Vildagliptin: Effect in Type 2 Diabetes
Vildagliptin (brand names Galvus, Eucreas in combination with metformin, and generics) is a DPP 4 inhibitor (dipeptidylpeptidase 4 inhibitor, gliptin) for the treatment of type 2 diabetes. Licensed in Europe since 2008, it belongs to the class of incretin enhancers, which increase insulin secretion and reduce glucagon release in a glucose dependent manner. Hypoglycaemia occurs very rarely with vildagliptin monotherapy, which makes this substance particularly attractive in elderly patients and in polypharmacy.
Compared to other antidiabetic agents, vildagliptin has a moderate HbA1c lowering profile (approximately 0.7 to 1.0 percent), is weight neutral, and well tolerated. In clinical practice, it is used as monotherapy for metformin intolerance or as add on to metformin. In combination preparations with metformin (Eucreas, Jentadueto in some countries), therapy adherence is often better than with two separate tablets.
Mechanism of Action
Vildagliptin selectively and reversibly inhibits the enzyme dipeptidylpeptidase 4 (DPP 4) in plasma and tissue. DPP 4 degrades the incretins GLP 1 (glucagon like peptide 1) and GIP (glucose dependent insulinotropic peptide), which are released from the intestine after meals. By inhibiting DPP 4, endogenous incretin levels rise approximately two to threefold, which increases insulin secretion in the beta cells of the pancreas in a glucose dependent manner and simultaneously reduces glucagon release in the alpha cells.
The glucose dependent action is the key to the low hypoglycaemia risk: at low blood glucose, incretins are barely active, and insulin secretion remains normal. Unlike sulphonylureas or insulin, DPP 4 inhibitors therefore cannot cause hypoglycaemia outside of combination therapies. This property is clinically particularly valuable in elderly patients who are at high risk with hypoglycaemic episodes.
Pharmacokinetically, vildagliptin shows good oral bioavailability (approximately 85 percent), the half-life is 2 to 3 hours, which allows twice daily administration. Metabolism occurs primarily through hydrolysis in plasma and tissue. Renal elimination plays a relevant role, which is why dose adjustment is necessary in renal insufficiency.
Indications
- Type 2 diabetes mellitus as monotherapy for metformin intolerance
- Add on to metformin for insufficient metabolic control with metformin alone
- Add on to sulphonylureas for insufficient efficacy
- Triple therapy with metformin and sulphonylurea or glitazone
- Add on to insulin for insufficient metabolic control
Vildagliptin is not indicated in type 1 diabetes, in acute treatment of diabetic ketoacidosis, or as monotherapy in patients who are well controlled with metformin. In patients with prior cardiovascular disease or chronic kidney disease, SGLT 2 inhibitors or GLP 1 receptor agonists are often the better choice today because they offer additional endpoint reduction.
Dosage and Administration
Standard dose adults: 50 mg twice daily orally, morning and evening. In combinations with sulphonylureas or insulin: 50 mg once daily in the morning to reduce hypoglycaemia.
Renal insufficiency: for eGFR 30 to 60 ml per minute dose reduction to 50 mg once daily. For eGFR below 30, 50 mg once daily, in some countries dosing is even lower.
Hepatic insufficiency: if liver transaminases are above 2.5 times the normal range, vildagliptin should not be used because the risk of hepatotoxicity is increased.
Administration: with or without food, adequate water. Swallow tablets whole without chewing.
Therapy initiation: measure liver transaminases before therapy. Check liver transaminases every three months during the first 12 months, then at regular intervals.
Duration of therapy: long term, as long as efficacy and tolerability are given. An HbA1c reevaluation after 3 to 6 months is worthwhile to assess efficacy.
Adverse Effects
Frequent: dizziness, headaches, tremor, increased liver transaminases.
Occasional: constipation, fatigue, respiratory tract infections, hypoglycaemia (especially in combination with sulphonylureas or insulin), allergic skin reactions.
Rare but relevant: hepatotoxicity with increased liver transaminases, in individual cases clinically significant liver inflammation. Acute pancreatitis as a class adverse effect of incretin based therapies.
Rare: bullous pemphigoid, Stevens Johnson syndrome, angioedema (especially with concomitant use of ACE inhibitors), arthralgias.
In combination with ACE inhibitors: increased risk of angioedema, especially in the first 4 weeks of combination therapy. Patients should be informed about symptoms such as swelling of lips, tongue, or airways.
Drug Interactions
- Metformin: intended combination, no direct interaction mechanism, additive HbA1c lowering.
- Sulphonylureas (glibenclamide, glimepiride): increased hypoglycaemia risk, reduce sulphonylurea dose in combination.
- Insulin: increased hypoglycaemia risk, adjust insulin dose.
- ACE inhibitors: increased angioedema risk, discontinue immediately upon occurrence.
- Other DPP 4 inhibitors (sitagliptin, saxagliptin, linagliptin): no combination because of same mechanism of action.
- GLP 1 receptor agonists (liraglutid, semaglutid): theoretically synergistic effect, clinically not routinely combined due to cost considerations.
- SGLT 2 inhibitors (empagliflozin, dapagliflozin, ertugliflozin): synergistic HbA1c lowering, combination possible.
- Diuretics and corticosteroids: may increase blood glucose, therapy adjustment may be necessary.
Special Precautions
Pregnancy: limited data. Use is not recommended. Insulin is the established therapy in pregnancy. Breastfeeding: transfer into breast milk not sufficiently investigated, use not recommended.
Children and adolescents: not approved for children under 18 years of age.
Elderly patients: well suited due to low hypoglycaemia risk. Pay attention to renal insufficiency and adjust dose.
Before starting therapy: HbA1c, fasting blood glucose, liver transaminases, eGFR, history of pancreatitis. Do not use vildagliptin if liver transaminases are above 2.5 times normal.
Liver monitoring: check liver transaminases every 3 months during the first 12 months. If increase above 3 times normal range, stop therapy and have it medically evaluated.
Pancreatitis risk: if acute abdominal pain, persistent vomiting, or clinical suspicion of pancreatitis occurs, immediately discontinue therapy and arrange lipase, amylase testing, and imaging.
Lifestyle in type 2 diabetes: dietary modification, regular physical activity, weight management, smoking cessation, blood pressure control, and cholesterol management are the foundation. Vildagliptin complements these measures.
Driving ability: generally preserved, should be individually assessed in case of dizziness or hypoglycaemia.
You Might Also Be Interested In
- Ertugliflozin, SGLT 2 inhibitor with cardiovascular endpoint reduction
- Liraglutid, GLP 1 receptor agonist with similar incretin mechanism
- Glucagon, emergency hormone in severe hypoglycaemia
- Creatinine, marker for dose adjustment in renal insufficiency
- Blood pressure medications, overview of antihypertensive agents in diabetes
Frequently Asked Questions
How do DPP 4 inhibitors differ from GLP 1 receptor agonists?
Both belong to incretin based therapy. DPP 4 inhibitors like vildagliptin are oral tablets that protect endogenous incretins from degradation. GLP 1 receptor agonists like liraglutid or semaglutid are injectable or available as oral semaglutid and directly mimic GLP 1. GLP 1 agonists have stronger effects on weight and in many cases cardiovascular endpoint reduction, but are more expensive.
Why does vildagliptin not cause hypoglycaemia as monotherapy?
The effect of vildagliptin is glucose dependent: the endogenous incretins GLP 1 and GIP only act insulinotropically at elevated blood glucose. At normal or low blood glucose, insulin secretion remains normal. Therefore, vildagliptin as monotherapy cannot cause hypoglycaemia. In combination with sulphonylureas or insulin, the hypoglycaemia risk arises from the partner substances.
What liver monitoring do I need while taking vildagliptin?
Measure liver transaminases before starting therapy. Check every 3 months during the first 12 months. If transaminases increase above 3 times the upper normal range, therapy should be discontinued. Vildagliptin is not suitable for patients with pre-existing liver disease (transaminases above 2.5 times normal).
What are the advantages compared to sulphonylureas?
Vildagliptin has significantly lower hypoglycaemia risk, is weight neutral, and well tolerated. Sulphonylureas are more cost effective but carry hypoglycaemia and weight gain. In elderly patients and in polypharmacy, vildagliptin is often preferred. In younger patients without these risks, sulphonylureas may remain an option.
Sources
- EMA, Galvus (Vildagliptin) EPAR
- Gelbe Liste, Vildagliptin active substance profile
- BfArM, Federal Institute for Drugs and Medical Devices
- AWMF, National Care Guideline Type 2 Diabetes
- German Diabetes Society
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