Set Of Newer Diabetes Medications Containing Saxagliptin And Alogliptin Also Being Investigated By FDA For Increased Risk Of Renal Failure
On April 5, 2016 the FDA took regulatory action by mandating that the pharmaceutical companies AstraZeneca and Takeda make label changes for some of their still relatively new diabetes drugs. This move was announced by means of "FDA Drug Safety Communication: FDA adds warnings about heart failure risk to labels of type 2 diabetes medicines containing saxagliptin and alogliptin".
The diabetes drugs covered by this FDA action are:
AstraZeneca’s Onglyza (saxagliptin)
AstraZeneca’s Kombiglyze XR (saxagliptin and metformin extended release)
Takeda’s Nesina (alogliptin)
Takeda’s Kazano (alogliptin and metformin)
Takeda’s Oseni (alogliptin and pioglitazone)
Apparently, the FDA's decision to order the label changes for this class of diabetes drugs was based on the evaluation of two large clinical trials conducted in patients with heart disease that were discussed at FDA’s Endocrinologic and Metabolic Drugs Advisory Committee meeting in April 2015.
And, some of you may recall this previous MedWatch alert, "Saxagliptin (marketed as Onglyza and Kombiglyze XR): Drug Safety Communication - FDA to Review Heart Failure Risk", from back in February 2014.
The recent April 2016 FDA action concerning Onglyza is an update to that earlier February 11, 2014 FDA Drug Safety Communication, and now the FDA is warning about an increased risk of heart failure being linked to Nesina and other diabetes drugs containing alogliptin.
Strictly Confidential, No Obligation.
From this April 5 FDA MedWatch email alert "Diabetes Medications Containing Saxagliptin and Alogliptin: Drug Safety Communication - Risk of Heart Failure", we get this basic information about why the FDA took this regulatory action concerning the set of Type-2 diabetes medicines containing saxagliptin and alogliptin:
ISSUE: An FDA safety review has found that type 2 diabetes medicines containing saxagliptin and alogliptin may increase the risk of heart failure, particularly in patients who already have heart or kidney disease. As a result, FDA is adding new warnings to the drug labels about this safety issue.
BACKGROUND: Saxagliptin and alogliptin are part of the class of dipeptidyl peptidase-4 (DPP-4) inhibitor drugs, which are used with diet and exercise to lower blood sugar in adults with type 2 diabetes.
RECOMMENDATION: Health care professionals should consider discontinuing medications containing saxagliptin and alogliptin in patients who develop heart failure and monitor their diabetes control. If a patient’s blood sugar level is not well-controlled with their current treatment, other diabetes medicines may be required.
Patients taking these medicines should contact their health care professionals right away if they develop signs and symptoms of heart failure such as:
• Unusual shortness of breath during daily activities
• Trouble breathing when lying down
• Tiredness, weakness, or fatigue
• Weight gain with swelling in the ankles, feet, legs, or stomach
Patients should not stop taking their medicine without first talking to their health care professionals.
Now we move to the increased risk of renal failure associated with Onlyza, Nesina, and the other diabetes medications containing saxagliptin and alogliptin, as well as some other drugs.
From this March 29, 2016 Medscape investigative report, "Possible Drug Risks Buried in Delayed FDA 'Watch Lists'" (registration required) we learned that the FDA is evaluating the need for regulatory action for the following group of 11 dipeptidyl peptidase IV (DPP-IV) inhibitor drugs due to the serious side effect of renal failure, or kidney failure:
- Onglyza (saxagliptin) tablet
- Kombiglyze XR (saxagliptin/metformin HCl) extended-release tablet
- Nesina (alogliptin) tablet
- Kazano (alogliptin/metformin HCl) tablet
- Oseni (alogliptin/pioglitazone) tablet
- Glyxambi (empagliflozin/linagliptin) tablet
- Janumet XR (sitagliptin/metformin HCl) extended release tablet
- Janumet (sitagliptin/metformin HCl) tablet
- Januvia (sitagliptin) tablet
- Jentadueto (linagliptin/metformin HCl) tablet
- Tradjenta (linagliptin) tablet
The source of this information is the FDA document "Potential Signals of Serious Risks/New Safety Information Identified by FAERS, July–September 2015", which was only recently made public according to the March 2016 Medscape article mentioned above.
We will continue to watch for reports of heart failure and kidney / renal failure in patients using Onglyza, Nesina, and the other Type-2 diabetes drugs containing saxagliptin and alogliptin.