Jul 9, 2012

By Trevor Shewfelt, Pharmacist at the Dauphin Clinic Pharmacy

On the TV show Big Bang Theory, the character Sheldon has an eidetic or photographic memory. The only person Ive met with a photographic memory was a physiology prof we had in first year pharmacy school. Unlike the physiology prof, I dont have a photographic memory, and today I cant even remember his name. But he knew all of our names. It was a little disconcerting. He had all 50 pharmacy student names memorized after meeting us just once. But he also taught medical students and dental students. So he had hundreds of names to keep straight, and he did. If he met me in the hallway, he would never get my name wrong. I might not remember his name, but I remember his Valsalva Maneuver story. Weve all done the Valsalva Maneuver. It is when you are sitting on the toilet and you hold your breath a little bit and bear down to go number 2. The physiology prof was explaining how the Valsalva Maneuver worked and what it did to the blood vessels and heart rate. Then he talked about how he went on vacation for a hike in the Himalayas. He said during this excursion, several of the young fit hikers kept passing out on the toilet. The older people, like the physiology prof, had no problems. The prof explained that at altitude the young fit people were experiencing a temporary lack of oxygen to their brains during the Valsalva Maneuver and that made them pass out. However, the prof said, the older people had older brains, and these older brains were used to going without oxygen for longer periods of time. So the older hikers didnt fall over during their Valsalva Maneuvers. This story made me think differently about older brains versus younger brains. It is that kind of different thinking we need to deal with type 2 diabetes. That different kind of thinking about type 2 diabetes might be incretins.


Before we talk about how incretins work, lets do a quick refresher on diabetes. There are two main types of diabetes, type 1 and type 2. In type 1 diabetes, the special cells that make insulin stop working. So type 1 diabetics must inject insulin or they will die. Type 1 diabetics only account for about 20% of the diabetics in Canada. Almost 80% of diabetics out there have type 2 diabetes. In type 2 diabetes, the person is still produces insulin, but the muscle, fat and other cells dont listen to the signal from the insulin to suck up glucose from the blood stream.


We often treat type 2 diabetes with pills. These pills have names like glyburide, metformin, pioglitazone and acarbose. Unfortunately, we arent winning the war on type 2 diabetes. Type 2 diabetes is becoming more common. The increase is partially because we are getting less active, eating more poorly and getting more obese. Diabetes can lead to serious complications. These include the big four: blindness, heart disease, kidney disease and amputation. And even in the patients we are treating now, it seems like their blood sugars keep going up despite the fact we are using multiple medications and insulin on them. It sure would be nice if we had some new tools in the diabetes tool box.


Incretins qualify as new diabetes tools. Incretins are hormones made in your gut. They are released when you eat food with carbohydrates in them. There are several naturally occurring incretins but we are going to talk about Glucagon Like Peptide 1 (GLP-1). GLP-1 does some interesting things. It delays the emptying of the stomach, it makes beta cells in the pancreas produce more insulin, it reduces glucagon secretion and it convinces your brain that you are less hungry.


Scientists found if GLP-1 was injected directly into patients it reduced blood sugar levels, had a low risk of making the blood sugar go too low, caused weigh loss, helped the insulin making cells stay healthy, but it caused some nausea and vomiting. That was good, but the injected GLP-1 was broken down by the body within minutes. To get any good effects they had to continuously pump it into the test subjects. That would not be practical for the average type 2 diabetic.


So the drug companies have developed two different types of GLP-1 like products. The first type of incretin is called a DDP-4. The DDP-4s block the enzyme that breaks down GLP-1. This makes the GLP-1 in the body last longer. DDP-4s are oral pills and have names like Januvia (sitagliptin), and Onglyza (saxagliptin). The oral incretins like sitagliptan and saxagliptin dont reduce the blood sugars as much as the injectables so should be used in more moderate diabetics. The second type of incretin is called a GLP-1 analog. GLP-1 analogues act like GLP-1 in the body, but they arent broken down as fast. The first GLP-1 analogue available in Canada was called Victoza or liraglutide. The newest one is called Byetta or exenatide. GLP-1 analogues need to be injected. The injectable incretins reduce blood sugar a little more than the oral ones and may cause more weight loss than the oral pills.


The latest change in the incretins isnt how they work but how they are paid for. With the latest formulary update, Manitoba Health will now consider paying for the oral pills sitagliptan and saxagliptin. A person on the Manitoba Health help line said MB Health will consider paying for the injection liraglutide. Manitoba Health will still not consider paying for exenatide, the newest injection. Payment for incretins is still not guaranteed. Your doctor has to fill out paperwork on your behalf called a Part 3 Exceptional Drug Status (EDS) request. If Manitoba Health likes how your doctor did the paperwork, you will get a letter saying you have Part 3 EDS coverage for that incretin. Your pills still arent free yet. Next you have to spend enough to go over your Pharmacare deductible. So, it is not fast or easy to get your incretins to be paid for by Manitoba Health, but it is now possible.


Just like lack of activity and poor diet in our population is leading to more type 2 diabetes, sometimes I think my brain is getting slower and lazier everyday. I definitely dont have a photographic memory, and my kids often roll their eyes at me when they think Ive said or done something dumb. I get a little paranoid sometimes that they are right and my aging brain is failing me. But then I remember the Valsalva Maneuver story, and I think Ill just organize a hiking trip into the Himalayas and see whose brain wins.


As always if you have any questions or concerns about these products, ask your pharmacist.

The information in this article is intended as a helpful guide only. It is not intended to be used as a substitute for professional advice. If you have any questions about your medications and what is right for you see your doctor, pharmacist or other health care professional.

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