Triple Oral Therapy vs Insulin (specifically metformin (met) + sulfonylureas (su) + thiazolidinediones (TZD))

I decided to start a new topic as I’m hoping to catch the eye of anyone who may have some knowledge or experience with triple therapy…

Specifically metformin (met) + sulfonylureas (su) + thiazolidinediones (TZD)

So let me just tell you this first off-I successfully stopped mixed insulin late August 2019… my edema on the lower legs disappeared after 4 days and I’ve felt a whole lot better since… I continue to use Glucophage XR (1 x 500mg morning and 2 x 500mg before bed) and have now added (after consultation with my GP) Glycomin (Glibenclamide from the sulphonlureas family (1 x 5mg morning and 2 x 5mg early evening) and there has been some, but not nearly enough, progress.

I’m very happy to report that my numbers are constantly low-teens now (I now consider a “high” at 15 mmol/L whereas prior to this I regularly had 18 mmol/L and higher after meals) but I’m very disappointed that, even with my change of eating habits (I now fast for a minimum of 15 hours per day) that I’m never lower than low-teens.

Essentially it does not matter how long I fast, (or not fast) I will always, always be higher than 10 mmol/L (I’ve been monitoring for 2 weeks now and it doesn’t matter if I test upon waking up, or upon fasting from 7pm the previous evening to 2pm current day it’s never less than 10 mmol/L).

Before I give up and go back to insulin’s I do want to consider tri-therapy and my option is to add a pioglitazone to the mix. What are your thoughts guys? Do you have experience with them? Just in case you were wondering I have appointment with GP soon to discuss and get his opinion too…

I’ve done some research and found that pioglitazone has been shown to reduce the risk of heart disease and the first-ever diabetes drug shown to reduce the risk of strokes(which is always good)but at the same time I’ve read that it has become less popular with patients due to side effects (including weight gain (which is the last thing I need), increased edema and bone fracture risk and some have been diagnosed with bladder cancer) but perhaps the pro’s outweigh the cons? Maybe this could be the one that tips my favour?

Whilst I’d love to be able to afford medications like Jardiance it just isn’t financially feasible so it’s a process of elimination I guess? Your thoughts?


The major diabetes associations recommend keeping post-meal spikes below 8.9 - 10 mmol/L (160-180 mg/dL). Between meals, values should be closer to the 4.5-6.5 mmol/L range.

I don’t mean to be callous or rude, but never having a value below teens will create long-term damage. I’m not really sure why you aren’t on insulin, but if I were you, I would emphatically insist upon it.

I have used metformin before, but I have not used the other medicines. Perhaps you already know this, but metformin works by increasing a person’s sensitivity to insulin. I would recommending maxing out your Metformin dose before using products that exhaust your beta cells. My understanding of Sulfonylureas is that they can exhaust your beta cells further, making them work overtime. That can result in the disease progressing further to where you have fewer beta cells to produce the insulin that is needed. If I were in your position, I would much prefer giving myself insulin in conjunction with activity and exercise. I’m sorry I can’t be of more help regarding the combo of the three drugs you mentioned.

Some people react badly to certain insulins. You may have a better experience on a different insulin. I have never experienced edema as a result of any of the insulins I have taken, but I have found that my body responds better to certain insulins vs others.

I don’t see anywhere in your post what your exercise or activity levels are. These have a real impact on insulin sensitivity and weight (I’m sure you already know this). Exercising regularly and remaining active on a day-to-day basis is one of the easiest ways for me to get my numbers in range. I respond to insulin much better when I’ve been active. A few days with minimal activity always raises my insulins needs.

Regardless of whether you use insulin or any of these other drugs, any form of exercise (swimming, walking, anything else you are able to do) can play a huge role in getting your numbers into a range that is healthy for you.

Thank you for all your valuable feedback! It is sincerely appreciated!!

I am desperate to try avoid insulin, after a 2 year nightmare situation of using a pre-mixed insulin I asked my treating provider to allow me the opportunity of coming off insulin, adding a sulfonylureas to my maxed out dose of Metformin (stomach issues if I go any higher) and changing my diet and exercise…

I have managed to progress quite well in the last 2 months and have lost 5kgs through change of diet, this is also reflecting on my sugar readings (which I consider to be good for me, because I used to be so much higher on insulin) and I was hoping that by adding a third I might just get to what is considered normal ranges (as you mentioned 4.5-6.5 mmol/L between meals).

I am really averse to insulin and I was under the impression that the beta cells were affected even more by insulin than by su’s so you have given me a lot to think about for sure!!!

Really appreciate it!