How a Low-Carb Diet is Surprisingly Similar to a Class of Diabetes Medications

Why you shouldn't combine a low-carb diet with SGLT2 inhibitors

Did you know that a low-carb diet can produce effects similar to a class of diabetes medications known as SGLT2 inhibitors (sodium-glucose co-transporter 2 inhibitors)? I know - it’s a mouthful to pronounce and not the easiest name to remember but perhaps you’ve heard of names like Invokana (canagliflozin), Forxiga (dapagliflozin), or Jardiance (empagliflozin).  But how exactly are they similar? These drugs pump sugar out of your kidneys and a low carb diet is just not eating carbs…

They are similar enough that you shouldn’t be on both though. If you’re going to embark on a low-carb journey, you should drop the SGLT2 inhibitor for safety reasons. If you’re on an SGLT2 inhibitor for cardiovascular and/or renal reasons and your doctor forbids you from stopping it, then you just shouldn’t go on a low carb diet. By the way, there are varying degrees of low carb… and depending on what source you use, some may say it is 50 grams or less and some may say 50-150 grams of carbs. At the end of the day, it’s just a matter of mild, moderate or severely low carb. 

So…what is the problem with taking an SGLT2 inhibitor while on a low carb diet? It is the risk of euglycemic ketoacidosis (euDKA) - a potentially life-threatening condition where the body develops high levels of ketones, leading to dangerous acidity in the blood but without the high blood glucose levels typically associated with diabetic ketoacidosis which makes it harder to recognize since blood glucose remains normal and typical signs of high blood sugar may not be present. Without clear signs, euDKA can go unrecognized, delaying critical treatment and increasing the risk of severe health consequences. If left untreated, it can lead to severe health complications like organ damage and potentially life-threatening consequences (eg. death). 

On their own, SGLT2 inhibitors can very rarely cause euDKA; the incidence is like 0.1 - 0.5% per year. But how about a healthy individual on a low carb diet? I wouldn’t say it’s impossible but it is extremely unlikely unless someone has type 1 diabetes or a pancreas that isn’t able to produce insulin anymore because in healthy individuals, the pancreas produces enough insulin to prevent excessive ketone buildup, even when following a low-carb or ketogenic diet. In other words, as long as you’re able to produce insulin, you won’t go into ketoacidosis because insulin regulates ketone production. As a result, healthy individuals can enter nutritional ketosis (a mild, safe form of ketosis) without ketones reaching dangerous levels. 

Basically, if you’re taking an SGLT2 inhibitor, a low carb diet might be enough to tip you into euDKA. Of course, there are other factors that can increase your risk of euDKA while on SGLT2 inhibitors and they include: fasting/skipping meals, dehydration, illness and excessive alcohol consumption so don’t combine these with an SGLT2i either.

Enough of euDKA. What else can an SGLT2i do that a low carb diet can do as well?

1. Lower blood sugar levels

2. Lower insulin demand and 

3. Help you lose weight

By reducing carbohydrate intake, you naturally limit the amount of sugar (glucose) entering the bloodstream so your blood sugars will just stabilize at a lower level. Fewer carbs also means lower/fewer blood sugar spikes, so your body doesn’t need as much insulin to manage blood glucose levels. Remember - insulin is the hormone that helps to bring down blood sugars. Naturally, a lower carb diet reduces your insulin demand and over time, this can lead to improved insulin sensitivity, a key factor in managing or preventing Type 2 diabetes. With lower circulating levels of insulin, your body will also start to break down stored fat for energy and it is this shift from glucose to fat as the main energy source that promotes fat loss (and therefore, weight loss) over time.

SGLT2 inhibitors on the other hand, reduce blood sugars by preventing the reabsorption of glucose in the kidneys, allowing excess glucose to be excreted in the urine. This directly lowers blood glucose levels without the need for insulin and by expelling the glucose into the urine, you lower the demand for insulin and cause a caloric deficit. This deficit in turn can also promote some fat loss. 

Similar right? 

Well it doesn’t stop there. They also produce similar side effects like:

• Dehydration

• Frequent urination

• Electrolyte imbalance

• Flu-like symptoms

Dehydration/Frequent Urination
Whether you are on a low carb diet or taking an SGLT2 inhibitor, it is very important to drink enough fluids as both can dehydrate you. By expelling glucose into the urine, SGLT2 inhibitors make you pee more because water follows glucose by osmotic diuresis (eg. glucose has an osmotic effect, meaning it attracts water. When glucose is excreted in the urine, it draws water along with it). On the other hand, carbohydrate restriction reduces glycogen stores, which are bound to water. As glycogen is depleted, water is released and excreted, leading to increased urination and a higher risk of dehydration. Technically, this is also why you see pretty immediate weight loss with a low carb diet because the initial loss is actually just water weight.

Electrolyte Imbalance
Increased urinary output from SGLT2 inhibitors can basically lead to the loss of electrolytes. And actually, the transporter that prevents the reabsorption of glucose is responsible for the transport of both glucose and sodium. So by inhibiting the transport of glucose, you also inhibit the transport of sodium. In contrast, a low carb diet makes you lose electrolytes in a few different ways. The first is that insulin regulates sodium retention and when insulin levels drop, the kidneys begin to excrete more sodium. As the body loses sodium, other electrolytes like magnesium and potassium follow as well. Lastly, a lot of the potassium and magnesium-rich foods are found in higher carbohydrates foods so if you’re eating a low carb diet, you’re also probably excluding these foods too (eg. bananas) 

Flu-like symptoms
The flu-like symptoms are pretty much a result of dehydration and electrolyte imbalances and are further compounded by the body transitioning from burning glucose to burning fat. Generally, the greater the level of ketosis, the greater the intensity of the side effects. SGLT2 inhibitors produce mild ketosis so you can expect the flu-like symptoms but they are likely a bit more pronounced while on a low carb diet. 

Here are the flu-like effects you can expect:

• Headache

• Fatigue and low energy

• Nausea

• Dizziness or lightheadedness

• Irritability or mood changes

• Muscle cramps or soreness

• Difficulty sleeping

• Constipation

These symptoms are usually temporary and tend to last anywhere from a few days to a week, though some people may experience symptoms for up to two weeks as their body adjusts to the changes. As the body becomes more efficient at using ketones for energy, the side effects will start to go away.

How to Manage The Side Effects of a Low Carb Diet or SGLT2 inhibitor:
Whether you are on a low carb diet or taking an SGLT2 inhibitor, you should definitely do the following:

1. Stay hydrated: increase your water intake to counteract the dehydration

2. Replenish electrolytes: focus on consuming adequate electrolytes (sodium, potassium, and magnesium) through diet or supplements. Salt your food.

3. Monitor Symptoms: Be vigilant for signs of dehydration, dizziness, or unusual fatigue, and seek medical guidance if they become severe. 

My final thoughts
While I am an advocate of a low/lower carb diet, I don’t necessarily think it is appropriate for everyone. For example, I would not recommend a very low carb diet to someone with heart failure or a number of pre-existing cardiovascular conditions. I do believe in a lower carb diet for these individuals with diabetes so perhaps you can think of lower carb (instead of LOW carb) as a gentler approach.

As well, I do need to point out that SGLT2 inhibitors have unique benefits that go beyond what a diet alone can provide, particularly for those with pre-existing cardiovascular conditions or chronic kidney disease (CKD):

1. Kidney Protection: SGLT2 inhibitors help protect kidney function by preventing hyperfiltration (kidneys filtering blood at a faster rate), reducing intraglomerular pressure (blood pressure inside the tiny filtering units of your kidneys) and reducing protein leakage into urine. This kidney-protective effect is beneficial for individuals at risk of CKD progression.

2. Heart Health Benefits: SGLT2 inhibitors can reduce the risk of heart failure hospitalization and major cardiovascular events in people with diabetes or existing cardiovascular disease. This is due to reduced blood pressure, lower blood glucose levels, and improved heart and renal function.

For those struggling with blood sugar control and weight loss, a low-carb diet in my opinion is worth trying -provided it’s implemented safely and appropriately. But if you’re on an SGLT2 inhibitor, definitely talk to your doctor about coming off it when starting the low carb diet so that you don’t go into ketoacidosis!