gliptins

Last edited 07/2018 and last reviewed 01/2022

• in response to a meal, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are released (these hormones are termed incretin hormones)
  • these incretin hormones stimulate insulin and suppress glucagon release (both in a glucose-dependent manner), delay gastric emptying, and increase satiety
  • incretins are rapidly degraded by dipeptidyl peptidase-4 (DPP-4)
    
    
• DPP-4 inhibitors are a class of oral antihyperglycemic agents that work via slowing incretin degradation
  • DPP-4 inhibitors enhance meal-stimulated active GLP-1 and GIP levels by two- to threefold
  • DPP-4 inhibitors reduce the enzymatic degradation of the incretin hormones, GLP-1, and glucose-dependent insulinotropic polypeptide by reducing the activity of serum DPP-4 by >=80% (1)
    • leads to an increased availability of endogenous incretins, stimulating insulin secretion from pancreatic beta-cells and inhibiting glucagon release from pancreatic alpha-cells in a glucose-dependent manner
      
      
• there are currently five gliptins available in the UK:
  • alogliptin
  • linagliptin
  • saxagliptin
  • sitagliptin
  • vildagliptin
    
    
• glycaemic control
  • in a meta-analysis, DPP-4 inhibitors were associated with mean changes from baseline in HbA1c of -0.6% to -1.1% (without adjustment for background therapies, blinding, or placebo comparators) (2)
    
    
• changes in body weight associated with gliptin therapy
  • these agents are regarded as weight neutral with respect to changes of body weight (3)
    
    
• if a gliptin is in combination with sulfonylurea, a lower dose of the sulfonylurea may be needed to reduce the risk of hypoglycaemia
  
  
• in people with renal impairment
  • because most DPP-4 inhibitors are eliminated from the body by renal pathways, dose adjustment is required for patients with moderate or severe renal impairment when treated with alogliptin, sitagliptin, saxagliptin, or vildagliptin
  • linagliptin is primarily cleared by nonrenal mechanisms and therefore does not require dosage adjustment in patients with renal impairment (4)
    
    
• summary of adverse effects associated with gliptin therapy
  • generally have a good safety profile and are well tolerated, with a low risk of hypoglycemia (except when used in combination with insulin or insulin secretagogues)
  • gastrointestinal disturbances are common
  • nasopharyngitis may occur
  • serious hypersensitivity reactions, including anaphylaxis, angioedema, and exfoliative skin reactions, have been reported
  • musculoskeletal and connective tissue disorders (including back pain, arthralgia, myalgia, and arthropathy) may occur
  • there have been reports of acute pancreatitis in patients treated with DPP-4 inhibitors
    • prompt discontinuation of DPP-4 inhibitor treatment is recommended if pancreatitis is suspected (4)

For detailed and up to date information then consult the respective Summary of Product Characteristics (SPC) before prescribing a gliptin.

Reference:

1. Drucker DJ, Nauck Ma. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet. 2006 Nov 11;368(9548):1696-705.
2. Aroda, V.R., Henry, R.R., Han, J. et al. Efficacy of GLP-1 receptor agonists and DPP-4 inhibitors: meta-analysis and systematic review. Clin Ther. 2012; 34: 1247-1258.e1222
3. Scheen, A.J. Safety of dipeptidyl peptidase-4 inhibitors for treating type 2 diabetes. Expert Opin Drug Saf. 2015; 14: 505-524
4. Thrasher J. Pharmacologic Management of Type 2 Diabetes Mellitus: Available Therapies.Am J Cardiol. 2017 Jul 1;120(1S):S4-S16