The Low-Down on Incretin Therapy

Incretin therapies include GLP-1 analogues such as exenatide (Byetta) and liraglutide (Victoza) as well as dipeptidyl peptidase-4 (DPP-4) inhibitors such as sitagliptin (Januvia), saxaglipitn (Onglyza) and linagliptin (Tradjenta). These therapies are relatively new compared to older agents such as metformin and sulfonylureas. However, data presented at the EASD looked at both safety and long term efficacy. Mixed results left some diabetes experts taking sides. 

Two studies using DPP-4 inhibitors appeared to demonstrate long term maintenance of glycemic control. In one RCT, 6 month treatment with the DPP-4 linagliptin (Tradjenta) resulted in a mean 0.8% decline in HbA1c. More importantly, after about 2 years, this A1c decline was maintained. A second study with saxaglipitn (Onglyza) added to insulin showed a 0.37% drop in A1c that was maintained for over a year. 

Possibly even more exciting is the possibility that gliptins might be cardioprotective. One meta-analysis of 53 published trials of vildagliptin (Galvus); sitagliptin (Januvia); saxagliptin (Onglyza); alogliptin (Nesina); linagliptin (Tradjenta) and dutogliptin lasting at least 24 weeks in type 2 diabetic patients in which gliptins were compared with placebo or with other drugs found reported CV events in 42 of these trials (137 vs. 120) which amounted to a 31% decrease in major cardiovascular events for patients taking a gliptin (P=0.006).

However, not all news out of the EASD was good for the incretin therapies. One topic of discussion was a paper from Gastroenterology that found higher rates of pancreatitis and pancreatic cancer in patients on either sitagliptin (Januvia) or exenatide (Byetta) using the FDA's adverse events reporting system. The FDA and others are also concerned about certain thyroid tumors, including thyroid cancer, that have been seen in some rats and mice taking liraglutide (Victoza). It is not known whether these tumors will be seen in diabetics taking GLP-1 products.

Presented at European Association for the Study of Diabetes Meeting, Sept. 2011