DPP 4 Inhibitor Prescribing

Dipeptidyl peptidase 4 inhibitors raise endogenous GLP 1 and GIP concentrations, increasing glucose-dependent insulin release and lowering glucagon. They are oral, weight neutral, rarely cause hypoglycaemia, and lower HbA1c modestly, by about 5 to 8 mmol/mol (0.5 to 0.8%). They suit older and frail patients and those with kidney impairment.

No cardiovascular benefit. They are cardiovascularly neutral, with a heart failure signal for saxagliptin and possibly alogliptin.

Preferred where renal or hepatic function is reduced. Linagliptin needs no kidney or liver adjustment.

Avoid. In heart failure use neither saxagliptin nor alogliptin. In a history of pancreatitis avoid all agents. Do not combine with a GLP 1 receptor agonist.

Vildagliptin. Liver tests are needed, and it is avoided in hepatic impairment.

Sitagliptin. 100 mg orally once daily; 50 mg once daily if eGFR is 30 to 44; 25 mg once daily if eGFR is under 30 or on dialysis.

Linagliptin. 5 mg orally once daily at all levels of kidney function.

Saxagliptin. 5 mg orally once daily; 2.5 mg once daily if eGFR is under 45 or with strong CYP3A4 inhibitors such as clarithromycin and ketoconazole.

Alogliptin. 25 mg orally once daily; 12.5 mg if eGFR is 30 to 59; 6.25 mg if eGFR is under 30.

Vildagliptin. 50 mg orally twice daily; 50 mg once daily with a sulphonylurea or if eGFR is under 50.

Combination therapy. Add to metformin. With a sulphonylurea or insulin, consider reducing the sulphonylurea or insulin dose to avoid hypoglycaemia.

Special groups. - Pregnancy: avoid; use insulin. - Breastfeeding: not advised. - Older adults: well tolerated; first-choice add-on when hypoglycaemia is a concern. - Liver disease: linagliptin and sitagliptin acceptable; avoid vildagliptin.

Monitoring. HbA1c at 3 months; stop if the fall in HbA1c is under 5 mmol/mol (0.5%) by 6 months. Kidney function at baseline and at least annually.

Adverse effects. Nasopharyngitis, headache, pancreatitis (rare), severe joint pain, and bullous pemphigoid.

Stopping. Stop for suspected pancreatitis, bullous pemphigoid, disabling arthralgia, or heart failure on saxagliptin or alogliptin.

Referral and escalation. Refer if blistering skin eruptions develop or if abdominal pain suggests pancreatitis.