Ask the Pharmacist

Q. I feel as though I am trapped in a vicious cycle with managing my diabetes. Despite trying to watch my diet, I find it difficult to find the energy to exercise which results in an increase in my medication dose and in turn leads to more weight gain. Is there anything I can do to get out of this cycle?

A. If you have been on the same regimen for many years, it might be time to review both the medications and your non-pharmacological (i.e. lifestyle choices) treatment. Hopefully you have been routinely getting bloodwork done to get an accurate picture of how your blood sugars have been. More specifically, the bloodwork that your doctor will want to see is your A1C, which gives an average blood sugar value over the last 3 months. This A1C is a more accurate look than the daily finger test you likely do at home.

Many people have confided that if the blood sugar result is higher than they would like on their home monitor, they either don’t record it or delete the result altogether. The A1C result however cannot be altered to suit your wishes and desires. The ultimate goal to aspire to is an A1C below 7%. Though that number might seem too challenging to achieve, it is definitely attainable.

It is very normal and natural that as we age our bodies will change and so might our treatment of diabetes. Lifestyle modifications is first and foremost the key step in the diabetes treatment no matter whether you’re totally dependent on insulin or taking only a single pill. Depending on how high your blood sugars are, you may also be prescribed pharmaceutical treatments at the time of diagnosis. It is important to realize that not everyone will be successful in managing their diabetes with diet and exercise alone.

One of the most common diabetes medications on the market is metformin which has been around for decades and for the most part is well tolerated once you get past the GI symptoms (such as diarrhea, gas and bloating) that arise initially. However, since diabetes continues to progress in our body, we may eventually find ourselves at a point of requiring additional medications and then perhaps adding an insulin to the treatment plan. Often, people will find that they are still not at the target A1C with their chosen regimen.

One option might be to increase the insulin dose to try and better manage the diabetes. This may be viable in some people while others may find that every time they increase their insulin dose it results in an increase in their weight and a decrease in their energy. Insulin is a great medication, in almost all respects, but it does contribute to weight gain which many users are unaware of. Anyone who is trying to maintain or increase their exercise routines may find this frustrating as they can no longer find the ambition to do so. It also increases the risk of hypoglycemia (low blood sugars).

Another option to consider is to add yet another medication that lowers sugars to the regimen. In fact, many companies have now banded two diabetes medications together into 1 tablet which allows the person to take the same or more of the drug in a fewer number of pills. This can be very convenient for people that do not like the thought of taking so many tablets.

A third option and one that is becoming more and more popular with many physicians is the addition of a medication that will not only help lower the A1C but also provide other benefits. These include the lowering of the cardiovascular risk (like heart disease or a stroke) that goes along with having diabetes, lowering the risk of hypoglycemia and helping with weight loss. There are two groups of medications that can assist with this;

  • Glucagon-like peptide-1 receptor agonists (GLP-1 RA’s) such as
    – Dulaglutide (Trulicity)
    – Liraglutide (Victoza)
    – Semaglutide (Ozempic)
    – Exenatide (Byetta)
  • Sodium-glucose co-transporter 2 inhibitors (SGLT2 inhibitors)
    – Canagliflozin (Invokana)
    – Dapagliflozin (Forxiga)
    – Empagliflozin (Jardiance)

SGLT2 inhibitors focus on excreting glucose from the body via the kidneys and has no effect on the action of insulin in the body. This class of medications has been shown to significantly reduce both A1C’s and weight gain and can also improve LDL (bad cholesterol) and blood pressure in some people. Since there is an increased amount of sugar in the urine, it is important to ensure you drink plenty of water to reduce the risk of urinary infections. There is an increased risk of amputations with SGLT2 inhibitors with studies showing a doubling of this risk although the actual numbers are still very low.

Bear in mind that people that have diabetes are already at risk of amputations which is why it is so important to get your diabetes under strict control. Individuals that have a history of foot ulcerations, neuropathy and/or vascular diseases (diseases that affect circulatory system such as hypertension, stroke, peripheral vascular disease) would already have a higher risk of amputations and therefore this class of medications needs to be used with extra caution after weighing the benefits vs the risks.

There are also unexplained reports of kidney damage from SGLT2 inhibitors and thus it is suggested to monitor kidney function beforehand and during the course of treatment.

GLP-1 RA’s work by mimicking the hormone in our body called glucagon-like peptide 1. This hormone stimulates the body to produce more insulin when our blood sugar rises after eating. This class of medications is very effective at reducing the A1C and improving weight loss. How they work to reduce weight is not fully understood but it is thought to be related to their ability to curb our hunger and slow the movement of our food from our stomach to our small intestine. This in turn helps us reduce our food intake since we may feel full longer. There are also improvements in both systolic and diastolic blood pressures as well as cholesterol. There is an association with acute pancreatitis and thus should be avoided in anyone with a history of pancreatitis.

Studies have shown an increase in thyroid tumours in rats but this has not been shown in humans to date. As a result, these medications should also be avoided in anyone with a family or personal history of thyroid cancer or multiple endocrine neoplasia.

SGLT2 inhibitors are medications taken by mouth, whereas all but one of the GLP-1 RA’s are administered as an injection. One recent chart comparing these two classes of medications shows a reduction of A1C of 0.5%-0.7% with SGLT2 inhibitors and 0.9%-2.3% with GLP-1 RA’s. Obviously this shows that the GLP-1 RA’s are more effective at blood sugar control and they appear to be better at helping with weight loss as well. It is interesting to note that semaglutide is the one GLP that is available both as a weekly injection and a tablet to be taken orally daily, however, the A1C lowering is markedly improved with the injection (2.3%) form as compared to the tablet (1.3%).

According to the Diabetes Canada 2020 CPG pharmacological update, anyone 60 years of age or older with at least two cardiovascular risk factors such as dyslipidemia, hypertension, smoker or obesity or in people that have atherosclerotic cardiovascular disease should consider starting a GLP1-RA that has proven CV benefits. They consider it a good idea even if your blood sugars are well controlled on your current regimen.

If you are not already on either of these medications, the GLP-1 RA should be considered for people at high risk of cardiovascular disease whereas SGLT2 inhibitors should be considered for people with heart failure or chronic kidney disease. These classes of medications have very different mechanisms of action in our body and therefore it is fine to be on both, if necessary. The combination has shown additive effects on lowering the A1C, systolic blood pressure, weight loss and reducing the cardiovascular risk.

For more information on this or any other health topic, contact your pharmacist.