T2DM medication treatment pathway

Question

I am looking at the T2DM medications specified here and have a few questions about them.

1) Why don't I see drugs like Troglitazone, Tolazamide, Acarbose, Acetohexamide, Chlorpropramide, Miglitol? Aren't these drugs used to treat diabetes?

2) I see in drug treatment, we have terms like monotherapy (single drug) and combination therapy (multiple drugs). But what is the combination window usually considered for calling a treatment combination therapy?

By combination window, I mean the number of days both Drug 1 and Drug 2 should overlap. For example, let's say Jacky takes Drug A from Jan 1st till Jan 21st. He also takes Drug B from Jan 11th to Jan 21st. We see that there is an overlap of 10 days. Is there any minimum number of days that you look for to call a treatment combination therapy?

Answer 1

The Mayo Clinic page shows only some antidiabetic drugs; they just didn't mentioned few more as you did.

A combination therapy for diabetes type 2 (UpToDate) is a combination of at least 2 oral antidiabetic drugs, or a combination of one or more oral antidiabetic drugs with insulin. The term is used when the therapy is planned as combined and not when it occurs "by chance," for example, when a doctor plans to discontinue one drug and introduce another drug before discontinuing the first one. I can't say what was the intent of the doctor who prescribed the drugs in your case, but if the first drug was discontinued and the second one continued after 21st, it was obviously not meant as a combination therapy. There is no official minimal time required to say it's a combination therapy, but it usually lasts at least few weeks, during which time its efficacy can be evaluated.

Combinations of various drugs are possible, including the ones you've mentioned.

A common side effect of antidiabetic drugs is hypoglycemia, which can be treated by temporary discontinuation of a drug or by other measures, including glucose injection, etc. Other side effects may need treatment with other drugs, but this is too broad to discuss here.

Answer 2

I want to add a supplementary answer which provides a useful infographic produced by the British Medical Journal and based on the diabetes guideline issued by the UK National Institute for Health and Care Excellence (NICE).

The guide shows the advisable combinations of oral medication in type 2 diabetes (there are a few possible combinations) and when to consider insulin therapy.

Click the image for a link to the PDF.

Treatment usually starts with metformin, if it is tolerated and not contraindicated (e.g. rental impairment). Second and third-line agents are then added, usually with at least three months between initiation (this is because HbA1c values used for monitoring only change slowly, due to the long lifespan of a red blood cell).

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One point regarding side effects - hypoglycaemia is a common side effect of some oral diabetes drugs, but not all. Sulphonylureas (e.g. gliclazide) can definitely cause hypoglycaemia as they increase insulin production, but others, like l metformin, which reduces peripheral insulin resistance, will essentially never cause hypoglycaemia but very commonly cause gastrointestinal side effects.

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N.B. This relates to the UK. Different drugs may or may not be licensed for use in other countries. Acarbose has been around a long time and is only used in a few situations and nowhere near first line, due to limited benefit and side effect profile.

Additional reference: BNF Diabetes Treatment Summary