When the FDA approves a new drug it requires no proof that the drug is more effective than similar, existing drugs, only that it is better than placebo. Which is something to keep in mind as Bristol-Myers Squibb unveils what is sure to be a saturation advertising campaign for its new DPP-4 inhibitor, Onlgyza.
This mellifluous moniker is the brand name for Saxagliptin, which alert followers of drug news remember as the Januvia clone developed at the same times as Januvia whose release has been blocked due to its ability to cause "skin lesions" some of which necrotized (i.e. died and fell off) in monkeys.
I have read through the Prescribing Information for Onglyza and cannot see any benefit it offers in comparison to Januvia, the other DPP-4 inhibitor currently on the market.
Setting aside for the time being the advisability of controlling your blood sugar by turning off a tumor suppressor gene Onglyza offers nothing not offered by Januvia.
Both inhibit the expression of the DPP-4 gene for a full 24 hours--which means that if your body was fighting a new, very small DPP-4 sensitive tumor, like ovarian cancer, melanoma, prostate cancer or lung cancer, the drug would keep DPP-4 from killing off the tumor cells.
1. Feeble impact on blood sugar: Onglyza lowered A1cs that averaged 8% by .5%, which does not bring them anywhere near a safe level even by the anemic standards of the ADA. When the highest dose of Onglyza was compared to a placebo, it allowed only 14% more of those taking it to achieve 7% A1cs.
To better understand how "Effective" it is, consider what that A1c really meant: Onglyza lowered the average fasting glucose in those who took it from 171 mg/dl to 162 mg/dl (9.5 mmol/L) to 162 mg/dl (9 mmol/L). It lowered the average two hour post-meal blood sugar reading from a damaging 278 mg/dl (15.4 mmol/L) to an equally complication-guaranteeing 235 mg/dl (13 mmol/L).
So my immediate question would be: Why take this drug which is likely to cost 3 or 4 dollars a day to "achieve" blood sugars that are still high enough to lead to amputation, blindness and kidney failure when for the same money or less you could use insulin to get normal blood sugars?
2. Negative impact on the immune system. Inhibiting the DPP-4 gene, which produces an enzyme that rids the body of GLP-1 by chopping it up, lowers blood sugar because GLP-1 lowers blood sugar. However DPP-4 is used by the immune system for other functions most doctors know nothing about. Januvia's initial testing showed that it caused changes in white blood cell counts which the drug company dismissed as being of unknown significance.
Onglyza has a stronger impact on your immune system's white blood cells. In the prescribing information we read:
There was a dose-related mean decrease in absolute lymphocyte count observed with ONGLYZA. From a baseline mean absolute lymphocyte count of approximately 2200 cells/microL, mean decreases of approximately 100 and 120 cells/microL with ONGLYZA 5 mg and 10 mg, respectively, relative to placebo were observed at 24 weeks in a pooled analysis of five placebo-controlled clinical studies. Similar effects were observed when ONGLYZA 5 mg was given in initial combination with metformin compared to metformin alone. There was no difference observed for ONGLYZA 2.5 mg relative to placebo. The proportion of patients who were reported to have a lymphocyte count ≤750 cells/microL was 0.5%, 1.5%, 1.4%, and 0.4% in the saxagliptin 2.5 mg, 5 mg, 10 mg, and placebo groups, respectively. In most patients, recurrence was not observed with repeated exposure to ONGLYZA although some patients had recurrent decreases upon rechallenge that led to discontinuation of ONGLYZA.
Translated into English, this means than in 1 person in 100 who take it, Onglyza lowers the white blood count to a dangerously low level.
If your doctor prescribes Onglyza without requiring that you have a blood count periodically, you can be sure the doctor has not read the prescribing information. Few doctors do.
3. Onglyza conflicts with common drugs and grapefruit juice Because of the way it is removed from the body Onglyza may build up in the blood stream when taken with common yeast medication, ketoconazole, as well as with erythromycin, calcium channel blocker verapamil, and grapefruit juice. Onglyza levels also rise in people with poorly functioning kidneys. The manufacturer says that dose must be cut back in people using these drugs. Whether busy doctors will know this and warn patients about lowering the dose when needed is another story.
4. Onglyza raises the peak Concentration of Sulfonylureas and TZDs. This makes it more likely people whose doctors prescribe this new drug with a sulfonylurea drug will experience hypos. Onglyza also reduces the peak concentration of metformin.
5.Side effects The main side effects reported with Onglyza are the headache and runny nose that are also found with Januvia and which result from the inhibition of the immune system these drugs cause. Over time, my experience with taking Januvia for several months was that the headaches increased in intensity in a way that made me glad to stop taking the drug.
However, Onglyza also causes other immune reactions: As reported, "Hypersensitivity-related events, such as urticaria [rash] and facial edema [swelling] in the 5-study pooled analysis up to Week 24 were reported in 1.5%, 1.5%, and 0.4% of patients."
Januvia also turns out to cause rashes, including, very rarely, the life threatening Stevens-Johnson syndrome where people's skin peels off the body. It is significant, though that rash did not appear as a side effect of Januvia until after the approval testing was complete. That Onglyza produced such a high rate of rash during testing seems to suggest that it has a higher potential to disrupt the immune system.
6. No evidence that this or any other DPP-4 inhibitor preserves beta cells I mention this because the drug reps are selling these drugs to doctors claiming, based on weak animal evidence that these drugs preserve beta cells. No drug can preserve or regenerate beta cells when blood sugars are rising over 140 mg/dl for long periods of time, because sustained high blood sugars cause glucotoxicity--poisoning of beta cells. With the many years that BMS has been testing Onglyza you can be sure they have run every test they could find to demonstrate beta cell preservation and the complete lack of any cite to this in the prescribing information suggests they could not find it.
Why Take Onglyza?
Nothing in the prescribing information suggests any advantage in taking Onglyza compared to Januvia, while at the same time suggesting strongly that Onzglya's impact on the immune system is stronger than Januvia's. No research was done into whether Onglyza increases the incidence of tumors in those who take it, and because of the very small numbers involved in the clinical trials and the way the drug companies bury tumor incidence (combining benign and cancerous tumors in one category, as in the Januvia trials), that data is not likely to emerge.
Nevertheless, I'm sure a BMS drug rep is hard at work motivating doctors to switch patients to their new drug. Don't be surprised if your doctor suggests you enroll in a "study" using Onglyza, as this is a common way to divert patients from an existing drug. The "study" will provide you with one or two month's free supply of the drug because the companies know that once you are used to taking it you are likely to continue taking it. You'll be seeing free samples and eventually saturation advertising on diabetes web sites and TV.
The really sad part is that the net effect of all this will be only that patients with A1cs of 8% whose fasting blood sugar is well over 150 mg/dl and whose post meal blood sugars are in the range the ADA long ago defined as causing blindness (over 200 mg/dl two hours after eating) will take another expensive drug that ensures they won't get the kind of control that prevents the classic complications.
If you have blood sugars that high before you pay a couple hundred bucks a month for a potentially harmful new drug try the following:
1. Try the technique described here: How to Get Your Blood Sugar Under Control. It really works. Even for people who have had diabetes for as long as a decade.
2. Add extended release metformin if you can tolerate it and have no kidney or liver problems. Metformin is much more effective and less prone to cause digestive distress when used along with a diet lower in carbohydrate.
3. If cutting back on the carbs in your meals and adding metformin doesn't lower your blood sugar to safe levels (Under 140 mg/dl after eating) demand that your doctor send you to an endocrinologist so that you can get a tailored insulin regimen that gives you normal blood sugars.
Do not settle for the kind of insulin regimen family doctors usually prescribe which almost always leave you with blood sugars that are damagingly high. These inadequate insulin regimens are designed to keep your blood sugar high so as to avoid hypos--and to avoid the need to give you the kind of diabetes education routinely offered people with Type 1. With proper diabetes education you can avoid hypos and get great control. But for most Type 2s, to get the right kind of insulin regimen prescribed you will have to find a young, knowledgeable endocrinologist who will take the time to work with you on tuning your insulin regimen.
If your doctor won't help you get normal blood sugars, and insists that all you need are oral drugs fire him or her and find one who will give you the help you need.
Every person with diabetes can achieve normal blood sugars and normal blood sugars produce normal health.