This section is for type twos and type ones with any degree of insulin resistance. If you are a slim type one you may skip over to the How To: Use Bolus Insulins Effectively section.
For many years there were only two types of drugs offered to people with type two diabetes, metformin and sulphonureas. More recently the glitazones and the meglitinides have been prescribed. Last year several other medications such as januvia and byetta have come along too.
As the number of people with type one diabetes who have also developed insulin resistance has increased there has been more experimentation with oral drugs as well as insulin. The insulin resistance is usually related to weight gain and high amounts of injected insulin which are necessary to cover a high carbohydrate diet.
As the number of people with type two diabetes who have not been able control their blood sugars on oral drugs increases there are more type twos on combinations of oral drugs and insulins. This rise is related to worsening insulin resistance at least partly due to high amounts of ingested refined carbohydrate and beta cell failure partly due to the toxicity of high blood sugars on beta cells over a long period of time.
In this section I will be discussing some points about the older oral drugs for diabetes. As users of the newer drugs gain experience with them I would hope more information on this expanding area of prescribing can be given.
Sulphonureas work by making your pancreas release more insulin. Although sulphonureas sometimes don’t work when first given they almost always stop working later on. Every year secondary sulphonurea failure occurs in 5-10 per cent of people taking them. 50% of people taking a sulphonurea will have beta cell failure by six years.
Going on this drug may seem like a good way of avoiding insulin injections to start with. But it really just delays the point at which most people are likely to need an alternative treatment or insulin. Remember that your pancreas is smarter than you are when it comes to fine tuning your blood sugars. Even a little bit of useful pancreatic function could make a big bit of difference later on.
There are also worries about increased cardiac mortalilty with sulphonurea use. An epidemiological association between hyperinsulinaemia and cardiovascular disease has raised concerns about the safety of sulphonureas.
Sulphonureas are popular with physicians and patients because they tend to be well tolerated. They do cause significant weight gain in many patients but this is not apparent right away.
The fear of injections in patients and the burden of patient education about insulin use in doctors seem to keep the prescriptions for this drug flowing along. Before you start this drug however there are some things it may be helpful to ask both yourself and the doctor.
1. Is there any alternative medication or supplement that could help to get my blood sugars down?
2. Would a low carb diet be a better alternative course of action for me?
3. Would an exercise programme be a better alternative for me?
4. How much pain is involved with injections? Could I try one to see?
5. Have I a particularly reduced life expectancy that could make a sulphonurea a more favourable alternative to insulin injections?
6. How expensive is the insulin versus the sulphonurea?
Once you have asked these questions and given realistic answers you will be in a much better position to make a well informed decision that your future self will be happy with.
Meglitinides :The Prandial Glucose Regulators
Repaglinide (Novonorm) and Nateglinide (Starlix) are chemically unrelated to sulphonureas. But again they work by squeezing more insulin out of the pancreas. They are taken just before meals to stimulate insulin for just that meal. They are usually taken three times a day. They are not used with sulphonureas but can be used with metformin. They can cause gut upset and hypoglycaemia.
At the moment we don’t know the long term effects that these drugs have in the way we do about sulphonureas. Because they have a similar action on the pancreas they may also be expected to lead to premature beta cell failure but we just don’t know. They are active for a shorter time than sulphonureas and that may influence things.
Pragmatically it would be worth asking yourself and your physician the sulphonurea questions. If you are leaning towards sulphonureas a meglitinide may be a better longer term option. We just don’t know.
Metformin does not tend to cause weight gain which is important for many people with type two diabetes. It is particularly useful when fasting hyperglycaemia is present. It causes some beneficial effects on blood lipids. It lowers blood glucose mainly by reducing the production of glucose from the liver. It may increase the sensitivity of the muscle cells to insulin and slow the uptake of glucose from the intestine. It does not depend on stimulating insulin secretion as the sulphonureas do. About ten percent of patients fail to respond to it when it is first used and the secondary failure rate is 5-10 per cent a year.
Metformin therapy in the prediabetic patient reduces the onset of type two diabetes mellitus by 31%. Visceral fat is reduced in metformin therapy. Visceral fat is more metabolically active and produces adipocytokines which contribute to insulin resistance.
Metformin has benefits outwith the lowered hbaic compared to sulphonureas and insulin.
Gastrointestinal side effects can be minimised by starting with a single dose of 500mg after the evening meal. The maximum glucsose lowering dose is 2g daily. A long acting version of this drug can be particularly helpful for those with gastric side effects on the regular medication and also can be given in the evening to reduce the high morning blood sugars caused by the dawn phenomenon.
Important though uncommon side effects include lactic acidosis, especially if renal failure is present, and B12 deficiency.
The glitazones are the first group of drugs for diabetics that directly reverse insulin resistance. Rosiglitazone and pioglitazone were released in Europe in 2000. Neither drug has been linked to liver damage. They cause changes in the muscle and fat cells where the insulin resistance resides. They also enhance the actions of insulin in the liver.
The glitazones have their greatest effect on blood sugar after eating rather than the first morning glucose.
Glitazones are insulin sparing meaning that the body does not have to make as much insulin to control the blood sugar when a glitazone has been given.
So far secondary failure does not seem to be a problem.
Glitazones take 12 weeks to give the maximum benefit. You should only be given a glitazone in combination with a sulphonurea if you can’t tolerate metformin or there is some other reason why you can’t take it.
You can be offered a glitazone in addition to metformin and a sulphonurea if your blood sugars aren’t well controlled enough as an alternative to starting on insulin.
Glitazones can cause hypoglycaemia if used with a sulphonurea or insulin.
Glitazones have demonstrated beta cell preservation which delays or prevents insulin therapy. This has not been seen in patients treated with sulphonureas or metformin.
Glitazones directly improve insulin resistance and reduce hyperinsulinaemia. They also raise HDL and give less dense LDL, give improved endothelial function and slightly reduce diastolic blood pressure.
The glitazones become less effective as the duration of diabetes goes on and endogenous insulin production from the pancreas lessens.
The data for beta cell preservation is good and makes glitazones a favourable choice early in the course of type two diabetes. Problems are fluid accumulation and the effect of precipitating heart failure.
Glitazones have been shown to give increased osteoporosis at unusual sites such as the upper limb. In addition Rosiglitazone may increase the risk of cardiac death. Until more is known about the effects of Rosiglitazone it may be best to use Pioglitazone if this class of drug is being considered. Pioglitazone has been shown to have a favourable effect on cardiac risk.
Both metformin and the glitazones have been used in insulin resistant type ones. Metformin seems to be a very helpful add on medication for this group but the glitazones have been disappointing.
There is no quiz for this section.
Acknowlegements to Dr. Bernstein’s Diabetes Solution and Sarah Jarvis and Alan Rubin’s book “Diabetes for Dummies, UK Edition / Diabetes for Dummies
Where to Next:
Please all continue to the How To: Use Bolus Insulins Effectively section.