gliptin; dipeptidyl peptidase-4 inhibitor; DPP-4 inhibitor
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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]
- drug interaction(s) of gliptins with sulfonylureas
- drug interaction(s) of fluoroquinolones with hypoglycemic agents
Mechanism of action
- dipeptidyl peptidase-4 inhibitor
- inhibits incretin catabolism (compare with incretin mimetic)
- enhances incretin system
- slows gastric emptying[7]
- 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]
- gliptins cost about $3000/year vs $40/year for metformin or sulfonylurea[3]
More general terms
More specific terms
- alogliptin (Nesina)
- linagliptin (Tradjenta)
- saxagliptin (Onglyza)
- sitagliptin (Januvia)
- vildagliptin (Galvus)
Additional terms
References
- ↑ Prescriber's Letter 12(9): 2005 Investigational Medicines for Diabetes: Sitagliptan (Januvia) and Vildagliptan (Galvus) Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=220715&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Prescriber's Letter 13(11): 2006 New Drug: Sitagliptin (Januvia) Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=221102&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 3.0 3.1 3.2 3.3 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: https://www.ncbi.nlm.nih.gov/pubmed/22411919
- ↑ 4.0 4.1 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#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=280614&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 5.0 5.1 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. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23440284 <Internet> http://archinte.jamanetwork.com/article.aspx?articleid=1656537
- ↑ 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
- ↑ 7.0 7.1 7.2 7.3 7.4 7.5 7.6 Medical Knowledge Self Assessment Program (MKSAP) 17, 18, American College of Physicians, Philadelphia 2015, 2018.
- ↑ 8.0 8.1 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26888822 Free full text <Internet> http://www.bmj.com/content/352/bmj.i610
- ↑ 9.0 9.1 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27029547 <Internet> 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27029501 <Internet> http://www.bmj.com/content/352/bmj.i1663 - ↑ 10.0 10.1 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27142267 Free full text <Internet> http://www.bmj.com/content/353/bmj.i2231
- ↑ 11.0 11.1 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. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27659407 <Internet> 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28108536 <Internet> http://care.diabetesjournals.org/content/40/2/161 - ↑ 12.0 12.1 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: https://www.ncbi.nlm.nih.gov/pubmed/28596247 Free PMC Article
- ↑ 13.0 13.1 13.2 13.3 Therapeutics Letter #108. Therapeutics Initiative Drugs to Avoid. http://www.ti.ubc.ca/2018/01/04/108-drugs-avoid/
- ↑ 14.0 14.1 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29563098 <Internet> http://www.bmj.com/content/360/bmj.k872
- ↑ 15.0 15.1 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: https://www.ncbi.nlm.nih.gov/pubmed/30518618 https://www.bmj.com/content/363/bmj.k4880
- ↑ 16.0 16.1 16.2 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: https://www.ncbi.nlm.nih.gov/pubmed/31431452 https://care.diabetesjournals.org/content/42/11/2057
- ↑ 17.0 17.1 Geriatric Review Syllabus, 10th edition (GRS10) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2019
- ↑ 18.0 18.1 18.2 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: https://www.ncbi.nlm.nih.gov/pubmed/34380754 https://n.neurology.org/content/early/2021/08/11/WNL.0000000000012534 - ↑ 19.0 19.1 NEJM Knowledge+ Endocrinology