Type 2 Treatment And Management
Unlike type 1's there are a number of type 2 treatment options available. As they have insulin resistance rather than no beta cells they usually do not require external insulin.
The type of treatment plan they are put on will depend on the strength of the insulin resistance and the condition of the pancreas.
Nobody can be sure at the start which treatment will work best for any particular individual - there is a saying, often seen abbreviated on forums to YMMV, which means Your Mileage May Vary, and it really does, we only have one thing in common - high blood glucose!
So where does one start? That depends, to a certain degree, on how high your BG is when you are diagnosed. The doctor will want to get them down as quickly as possible before they do irreparable damage. See Diabetic Complications.
If they are not to high he may opt for diet and exercise as being sufficient, if they are going through the roof he may put you in hospital on insulin until they are under control and then decide where to go next. These are the two extremes, there are plenty of options in-between, featuring oral medications or insulin.
So let us deal with one of the first lines of defence, exercise.
This is going to be important to you whatever treatment plan you are on. As type 2's we are generally overweight and, as this increases insulin resistance (IR) it is a good idea to get some of that weight off.
A few pounds will help
and the closer you get to your correct weight the less IR you will have. It is often said that a 30 minute walk once a day is sufficient to make a considerable change. So come on you couch potatoes, give it a go. Who knows, you may grow to like it - sigh...........
Then there is the 'D' word - DIET.
Again, most of us type 2's have been through every diet in the book trying to get, and keep, that weight off. It is a bit of a vicious cycle because the heavier we get the more IR we have, but the more insulin resistant we are the more our bodies store fat - does anyone else feel picked on?
As diabetics however our 'diet' is not about losing weight, though that could be a sideline benefit, it is about controlling the amount of glucose in our blood.
One needs to get past the idea that eating large amounts of sugar in the form of that white or brown granulated stuff is responsible for our high blood sugars.
It contributes of course, but worse by far are carbohydrates. So keeping a lid on those carbs is the backbone of the diabetic eating plan.
In addition to the general diets and exercise listed elsewhere, we have recently found an e-book that really addresses the issues faced by diabetics in their quest to both lose weight and build up glucose burning muscle.
The 340 page e-book deals with both the weight loss and muscle building aspects in detail.
We suggest that you read our review on the
Burn The Fat, Feed The Muscle page.
However, we are eating correctly and exercising frantically and still our BG readings are far to high - what now?
Well, here is where the oral medications play their part.
There are a number of different types that work in different ways. Your doctor may prescribe any one of these, or occasionally a combination. I will describe them briefly here.
The list of drugs is growing so we have placed a sub-menu here for your convenience. You can still read down for the general overview, or if you wish, you can jump down-page to the drug you are interested in using the sub-menu below.
Biguanides
(Metformin or Glucophage)
sulphonylureas
Orinase (generic - tolbutamide).
Tolinase (generic - tolazamide).
Diabinese (generic - chlorpropamide).
Dymelor (generic - acetohexamide).
Glucotrol (generic - glipizide)
GlibeneseR (generic - glipizide - UK)
MinodiabR (generic - glipizide - UK)
DiamicronR (generic - Gliclazide - UK)
Micronase,
Diabeta
Glynase
(all above 3 contain glyburide)
Amaryl (generic - glimepiride)
Thiazolidinediones (Glitazones)
Rosiglitazone - Avandia
Pioglitazone - Actos
Glitazones - Good Or Bad?
Alpha-glucosidase inhibitors
Acarbose - Precose, Glucor & Prandase
Miglitol - Glyset
Prandial glucose releasing agents
Nateglinide - Starlix
Repaglinide - Novonorm & Prandin
Insulin
Symlin
Byetta
Januvia
Janumet
Liraglutide
Biguanides.
The only drug in this category at the moment is Metformin. The brand name is Glucophage, so you may hear it called by either of these names. The active ingredients are identical.
Biguanides work in 3 different ways:-
1. They decrease the production of glucose in the liver.
2. They decrease the absorption of glucose by the intestines.
3. They decrease insulin resistance by increasing the bodies ability to use insulin more effectively.
Metformin is usually the first oral med. suggested by your doctor, especially if you happen to be overweight or obese because, unlike other oral meds, it does not normally cause weight gain.
It comes in regular-release or extended-release tablets and how many you take will be determined by your doctor.
In some folk, ( and did I have to be part of the 'some'?), it causes initial abdominal pain, nausea and diarrhoea that do go away with time. For that reason the doctor may start you on a low dose and slowly increase it, as this tends to lessen the side effects.
Also, if the diarrhoea is very bad and or does not go away, then it may be beneficial to switch to the Metformin SR or sustained release version of Metformin. Due to its slow release it may have less side effects for you.
Sulphonylureas.
These are the oldest of the oral drugs used to control diabetes so there are quite a few available.
The oldest are often called first generation sulphonylureas while the next are second generation. A third generation one is now available.
They all work in the same way, by stimulating the pancreas to produce more insulin so are only of use if you still have enough functioning beta cells.
They are now often given as a second line defence when Metformin on it's own is insufficient to lower BG levels.
First generation sulphonylureas are:-
Orinase (generic - tolbutamide).
Tolinase (generic - tolazamide).
Diabinese (generic - chlorpropamide).
Dymelor (generic - acetohexamide).
Second generation sulphonylureas are:-
Glucotrol (generic - glipizide)
GlibeneseR (generic - glipizide - UK)
MinodiabR (generic - glipizide - UK)
DiamicronR (generic - Gliclazide - UK)
Micronase,
Diabeta
Glynase
(all above 3 contain glyburide)
Third generation sulphonylureas:-
Amaryl (generic - glimepiride)
The first generation drugs are not often prescribed any more because the second generation ones have less side effects and less interactions with other drugs.
Which of the drugs you take will depend on your doctor. They are all much the same.
There are a few slight differences, in that Glipizide lowers blood sugar faster than glyburide but then glyburide is more potent than glipizide so you can take a lower dose.
Amaryl is longer acting so need only be taken once daily instead of twice.
Side effects include:-
1. Hypoglycaemia - Low blood sugar.
2. Water retention.
3. Weight increase.
4. Allergic reaction, in those people allergic to sulfa drugs.
Sulfonylureas are not recommend for use during pregnancy.
These drugs should always be taken with meals and preferably at the same time each day.
They can be used in combination with certain other oral diabetic drugs.
Thiazolidinediones.
(Glitazones to those of us who find the former too much of a mouthful)
Like Metformin, these target insulin resistance.
Because of their expense and potential side effects they are seldom used on their own but given as second line drugs, being added to either Metformin or a sulphonylurea when a combination of those two does not agree with the patient.
As long as you take them regularly the time of day you chose to take them does not matter.
They will not show instant results. Expect to wait between 2 - 12 weeks before getting a good response.
At the moment two are available:-
1. Rosiglitazone - Avandia
2. Pioglitazone - Actos
An earlier drug in this class was withdrawn when it was found to have serious effects on the liver. While these two do not appear to have the same problem it might be wise to have regular liver function tests while on either of these drugs.
Also, contact your doctor immediately if you have symptoms such as:-
1. Nausea or vomiting.
2. Loss of appetite.
3. Yellow discoloration of the whites of the eyes.
4. Urine is 'tea coloured'.
All the above are symptomatic of liver damage.
Side effects:-
1. Weight gain.
2. Fluid retention e.g. swollen ankles.
3. Anaemia.
4. Cholesterol increase.
5. Increase in fertility in pre-menopausal women which can result in ovulation and the possible chance of a pregnancy.
Please read our new page - Glitazones good or bad?
Alpha-glucosidase inhibitors.
The simple name for these drugs is starch blockers - much easier to say isn't it? They work quite differently from the other medications we have looked at, having nothing directly to do with insulin resistance or production.
Instead they inhibit enzymes in the intestine from breaking down carbohydrates, thus slowing down the absorption of glucose. When blood glucose rises slowly instead of spiking after a meal the body's reduced insulin production is more able to cope.
They are very useful for people with postprandial hyperglycaemia (high BG's after meals) and those who cannot keep their BG controlled even though they are on a combination therapy. They also do not cause weight gain or low blood sugars.
There are two of these starch blockers available:-
1. Acarbose - Sold under the brand names of Precose in the United States and Glucobay, Glucor & Prandase in Europe and Latin America.
2. Miglitol - Brand name Glyset
The pills must be taken along with your first mouthful of food, with each meal. If you skip a meal you skip a pill, if you add a meal you will need to add a pill.
The dose is usually between 25-100 mg. three times a day with meals.
Side effects:-
Because of the way these work their most common side effects are those embarrassing digestive ones:-
1. Abdominal bloating,
2. Gas, flatulence - call it whatever polite term you like, you all know what I mean.
3. Diarrhoea.
Thankfully these are often temporary and can be reduced by eating less complex carbohydrates like bread, rice, pasta and potatoes to begin with. Also starting on a minimal dose and increasing it slowly helps.
Prandial glucose releasing agents.
These are relatively new drugs that, like the sulphonylureas, stimulate the pancreas to produce insulin.
However, they have a different method of action, they only stimulate insulin release in the presence of glucose. The higher the glucose levels, the more the stimulation.
They are absorbed very fast, act rapidly and for a short period of time, do not build up in the blood stream and are excreted from the body very quickly.
They therefore work well to control postprandial hyperglycaemia (mealtime spikes). If you can lower your mealtime spikes then you can lower your HbA1c.
Because they trigger insulin release at the start of a meal they need to be taken immediately before each meal. If you skip a meal then you skip the drug.
This does allow for flexibility. If you do not feel like eating you don't have to, unlike with other slow acting meds. Taking the tablet with or after the meal substantially lowers it's effectiveness.
The two Prandial glucose releasing agents are:-
1. Nateglinide - Starlix
2. Repaglinide - Novonorm in Europe - Prandin in the USA.
They can be taken on their own but are especially helpful when taken along with a drug like Metformin.
As Metformin mainly helps reduce blood sugar levels between meals (fasting blood sugar levels) the addition of a drug that reduces the meal time spikes could be of immense help to some people.
Repaglinide has the added advantage of being excreted mainly in the faeces which is an advantage for those with decreased kidney function.
Now we are at the point where we have tried a number of different treatment packages but still our BG's are climbing. What's left?
Insulin, that's what.
The mention of going onto insulin usually sends folk into a tizzy. The seem to feel that they have failed somehow, reached the end of the road and now have to resort to 'unnatural' means of control.
The latter boggles my mind. After taking all those manufactured and engineered tablets why would you not want to take something that the body produces naturally?
Non-diabetics control their blood sugars with insulin made by the pancreas, we just take another route and control it with insulin made for us by bacteria - so what, it is still human insulin!
In fact it is sometimes better for a type 2 to go onto insulin early and give their poor overworked beta cells a rest and time to recuperate.
The insulin used by type 2's is the same as that of type 1's. You and your doctor will need to work out how much of what kind is best for you. It may be that he will combine insulin with one of the oral meds to get the best results.
Symlin.
Just as Symlin can be used for type 1' so it can be used for type 2's who take insulin. The manner of application and the potential benefits and side effects are exactly the same, with the added benefit for type 2's of possible weight loss. See Type 1 Treatment for more information on this drug.
Byetta.
And now the very latest injectable drug produced for type 2's only, Exenatide, brand named Byetta.
Mention of this drug always makes me grin and you may well ask why. You see, it originally came from the saliva of the Gila Monster! Now I have this image of some researcher, on a hike through a desert in Southwest America, suddenly clapping his eyes on this 2 foot, brightly coloured lizard and thinking "Eureka, just the spit I need to make a new diabetic drug". I mean, that is how we would all react wouldn't we?
Sorry, just my foray into flights of fancy. I understand the truth is that a researcher who had developed a new type of chemical assay wanted to use it to detect new hormones and got a sample of Gila monster saliva from a lab in Utah. He had actually never seen a Gila monster.
Gila monsters eat infrequently, and this chemical helps them digest meals slowly over time. Definite advantageous for diabetics there!
Be assured that no animal/reptile has been harmed to produce your shot of Byetta, it is a synthetic version of a protein found in the saliva.
Byetta is the first so-called "incretin mimetic". What that means is that it mimics the way the hormone Glucagon Like Protein-1( GLP-1), a naturally occurring incretin hormone secreted by the intestine, regulate glucose.
It works by:-
1. Stimulating the islets to produce insulin.
2. Reducing the adsorption of glucose from the intestine into the blood.
3. Reducing the production of glucose by the liver.
It has the advantage of a longer period of control than GLP-1, hours more in fact, and it acts only when blood sugar is high, therefore does not tend to increase the risk of hypoglycemia on its own like other oral drugs. Hypoglycemia can occur if taken in conjunction with a sulfonylurea.
Byetta must be taken by injection, twice a day, within an hour of breakfast and dinner. There are reports from people on this drug that the nausea it causes is not so bad if you give yourself the injection just before you take your first bite of food.
It is a protein and as a tablet it would enter your stomach where it would be broken down in the same way protein in the foods you eat are, hence this method of application, which is one of it's disadvantages. It is supplied in a pen form, which makes things easier.
Another disadvantage is that it must be maintained at 36 to 46 deg F (2 to 8 deg C), which means refrigerated. This can be a problem when travelling. See travelling with Byetta for solutions.
Side Effects reported:-
1. Nausea. Not everyone gets it but many do and it is really bad.
2. Hypoglycaemia. This seems to occur mainly in those folk who are also taking sulfonylureas. It may be necessary to reduce the dose of your sulfonylurea if going onto Byetta.
3. Jitteriness.
4. Dizziness - possible due to a drop in blood pressure.
5. Headache.
6. Dyspepsia.
7. Tiredness and lack of energy.
8. Decreased appetite. GLP-1 is known to be one of the hormones which have a feedback role in appetite control in the brain, and this is a mimetic after all.
9. Decreased number of bowel movements, constipation or diarrhoea.
10. Feeling cold after an injection, sometimes followed by a flush.
For more in-depth information on Byetta visit our page on the use and side effects of Byetta
Januvia
It seems that new drugs for type 2 diabetes are suddenly coming thick and fast. Only last year the FDA passed Byetta and now they have given the go ahead for yet another drug, Januvia.
If you are wondering where the name comes from it was apparently ‘made up’ by the marketing department of the manufacturers, Merck & Co, and is supposed to make one think of ‘rejuvenation’. I have to go with a comment I read on the web – it sounds more like the name of a Shakespearean character than anything else. Mind you who am I to comment, I doubt if I could do any better if asked to name a drug.
So what have we got here and how and why does it work?
Januvia, or sitagliptin phosphate to give it it’s technical name, belongs to a class of drugs known as DPP-4 inhibitors (dipeptidyl peptidase-4 inhibitors).
As always the medical jargon is complicated but I will try to explain what it all means.
Let us start with an incretin hormone known as Glucagon-like peptide-1 (GLP-1). This is secreted from the intestine in response to the intake of food.
It binds to receptors on the beta cells of the pancreas, stimulated the beta cells to produce insulin.
It also suppresses the secretion of glucagon, delays gastric emptying and helps make one feel full as well as stimulating peripheral glucose uptake.
It is also thought to preserve beta and alpha cell function. Sounds as if it would do the trick as a therapeutic treatment for type 2 diabetes fantastically doesn’t it?
However, there is a problem as always. Naturally produced GLP-only survives for a very short time, around 1.5 - 2 minutes’ before it is degraded, so is not much use as a therapeutic agent.
Now we come to the enzyme dipeptidyl-peptidase 4 (DPP-4). It is what is responsible for degrading GLP-1. Obviously if one could find some way of preventing DPP-4 from deactivating GLP-1 then you would have more of it around, for longer, doing all the good things it’s supposed to.
This is where Januvia comes in. It is a DPP-4 inhibitor, in other words it interferes with DPP-4’s degradation of GLP-1 so you get larger concentrations of it around, thus increasing it’s benefits.
There are really only two ways to address type 2 diabetes –
either
1) improve insulin resistance
or
2) solve the problems of insulin lack and the overproduction of glucose by the liver due to the dysfunction of the alpha and beta cells.
So Januvia has a two fold effect. By blocking DPP-4 it causes the pancreas to produce more insulin while at the same time telling the liver to quit making glucose
Because of it’s mechanism of operation, Januvia only starts working when there is an excess of glucose. Therefore it causes a release of insulin and a decrease of glucagon only when they are needed, so there is little chance of it causing hypoglycaemia.
An advantage it has over many of the oral diabetic drugs is that it appears to be ‘weight neutral’ – in other words it causes neither weight loss or weight gain.
Januvia is administered orally and one 100mg tablet a day, with or without food, is the recommended dose.
Januvia is removed from the body by the kidneys and therefor if one has any problems with ones kidneys, as so often happens with diabetes, the dose may have to be adjusted.
For patients with mild kidney problems the normal dose should be okay.
For those with moderate renal problems or needing hemodialysis smaller doses may be required, such as 50mg once a day.
For those with severe kidney dysfunction or requiring dialysis the dose is smaller yet, just 25mg a day.
As there is this need to adjust the dose for kidney problems it is a good idea, if there is any suspicion of such problems, to have ones renal function assessed before taking Januvia and periodically thereafter.
Like all diabetic drugs there are some side effects. These appear mainly to be confined to respiratory problems such as runny or stuffy noses, sore throats or upper respiratory infections as well as headaches and diarrhoea.
As yet it is not known how safe Januvia is for babies and children and no adequate studies have been done on pregnant women or breast feeding mothers.
At first the price may be a stumbling block, especially when asking one’s insurance to cough up - compared to the older drugs like Metformin it is not cheap, expecting to sell at around $4.86 per tablet. The older drugs costs around 50c a day.
The FDA has approved Januvia to be used either on it’s own or in combination with Metformin or the thiazolidinediones, Avandia and Actos.
At the moment the pills will have to be taken separately but Merck are hoping to have a tablet combining Metformin and Januvia available somewhere around March next year.
While Januvia works on solving the problems caused by diminished insulin release due to beta-cell dysfunction and uncontrolled production of glucose by the liver Metformin and the thiazolidinediones are insulin sensitizers addressing the problem of insulin resistance, thus a combination would attack diabetes on two fronts.
Januvia is the first oral drug to target the incretin pathway.( Byetta also does this but has the disadvantage that it has to be injected). Novartis is expected to get FDA approval by the end of the year for a very similar drug, named Galvus. This may sound like an accompanying character in the Shakespearean play to Januvia but apparently it’s name comes from it’s “galvanising" effect on pancreatic cells”.
Byetta as opposed to Januvia
Byetta, or to give it it’s proper name, Exenatide, is a GLP-1 receptor agonist. In other words it mimics GLP-1. It is basically a synthetic version of GLP-1. Although it is very similar to GLP-1 it does differ in some small ways so it is not as susceptible to DPP-4, giving it has a much longer lifespan, of around 2.4 hours.
It does have the disadvantage that it must be administered by injection twice a day and kept refrigerated but for us overweight folk it has the great advantage that it is known to cause weight loss.
Janumet
On the 7th April 2007 yet another medication for type 2 diabetes was passed by the FDA.
It is called Janumet, made by Merck & Co., Inc.
It’s name should give away the fact that it is not technically a ‘new’ medication but rather a combination of two other medications already in use, Januvia and Metformin.
Januvia (sitagliptin), which itself was only approved in October 2006, is the first dipeptidyl peptidase-4 (DPP-4) inhibitor on the market.
Metformin, approved as long ago as March 1994, is the first line of defence for most type 2 diabetics.
Diabetics have been taking these two medications together as separate tablets but it is hoped that combining the tablets will help in a number of ways…..
1. Firstly a single tablet will simplify a patient’s drug regime (less pills to swallow) and thus help with patient compliance.
2. It will be easier for doctors as they only have to prescribe a single tablet.
3. For people who have insurance that requires co-payment for their medications there will only be a single co-payment instead of two separate ones.
One disadvantage is that using such a combination tablet gives one less flexibility when it comes to adjusting doses. If you adjust the dose of one component you automatically adjust the dose of both.
In the studies done the weight loss achieved on the combination tablet was the same as that seen in patients on Metformin alone, not surprising as Januvia is described as ‘weight neutral’, in other words you neither gain or loose weight on it.
Likewise the adverse gastrointestinal effects were the same as those for people on Metformin alone.
The risk of hypoglycaemia was the same as taking either of the tablets on their own.
For any contra-indication see those listed for Metformin i.e. not to be taken by those with any condition that may increase the risk of lactic acidosis such as kidney disease, liver disease, heart failure or lung disease.
Not for use by those with type 1 diabetes.
Liraglutide
This is another GLP-1 mimic, made by Novo Nordisk. As yet it is still undergoing phase 3 trials but appears to be very effective, both in lowering HgA1c and in causing weight loss. An unexpected side effect has been a reduction in blood pressure in some patients.
Apparently the liraglutide molecule is combined with albumin. This results a slow release from subcutaneous tissue after the drug is injected. Because of this it has a longer life even than Byetta, 10-13 hours in fact, so can be given, again by injection, once a day.
It is expected to go for FDA approval in 2008 and be on the market in 2009. Novo Nordisk hope this will be in advance of Amylin Pharmaceuticals/Eli Lilly’s promised single dose Byetta.