Glyxambi
Glyxambi
Generic Name
Glyxambi
Mechanism
- Sitagliptin: Irreversibly inhibits dipeptidyl‑peptidase‑4 (DPP‑4), prolonging the action of incretin hormones (GLP‑1, GIP). This leads to:
- ↑ insulin secretion in a glucose‑dependent manner
- ↓ glucagon release when glucose is high
- ↓ post‑prandial glucose excursions
- Empagliflozin: Selectively blocks sodium‑glucose cotransporter‑2 (SGLT2) in the proximal renal tubule, promoting:
- ↑ urinary glucose excretion (≈200–300 g/day)
- ↓ intraglomerular pressure, improving renal hemodynamics
- Mild natriuretic effect → ↓ blood pressure
The dual‑mechanism yields additive HbA1c reductions, cardiovascular risk diminution, and weight loss.
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Pharmacokinetics
| Property | Sitagliptin | Empagliflozin |
| Absorption | Rapid, ~70 % bioavailability | Rapid, ~81 % bioavailability |
| Tmax | ~1‑3 h | ~0.5‑1 h |
| Half‑life | 12–14 h | 12–17 h |
| Metabolism | Minimal CYP involvement (renal excretion) | Hepatic (CYP3A4) → ~10 % renal unchanged |
| Renal clearance | Major (≈80 %) | Major (≈80 %) |
| Dose adjustment | eGFR ≥ 30 mL/min: no change; <30 mL/min: hold | eGFR ≥ 45 mL/min: same; 30–45 mL/min: 10 mg; <30 mL/min: contraindicated |
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Indications
- Type 2 Diabetes Mellitus (adult)
- Adjunct to diet, exercise, and/or other antihyperglycemics.
- Preferred in patients requiring ≥ 0.5 % HbA1c reduction with weight loss or blood‑pressure support.
- Cardiovascular benefit
- Empagliflozin component confers major adverse cardiovascular event (MACE) reduction (EMPA‑REG OUTCOME).
- Consider in T2DM patients with established ASCVD or heart‑failure with reduced EF.
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Contraindications
| Category | Key Points |
| Contraindications |
• Severe renal impairment (eGFR < 45 mL/min).
• Type 1 diabetes or diabetic ketoacidosis. |
| Warnings |
• Euglycemic ketoacidosis (esp. peri‑surgical periods, prolonged fasting).
• Volume depletion → hypotension, orthostatic symptoms.
• Genitourinary infections (candidiasis, cystitis).
• Acute kidney injury (AKI) in patients exposed to contrast or nephrotoxic agents. |
| Drug Interactions |
• CYP3A4 inhibitors/inducers minimally affect empagliflozin.
• SGLT2 inhibitors + other glucose‑lowering drugs may ↑ hypoglycemia risk. |
| Special Populations |
• Pregnancy: category C; FDA recommends discontinuation.
• Lactation: not recommended. |
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Dosing
| Age / Renal Function | Starting Dose | Titration | Max Dose | Administration |
| Adults, eGFR ≥ 45 mL/min | 1 tablet once daily (dose of 1 tablet) | Maintain ≤ 1 tablet if HbA1c < 6.5 % | 2 tablet once daily | With or without food, same time daily |
| Adults, eGFR 30–44 mL/min | 1 tablet once daily | No titration | 1 tablet | Same as above |
| Elderly: no adjustment needed unless renal decline |
• Swallow whole; do not crush or chew.
• Avoid drinking large volumes of water at dosing to reduce genital infection risk.
• For ≥ 12‑hour fasting states, baseline serum creatinine should be re‑checked three days after initiating therapy.
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Adverse Effects
Common (≤ 5 %)
• Genital mycotic infections (vaginal/penile)
• Urinary tract infections
• Mild nasopharyngitis
• Headache
Serious (≤ 1 %)
• Cardiac death (rare; confounded by cardiovascular comorbidities)
• DKA (euglycemic), especially after abrupt discontinuation or surgery
• Severe volume depletion → hypotension, renal dysfunction
• Fournier’s gangrene (rare)
> Patient Education: Monitor for burning during urination, foul odor, or vaginal discharge; report promptly.
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Monitoring
| Parameter | Frequency | Rationale |
| HbA1c | 3 months after initiation, then every 3–6 months | Assess glycemic efficacy |
| Renal function (serum creatinine / eGFR) | Every 6 months (or sooner if symptomatic) | Detect renal decline |
| Blood pressure | At each clinic visit | Empagliflozin lowers BP |
| Weight | Every visit | Monitor weight loss/gain |
| Ketone bodies (urinal / plasma in at-risk patients) | At the first post‑discontinuation or peri‑operative event | Detect DKA early |
| Volume status (orthostatic vitals) | Per visit if symptomatic | Identify dehydration |
| Liver function tests | Baseline, then annually | Rare hepatotoxicity |
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Clinical Pearls
- Dual cardiovascular advantage: empagliflozin’s reduction in MACE extends to non‑cardiovascular mortality; consider it a first‑line option in T2DM patients with ASCVD.
- Weight & BP synergy: The SGLT2 component induces osmotic diuresis, leading to sodium excretion and modest BP reduction, which may eliminate the need for separate antihypertensives.
- Surgical caution: Hold Glyxambi 48 h before elective surgery to avoid postoperative volume depletion and peri‑operative ketoacidosis.
- Metformin combo: When co‑administered with metformin, monitor for lactic acidosis risk; ensure eGFR ≥ 45 mL/min.
- Pregnancy & breastfeeding: Contraindicated; refer for contraceptive counseling if applicable.
- Elderly & renal function: The package narrows the usable range; frequent eGFR checks every 6 months during the transition from 45 to 30 mL/min.
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• *Prepared for medical students and clinicians seeking a quick‑reference, evidence‑based snapshot of Glyxambi.*