SGLT2 Inhibitors — Informed Consent (Off‑label Longevity / Health Optimization)

INFORMED CONSENT FOR SGLT2 INHIBITOR THERAPY

§1 PURPOSE AND SCOPE OF THIS DOCUMENT

§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. Its purpose is to ensure that the Patient has received, understood, and accepted comprehensive information regarding the proposed pharmacological use of a sodium‑glucose co‑transporter 2 (SGLT2) inhibitor.

§1.2 Health optimization context: The Patient understands that the Clinic operates as a proactive health optimization / longevity practice and is not acting as the Patient’s emergency provider. This consent is intended to document informed decision‑making in that context.

§1.3 Not diabetes treatment / not disease management: The Patient understands that this prescription is not being issued by this Clinic for the diagnosis or treatment of diabetes mellitus. 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 Regulation (EU) 2016/679 (General Data Protection Regulation), the Danish Health Act (Sundhedsloven), and applicable pharmaceutical regulation.

§1.6 By signing this document, the Patient confirms that they have been given adequate time and opportunity to read, consider, and ask questions about its contents before providing consent.

§3 DESCRIPTION OF THE PROPOSED TREATMENT

§3.1 The Prescribing Physician has recommended treatment with a medication belonging to the class of sodium‑glucose co‑transporter 2 (SGLT2) inhibitors, also known as gliflozins.

§3.3 Intended use in this Clinic: The Patient understands that the medication is being prescribed for the purpose of proactive metabolic health optimization and potential risk‑modification of age‑associated conditions. The Patient understands that this intended use is distinct from traditional prescribing for type 2 diabetes mellitus and may be outside the authorised indication for the Patient’s circumstances.

§3.4 SGLT2 inhibitors are oral medications that reduce renal reabsorption of glucose in the proximal tubule, thereby increasing urinary glucose excretion (glucosuria). This can create a mild “calorie loss” state and is associated with osmotic diuresis and natriuresis.

§3.4 Examples of SGLT2 inhibitors include:

  • Empagliflozin (brand name: Jardiance)
  • Dapagliflozin (brand name: Forxiga)
  • Canagliflozin (brand name: Invokana)
  • Ertugliflozin (brand name: Steglatro)

§3.5 The treatment will be administered orally, typically once 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 The medication prescribed has been authorised by the European Medicines Agency (EMA) for use within the European Union.

§4.2 EMA‑approved indications for SGLT2 inhibitors generally include:

  • Type 2 diabetes mellitus (as monotherapy when metformin is contraindicated, or as add‑on therapy)
  • Heart failure with reduced ejection fraction (HFrEF) in adults
  • Heart failure with preserved ejection fraction (HFpEF) in adults (for some agents)
  • Chronic kidney disease (CKD) in adults at risk of progression

§4.3 Off‑label longevity / healthspan intent: The Patient understands that prescribing an SGLT2 inhibitor primarily for “longevity,” “healthspan,” “geroprotection,” or proactive metabolic optimization is off‑label and is not an EMA‑approved indication.

§4.4 The Patient understands that evidence supporting such off‑label use is derived largely from:

  • Randomised controlled trials in patients with type 2 diabetes, heart failure, and/or chronic kidney disease; and
  • Observational studies and mechanistic research proposing broader system‑level benefits.

§4.5 The Patient understands that results observed in populations with established disease may not translate to comparable magnitude of benefit in healthier, non‑diabetic populations, and that prevention of disease and extension of lifespan in an individual patient cannot be guaranteed.

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

§5 MECHANISM OF ACTION AND CLINICAL PHARMACOLOGY

§5.1 SGLT2 is a protein expressed primarily in the proximal convoluted tubule of the kidney. Under normal physiological conditions, SGLT2 is responsible for reabsorbing approximately 90% of the glucose filtered by the glomerulus back into the bloodstream.

§5.2 SGLT2 inhibitors selectively and reversibly block this transporter, causing glucose that would otherwise be reabsorbed to be excreted in the urine (glucosuria). This results in a reduction in plasma glucose levels.

§5.3 Secondary effects of SGLT2 inhibition include:

  • Osmotic diuresis (increased urine volume due to glucose in the urine)
  • Natriuresis (increased sodium excretion)
  • Reduction in blood pressure
  • Modest weight loss (primarily due to caloric loss and fluid shifts)
  • Reduction in uric acid levels
  • Favourable effects on cardiac preload and afterload

§5.4 The cardiovascular and renal protective effects of SGLT2 inhibitors are believed to extend beyond glucose lowering and may involve haemodynamic, metabolic, and cellular mechanisms that are subjects of ongoing research.

§5.5 Proposed “geroprotective” mechanisms (hypothesis): The Patient understands that some authors and researchers have proposed that SGLT2 inhibitors may upregulate nutrient‑deprivation signaling and downregulate nutrient‑surplus signaling, potentially influencing pathways associated with cellular maintenance (e.g., autophagy), oxidative stress reduction, mitochondrial health, inflammation, and fibrosis. These mechanistic claims are not a guarantee of clinical longevity benefit for an individual patient and remain an area of ongoing research.

§6 EXPECTED BENEFITS OF TREATMENT

§6.1 The Patient understands that the potential benefits of SGLT2 inhibitor therapy in the context of metabolic health optimization may include, but are not limited to:

§6.1.1 Metabolic marker effects (including fasting insulin): Modest effects on weight, fasting glucose, HbA1c, and markers of insulin resistance (including fasting insulin and related calculated indices such as HOMA‑IR) may occur. In non‑diabetic individuals, glycaemic marker effects may be smaller, and changes in standard markers may be minimal or variable.

§6.1.2 Blood pressure and volume effects: Mild reductions in blood pressure may occur due to natriuresis and osmotic diuresis.

§6.1.3 Cardio‑renal outcomes (evidence primarily from higher‑risk populations): In large clinical trials in patients with type 2 diabetes, heart failure, and/or chronic kidney disease, SGLT2 inhibitors have demonstrated reductions in heart‑failure hospitalisation and slowing of kidney disease progression. Some benefits appear partly independent of glucose lowering.

§6.1.4 Potential broader healthspan hypothesis: The Patient understands that some literature proposes associations between SGLT2 inhibitor use and reduced risks of certain age‑associated conditions (e.g., heart failure, chronic kidney disease, gout, atrial fibrillation) and proposes mechanisms involving improved cellular stress responses (including autophagy). The Patient understands that these proposed broad benefits are not established as an approved clinical indication and may not apply to healthier, non‑diabetic individuals.

§6.2 No guarantee of benefit / prevention: The Patient acknowledges that any benefits are potential and not guaranteed. The Patient understands that this prescription does not guarantee prevention of disease, extension of lifespan, or improvement in healthspan.

§7 MATERIAL RISKS AND ADVERSE EFFECTS

§7.1 The Patient has been informed of the following risks and adverse effects associated with SGLT2 inhibitor therapy. The Patient understands that this list is not exhaustive and that other adverse effects may occur.

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

  • Genital mycotic infections (e.g., vulvovaginal candidiasis in women, balanitis/balanoposthitis in men)
  • Urinary tract infections
  • Increased urination (polyuria, pollakiuria, nocturia)
  • Thirst
  • Dizziness or lightheadedness (particularly upon standing)
  • Constipation
  • Mild nausea

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

  • Dehydration
  • Hypotension (low blood pressure)
  • Rash or pruritus
  • Dysuria (painful urination)
  • Elevated haematocrit

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

§7.4.1 Euglycaemic diabetic ketoacidosis (euDKA): A rare but potentially life‑threatening condition in which the body produces excess ketones leading to metabolic acidosis, even when blood glucose levels are normal or only mildly elevated. Symptoms include nausea, vomiting, abdominal pain, excessive fatigue, and difficulty breathing. The Patient must seek emergency medical care immediately if these symptoms occur.

§7.4.2 Acute kidney injury: Dehydration associated with SGLT2 inhibitors may rarely precipitate acute kidney injury, particularly in patients taking diuretics, NSAIDs, or ACE inhibitors/ARBs, or in those with pre‑existing renal impairment.

§7.4.3 Bone fractures: Some studies have suggested an increased risk of bone fractures, although data are inconsistent. Patients with osteoporosis or at high risk of fractures should discuss this with their clinician.

§7.4.6 Hypoglycaemia: SGLT2 inhibitors alone rarely cause hypoglycaemia. However, when combined with insulin or sulfonylureas, the risk of hypoglycaemia increases. Dose adjustments of concomitant medications may be required.

§8 CONTRAINDICATIONS AND PRECAUTIONS

§8.1 The Patient confirms that they have disclosed all relevant medical history to the Prescribing Physician. SGLT2 inhibitors are generally contraindicated or require special caution in the following circumstances:

§8.2 Absolute contraindications:

  • Known hypersensitivity or allergy to the prescribed SGLT2 inhibitor or any of its excipients
  • Severe renal impairment (eGFR <20–30 mL/min/1.73m², depending on the specific agent) or end‑stage kidney disease requiring dialysis
  • Type 1 diabetes mellitus (unless specifically approved and closely monitored)

§8.3 Relative contraindications and precautions:

  • History of diabetic ketoacidosis
  • Moderate renal impairment (requires dose adjustment and monitoring)
  • Recurrent urinary tract infections or genital mycotic infections
  • Volume depletion or hypotension
  • Concurrent use of loop diuretics or high‑dose thiazide diuretics
  • Active foot ulcers or at high risk of ulceration
  • Elderly patients (≥75 years) who may be more susceptible to dehydration

§9 DRUG INTERACTIONS

§9.1 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:

§9.2 Diuretics (loop diuretics, thiazides): Concomitant use may increase the risk of dehydration and hypotension. Dose adjustment or closer monitoring may be required.

§9.3 Insulin and sulfonylureas: Concomitant use increases the risk of hypoglycaemia. Dose reduction of insulin or sulfonylurea may be necessary.

§9.4 ACE inhibitors and ARBs: Combined use in the setting of dehydration may increase the risk of acute kidney injury.

§9.5 NSAIDs (e.g., ibuprofen, naproxen): May reduce renal blood flow and increase the risk of acute kidney injury when combined with SGLT2 inhibitors and dehydration.

§9.6 Lithium: SGLT2 inhibitors may affect lithium levels; monitoring is advised.

§9.7 The Patient agrees to inform the Clinic before starting any new medication.

§10 MONITORING REQUIREMENTS

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

§10.2 Baseline assessments:

  • Renal function (serum creatinine, eGFR)
  • Metabolic markers (e.g., HbA1c and fasting glucose) to document baseline and safety, as clinically appropriate
  • Blood pressure
  • Volume status assessment
  • Foot examination (if at risk)

§10.3 Ongoing monitoring:

  • Renal function: typically at 1–3 months after initiation, then at least annually
  • Metabolic markers (e.g., HbA1c/fasting glucose) as clinically appropriate
  • Blood pressure and volume status: as clinically indicated
  • Symptoms of genital or urinary infection
  • Symptoms of ketoacidosis
  • Foot health (for at‑risk patients)

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

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

  • SGLT2 inhibitors should be temporarily stopped during acute illness associated with reduced oral intake, dehydration, or risk of volume depletion (e.g., vomiting, diarrhoea, fever).
  • SGLT2 inhibitors should be stopped at least 3 days before elective surgery and not restarted until the patient is eating and drinking normally.
  • SGLT2 inhibitors should be stopped during prolonged fasting (e.g., religious fasting, very low‑calorie diets).
  • The Patient should contact the Clinic for guidance before restarting the medication after a sick‑day pause.

§11 ALTERNATIVE TREATMENTS

§11.1 The Patient has been informed of the following alternatives to SGLT2 inhibitor therapy:

§11.2 Lifestyle modification: Dietary changes, increased physical activity, weight management, and smoking cessation remain the foundation of metabolic health management.

§11.3 Other strategies: Alternatives may include no pharmacotherapy, other evidence‑based lifestyle programs, or other pharmacological options discussed in a longevity context (e.g., metformin or other therapies) depending on the Patient’s goals and risk profile.

§11.4 No treatment: The Patient may choose not to use pharmacological therapy for health optimization.

§11.5 The Patient confirms that these alternatives have been discussed and that they have chosen to proceed with SGLT2 inhibitor therapy in an off‑label health optimization context.

§13 PATIENT RESPONSIBILITIES AND OBLIGATIONS

§13.1 The Patient agrees to:

  • Take the medication as prescribed and follow dosing instructions.
  • Attend scheduled follow‑up consultations and complete recommended laboratory tests.
  • Report any adverse effects, new symptoms, or changes in health status promptly.
  • Inform the Clinic before starting any new medications or supplements.
  • Follow sick‑day rules as described in §10.4.
  • Seek emergency medical care for symptoms of ketoacidosis, severe infection, or other urgent conditions.
  • Inform other healthcare providers that they are taking an SGLT2 inhibitor.

§13.2 Failure to comply with these responsibilities may affect the safety and efficacy of treatment and may limit the Clinic's ability to provide optimal care.

§14 LIMITATION OF LIABILITY

§14.1 The Patient understands and acknowledges that:

§14.1.1 No guarantee of outcome: Medicine is not an exact science. The Prescribing Physician and the Clinic cannot guarantee any specific outcome from treatment. The decision to prescribe is based on the best available evidence and clinical judgement, but individual responses vary.

§14.1.2 Inherent risks: All medical treatments carry inherent risks. The Patient accepts that adverse effects may occur despite appropriate prescribing and monitoring.

§14.1.3 Patient responsibility: The Patient's own actions, including non‑compliance with prescribed regimens, failure to disclose relevant information, or failure to seek timely medical attention, may affect outcomes.

§14.1.4 Force majeure: The Clinic shall not be liable for delays or failures in treatment caused by events beyond its reasonable control, including but not limited to pandemics, natural disasters, or disruptions to healthcare systems.

§14.2 The above limitations do not exclude or limit liability for death or personal injury caused by negligence or any other liability that cannot be excluded under applicable Danish law.

§15 WITHDRAWAL OF CONSENT

§15.1 The Patient has the right to withdraw consent to this treatment at any time, without providing a reason and without prejudice to future care.

§15.2 To withdraw consent, the Patient should contact the Clinic in writing (email or secure message) or verbally during a consultation.

§15.3 Upon withdrawal of consent, the Prescribing Physician will provide guidance on how to safely discontinue the medication, if applicable.

§15.4 Withdrawal of consent does not affect the lawfulness of processing carried out before withdrawal.

§16 DATA PROTECTION AND CONFIDENTIALITY

§16.1 The Patient's personal data, including health information, will be processed in accordance with Regulation (EU) 2016/679 (General Data Protection Regulation) and applicable Danish data protection laws.

§16.2 Personal data will be used for the purposes of providing medical care, maintaining medical records, communicating with the Patient, and fulfilling legal and regulatory obligations.

§16.3 The Patient has the right to access, rectify, erase, restrict processing of, and receive a copy of their personal data, subject to applicable legal requirements.

§16.4 Medical records will be retained in accordance with Danish law and professional guidelines.

§16.5 For further information, please refer to the Clinic's Privacy Policy.

§17 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 the nature of the medication prescribed and how it works (including glucosuria and diuretic/natriuretic effects).
  • I understand that this prescription is being provided in a proactive health optimization / longevity context and is not being provided by this Clinic for diagnosis or treatment of diabetes.
  • I understand that prescribing an SGLT2 inhibitor primarily for longevity/healthspan is off‑label and not an EMA‑approved indication.
  • I understand that evidence for broader healthspan/longevity benefits is incomplete and that benefits are potential and not guaranteed.
  • I have been informed of the material risks and adverse effects, including the risks of euglycaemic ketoacidosis and genital/urinary infections.
  • I understand and will follow the sick‑day rules described in §10.4.
  • I have been informed of alternative treatments and have chosen to proceed with SGLT2 inhibitor therapy.
  • I have disclosed all relevant medical history, current medications, and allergies to the Clinic.
  • I understand that I must maintain appropriate primary care and seek urgent/emergency care when needed; this Clinic is not an emergency service.
  • I understand my responsibilities as a patient, including compliance with the prescribed regimen and follow‑up requirements.
  • I have had the opportunity to ask questions, and my questions have been answered to my satisfaction.
  • I voluntarily consent to commence or continue treatment with the prescribed medication as prescribed by the Prescribing Physician.