Januvia and Galvus
Galvus is a similar medication, and would compete directly with Januvia. Galvus was initially assumed to be approved by the FDA shortly after Januvia was approved, but the FDA asked for additional safety data: see Upcoming Diabetes Medications: vildagliptin (at the Diabetes Monitor). Galvus is approved in Europe and other countries.
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It sounds to me that some think this will more likely to replace metformin rather than byetta. It'll be interesting to see what the drs think about it. (Comment this)
I am on Byetta andwondering the same thing about Januvia. I have a doctor's appointment this week to see if I can change to this medication. I would rather take a pill, too. I think I would be more on schedule with the oral medication. I will let you know if you would like. (Comment this)
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So he gave me some samples. I have been trying it for the last 2 days in place of Byetta.
From the studies, Januvia is weight neutral --i.e., it causes no weight loss or weight gain, unlike Byetta. I don't know if you are likely to gain weight if you change from Byetta to Januvia.
In the 2 days so far, I don't think that Januvia works as well as Byetta does -- either for FBS or for post-prandial glucose control. This morning, my FBS was 135. This afternoon, 2 hours after a half-size pecan chicken salad, a glass of Reiseling, and a single scoop of ice cream at O'Charley's, my glucose was 179 -- much higher than it would have been on Byetta. My FBS is usually 120 or so.
I realize it's only 2 days, but I thought I would report my experience so far.
Incidentally, Januvia is much more like Byetta than it is like metformin. They both involve a "gut hormone" called GLP-1 (glucagon-like peptide-1). GLP is secreted by the digestive system in response to a meal. It revs up the beta cells in the pancreas to produce more insulin -- but only while the blood glucose is high.
But GLP doesn't last very long in the body, because it is metabolized in minutes. So there are at least 2 ways of making the GLP effect last longer. One way is to find a compound that acts like GLP, but isn't metabolized so fast -- that would be Byetta (exenatide). The other way is to stop the body from metabolizing it's own GLP so fast. That's what Januvia does -- it inhibits DPP-4, the enzyme that metabolizes GLP-1.
So, you see -- one drug mimics the effects of GLP and the other makes it stay around longer. That's why Byetta is similar to Januvia.
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I have been on Avandia (4mg twice a day) and I can't take Metformin--so this was wonderful for me since I have been struggling with 200+ BS most of the time. (Comment this)
FYI:
I just got my Rx for Januvia filled today, and will start it tomorrow. My Dr. gave me the script last week. Anthem , my insurer, had not heard of it...called back today and it had made their list.
Druggist, who also was unaware of it before my call, had also received 1(only) vial of 30 -100mg. tablets for me.
Best',
Joe
Cape Elizabeth, Maine, USA. (Comment this)
I just went to the Dr today and he gave me samples of Januvia. I was told by my health insurance provider that the drug is in stock now. You might try again to see if it is in your local area. (Comment this)
I also am not getting as good results on Januvia as on Byetta -- particularly with post-prandial glucoses. FBS also not as good as on Byetta. I still might use it as a substitute for Byetta on trips where access to refrigeration is iffy. I would just have to take Prandin before meals, I guess.
Elaine (Comment this)
I'm hoping Galvus will be out soon since it's supposed to be so beneficial for IR. (Comment this)
Am currently on Byetta and am tired of the nausea. It lasts over 9 hours every day. I have only been on this a week and find it hard to function. I also am taking 1 mcg of amaryl, and have severe hypoclycemia approximately 2 hrs after taking the Byetta. My diabetes has taken over my life and I don't like it one bit!
I wanted the weight loss, but not the nausea. I will begin the Januvia now, with hopes that decreasing the metforin and eliminating the amaryl will stop the weight gain. I will have to lose weight the old fashioned way..by cutting down and exercising.
Thanks,
Marilyn (Comment this)
Marilyn (Comment this)
I will start my Januvia tomorrow. 100mg tablet. I am taking it glyburid/met with the Januvia. Have you had any side effects taking Januvia?
Mona Lisa (Comment this)
This is an excellent statement paraphrased from Elaine from VA Blog 11 Januvia is like Byetta. They both involve a "gut hormone" called GLP-1 (glucagon-like peptide-1). GLP is secreted by the digestive system in response to a meal. It revs up the beta cells in the pancreas to produce more insulin -- but only while the blood glucose is high.
GLP doesn't last very long in the body, because it is metabolized in minutes. So there are at least 2 ways of making the GLP effect last longer. One way is to find a compound that acts like GLP, but isn't metabolized so fast -- that would be Byetta (exenatide). The other way is to stop the body from metabolizing its own GLP so fast. That's what Januvia does -- it inhibits DPP-4, the enzyme that metabolizes GLP-1.
So, you see Byetta mimics GLP-1 and Januvia and Galvus makes it stay around longer. Both work to give the body more GLP-1.
However, type 2 diabetes usually involves two failings, or more, in the body: (1) insulin production and (2) insulin resistance. DPP-4 and GLP-1 address insulin production only. One study I saw reported 2.7 % decrease in Hemoglobin 1A-c results typically after 24 weeks on a Pioglitazone like Actos 30 mg and a DPP-4 inhibitor. Drugs like Pioglitazone work to help muscle cells take up the glucose in the presence of insulin. They decrease the insulin resistance. I think these results are from the type II trials of Galvus. There may be some differences between these two DPP-4 inhibitors. I am currently on Prandin and Pioglitazone but I can go low blood sugar and then I eat a lot of carbohydrates resulting in weight gain.
I think many of the side effects of nausea may come from the slowing of stomach emptying effects of Januvia and Galvus. Think of it as chemical stomach stapling, you can’t eat as much as you did without feeling sick. I theorize that this slowing of stomach empting will help in some areas of nutrition. For example, Vitamin B12 absorbs in the stomach, empty it out quickly and you don’t get as much. This action slows the transit through the small intestines known as the ileum where the real digestion work is done. I theorize that this is not a side effect but a return of a more efficient digestive process. In the long run there should be weight loss, because you feel full sooner and get better nutritional uptake.
The liver has the ability to release sugars. In one report I read it said that Januvia and Galvus do not release the sugar from the liver in the process of producing insulin, (like other diabetic medication). There is hope that DPP-4 inhibitors and GLP-1 regulation will improve liver function. We need to watch triglyceride levels and cholesterol.
The trials indicate that approximately 2/3 of the individuals in the trials had long term Hemoglobin 1A-c measurements less than 7 at the end of a 24 week study. Therefore, it looks like 1/3 of the individuals will not get to 7 or below. The question for them will be whether or not another mixture of drugs will work better. This drug combination may not work for 1/3 of the people.
Therefore, please ask your doctor for something to help with insulin resistance like a Pioglitazone with a drug that stimulates insulin production, and then give it some time to work. The trials charts I have observed typically show continual improvement over a 24 week period. Whether this is from the islet cells beginning to regain capacity or we learn better how to eat and take the medication I don’t know, but beware of short term results positive or negative. We suffer from a very complicated disease affecting, hormone levels, brain, adipose tissues, liver, pancreas, stomach, electrolyte balance, cellular uptake of insulin and digestion. Often we exhibit sings of weight gain, high blood pressure, high cholesterol, high triglycerides, and high blood sugars. Good therapies will help all of these things. Chances are your on blood pressure medication, cholesterol reducing drugs, and aspirin with diabetic medication to help all of the problematic symptoms: Actos, Vytorin, Lisinopril, Prandin, and Aspirin. I want to substitute Januvia for Prandin.
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Alas, my reading is that the once a week won't be until 2008!
See the last conference call on the Byetta website.
Elaine (Comment this)
In contrast to Byetta, Januvia has been shown in studies to be "weight-neutral." i.e. it doesn't cause weight loss like Byetta. Since metformin assists with weight-loss a bit, I would be more anxious, if I were you, to eliminate the Amaryl first, which does cause weight increases. Januvia's manufacturer does not list nausea as a side effect. See:
www.Januvia.com
Elaine (Comment this)
I have never heard of Aprida, nor can I find it in the online PDR. Is it a type of insulin? Are you sure you are spelling it right?
Elaine (Comment this)
There is a small incidence of nausea with Januvia. This is from the prescribing information:
"The incidence of selected gastrointestinal adverse reactions in patients treated
with JANUVIA was as follows: abdominal pain (JANUVIA 100 mg, 2.3%; placebo, 2.1%), nausea (1.4%,
0.6%), and diarrhea (3.0%, 2.3%)."
In other words, Januvia was associated with nausea in .8% more people given Januvia than in those given placebo.
Contrast this with Byetta in which 44% of those taking Byetta experienced nausea vs. 18% on placebo. Why the Byetta placebo causes substantially more nausea than the Januvia placebo, I don't know. Perhaps injecting something, even though it may be saline solution, has more of a psychological effect than taking an inactive pill.
Elaine (Comment this)
Further discussion of this insulin should be at Other Medications, please!
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Since Januvia is a primarily a blood sugar control drug there was no need to establish weight loss as a side effect to get approval.
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“..LAF237 did not lose a significant amount of weight compared with those receiving placebo. In both groups, there was a slight decrease of 0.2 kg.
In an interview with Medscape, Dr. Ahren said that ‘I'm not sure you should expect more than body neutrality, which is a good effect when you have good metabolic control, so I don't think you should expect a [weight] reduction.’
The LAF237 study involved 107 patients who were inadequately controlled on metformin at doses ranging from 1,500 to 3,000 mg per day. Patients were randomly assigned to receive 50 mg orally of LAF237 once daily or placebo plus metformin. They were evaluated at baseline and at various time points up to one year for A1c, fasting plasma glucose, insulin levels, lipid levels, and adverse effects. The adjusted mean A1c was 7.7% at baseline, with no significant difference between the treatment or placebo groups.
The authors found that patients in the LAF237 group had a mean A1c that was 1.1% lower than those receiving placebo. The rate of increase in A1c was 0.013% per month in patients receiving LAF237 compared with 0.0655% per month in the placebo group, which is not statistically different from zero, Dr. Ahren said. The between-group difference in adjusted mean A1c at study end point was -1.1 ± 0.2% (P = .0001).” http://www.medscape.com/viewarticle/480408
440 individuals in the Galvus testing with A1c levels above 9 had an average reduction of 1.7, 9 – 1.7 = 7.3
For individuals with BMI >= 30 (759 Obese Individuals) reported 0.6 KG weight loss. 541 individuals < 30 BMI (Less Obese Individuals) reported 0.1KG weight gain. If you are obese you should expect some weight loss.
Galvus claims neutral effect o n lipids, however, HDL-c- improved 3.8% and LDL-c reduced 2.1%. Therefore, good cholesterol is up some and bad cholesterol down some, this is a small but good result. Even though it is overall neutral the swing between good and bad is something. Novartis titles this “Favorable Trends on Lipids.”
Galvus and Pioglitazone 30mg resulted in reduction of 1Ac of 1.9% for baseline average of 8.7% in 24 weeks. 8.7 – 1.9 = 6.8 Averages for individuals baseline approximately 10% 1Ac was a reduction of 2.8%, 10 – 2.8 = 7.2.
http://www.novartis.com/downloads_new/investors/Congresses/2006_06_13_ADA.pdf
Main arguments for trying Byetta, Januvia or Galvus, current drug therapies have significant long term failings:
1. A1c levels worsen over time with treatment
2. Weight gain over time
3. Hypoglycemia or low blood sugar episodes
4. Edema or swelling of feet and hands
My question is Galvus a better drug than Januvia?
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Anyone else hearing this? (Comment this)
Also you should read everything you can on the internet about DPP-4 and GLP-1. (Comment this)
Do you work for Merck that you are SO positive about this drug? I've looked at the trial data, and I'm not impressed by it. Most of the patients in the trials were discontinued on other medications for several weeks before being put on Januvia. It seems several of the people posting on here have stakes in Merck doing well with this product without really having merit to comment on the ability of this product to control blood sugars better than anything else out there? (Comment this)
At this point three drugs seem to have great promise in this drug, Bayetta, Januvia and Galvus. Frankly, Bayetta is an injection and causes a high amount of nausia. Januvia is a first generation DPP-4 inhibitor and the literature is scant. Since it does not have the assoited weitht loss, I don't think it is perfect or better than Bayetta. I like the research on Galvus, but it has not yet been released. Right now I'm waiting for Galvus and will ask my Doctor for a trial. I'm currently on Prandin .2 mg before meals. It is a good drug, but on occasion I get a low blood sugar incident with it. I love eating the carbs, but I'm getting fat. I think whatever drugs I'm taking they must allow for weight loss, of my desease is prgressing.
I want to combat my disease, blindness, amputation, feeling bad, and dieing young. I've got the "Metabolic Syndrome" or "Syndrome X".
High Blood Sugar, High Blood Pressue, High Cholesteral, gaining weight, edema, slow to heal and High Triglicerides, yuck. Left without reversal in all of these areas I will die young, like my grandfather in the next decade. As the doctors would say reduce mobidity and mortality.
When I first was diagnosed about 1998 I asked my doctor what causes Type 2 diabetes, so I could understand. He said at the time we don't fully understand the causes, your body produces insulin and you are insulin resistant try these drugs they help. Most did not. I treated myself with Atkins like diet for approximately 6 years.
Last year Atkins diets stoped contoling my blood sugar and I began spilling a little protien in the urine and I went on Actos and Prandin, reasarch showed 2.1 1Ac improvement.
I am looking here for actual results from people who are taking Januvia. The published trial informaiton looks great, but there is not enough information on how it wouls with multiple drugs.
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O have been taking Januvia for about 2 weeks. Deamatic increase in BS control and was able to drop my daily Avandia. Still also takung Metformin 500mg x2 x2, and Glyburide 5mg x1.5& x1 tablrts. Had some lows initially whilse still taking Avandia. Had some vary low ranges since , but overall good.
Might be a coincidence, but last couple of weeks I've had knee & toe pain...
Joe
Cape Elizabeth, Maine. (Comment this)
Novartis AG said the Food and Drug Administration needs three more months to determine whether problems encountered by animals taking the diabetes drug Galvus may pose risks to humans… Novartis said it has presented the FDA with further evidence that skin findings, including lesions, identified in monkeys during a preclinical animal study have not been seen in clinical studies with patients treated for type 2 diabetes. The skin problems developed by the animals weren't fatal, added James Shannon, head of development.
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I looked briefly around the Internet and didn't see any clarification on what the monkey skin lesions are, but clearly something was brewing in their preclinical data.
Raises two obvious questions:
1) despite Merck's disclaimers, is this a class effect -- was anything seen in animal or human trials of Januvia?
2) Why Novartis didn't display this data to the analysts sooner: "The announcement is a bit of a surprise as we were expecting to see the FDA approve Galvus imminently, especially since Merck's Januvia was recently approved smoothly," said Alexandra Hauber, an analyst with Bear Stearns, in a note to clients.
Any safety issue with these drugs could backfire all over the place. For example, I'll bet FDA is combing through the human trial data looking for any skin issues with both Galvus and Januvia -- and if they find ANYTHING, all bets are off on whether they put Januvia as well as Galvus on hold.
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I don't have any stock in Merck but am still happy with my change from Byetta to Januvia on 11/3/06. Was on Byetta for a year and while I was thrilled with the results the side effects still plagued me now and then and there were some foods/beverages I just couldn't tolerate. Not so with Januvia.
Also, I'm very IR and my last c-peptide test was 6.9 when the range was 0.3-3.8 from my lab. It appears Byetta more than did it's job of encouraging regrowth of the Isles of L..... that produce insulin. Unfortunately my cells just aren't able to use it. Hopefully with Januvia, and then Galvus when it comes out, will help with the IR. The Galvus info does say that after 6 weeks an improvement is noted.
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Some basic info on type II meds: Metformin-- cheap, effective Biguanide that is does a good job at lowering A1C. Lots of history/data, some GI side effects; docs use them ALOT because they are cheap and effective at addressing insuling resistance/increasing peripheral uptake of glucose in fat/muscle. 2. sulfonylureas--cheap and effective at lowering AIC. Several possible side effects, including hypoglycemia. docs use them ALOT because they are cheap/have alot of data/are efficacious. They lower glucose in a glucose-independent manner, meaning your blood sugar will go down whether or not your body needs it, hence the hypo risk. 3. Byetta--incretin mimetic/GLP-1 analog. Synthetic GLP-1, injected 2x/day, which is resistant to degredation by the DPP-IV enzyme due to its synthetic nature. Big weight loss potential/efficacious. 4. TZDs(Actos/avandia)--thiazoledinediones. Insulin sensitizers taken orally; efficacious, can be taken with metformin/SFUs and others. Side effects include possible weight gain/edema/poss. cardiac issues. Liver enzyme tests req'd. 5. Januvia(and eventually Galvus)--DPP-IV inhibitors. Taken once daily, with/without food. Data shows promising efficacy in lowering A1C,without the side effects of metformin/TZDs/SFUs, etc. Addresses beta cell dysfunction and alpha cell dysfunction(uncontrolled hepatic glucose production) in Type II's. The product is NOT oral Byetta; inhibits degredation of GLP-1 & GIP incretins/Byetta floods the system with synthetic GLP-1. Weight neutral. Can be use as monotherapy or in combo withTZDs or metformin. Galvus has not been approved yet(was delayed until late Feb2007).
The bottom line with these meds is efficacy, and to a lesser extent safety and tolerability. I like Januvia and the new class because it is allowing an endogenous system in the body to have a natural response to increased blood sugar. But if you are evaluating this class with other products, make sure you are comparing apples to apples with A1C reductions---- make sure baseline A1Cs at study entry are the same, and make sure you consider patient profile(are they drug naive versus currently medicated versus currently medicated and have gone thru a washout period). Patients that are drug naive will have GREATER A1C reductions versus patients currently on other meds or previously medicated. The higher the baseline A1C, the greater the reduction from ANY med. A1Cs from 7%-8% are potentially the hardest to treat in terms of getting to <7%.
New drugs will always take time to be adopted, but this new class will have a quick uptake IMO, due to the high degree of safety and tolerability. (Comment this)
Just a thought!
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Please help me understand.
Thanx. (Comment this)
I think I can explain this as an example of 100mg once a day. At 8 hours you have blood leveles equivalent to about 50mg at 16 hours 25mg and at 24 you have approximately 12mgs. This is an estimate with a 8 hour half life.
6 hours half life 50mg, 12 hours 25mg, 18 12mg and 24 6mg.
Therefore, based on the half life some blood level exists at the time of the next dose. Since there is some blood level present at the end of 24 hours over several weeks the residual would rise to some level higher than these estimates and level off. To understand it better you would need to test actually what happens.
Since this drug need glucose in the islet cells to produce insulin, it does not have the low blood shurgar issues of other drugs at the higher levels. The higher dosage seems to be the best bet.
However, there is some reports of nausia, so a lower dose might be indicated if your experience side effects.
Understanding this, is it better to dose at night or in the morning? I'm thinking at night because of morning rebound and low fasting blood sugars, any ideas?
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