Usage
- Alogliptin + Metformin is prescribed for type 2 diabetes mellitus in adults as an adjunct to diet and exercise to improve glycemic control. It is used when metformin alone or metformin combined with other oral antidiabetic medications, including pioglitazone or insulin, do not provide adequate glycemic control. It is not indicated for type 1 diabetes.
- Pharmacological Classification: Antidiabetic combination; Dipeptidyl peptidase-4 (DPP-4) inhibitor (alogliptin) and biguanide (metformin).
- Mechanism of Action: Alogliptin increases incretin levels (e.g., GLP-1 and GIP), which in turn increase insulin secretion and decrease glucagon secretion, especially after meals. Metformin decreases hepatic glucose production, decreases intestinal glucose absorption, and improves insulin sensitivity.
Alternate Names
- Alogliptin benzoate/metformin HCl
- Alogliptin benzoate/metformin hydrochloride
- Brand Names: Kazano, Vipdomet
How It Works
- Pharmacodynamics: Alogliptin enhances glucose-dependent insulin secretion and suppresses glucagon secretion. Metformin reduces hepatic glucose production, decreases intestinal glucose absorption, and improves peripheral insulin sensitivity.
- Pharmacokinetics: Both drugs are orally administered. Alogliptin is rapidly absorbed and extensively metabolized, primarily via CYP2C8 and CYP3A4, with renal elimination being the major route. Metformin is absorbed slowly and incompletely, is not metabolized, and is excreted primarily by the kidneys.
- Mode of Action: Alogliptin inhibits DPP-4, the enzyme responsible for degrading incretins like GLP-1 and GIP. Metformin’s exact mechanism is not fully understood but involves activation of AMP-activated protein kinase (AMPK).
- Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Alogliptin inhibits DPP-4. Metformin activates AMPK.
- Elimination Pathways: Alogliptin is primarily eliminated renally. Metformin is excreted unchanged in the urine.
Dosage
Standard Dosage
Adults:
- Initial: Alogliptin 12.5 mg + Metformin 500 mg or 1000 mg twice daily, orally with food.
- Maintenance: Adjust based on efficacy and tolerability up to a maximum of Alogliptin 25 mg + Metformin 2000 mg per day.
Children:
- Not recommended. Safety and efficacy not established.
Special Cases:
- Elderly Patients: Start with a low dose and titrate cautiously due to potential renal impairment.
- Patients with Renal Impairment: Contraindicated in severe renal impairment (eGFR < 30 mL/min/1.73 m²). Not recommended in moderate renal impairment (eGFR 30-45 mL/min/1.73 m²). Dose reduction may be required for mild renal impairment.
- Patients with Hepatic Dysfunction: Not recommended.
- Patients with Comorbid Conditions: Use with caution in patients with congestive heart failure or a history of pancreatitis.
Clinical Use Cases
- Not typically used in acute clinical settings like intubation, surgical procedures, mechanical ventilation, ICU, or emergency situations. Its primary role is in the chronic management of type 2 diabetes.
Dosage Adjustments
- Adjust based on renal function, hepatic function, and concomitant medications. If eGFR falls below 45 mL/min/1.73 m², reassess the risks and benefits of continuing therapy. Temporarily discontinue before procedures requiring iodinated contrast media.
Side Effects
Common Side Effects
- Upper respiratory tract infection, nasopharyngitis
- Diarrhea
- Headache
- Back pain
- Hypertension
Rare but Serious Side Effects
- Lactic acidosis (especially with renal impairment)
- Severe joint pain
- Pancreatitis
- Bullous pemphigoid
- Hepatic dysfunction
- Angioedema
Long-Term Effects
- Vitamin B12 deficiency (with long-term metformin use)
Adverse Drug Reactions (ADR)
- Lactic acidosis
- Bullous pemphigoid
- Angioedema
- Severe hypersensitivity reactions
Contraindications
- Severe renal impairment (eGFR < 30 mL/min/1.73 m²)
- Acute or chronic metabolic acidosis, including diabetic ketoacidosis
- Hypersensitivity to alogliptin or metformin
Drug Interactions
- Alcohol (increased risk of lactic acidosis)
- Iodinated contrast media (increased risk of lactic acidosis and renal impairment)
- Cimetidine (increased metformin levels)
- Medications that inhibit renal tubular secretion (increased metformin levels)
- Some diuretics, corticosteroids (hyperglycemia)
- Insulin secretagogues, insulin (hypoglycemia)
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C (Australia); Not assigned (US FDA).
- Insufficient data in humans. Poorly controlled diabetes in pregnancy poses risks to both mother and fetus. Metformin has been associated with some fetal risks at very high doses in animal studies. Alogliptin crosses the placenta in rats.
- Not recommended during breastfeeding (metformin is excreted in breast milk).
Drug Profile Summary
- Mechanism of Action: Alogliptin: DPP-4 inhibitor; Metformin: reduces hepatic glucose production, decreases intestinal glucose absorption, improves insulin sensitivity.
- Side Effects: Diarrhea, upper respiratory tract infection, headache, back pain, hypertension. Serious: lactic acidosis, pancreatitis, bullous pemphigoid, angioedema.
- Contraindications: Severe renal impairment, metabolic acidosis, hypersensitivity.
- Drug Interactions: Alcohol, iodinated contrast media, cimetidine, insulin secretagogues, insulin.
- Pregnancy & Breastfeeding: Not recommended.
- Dosage: Initial: Alogliptin 12.5 mg + Metformin 500/1000 mg BID; Max: Alogliptin 25 mg + Metformin 2000 mg daily.
- Monitoring Parameters: HbA1c, fasting blood glucose, renal function, liver function tests, signs/symptoms of heart failure and pancreatitis.
Popular Combinations
- Pioglitazone, basal insulin: For patients inadequately controlled on dual therapy.
Precautions
- General Precautions: Assess renal function before and during therapy. Monitor for signs and symptoms of lactic acidosis, pancreatitis, hypersensitivity reactions.
- Specific Populations: Pregnancy/Breastfeeding: Not recommended. Children: Not recommended. Elderly: Dose adjustment may be necessary.
- Lifestyle Considerations: Advise on diet, exercise, and limiting alcohol intake.
FAQs (Frequently Asked Questions)
A: Initial: Alogliptin 12.5 mg + Metformin 500 or 1000 mg twice daily. Max: Alogliptin 25 mg + Metformin 2000 mg per day. Adjust based on efficacy, tolerability, and renal function.
Q2: What are the common side effects?
A: Upper respiratory infections, diarrhea, headache, back pain, and hypertension.
A: In severe renal impairment, metabolic acidosis (including diabetic ketoacidosis), and hypersensitivity to either drug.
A: Alogliptin increases insulin release and decreases glucagon release by inhibiting DPP-4. Metformin reduces hepatic glucose production, decreases intestinal glucose absorption, and improves insulin sensitivity.
A: Not recommended. Insufficient data in humans. Poorly controlled diabetes poses risks to mother and fetus.
Q6: What are the important drug interactions?
A: Alcohol, iodinated contrast media, cimetidine, drugs affecting renal function, insulin secretagogues, and insulin.
Q7: What monitoring is required during treatment?
A: HbA1c, blood glucose, renal function, liver function tests (as indicated), and signs/symptoms of heart failure and pancreatitis.
A: Yes, it can be used with pioglitazone and insulin. Dose adjustments may be necessary.
Q9: What should I advise my patients about lifestyle modifications?
A: Advise patients on diet, exercise, and limiting alcohol intake.
Q10: What is lactic acidosis and how does it relate to this medicine?
A: Lactic acidosis is a rare but serious side effect primarily associated with metformin. It’s characterized by a buildup of lactic acid in the blood. Risk factors include renal impairment, dehydration, and excessive alcohol consumption. Patients should be educated on recognizing the symptoms (e.g., muscle pain, weakness, nausea, vomiting, difficulty breathing).
