Insulin Injection Pen (VetPen): More Questions (and Answers) about this New Diabetic Product

Since the FDA approved the use of a new insulin injection pen (VetPen) made by Merck Animal Health last week (1,2), I've received a number of questions from both veterinarians and owners of diabetic pets. Listed below are some of the most common questions with my responses.

Do we buy a single VetPen and use it forever? Or does the VetPen have to be replaced after a month or two?

The VetPen has been tested for at least 3,000 actuations (i.e., how many times the insulin release button is pressed and released). Therefore, a single VetPen is likely to last a lifetime for the majority of dogs and cats treated with diabetes.

How are the pens and cartridges sold? 
The reusable VetPen is supplied in a Starter Kit which contains everything you need to get started (see below). This included everything except the Vetsulin cartridges, which are supplied separately in cartons of ten, 2.7-mL cartridges.

The VetPen itself is available in 2 sizes. For greater accuracy at low doses, the first option (blue cap) has a maximum total dose of 8 units, allowing for dosing increments of 0.5 unit per injection. If higher insulin doses are being administered, the second VetPen option (tan cap) has a maximum total dose of 16 IU per injection, with dosing increments of 1 unit.

What is in each VetPen Starter Kit?
Each Starter Kit contains either an 8-unit or 16-unit VetPen with an instruction leaflet.

The kit also contains a box of 28-g, ultra-thin needles that feature a silicone coating to help minimize injection discomfort, as well as a needle remover that helps to remove used needles, while minimizing the risk of accidental needle stick injury. There is also a travel pouch to hold all of the components.

The kit also contains two adaptors to assist those with dexterity issues. The dose selector adaptor may be used to provide a better grip when selecting a dose. The release button extension may be used to provide a better grip when giving injections.

Are the VetPens an accurate way for insulin dosing?
The VetPen is ideal for cats and small dogs on low doses of insulin, in which dosing accuracy can be a concern (3,4). A recent study comparing the precision and accuracy of the VetPen to U40 syringes demonstrated that even when doses were drawn up by trained laboratory technicians, syringes were found to deliver at least 20% to 25% more insulin than needed for a 1-unit dose (5).

In contrast, VetPen enables doses to be delivered with accuracy and precision down to 0.5 units. In large dogs, dosing accuracy is generally not a problem.

Do the pens and cartridge need to be refrigerated? Other handling precautions?
The VetPen cartridges should be refrigerated (not frozen) and protected from light before opening.

VetPen does not need to be refrigerated after a cartridge has been started (4), although it probably is best to do so. The loaded VetPen can be stored on its side in the refrigerator.

VetPen should always be stored or carried with the needle removed and the cap on. To clean the device, wipe with a damp cloth. Do not immerse in water.

Are the VetPens expensive? How would the costs of the VetPen compare to those associated with the standard insulin vial/syringe method?

The cost of treatment will depend upon the size of the diabetic pet. For smaller dogs and cats, the price of the VetPen with the Vetsulin cartridges and needles will be similar to the cost of the standard 10-mL Vetsulin vial and U-40 insulin syringes.   For larger dogs, the standard way of administering Vetsulin (via an insulin syringe) would generally be a more economical way to provide insulin treatment.

Bottom Line:

These insulin pen devices are an alternative to the traditional insulin vial-and-syringe method and offer many advantages. In human diabetic patients, insulin pens have also been found to be less painful than the vial-and-syringe method and are often associated with greater patient preference and social acceptability (6-11).  Similar preliminary findings have been documented in dogs and cats (12,13). As a result, this method of insulin delivery may ultimately help to improve glycemic control and should be considered as an alternative insulin delivery method.

Insulin pens are designed to deliver a fixed insulin dose while insulin syringes rely on the ability of the user to accurately draw up the required insulin dose. One recent study reported that for low doses (below 8 units), the VetPens were more precise and accurate than the insulin syringes (5). In particular, insulin syringes tend to over-deliver, compared to the insulin pen, for very low doses (1 unit). For higher doses (16 units), both devices were comparable (5).

Similar findings have been reported in human pediatric patients, in which very low doses of insulin must be administered. One older study looked at the reliability of using U100 syringes for accurately administering low doses of insulin in the hospital by pediatric nurses. In that study, attempts to administer doses of 0.5 U or 1.0 U of U-100 insulin resulted in overdosage of 95% and 66%, respectively (14). Based on this study, it's no wonder that small diabetic dogs or cats are often a challenge to regulate when small insulin doses are needed.

References: 

1. FDA website. FDA Approves First Insulin Product for Use with Automatic Injection Pen in Cats and Dogs.
2. Press release. Merck Animal Health Receives FDA Approval of VetPen  
3. Merck Caninsulin website. Caninsulin® VetPen® helps make pet diabetes management easier 
4. Pet Diabetes website. What you need to know about the Caninsulin VetPen. 
5. Burgaud S, Riant S, Piau N. Comparative laboratory evaluation of dose delivery using a veterinary insulin pen. Proceedings World Congress ASAVA/FECAVA/BSAVA 2012;567.
6. Molife C, Lee LJ, Shi L, et al. Assessment of patient-reported outcomes of insulin pen devices versus conventional vial and syringe. Diabetes Technol Ther 2009;11:529-538. 
7. Pearson TL. Practical aspects of insulin pen devices. J Diabetes Sci Technol 2010;4:522-531. 
8. Wright BM, Bellone JM, McCoy EK. A review of insulin pen devices and use in the elderly diabetic population. Clin Med Insights Endocrinol Diabetes 2010;3:53-63. 
9. Cuddihy RM, Borgman SK. Considerations for diabetes: treatment with insulin pen devices. Am J Ther 2013;20:694-702. 
10. Davis EM, Foral PA, Dull RB, et al. Review of insulin therapy and pen use in hospitalized patients. Hosp Pharm 2013;48:396-405. 
11. McCoy EK, Wright BM. A review of insulin pen devices. Postgrad Med 2010;122:81-88. 
12. Burgaud S, Guillot R, Harnois-Milon G. Clinical evaluation of a veterinary insulin pen in diabetic cats. Proceedings World Congress ASAVA/FECAVA/BSAVA 2012;499.
13. Burgaud S, Guillot R, Harnois-Milon G. Clinical evaluation of a veterinary insulin pen in diabetic dogs. Proceedings World Congress ASAVA/FECAVA/BSAVA 2012;568.
14. Casella SJ, Mongilio MK, Plotnick LP, et al. Accuracy and precision of low-dose insulin administration. Pediatrics 1993;91:1155-1157. 

FDA Approves First Insulin Automatic Injection Pen for Diabetic Dogs and Cats

VetPen, for use with Vetsulin (in USA) and Caninsulin (outside USA)

The U.S. Food and Drug Administration (FDA) has approved the first insulin injection pen (VetPen, Merck Animal Health) for diabetic cats and dogs, the agency announced today, March 19, 2014 (1).

2 Sizes of VetPens

The VetPen may now be used to administer Vetsulin insulin cartridges, also made by Merck Animal Health. The refillable VetPen automatically measures the prescribed insulin dose and provides the owners of diabetic dogs and cats with an additional option for insulin delivery.

There are two sizes of refillable VetPens. One (tan cap) dispenses insulin doses from 1-16 units per dose in full unit increments. The other (blue cap) dispenses 0.5-8 unit doses in full or half unit increments. Both pens use 2.7 ml insulin cartridges which hold a total of 108 units (IU) of U-40 Vetsulin (or Caninsulin).

Vetsulin is an FDA-approved insulin for use in dogs and cats (2). This insulin is identical to Caninsulin, the brand name of the insulin sold in Europe (3).

Merck said the VetPen is easier to dose and administer and is more accurate than traditional delivery systems, such as syringes and vials (4). “For years, insulin pens have made managing diabetes more convenient for human diabetics,” the company said. “Merck Animal Health has now brought the same technology to veterinary medicine.”

An informational website (2) provides tools for both veterinarians and pet owners to make managing pet diabetes easier. More online information about the VetPen can also be found on the Caninsulin website (5); the Pet Diabetes website has an informational brochure that can be downloaded (6).

Administering insulin to a cat with the VetPen

For questions on how to obtain Vetsulin or the VetPen, please contact Merck Animal Health Customer Service at 800-521-5767.

References: 

1. FDA website. FDA Approves First Insulin Product for Use with Automatic Injection Pen in Cats and Dogs.
2. Merck Vetsulin website. www.vetsulin.com
3. Merck Caninsulin website. www.caninsulin.com
4. Press release. Merck Animal Health Receives FDA Approval of VetPen  
5. Merck Caninsulin website. Caninsulin® VetPen® helps make pet diabetes management easier 
6. Pet Diabetes website. What you need to know about the Caninsulin VetPen. 

Combining Rapid and Long-Acting Insulin Analogs for Dogs with Diabetes

I am the owner of Coco, a 6-year old male Poodle who has been diagnosed with diabetes mellitus. I noticed the symptoms myself, as I too am a Type 1 diabetic (I was diagnosed 42 years ago at the age of 7 years). 

My dog's blood sugar was slightly more than 400 mg/dl when I brought him in for testing. That’s terribly high. I am a man with deep concern about this disease, and I personally keep myself in very good control (my A1-C tests are always in the 6’s). And thus, I am interested in having excellent control of my dogs health too. 

I’ve been directed by my veterinarian to give ”Coco” 2 daily injections of long-acting type insulin (I give him glargine (Lantus) since that’s what I use for my diabetes). So I started him 5 units of Lantus twice a day but still found him to be drinking far too much water and still having high sugar levels. So, I then added in small amounts of insulin lispro (Humalog) to better control his sugar. I’ve not yet taken him back in for spot checking of his blood, but I do notice the Humalog is helping decrease his water drinking and urinating at normal levels. So now, I give him 2 shots at breakfast and 2 at dinner—5 units of Humalog and 10 units of Lantus twice per day. And I watch him closely but find he is doing well. I see no signs of low blood sugar. 

Do you find my plan a good one? Am I overreacting by giving him Humalog in addition to the Lantus? I’m not a doctor, but I think a blood sugar curve should be between 70-150 mg/dl to keep him healthy, just like in human diabetic patients. Is this correct? Is there something better I can do? 

Finally, is there a simpler way to give the injections? I use a small needled Pen for his injections between his shoulders in a pinch of skin. Is there a needle-free ”Jet” type injection system that would be better than the needles? 

Thank you very much for any help advice you can share. 

My Response: 

Although insulin glargine (Lantus) can be used to treat diabetic dogs (1-3), it doesn't always work well as the sole insulin preparation, as you have discovered in your dog. Therefore, I don't usually start with glargine in dogs, but I use either NPH (Humulin) or lente (Vetsulin) insulins, which give us a higher success rate (4,5).

Your approach to combining a long-acting insulin analog (glargine; Lantus) with a rapid-acting analog (lispro; Humalog) is certainly an acceptable one. Insulin lispro has been proven to be effective in dogs (6) and combing Lantus with Humalog  has been recommended as an option by some investigators (1). If you use Lantus and Humalog yourself, this may be a good option for you. The rapid-acting Hunalog insulin will lower the blood sugar rise that occurs after meals, whereas the longer-acting Lantus will act as a background insulin to maintain glucose levels between meals.

You mention that you would like keep your dog's blood sugar well-controlled. That is a good idea, especially if you want to prevent the formation of diabetic cataracts, which are common in dogs with diabetes (7,8). However, to do that, the use of "spot checks" of his blood glucose concentration will not be enough. You are going to have to do periodic blood glucose curves, either done at home or in the hospital (9-11). 

Finally, our current options for insulin injections are either use of an insulin needle and syringe or an insulin pen, such as the Lantus SoloStar pen (12).Use of needle-free, jet injector for insulin delivery has been reported (13,14). However, to my knowledge, such jet injectors are not yet available commercially, and they certainly have not been tested in diabetic dogs.

References:

1. Mori A, Sako T, Lee P, et al. Comparison of time-action profiles of insulin glargine and NPH insulin in normal and diabetic dogs. Vet Res Commun 2008; 32:563-573. 
2. Fracassi F, Boretti FS, Sieber-Ruckstuhl NS, et al. Use of insulin glargine in dogs with diabetes mellitus. Vet Rec 2012;170(2):52.
3. Peterson ME. Treating diabetic dogs with insulin glargine. Blog post. May 3, 2012.
4. Palm CA, Boston RC, Refsal KR, et al. An investigation of the action of neutral protamine Hagedorn human analogue insulin in dogs with naturally occurring diabetes mellitus. J Vet Intern Med 2009;23:50–55. 
5. Monroe WE, Laxton D, Fallin EA, et al. Efficacy and safety of a purified porcine insulin zinc suspension for managing diabetes mellitus in dogs. J Vet Intern Med 2005;19:675-82.
6. Sears KW, Drobatz KJ, Hess RS. Use of lispro insulin for treatment of diabetic ketoacidosis in dogs. J Vet Emerg Crit Care (San Antonio) 2012;22:211-218. 
7. Beam S, Correa MT, Davidson MG. A retrospective-cohort study on the development of cataracts in dogs with diabetes mellitus: 200 cases. Vet Ophthalmol 1999;2:169-172. 
8. Wilkie DA, Gemensky-Metzler AJ, Colitz CM, et al. Canine cataracts, diabetes mellitus and spontaneous lens capsule rupture: a retrospective study of 18 dogs. Vet Ophthalmol 2006;9:328-334. 
9. Wiedmeyer CE, DeClue AE. Glucose monitoring in diabetic dogs and cats: adapting new technology for home and hospital care. Clin Lab Med 2011;31:41-50. 
10. Cook AK. Monitoring methods for dogs and cats with diabetes mellitus. J Diabetes Sci Technol 2012;6:491-495.
11. Davison LJ. Canine diabetes mellitus In: Mooney CT, Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology. Fourth ed. Quedgeley, Gloucester: British Small Animal Veterinary Association, 2012;116-132.
12. Association AD. Insulin administration. Diabetes Care 2001;24:1984-1987. 
13. Engwerda EE, Abbink EJ, Tack CJ, et al. Improved pharmacokinetic and pharmacodynamic profile of rapid-acting insulin using needle-free jet injection technology. Diabetes Care 2011;34:1804-1808. 
14. Engwerda EE, Tack CJ, de Galan BE. Needle-free jet injection of rapid-acting insulin improves early postprandial glucose control in patients with diabetes. Diabetes Care 2013;36:3436-3441. 

World Diabetes Day

Today, November 14th, is World Diabetes Day

World Diabetes Day is the primary global awareness campaign of the diabetes mellitus world and is held on November 14 of each year (1). It was introduced in 1991 by the International Diabetes Federation and the World Health Organization in response to the alarming rise of human diabetes around the world. 

World Diabetes Day is a campaign that features a new theme chosen by the International Diabetes Federation each year to address issues facing the global diabetes community. While the campaigns last the whole year, the day itself marks the birthday of Frederick Banting who, along with Charles Best, first conceived the idea which led to the discovery of insulin in 1922 (2).

Charles H. Best and Frederick G. Banting (on right) with one of the diabetic dogs used in their studies of insulin

This year's campaign theme is diabetes education and prevention. In the past four years alone, diabetes rates among dogs in the U.S. have increased roughly 33% among dogs and 16% among the nation's cat population, per a national analysis of pet health (3).  This emphasizes the importance of this disorder in our cats and dogs as well as human patients with diabetes.

To successfully manage diabetes in animals, one must understand the disease and monitor and provide daily treatments to the cat or dog with diabetes. Treatment involves a combination of weight loss (if obese), diet, and insulin injections generally twice daily.

References 

1. World Diabetes Day – Official website.
2. Frederick Grant Banting (1891-1941), codiscoverer of insulin. Journal of the American Medical Association 1966;198:660-661.
3. Washburn L. Human health risks on the rise in animals. The Record. April 20, 2011.

Overview of Feline Diabetes

Diabetes mellitus (often called simply diabetes) is a disorder in which blood sugar levels are too high.  Diabetes) is a chronic condition in which a deficiency of the hormone impairs the body's ability to metabolize sugar. It is one of the most common endocrine (hormonal) diseases of cats.

In cats, either a deficiency of insulin or a resistance to insulin causes the diabetes. A number of mechanisms are responsible for decreased insulin secretion or resistance, but most involve destroying islet cells, the cells of the pancreas that produce insulin. Obesity also increases the risk of insulin resistance in cats.

During digestion, carbohydrates are broken down into glucose (a simple sugar), which is absorbed into the bloodstream.  Once in the bloodstream, glucose must enter the body’s cells in order to be used for energy. Insulin signals the body’s cells to absorb glucose from the blood.

A lack of insulin (or insulin resistance) creates two dangerous conditions. First, the body’s cells cannot absorb glucose without insulin; they begin to starve despite the abundant glucose.  Second, because the body’s cells do not absorb glucose, the blood glucose level remains dangerously high. This excess glucose is eventually excreted from the body through the kidneys.  As the glucose passes through the kidneys into the urine, it pulls water with it by diffusion.  This causes increased urination, which leads to increased thirst.

With its cells starving for energy, the body begins to break down its protein, stored starches, and fat. In severe diabetes, muscle is broken down, carbohydrate stores are used up, and weakness and weight loss occur. As fat is broken down, substances called ketones are released into the bloodstream where they can eventually cause diabetic ketoacidosis, a severe complication of unregulated diabetes.

Diabetes can develop in cats of any breed, age or gender. However, older, overweight, and neutered male cats are predisposed to developing this disorder. Diabetes often develops gradually, and many owners may not notice the signs at first.

Diabetes Signs to Watch for in your Cat

• Increased thirst
• Increased frequency of urination
• Weight loss despite a good appetite
• Lethargy
• Poor body condition/poor hair coat
• Rear weakness (associated with diabetic neuropathy)


 Above and below: examples of neuropathy in cats

How is diabetes diagnosed in cats?

Diagnosis of diabetes is based upon the following:
• Complete medical history and thorough physical examination
• Complete blood count (CBC) to check for infection
• Urine analysis to check for glucose and ketones
• Serum chemistry testing to confirm a high blood glucose and to exclude other diseases
• Abdominal X-rays or abdominal ultrasound if complications or concurrent diseases, such as pancreatitis (inflammation of the pancreas), are suspected

Veterinarians diagnose diabetes when cats have high levels of sugar in the blood and urine after fasting.  In cats, the blood sugar level commonly increases under stress, such as when drawing a blood sample, and multiple evaluations may be needed to confirm the diagnosis.

How is diabetes treated in cats?

To successfully manage diabetes, you must understand the disease and take daily care of your cat. Treatment involves a combination of the following:

• Proper weight management
• Diet
• Exercise
• Insulin injections, generally twice daily
• Control of concurrent problems, such as urinary tract infections

Periodic reevaluation is necessary to ensure that the disease is being controlled.  Based on these reevaluations, you may have to change your cat’s treatment regimen over time.

Diabetes Home Care 

At home care involves administering prescribed medications, including insulin, as recommended. If the insulin is prescribed twice daily, try to give it 12 hours apart and at the same time each day. You should also work with your veterinarian to develop a weight management and feeding plan. Stick to regular feeding times.

Familiarize yourself with insulin, insulin syringes, insulin storage, and insulin handling; your veterinarian can help.

Observe your cat's thirst and frequency of urination. If these remain increased, your veterinarian may need to adjust the insulin dosage.

Checking urine or blood sugar concentrations at home can also be very useful in the regulation of your cat’s diabetes.

Insulin overdose may cause low blood glucose, potentially resulting in disorientation, weakness or seizures (convulsions). If you notice any of these symptoms in an otherwise responsive cat, offer food immediately. If the cat is unconscious, Karo® syrup can be applied to the gums. In either case, call your veterinarian as soon as possible.