Contents

Search

gliptin; dipeptidyl peptidase-4 inhibitor; DPP-4 inhibitor

Indications: - treatment of diabetes mellitus type 2 - may lower regional beta-amyloid burden in temporal lobes & parietal lobes [18] - may slow measures of cognitive decline more than other hypoglycemics [18] Dosage adjustment in renal failure: - chronic renal failure stage 4 [19] - eGFR < 50 mL/min 2.5 mg once daily (saxagliptin) Adverse effects: - nausea [7] - possible increased risk of pancreatitis [5,7,11,13,16] & pancreatic cancer [16] - anaphylaxis [13] - severe arthralgias - increased risk for infections [7] - increased risk for hospitalization due to heart failure (3.4% vs 3.0%), NNH = 250 [8] - increased risk of inflammatory bowel disease [14] - increased risk for cholangiocarcinoma [15] - no increased risk of mortality [12] - rarely causes hypoglycemia [17] * unfavorable adverse effect profile including anaphylaxis & pancreatitis [13] Drug interactions: - hypoglycemia when used in combination with sulfonylurea [7]* * associated with decreased risk for hypoglycemia (RR = 0.86) [9] * associated with increased risk for hypoglycemia (absolute risk 12% vs 7% for sulfonylurea alone [10] Mechanism of action: 1) dipeptidyl peptidase-4 inhibitor 2) inhibits incretin catabolism (compare with incretin mimetic) 3) enhances incretin system 4) slows gastric emptying [7] 5) inhibits glucagon secretion Clinical trials: - no increase in ischemic cardiovascular events - increased risk of hospitalization for heart failure with saxagliptin [7] Notes: - no better than metformin [3] - combination of metformin plus gliptin vs metformin plus sulfonylurea - less hypoglycemia - more weight loss - slightly inferior glycemic control [3] - can lower A1C about 0.7% [4] - gliptins cost about $3000/year vs $40/year for metformin or sulfonylurea [3]

Interactions

drug interactions drug adverse effects (more general classes)

Related

glucagon-like peptide 1 (GLP-1) receptor agonist; incretin mimetic; GLP-1 mimetic; GLP-1 agonist; glutide; GLP-1RA

Specific

alogliptin (Nesina) linagliptin (Tradjenta) saxagliptin (Onglyza) sitagliptin (Januvia) vildagliptin (Galvus)

General

enzyme inhibitor oral hypoglycemic agent

References

  1. Prescriber's Letter 12(9): 2005 Investigational Medicines for Diabetes: Sitagliptan (Januvia) and Vildagliptan (Galvus) Detail-Document#: 220715 (subscription needed) http://www.prescribersletter.com
  2. Prescriber's Letter 13(11): 2006 New Drug: Sitagliptin (Januvia) Detail-Document#: 221102 (subscription needed) http://www.prescribersletter.com
  3. Karagiannis T et al. Dipeptidyl peptidase-4 inhibitors for treatment of type 2 diabetes mellitus in the clinical setting: Systematic review and meta-analysis. BMJ 2012 Mar 12; 344:e1369 PMID: 22411919
  4. Prescriber's Letter 19(6): 2012 CHART: Drugs for Type 2 Diabetes ALGORITHM: Stepwise Approach to Selecting Treatments for Type 2 Diabetes (ADA) GUIDELINES: Management of Hyperglycemia in Type 2 Diabetes: A Patient-Centered Approach (2012) Detail-Document#: 280614 (subscription needed) http://www.prescribersletter.com
  5. Singh S et al Glucagonlike Peptide 1-Based Therapies and Risk of Hospitalization for Acute Pancreatitis in Type 2 Diabetes Mellitus. A Population-Based Matched Case-Control Study. JAMA Intern Med. 2013;():1-6. PMID: 23440284 http://archinte.jamanetwork.com/article.aspx?articleid=1656537
  6. FDA MedWatch. August 28, 2015 DPP-4 Inhibitors for Type 2 Diabetes: Drug Safety Communication - May Cause Severe Joint Pain. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm460238.htm
  7. Medical Knowledge Self Assessment Program (MKSAP) 17, 18, American College of Physicians, Philadelphia 2015, 2018.
  8. Li L, Li S, Deng K et al Dipeptidyl peptidase-4 inhibitors and risk of heart failure in type 2 diabetes: systematic review and meta-analysis of randomised and observational studies. BMJ 2016;352:i610 PMID: 26888822 Free full text http://www.bmj.com/content/352/bmj.i610
  9. Hippisley-Cox J, Coupland C Diabetes treatments and risk of amputation, blindness, severe kidney failure, hyperglycaemia, and hypoglycaemia: open cohort study in primary care. BMJ 2016;352:i1450 PMID: 27029547 http://www.bmj.com/content/352/bmj.i1450 - Montori VM Selecting the right drug treatment for adults with type 2 diabetes. BMJ 2016;352:i1663 PMID: 27029501 http://www.bmj.com/content/352/bmj.i1663
  10. Salvo F et al Addition of dipeptidyl peptidase-4 inhibitors to sulphonylureas and risk of hypoglycaemia: systematic review and meta-analysis. BMJ 2016;353:i2231 PMID: 27142267 Free full text http://www.bmj.com/content/353/bmj.i2231
  11. Tkac I, Raz I. Combined analysis of three large interventional trials with gliptins indicates increased incidence of acute pancreatitis in patients with type 2 diabetes. Diabetes Care 2017 Feb; 40:284. PMID: 27659407 http://care.diabetesjournals.org/content/40/2/284 - DeVries JH, Rosenstock J. DPP-4 inhibitor-related pancreatitis: Rare but real! Diabetes Care 2017 Feb; 40:161 PMID: 28108536 http://care.diabetesjournals.org/content/40/2/161
  12. Liu J, Li L, Deng K et al Incretin based treatments and mortality in patients with type 2 diabetes: systematic review and meta-analysis. BMJ. 2017 Jun 8;357:j2499. Review. PMID: 28596247 Free PMC Article
  13. Therapeutics Letter #108. Therapeutics Initiative Drugs to Avoid. http://www.ti.ubc.ca/2018/01/04/108-drugs-avoid/
  14. Abrahami D, Douros A, Yin H, et al Dipeptidyl peptidase-4 inhibitors and incidence of inflammatory bowel disease among patients with type 2 diabetes: population based cohort study. BMJ 2018;360:k872 PMID: 29563098 http://www.bmj.com/content/360/bmj.k872
  15. Abrahami D, Douros A, Yin H et al Incretin based drugs and risk of cholangiocarcinoma among patients with type 2 diabetes: population based cohort study. BMJ 2018;363:k4880 PMID: 30518618 https://www.bmj.com/content/363/bmj.k4880
  16. Lee M et al. Nationwide trends in pancreatitis and pancreatic cancer risk among patients with newly diagnosed type 2 diabetes receiving dipeptidyl peptidase 4 inhibitors. Diabetes Care 2019 Nov; 42:2057 PMID: 31431452 https://care.diabetesjournals.org/content/42/11/2057
  17. Geriatric Review Syllabus, 10th edition (GRS10) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2019
  18. George J Diabetes Drug Linked With Less Brain Amyloid. People with diabetes on DPP-4 inhibitors also showed slower cognitive decline. MedPage Today August 11, 2021 https://www.medpagetoday.com/neurology/alzheimersdisease/93999 - Jeong SH, Kim HR, Kim J et al Association of dipeptidyl peptidase-4 inhibitor use and amyloid burden in diabetic patients with AD-related cognitive impairment. Neurology 2021. Aug 11. PMID: 34380754 https://n.neurology.org/content/early/2021/08/11/WNL.0000000000012534
  19. NEJM Knowledge+ Endocrinology