Drug Summary - DPP-4 Inhibitors

(Refer to: Drug review - Dipeptidyl peptidase-4 inhibitors for review and references)

Mode of action and pharmacology	DPP-4 inhibitors (gliptins) are capable of inhibiting the degradation of endogenous GLP-1, thereby therapeutically raising circulating GLP-1 levels
Glycaemic efficacy and indications	Can be used as monotherapy in selected patients when there is intolerance to metformin (where there is a high risk for hypoglycaemia) Can be used as dual or triple therapy when added to metformin / sulphonylurea / SGLT 2 inhibitor / insulin HbA1C reduction when used as monotherapy is between 0.5 and 1.1 %
Macrovascular and Mortality Outcomes	Cardiovascular outcome safety trials for all 3 DPP-4 inhibitors have been neutral for major adverse cardiovascular events Saxagliptin was associated with increased rates of hospitalisation for heart failure
Hypoglycaemia	Hypoglycaemia rates are not different to placebo except when DPP 4 inhibitors are combined with insulin or insulin secretagogues
Non-glycaemic benefits	Weight-neutral
Side Effects and Precautions	Small absolute risk for pancreatitis. Increased risk of hospitalisation for heart failure with saxagliptin
Contraindications	Acute, chronic or recurrent pancreatitis or high risk for pancreatitis Pancreatic cancer All are contraindicated in severe liver disease Use saxagliptin and vildagliptin with caution in moderate liver disease Heart failure (saxagliptin)
Dosing	eGFR	Saxagliptin	Sitagliptin	Vildagliptin
	≥50 ml/min 30-50 ml/min <30 ml/min	5 mg daily 2.5 mg daily 2.5 mg daily	100 mg daily 50 mg daily 25 mg daily	50 mg twice a day 50 mg daily 50 mg daily
Cost at maximum dose: Moderate (R260 – 340 per month - single exit pricing as at March 2017)

 

(See Strength of Recommendations Taxonomy (SORT) for explanation of Grade A-C)

SEMDSA 2017 Recommendations for DPP-4 inhibitors
Consider a DPP-4 inhibitor as initial monotherapy when metformin is contraindicated or not tolerated	C
Consider a DPP-4 inhibitor as add-on to metformin or other initial drug therapy, in selected patients not achieving or maintaining their glycaemic targets	A
Consider a DPP-4 inhibitor as the third glucose lowering drug in selected patients not achieving or maintaining their glycaemic targets on an existing oral two-drug regimen	A
Combination DPP-4 inhibitor and insulin therapy should be initiated at specialist level	C
Be aware of dose adjustments for chronic kidney disease	C
Circumstances where a DPP-4 inhibitor may be preferred to other treatment options: As the 2nd add-on drug when gliclazide MR is contraindicated or not tolerated As the 3rd add on drug for most patients if HbA1C targets are potentially achievable Older patients with multiple comorbidities Patients with stage-4 chronic kidney disease (can be used without risk of hypoglycaemia) If a fixed-dose combination tablet will improve adherence, compliance and/or cost-effectiveness	C
Circumstances where a DPP-4 inhibitor may not be the preferred option: Very high HbA1C and the glycemic target is not likely to be achieved with a DPP-4 inhibitor History of pancreatitis or pancreatic tumour History of heart failure or high risk of heart failure (saxagliptin) Liver disease: moderate (do not use saxagliptin or vildagliptin) or severe (do not any DPP-4 inhibitor)	C

 

Caution:

Do not persist with any chosen treatment if the HbA_1C has not decreased by > 0.5% after six months

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