
  • Liver function tests
  • Vitamin B12 level (annually or as indicated, especially with long‑term use)
  • Clinical assessment of symptoms and adverse effects
  • Assessment of conditions that may require temporary discontinuation

§9.4 Sick‑day rules (critical safety information):

The Patient has been informed of and understands the following sick‑day rules:

  • Metformin should be temporarily stopped during acute illness associated with dehydration, reduced oral intake, or conditions that may impair renal function (e.g., vomiting, diarrhoea, fever, severe infection)
  • Metformin should be stopped before procedures involving iodinated contrast media and not restarted until renal function is confirmed to be normal
  • Metformin should be stopped before major surgery and not restarted until eating and drinking normally and renal function is confirmed
  • The Patient should contact the Clinic for guidance before restarting metformin after a sick‑day pause

§9.5 Dose adjustment: The Patient understands that metformin dosing may be adjusted based on clinical response, renal function, and adverse effects. The Patient agrees to follow dosing instructions and not to self‑adjust the dose.

§9.6 The Patient agrees to report significant adverse effects, especially symptoms of lactic acidosis, promptly.

§10 ALTERNATIVE TREATMENTS

§10.1 The Patient has been informed of the following alternatives to metformin for longevity/metabolic health optimization:

§10.2 Lifestyle interventions: Evidence‑based lifestyle interventions, including:

  • Caloric restriction or intermittent fasting
  • Regular physical activity (aerobic and resistance training)
  • Dietary modifications (e.g., Mediterranean diet, low‑carbohydrate diet)
  • Adequate sleep
  • Stress management
  • Weight management

§10.3 Other pharmacological interventions: Other medications or supplements that have been proposed for longevity/metabolic health (e.g., SGLT2 inhibitors, GLP‑1 receptor agonists), understanding that evidence for longevity benefit in healthy individuals is also limited.

§10.4 No treatment: The Patient may choose not to receive pharmacological intervention for longevity/metabolic health, understanding that this is a personal choice and that evidence for benefit is not established.

§10.5 The Patient confirms that these alternatives have been discussed and that they have chosen to proceed with metformin.

§12 LIMITATION OF LIABILITY / NO GUARANTEE

§12.1 The Patient understands that medicine is not an exact science and no outcomes can be guaranteed.

§12.2 The Patient understands that:

  • Clinical benefit for longevity/healthspan extension in healthy, non‑diabetic individuals is not proven
  • Metformin does not guarantee prevention of age‑related decline, extension of lifespan, or improvement in healthspan
  • Long‑term safety and efficacy for longevity use in healthy individuals are not established

§12.3 The Patient understands that adverse effects may occur despite appropriate prescribing and monitoring.

§12.4 Nothing in this consent excludes liability that cannot be excluded under applicable Danish law.

§13 WITHDRAWAL OF CONSENT

§13.1 The Patient may withdraw consent at any time by contacting the Clinic. The Prescribing Physician will provide guidance on safe discontinuation where applicable.

§14 DATA PROTECTION AND RECORDKEEPING

§14.1 The Patient's personal data and health information will be processed in accordance with GDPR and applicable Danish law.

§14.2 This consent may be retained as part of the Patient's medical record.

§15 ACKNOWLEDGMENTS AND DECLARATIONS

By consenting, the Patient confirms the following:

  • I have read this consent document in its entirety, or it has been read to me, and I understand its contents.
  • I understand that metformin is being prescribed for off‑label longevity/metabolic health use and that clinical benefit for longevity in healthy individuals is not proven.
  • I understand the medication prescribed (the prescribed medication) and the purpose of off‑label metformin therapy.
  • I understand that benefits are hypothetical and not guaranteed.
  • I understand the material risks, including gastrointestinal intolerance, vitamin B12 deficiency, and lactic acidosis (rare but potentially fatal).
  • I understand the contraindications, especially renal and hepatic impairment, and have disclosed all relevant medical history.
  • I understand and will follow the sick‑day rules described in §9.4, including stopping metformin during acute illness and before procedures involving contrast media.
  • I understand that regular monitoring (renal function, vitamin B12) is required.
  • I understand that I must avoid excessive alcohol consumption and inform the Clinic before procedures involving contrast media.
  • I have disclosed all relevant medical history and current medications to the Clinic.
  • I understand I must seek urgent/emergency care for symptoms of lactic acidosis or other severe symptoms and that the Clinic is not an emergency service.
  • I have had the opportunity to ask questions and my questions were answered.
  • I voluntarily consent to commence or continue treatment with the prescribed medication under the regimen agreed with my clinician.