Drug Safety Developments

Invokana / Jardiance / Farxiga: Increased Risk Of Pancreatitis, According To Health Canada Safety Review

 

Health Canada's safety review of sodium-glucose cotransporter-2 (SGLT2) inhibitors -- e.g., Invokana (canagliflozin), Farxiga (dapagliflozin), and Jardiance (empagliflozin) -- concluded in July 2018 with the finding that there may be a link between the use of SGLT2 inhibitors and acute pancreatitis. However there was limited evidence to suggest a link with chronic pancreatitis. Health Canada is working with the manufacturers to update the Canadian product monographs, or drug labels, for SGLT2 inhibitors to include this increased risk of pancreatitis.

 

• Summary of Safety Review by Health Canada

 

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Only Two out of Three Classes of Diabetes Drugs Help Reduce the Risk of Death

 

Written by: Heather Helmendach, Legal Assistant 
Law Offices of Thomas J. Lamb, P. A.

 

Class Comparisons

Three popular types of diabetes drugs include sodium-glucose cotransporter (SGLT-2) inhibitors, dipeptidyl peptidase (DPP-4) inhibitors, and incretin mimetics (also referred to as glucagon-like peptide (GLP-1) agonists).

The following table provides a list of some of these types of drugs:

SGLT-2 Inhibitors	SGLT-2 / DPP-4 Inhibitors	DPP-4 Inhibitors / Incretin Mimetics	Incretin Mimetics
Invokana	Glyxambi	Onglyza	Byetta
Invokamet (XR)	Qtern	Januvia	Bydureon
Farxiga		Janumet (XR)	Victoza
Xigduo XR		Kazano	Juvisync
Jardiance		Oseni
Synjardy (XR)		Tradjenta
Steglatro		Jentadueto
Steglujan		Nesina
Segluromet		Kombiglyze XR

 

Study Results

A recent study compared these three types of diabetes drugs in order to determine their effect on "all-cause mortality" in patients with type 2 diabetes.  While all three classes lowered blood sugar levels, only two reduced the risk of death.  

The researchers found the use of SGLT-2 inhibitors and incretin mimetics was associated with lower mortality rates than DPP-4 inhibitors.  More specifically, SGLT-2 inhibitors were associated with a 21% reduction in cardiovascular-related death, and incretin mimetics were associated with a 15% reduction.

However, DPP-4 inhibitors did not reduce the risk of death when compared to a placebo or no treatment at all.

One of the researchers acknowledged that further studies are needed to confirm their findings, and tracking participants for a longer period of time would be beneficial.

 

Side Effects

While the study did not aim to identify any particular harmful side effects directly caused by the drugs, numerous side effects have been associated with these classes of drugs in other studies.  As such, one must wonder how the benefits of these drugs weigh against their potentially-fatal side effects.

For example, users of SGLT-2 inhibitors have experienced the following side effects:

• Diabetic Ketoacidosis (DKA)
• Ketoacidosis
• Ketosis
• Leg Amputation
• Foot or Toe(s) Amputation
• Acute Kidney Injury

• Kidney Failure / Renal Failure
• Kidney Damage
• Pyelonephritis (kidney infection)
• Urosepsis (blood infection)
• Urinary Tract Infection (UTI)
• Bladder Cancer

As for DPP-4 inhibitors, these side effects have been observed:

• Heart Failure
• Kidney Failure / Renal Failure
• Kidney Problems
• Decreased Renal Function 
• Cerebral Infarction / CVA / Stroke
• Myocardial Infarction (MI) / Heart Attack

• Acute Pancreatitis
• Severe Joint Pain
• Inflammatory Bowel Disease (IBD)
• Ulcerative Colitis
• Crohn's Disease
• Rhabdomyolysis

Lastly, incretin mimetics carry a potential risk of pancreatic cancer.

Going forward, we will continue to monitor the medical literature concerning the side effects associated with these three classes of diabetes drugs.

In the meantime, we encourage you to fill out one of our free case evaluations concerning SGLT-2 inhibitors, DPP-4 inhibitors, and incretin mimetics.

 

 

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New SGLT2 Diabetes Drug, Steglatro, to Hit the Market in January 2018

 

Written by: Heather Helmendach, Legal Assistant 
Law Offices of Thomas J. Lamb, P.A.

 

Approval

On December 19, 2017, the FDA approved Merck & Co. and Pfizer's new diabetes drug, Steglatro, and its two combination versions, Steglujan and Segluromet.  These drugs are classified as sodium/glucose cotransporter 2 (SGLT2) inhibitors, and will be available this coming January.

Steglatro consists of ertugliflozin, while Steglujan combines it with Januvia (sitagliptin), and Segluromet combines it with metformin.

According to the drug label (for Steglatro, accessed 12/28/17), these drugs are "indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus."

A recent MedScape article provides the following information:

The new drug applications were accepted for review in March 2017 and were supported by studies from the VERTIS clinical development program for ertugliflozin, which consists of nine phase 3 trials in approximately 12,600 adults with type 2 diabetes.

Results from VERTIS MONO, VERTIS FACTORIAL, and VERTIS SITA2 were presented at medical congresses in 2016, and findings from VERTIS SU and VERTIS SITA2 were presented at the European Association for the Study of Diabetes (EASD) 2017 Annual Meeting in September 2017.

 

New Drug, Same Side Effects

Like other SGLT2 inhibitors -- such as Invokana, Farxiga, Jardiance, Synjardy, Glyxambi, and Qtern -- these new type 2 diabetes drugs also carry warnings of the following serious side effects:

• Ketoacidosis
• Acute Kidney Injury
• Impairment in Renal Function

There is also a lower-limb amputation warning for Steglatro and its counterparts.  This is particularly interesting, given that Invokana is the only other SGLT2 inhibitor at this time whose drug label also mentions this warning. 

However, unlike Invokana, Steglatro (and its combinations) do not include amputations in a so-called "Black Box" warning.  This is probably due to the label's claim that "A causal association between STEGLATRO and lower limb amputation has not been definitively established."

Perhaps the drug companies responsible for Steglatro, Steglujan, and Segluromet added this warning so as to protect themselves from lawsuits in the event that a causal relationship between these drugs and lower-limb amputations is definitively established in the future.

 

Class Effects

While other SGLT2 inhibitors are quick to distance themselves from the lower-limb amputation side effect, further clinical data may prove it to be a class effect.

The first three side effects mentioned above have been shown to apply to the entire class of SGLT2 inhibitors diabetes drugs, and as such, are mentioned in every single drug label for these drugs.

We will continue to monitor the medical literature on SGLT2 inhibitors and their relationship to lower-limb amputations and other serious side effects.  In the meantime, we encourage you to visit our website and complete a free case evaluation if you or someone you know has taken an SGLT2 inhibitor and suffered one of the serious side effects mentioned in this article.

 

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