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    Should the class of Incretin Mimetics be considered as a first line therapy for type 2 Diabetes???
    matt_1981 posted:
    I am a 31 year old Diabetic patient. I have been diabetic since age 22. I have a very complex case and severe insulin resistance, Fatty Liver or NAFLD (NASH) and sever hypertension that requires 4 meds to control. I also have high lipids. All are currently under control but requires an extreme amount of medication.

    I started to use the Incretin Mimetic drug Victoza in 2011. This class of drug is an injectable and includes Victoza, Byetta and the newer, 1x weekly version Bydureon. These drugs are quite unique. They offer the benefit of helping with elevated liver enzymes, have shown evidence of improving kidney function including very early onset kidney disease markers such as Microalbuminuria. They also are one of the only drugs for type 2 diabetics that doesn't only NOT cause weight gain but can in some cases promote weight loss. Generally, they do not induce hypoglycemia. So what else do they do? How do they work? Well, they have some impact on insulin resistance although not it's strongest charesteristic. It helps to prevent uptake of glucagon within the liver which leads to less sugar being released by the liver which also leads to improving liver function tests in those individuals that have elevated liver enzymes or fatty liver disease. They also, similarly to the DPP-4 inhibitors (Januvia, Onglyza) help your pancreas make and release more insulin when a detection in elevated sugars takes place. Some people have also reported improvements in blood pressure control and lipid management. While some of the positive aspects of these drugs are not directly related to their indication for prescribing or mechanism of action they are the kind of so called "side effects" that are very good for diabetics! Furthermore, imaging studies have found that while improving liver function tests that it also improves liver histology. When the liver is fatty, or inflamed it is also enlarged. When uncontrolled or with poor glycemic control this can lead to fibrosis (scarring) and eventually cirrhosis. More and more liver transplants are being performed for individuals with Fatty liver or NASH (Non-Alcoholic Steato-hepatitis) which is an advanced form of fatty liver where there is not just fat around the liver but the liver is inflamed and there can be some scarring. This can eventually can get to a point where it is irreversible creating a need for transplant. This class of drugs, specifically the newest drug Bydureon and Victoza have shown to be extremely beneficial at reversing and slowing this process. But thats not all! There is evidence that these drugs also promote the preservation and re-generation of Pancreatic Beta Cells! In type 2 diabetes the pancreas is overworked due to the effects on our bodies metabolism and insulin resistance related to type 2 diabetes. Most diabetes drugs try to compensate for type 2 diabetics by increasing insulin production vs. treating the real problem which is insulin resistance. Preserving Beta Cell function, which are the cells in our pancreas that make insulin is crucial to avoiding the need for insulin down the road as insulin production decreases over time. The only class of drugs designated as true insulin sensitizers is known as TZD's. These include Actos and Avandia. As most of you reading this may already know both of these drugs have been linked with very severe side effects and class action law suits. Avandia is almost never prescribed anymore and Actos as a last resort for most as well. Actos specifically, is great for doing all the things that the incretin mimetics can do but also targets insulin resistance. But the price to pay is weight gain (Typically 10-30 lbs.) bone and joint pain which can lead to fractures and bone density problems as well as the link to bladder cancer. I happen to be an individual that has no choice but to take Actos. I also take Bydureon and Lantus currently. So, while Metformin is typically the drug of choice for newly diagnosed
    laura2gemini2 responded:
    Couple thoughts on your post.

    I found it hard to read. The wall of words made it really easy to lose my place. It's all good information but would be easier to read if broken up a bit.

    Victoza and other drugs like is are very new and are way more expensive then the tried and true generic Metformin. Most insurance companies will only cover those meds if there is a medical reason you cant take anything else.

    Metformin does not increase insulin production but allows your body to use the insulin more effectively, and is also known for some to decrease weight.

    Because Victoza slows digestion, one of the major side effects is nausea and it also causes vomiting for some. I know people who couldnt take the medication just because they felt like they were going to vomit all the time. Also, those medications are injected and many do not want to go that route with their medication if they could just take a pill.

    I am glad you have found medication that works for you. Just remember that medication is only one aspect of controlling diabetes along with food management and exercise.
    matt_1981 replied to laura2gemini2's response:
    Laura, Thanks for the reply. Hmmm, I have to wonder, are you a doctor? I apologize for the difficulty in reading. As it was I ran out of characters and didn't get to finish my point so I will do that now. I also was writing it very quickly. The point was to bring up the theory that this class may be a better option to be used earlier in type 2 diabetics due to the fact that incretin mimetics have a better ability to preserve beta cell function, improve fatty liver disease, have impact on insulin resistance as well as reduce the uptake of glucagon and sugar production from the liver. They also improve insulin production and improve the release of insulin at the appropriate times. What I am saying is that by taking a drug that shows evidence of slowing the progression of the disease that normally over time gets worse and leads large and wide to increases in other health problems that cost more money this preventive measure may save more in the long run.

    I also feel the need to correct you on a few other things you had mentioned.
    1. Metformin does not promote weight loss as you stated, it simply has not been shown to promote weight gain.

    2. Metformin is not a true insulin sensitizer. There is speculation that it may improve insulin resistance as a possible result of its effects on AMPD/GLUT4. Again this is more speculative and somewhat propaganda oriented vs. hard evidence supporting this. Also, it also has some evidence towards increasing metabolism but again benefit is generally limited due to weak efficacy.

    3. Metformin's primary, known mechanism of action is to suppress the production of glucose from the liver. The other advertised benefits are largely debateable due to a solid lack of supporting studies and is speculative. Furthermore, as a whole Metformin, even if it does do the various other things that some advertising and literature suggest has an overall weak efficacy compared to most all diabetes drugs. This is why it is (by true experts) regarded as only effective in pre-diabetes or newly diagnosed.

    4. You mentioned problems with gastrointestinal upset relating to incretin mimetics, specifically Victoza. Less than 5% of people taking Victoza during clinical trials reported gastrointestinal upset. Specifically with Victoza, if the dose is properly titrated from .6mg at the start of administration that 5% is reduced even further. Also what many people report as gastrointestinal upset actually is a feeling of fullness due to the slower gastric emptying which curbs hunger. This is usually temporary. Metformin however causes gastrointestinal upset in over 50% of patients including uncontrollable bowel movements in the form of diarrhea. I apologize for this rant but I am tired of Metformin being paraded around as the best drug for type 2 diabetes when if you look at the details it clearly isn't. At the very least there is strong argument against it. Yes, I know doctors love to use it when they can in patients at all times regardless of pre, newly diag. or having diab. for several years already. It is a lot of hype however. There is strong evidence that it has no effect at all in people that have been diabetic from 2 years and longer.

    5. You comment that most insurance companies will not cover the Incretin Mimetics due to cost and that they require proof of failure on other meds first is not accurate. Many insurance companies will cover either Byetta or its newer version Bydureon as tier 2 meds and many times does not require a prior authorization. When Victoza came out Byetta moved to being a more widely covered drug as its price was lower. Bydureon is also covered by many plans as some companies prefer it to Byetta due to better patient compliance. Lower overall cost due to lack of additional needles and less side effects than its predecessor. Victoza, on some plans was available for less than a year and many did require a PA. I am running out of characters so I will finish on another reply.

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