Saxagliptin is a type-2 diabetes medication used to regulate insulin levels after eating, thereby helping to control blood sugar levels.

What is Onglyza?

Saxagliptin, sold under brand names of Onglyza and Kombiglyze XR, is a medication that is part of the drug class of incretin mimetics. These drugs stimulate insulin production in the pancreas.

What Does Saxagliptin Treat?

When used with proper diet and exercise, Onglyza is prescribed to treat type-2 diabetes. Because this condition is characterized by high blood sugar, Onglyza’s insulin stimulating properties make it an effective type-2 diabetes treatment.

Saxagliptin and other incretin mimetics became popular after Avandia, another diabetes medication, was recalled due to concerns of increased cardiac deaths.

What Are the Risks Associated with Saxagliptin?

According to drug manufacturers, Onglyza may result in the following side effects:

• Low blood sugar
• Joint pain
• Skin reactions
• Swelling and fluid retention
• Headaches
• Upper respiratory tract infections
• Urinary tract infections
• Pancreatitis

In 2015, the FDA released a statement warning patients that Onglyza may result in severe and debilitating joint pain for some patients. This pain may be serious enough that patients may want to look into alternative treatments for their diabetes.

In addition to these risks, Onglyza and Kombiglyze XR may, unfortunately, carry a risk of cardiac failure. In 2013, the SAVOR study was published in the New England Journal of Medicine which showed that the medications may carry an increased risk of hospitalization due to heart failure.

The SAVOR study examined 16,492 type-2 diabetes patients in the hopes of helping determine which medication is right for certain patients. The study revealed that patients taking saxagliptin are more likely to be hospitalized for heart failure. Although the increased risk of hospitalization for heart failure was not statistically significant, it caused concerns for experts.

The trial indicated that 3.5 percent of patients who took saxagliptin were hospitalized for heart failure, compared to only 2.8 percent of patients who were prescribed a placebo drug. This rate of heart failure indicates that an extra 7 people per 1,000 who take saxagliptin may develop heart failure compared to those who take other diabetes medications.

In April 2015, an FDA advisory committee required drug manufacturers AstraZeneca and Bristol-Myers Squibb to include information about the risk of heart failure on their saxagliptin drugs. However, for some patients, this warning came too late. Nearly 400,000 patients took saxagliptin drugs to control their diabetes that year.

What is Heart Failure?

Heart failure occurs when the muscles in the heart are too weak to sufficiently pump blood. This failure is often caused by conditions such as high blood pressure or coronary artery disease which cause the heart to overcompensate and eventually weaken.

Symptoms of heart failure include shortness of breath, fatigue, weakness, rapid or irregular heartbeat, persistent cough, rapid weight gain from fluid retention, lack of appetite, chest pain, and more.

There is no cure for heart failure. In mild cases, patients need to make lifestyle changes to help extend life expectancy and manage the condition. Many of these changes center around helping to improve cardiovascular wellness, including exercise, reducing sodium, managing stress, and losing weight.

Other treatments for the conditions include medication and surgery. Medications are usually combined to maintain as much heart health as possible. The type of medication prescribed is usually determined by the type and severity of heart failure.

In some cases, surgery may be necessary. Coronary bypass surgery is a procedure designed to unblock severely blocked arteries. Heart valve repair or replacement can help eliminate disrupted blood flow in the heart. A pacemaker may help a failing heart pump in a more regular, coordinated manner. The most severe cases of heart failure may require a complete heart transplant to resolve the condition.

Primary Care Diabetes Europe Offers New Guidelines

In October, the Primary Care Diabetes Europe (PCDE) published a new position statement on the suggested management of type-2 diabetes. According to Medscape, a total of nine primary care doctors and one primary care nurse worked on these new guidelines.

The new guidelines include a risk stratification system that places patients in a “very high cardiovascular risk” category if they were younger than 40 years old upon being diagnosed or those who have a history of heart disease, multiple cardiovascular risk factors or chronic kidney diseases. Cardiovascular risk factors include high blood pressure (hypertension), high fat content in the blood (hyperlipidemia), obesity, smoking/vaping, and/or being physically inactive.

The reason people who were diagnosed at a younger age are at a very high risk of cardiovascular issues is because they will live longer with the disease, which means their bodies will have increased risks of developing circulation problems due to the toll the diabetes takes on the vascular system.

The PCDE said they do not classify any type-2 diabetes patients as “low risk” or “moderate risk” and that anyone diagnosed after age 40, including obese patients, fall under the “high cardiovascular risk” category.

PCDE cited the VERIFY clinical trial that they said suggested a switch from the treat-to-failure approach to a treat-to-mitigate approach that combines medications who can benefit from early cardiovascular intervention. Patients who were diagnosed with heart failure were advised to take metformin and an SGLT2 inhibitor, but also to avoid taking saxagliptin or pioglitazone.

What Are Some Alternatives to Saxagliptin?

Saxagliptin is only one of several classes of medications designed to treat type-2 diabetes. One of the oldest and safest medications for this indication is metformin, which is derived from an old folk remedy made from the French lilac plant. Side effects of metformin are minimal and include constipation and flatulence.

Patients for whom metformin alone is insufficient to control blood sugar levels may benefit from sulfonylureas (Amaryl, DiaBeta, Glucotrol) and meglitinides (Prandin, Starlix). These medications stimulate the pancreas to produce more insulin, the hormone that metabolizes blood sugar. The primary side effects are weight gain and hypoglycemia.

GLP-1 receptor agonists (Byetta, Victoza, Ozempic) act by slowing down the digestive process, thus keeping blood sugar levels in check. Like sulfonylureas, these drugs stimulate insulin production and do not appear to have serious side effects for most patients.

Thiazolidinediones (Avandia, Actos) have a mechanism of action similar to metformin in that they “wake up” cells and make them more sensitive to insulin. However, drugs in this class (also known as glitazones) have been associated with serious side effects, including heart failure and bladder cancer. Because of this, thiazolidinediones are not recommended as a first-line treatment.

SGLT2 inhibitors are yet another alternative to saxagliptin. These drugs (Invokana, Farxiga, Jardiance) work by disabling the mechanism by which the kidneys reabsorb blood sugar, which is then passed through the urine. However, these drugs also have serious side effects, including ketoacidosis, urinary tract and vaginal infections, increased risk of amputation and a rare form of gangrene.

Several hundred lawsuits have been filed against AstraZeneca and Bristol-Myers Squibb by patients who claim that the drug manufacturers failed to warn them in time of the effects of saxagliptin.

Additionally, some patients believe that the drugs were rushed to market without sufficient research into the potential side effects. As the drug brings in more than $820 million a year and is prescribed to hundreds of thousands of patients, many people may be affected by its serious side effects. Several of the lawsuits filed against the drug companies have been combined into multidistrict litigation.

If you have developed heart failure after taking a drug containing saxagliptin, you may be eligible to speak with an attorney and join or file a class action lawsuit.