May 06, 2018 – In April 2016 the American Food and Drug Administration (FDA) took regulatory action by mandating label changes with new warnings about an increased risk of heart failure for new diabetes medicines in the dipeptidyl peptidase-4 (DPP-4) inhibitor drug class, including Saxagliptin (Onglyza), Saxaglitin/Metformin (Kombiglyze XR), Alogliptin (Nesina), Alogliptin/Metformin (Kazano), Alogliptin/Pioglitazone (Oseni), and Dapagliflozin/Saxagliptin (Qtern).
New research, which has been published on April 14, 2018 in the Journal Pharmacoepidemiology & Drug Safety, entitled “Cardiovascular safety signals with dipeptidyl peptidase‐4 inhibitors: A disproportionality analysis among high‐risk patients” has investigated heart-related side effects reports submitted to the FDA Adverse Event Reporting System (FAERS) from 2006 to 2015.
When concentrating this Postmarketing surveillance on the DPP‐4 class of anti-diabetes medicines, increased reporting of major adverse cardiac events (MACE)] were noted. In particular, signals of disproportional reporting (SDR) emerged for heart failure with drugs containing linagliptin (e.g., Linagliptin (Tradjenta), Linagliptin/Metformin (Jentadueto), Linagliptin/Empagliflozin (Glyxambi)), and saxagliptin (e.g., Saxagliptin (Onglyza), Saxagliptin/Metformin (Kombiglyze XR), and Dapagliflozin/Saxagliptin (Qtern)), for myocardial infarction with drugs containing alogliptin [e.g., Alogliptin (Nesina), Alogliptin/Metformin (Kazano), and Alogliptin/Pioglitazone (Oseni)), and for cerebral infarction with sitagliptin [e.g., Sitagliptin (Januvia), Sitagliptin/Metformin (Janumet), Sitagliptin (Juvisync), and Sitagliptin/Ertugliflozin (Steglujan)).
The collective evidence from these analyses would strongly suggest that drug label warnings about heart failure which were mandated by the FDA for certain DPP-4 diabetes drugs back in 2016 urgently need differential updating and strengthening in order to adequately inform physicians and patients alike about the potentially fatal risks associated with some DPP-4 class medications.
Thus, a more precise and stronger warning for myocardial infarction (heart attack) would be justified for Alogliptin (Nesina), Alogliptin/Metformin (Kazano), and Alogliptin/Pioglitazone (Oseni)). Likewise, a more precise and stronger warning for cerebral infarction (stroke) would be justified for Sitagliptin (Januvia), Sitagliptin/Metformin (Janumet), Sitagliptin (Juvisync), and Sitagliptin/Ertugliflozin (Steglujan). Hopefully, FDA will act swiftly upon.