Article ; Online: Dipeptidyl peptidase-4 inhibitors and cardiovascular and renal disease in type 2 diabetes: What have we learned from the CARMELINA trial?
Diabetes & vascular disease research
2019 Volume 16, Issue 4, Page(s) 303–309
Abstract: Dipeptidyl peptidase-4 inhibitors are a relatively new class of oral anti-hyperglycaemic drugs to treat type 2 diabetes through prevention of degradation of incretins by the dipeptidyl peptidase-4 enzyme. The large trials evaluating the dipeptidyl ... ...
| Abstract | Dipeptidyl peptidase-4 inhibitors are a relatively new class of oral anti-hyperglycaemic drugs to treat type 2 diabetes through prevention of degradation of incretins by the dipeptidyl peptidase-4 enzyme. The large trials evaluating the dipeptidyl peptidase-4 inhibitors sitagliptin, alogliptin and saxagliptin demonstrated safety for cardiovascular disease. Post hoc analyses on renal endpoints yielded similar findings. Linagliptin is the latest dipeptidyl peptidase-4 inhibitor evaluated in the CARMELINA trial. CARMELINA included individuals with type 2 diabetes and high cardiovascular and renal risk. Even in this setting, linagliptin displayed cardiovascular safety. CARMELINA also removed initial concerns for heart failure as a class-specific side-effect of dipeptidyl peptidase-4 inhibitors, as no signal for heart failure was found. Although numerically low, CARMELINA did confirm increased rates of pancreatitis in the linagliptin group, suggesting that pancreatitis is a class-specific side-effect of dipeptidyl peptidase-4 inhibitors. Linagliptin reduced progression of albuminuria, but had no effect on other hard renal endpoints. Overall, dipeptidyl peptidase-4 inhibitors are safe but do not confer significant reductions in complications observed for some of the other new glucose-lowering drugs. However, linagliptin is a safe alternative in renal impairment, without dose adjustment. Furthermore, dipeptidyl peptidase-4 inhibitors may hold value as alternatives to sulfonyl-urea derivatives or as an add-on therapy to delay insulin prescription given their favourable safety profile. |
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| MeSH term(s) | Animals ; Cardiovascular Diseases/diagnosis ; Cardiovascular Diseases/epidemiology ; Clinical Trials as Topic ; Diabetes Mellitus, Type 2/diagnosis ; Diabetes Mellitus, Type 2/drug therapy ; Diabetes Mellitus, Type 2/epidemiology ; Dipeptidyl-Peptidase IV Inhibitors/adverse effects ; Dipeptidyl-Peptidase IV Inhibitors/therapeutic use ; Health Status ; Humans ; Kidney Diseases/diagnosis ; Kidney Diseases/epidemiology ; Linagliptin/adverse effects ; Linagliptin/therapeutic use ; Patient Selection ; Risk Factors ; Treatment Outcome |
| Chemical Substances | Dipeptidyl-Peptidase IV Inhibitors ; Linagliptin (3X29ZEJ4R2) |
| Language | English |
| Publishing date | 2019-04-24 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't ; Review |
| ZDB-ID | 2250793-0 |
| ISSN | 1752-8984 ; 1479-1641 |
| ISSN (online) | 1752-8984 |
| ISSN | 1479-1641 |
| DOI | 10.1177/1479164119842339 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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