Synjardy
Synjardy
Generic Name
Synjardy
Mechanism
- Dapagliflozin – a selective sodium‑glucose cotransporter‑2 (SGLT2) inhibitor that blocks glucose re‑absorption in the proximal renal tubule, resulting in glucosuria and a net caloric loss (~200 kcal/day).
- Metformin – activates AMP‑activated protein kinase (AMPK), decreases hepatic gluconeogenesis, improves insulin sensitivity in muscle, and modestly increases peripheral glucose uptake.
- The dual action lowers plasma glucose via independent, non‑overlapping pathways, enhancing efficacy and providing a broader therapeutic profile.
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Pharmacokinetics
| Parameter | Key Data (dapagliflozin) | Key Data (metformin) |
| Absorption | Rapid; peak plasma conc. (t_max) ~2 h; ~60% orally bioavailable. | Rapid and linear; t_max 1–2 h; ~50% oral bioavailability. |
| Distribution | Vd ≈5–6 L; low protein binding (~20%). | Vd ≈58 L/kg; almost no protein binding. |
| Metabolism | Minimal; ~90% excreted unchanged. | Minimal metabolism; largely unchanged. |
| Excretion | Renal, via glomerular filtration and tubular secretion; elimination half‑life 12–13 h. | Renal, ~70% excreted by kidneys unchanged; t_½ ≈6–8 h. |
| Dose Adjustments | Reduce or discontinue when eGFR 45 mL/min. |
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Indications
- Adults with type 2 diabetes mellitus inadequately controlled on diet, exercise, and monotherapy.
- Adjunct to existing antihyperglycemic regimens (e.g., sulfonylureas, basal insulin) unless insulin‑dependent or type 1 diabetes.
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Contraindications
| Issue | Recommendation |
| Type 1 Diabetes | Contraindicated (risk of ketoacidosis). |
| Ketoacidosis | Avoid in patients with a history of diabetic ketoacidosis (DKA). |
| Severe Renal Impairment | Contraindicated if eGFR <30 mL/min/1.73 m². |
| Pregnancy / Lactation | Category C; avoid in pregnancy, discontinue before conception. |
| Hepatic Failure | Use with caution; no robust data in severe hepatic disease. |
| Genital or Urinary Tract Infection History | Monitor; predisposition to infections. |
| Use with SGLT2‑inhibitor‑induced Volume Depletion | Combine with diuretics cautiously. |
| Fournier’s Gangrene | Rare but severe; discontinue if necrotizing infection occurs. |
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Dosing
| Form | Starting Dose | Maximum Dose | Titration | Administration Notes |
| Synjardy 5 mg / 500 mg | 1 tablet once daily (anytime) | 10 mg / 1000 mg | Increase by 1 tablet after 4 weeks if HbA1c >7% | Take with or immediately after a meal to reduce GI upset. |
| Synjardy 10 mg / 1000 mg (if available) | Not recommended as initial; consider if inadequate response to 5 mg/500 mg after 12 weeks. | 10 mg / 1000 mg | Increase by 1 tablet at 4‑week intervals | Same meal timing. |
• Renal Function: If CrCl 30–45 mL/min, use dapagliflozin 5 mg/500 mg; consider metformin 500 mg only after confirming adequate renal clearance.
• Discontinuation: Stop dapagliflozin before surgery requiring general anesthesia; resume when renal function stabilizes.
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Monitoring
| Parameter | Frequency | Target / Note |
| HbA1c | Every 3 months | Aim <7% (adjust per patient). |
| Fasting glucose | Monthly initially, then every 3 months | Monitor for hypoglycemia risk if concomitant sulfonylurea/insulin. |
| eGFR / BUN | Every 3 months | Adjust dose if eGFR falls below thresholds. |
| Serum electrolytes | Every 3 months | Watch for hyperkalemia, hypophosphatemia. |
| Weight / BP | Every visit | Expect modest weight loss and BP reduction. |
| Symptoms of infection | At each visit | Urgent evaluation if fever, dysuria, or genital pain. |
| Pregnancy test | Prior to initiation in women of childbearing potential | Repeat if pregnancy suspected. |
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Clinical Pearls
- Cardiovascular Benefit – Synjardy lowers systolic BP by ~5 mmHg and modestly reduces albuminuria; may confer CV protection in high‑risk patients per DECLARE‑TIMI 58 data, especially when combined with metformin.
- Euglycemic DKA Awareness – Educate patients on signs: nausea, vomiting, abdominal pain, dyspnea; recommend glucose monitoring even in the absence of hyperglycemia during illness or rapid weight loss.
- Weight Management – The glucosuria‑driven caloric loss (~200 kcal/day) makes Synjardy advantageous for overweight/obese T2DM patients; monitor weight loss to avoid dehydration.
- Renal Considerations – Even mild CKD (eGFR 45–60 mL/min/1.73 m²) warrants caution; metformin dose limits apply, and dapagliflozin is not indicated below 30 mL/min.
- Drug Interactions – Avoid co‑administration with agents that can precipitate volume depletion (e.g., NSAIDs, ACE inhibitors) unless BP is well controlled; monitor electrolytes.
- Pregnancy & Lactation – SGLT2 inhibitors cross the placenta; discontinue if pregnancy is confirmed. No data on infant safety via breast milk; usually discontinued.
- Glycemic Monitoring on Holidays – Patients on Synjardy may experience reduced caloric intake during fasting; advise glucose checks to prevent hypoglycemia.
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• Synjardy represents a potent, dual‑mechanism strategy for T2DM management, offering glycemic reduction, weight loss, and cardiovascular benefit while requiring vigilant monitoring for rare but serious adverse events.