DPP-4 Inhibitors

Dipeptidyl peptidase-4 (DPP-4) inhibitors block the enzyme which breaks down incretins (GLP-1 and GIP) in the body. This prolongs the effect of endogenous incretins, reducing blood sugar by increasing insulin and decreasing glucagon secretion.

1. Therapeutic Considerations

 All information from medication product monographs unless referenced below. 

A1c Lowering 0.5 - 1.0% (median in studies is ≤ 0.7%)1
Hypoglycemia Risk  Low when used as monotherapy. 
Class Side Effects Generally well tolerated. Most common- nasopharyngitis. Rare - pancreatitis, severe joint pain, skin reactions. Some side effects are specific to individual brands- see below. 
Vascular Protection No 
Weight  Neutral 
Cost, Blue Cross coverage;  strengths;  dosing frequency; indications

Click to visit DPP-4 Inhibitors in Complete Diabetes Medications Table  

Combination Medications Click to visit combination meds in the Complete Diabetes Meds Table 
Advice for times of dehydration, vomiting, diarrhea Diabetes Canada advises this medication be taken as directed unless otherwise directed by a healthcare provider.
Other
  • Dosage modification required for renal impairment with all brands except for lingaliptin (Trajenta) -see Dosing Considerations. 
  • Saxagliptin has been associated with new development or worsening of congestive heart failure. The brands alogliptin (Nesina), linagliptin (Trajenta) and saxagliptin (Onglyza) are to be used with caution in patients with congestive heart failure.

 

2. Dosing Considerations

 

  • Refer to Therapeutic Considerations for Renal Impairment, Diabetes Canada for renal dosing recommendations.
  • Tablet taken once a day with or without food (unless part of combination medication with Metformin- then may be prescribed twice a day). 
  • All brands generally started at maximum dose (unless renal or other exceptions) and no need for dose titration. 

3. Brand Considerations

 

Alogliptin - Nesina®

  • See the Complete Diabetes Medication Table for: cost/month; Blue Cross coverage; available strengths;  dosing frequency; Health Canada indications
  • Side effects in addition to those listed in table above: headache, upper respiratory tract infection. 
  • Caution advised for those with pre-existing congestive heart failure. 
  • Postmarketing reports of fatal and non-fatal hepatic failure. Advise hepatic function tests assessed before treatment and periodically thereafter. 

 

Linagliptin - Trajenta®

  • See the Complete Diabetes Medication Table for: cost/month; Blue Cross coverage; available strengths;  dosing frequency; Health Canada indications
  • Recommend hepatic function tests assessed before treatment and periodically thereafter. 
  • Studies showing no increase to cardiovascular risk: 
    • Efficacy and Cardiovascular Safety of Linagliptin as an Add-On to Insulin in Type 2 Diabetes: A Pooled Comprehensive Post Hoc Analysis.2
    • Effect of Linagliptin vs Glimepiride on Major Adverse Cardiovascular Outcomes in Patients With Type 2 Diabetes: The CAROLINA Randomized Clinical Trial.3
  • Data from above studies also provides evidence that linagliptin is safe to use in addition to insulin (product monograph not yet updated). 

 

Saxagliptin - Onglyza®

  • See the Complete Diabetes Medication Table for: cost/month; Blue Cross coverage; available strengths;  dosing frequency; Health Canada indications
  • Side effects in addition to those listed in table above: headache, upper respiratory infection, urinary tract infection. 
  • Associated with new or worsening heart failure. Patients should be observed for signs and symptoms of heart failure and immediately report. 

 

Saxagliptin + Dapagliflozin - QTERN®

  • See Combination Medications in the Complete Diabetes Medication Table for: cost/month; Blue Cross coverage; available strengths; dosing frequency; Health Canada indications
  • See Saxagliptin above and Dapagliflozin on the SGLT class page. 

 

Sitagliptin - Januvia®

  • See the Complete Diabetes Medication Table for: cost/month; Blue Cross coverage; available strengths;  dosing frequency; Health Canada indications
  • The Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) did not show any increase in MACE (Major Adverse Cardiovasular Events). 

References: 

 1. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes: a patient-centred approach. Diabetes Care 2012; 35: 1364-79.   http://care.diabetesjournals.org/content/35/6/1364  (Accessed Feb 26, 2018). 
2. Rosenstock J, Kahn SE, Johansen OE, et al. Efficacy and Cardiovascular Safety of Linagliptin as an Add-On to Insulin in Type 2 Diabetes: A Pooled Comprehensive Post Hoc Analysis. JAMA 2019: doi: 10.1001/jama.2019.13772. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31536101 (Accessed Nov 13, 2019). 
3. Zinman B, Ahren B, Neubacher D et al. Effect of Linagliptin vs Glimepiride on Major Adverse Cardiovascular Outcomes in Patients With Type 2 Diabetes: The CAROLINA Randomized Clinical Trial. Canadian Journal of Diabetes 2016 Feb;40(1):50-7.