Why Low-Carb Diets and SGLT2 Inhibitors Are a Dangerous Combination

SGLT2 inhibitors are common diabetes drugs due to their skill to decrease blood glucose ranges, with a really low threat of hypoglycemia. These medicine don’t simply assist take away extra glucose out of your bloodstream — additionally they enhance and shield kidney perform, lower the chance of coronary heart failure, and assist with weight reduction.

Whereas these advantages can have a big effect in your diabetes administration and long-term well being, SGLT2s even have a harmful facet impact that many individuals are unaware of. These medicine can carry an unacceptably excessive threat of diabetic ketoacidosis (DKA) for individuals who observe a strict low-carb or ketogenic weight loss program.

How SGLT2 Inhibitors Work

In a nutshell, SGLT2 inhibitors forestall your kidneys from absorbing as a lot glucose out of your meals, stopping that sugar from getting into your bloodstream. As a substitute, that sugar is excreted by way of your urine. For a lot of, this ends in a direct lower in blood sugar ranges and infrequently some weight reduction.

SGLT2s embody empagliflozin (Jardiance), dapagliflozin (Farxiga), canagliflozin (Invokana), bexagliflozin (Branzavvy), and ertugliflozin (Steglatro). All manufacturers are capsules taken orally as soon as a day. 

Probably the most broadly identified facet impact is dehydration. This impact is comparatively easy: Because of elevated urination, chances are you’ll be very thirsty and have to drink a variety of water each day. In uncommon instances, dehydration might be extreme and harmful. Ingesting sufficient water each single day is a crucial a part of taking these drugs.

Different unintended effects of SGTL2s embody an elevated threat of yeast infections for girls (as a result of glucose in your urine feeds the expansion of micro organism) and males (balanitis). There have additionally been uncommon reviews of necrotizing genital infections.

Dangerous Enterprise: Low-Carb Diets & SGLT2s

Low-carb diets naturally improve your physique’s manufacturing of ketones — and that may be a superb factor for those who’re making an attempt to shed pounds. Whenever you’re consuming only a few carbohydrates, your physique burns fats extra rapidly for gas, utilizing the ensuing ketones for power. 

In small quantities, ketones are secure and regular. Most individuals, with or with out diabetes, produce small quantities of ketones within the fasting state (like earlier than consuming breakfast). However very giant quantities of ketones can result in DKA, a harmful and probably even lethal situation.

Diabetic ketoacidosis (DKA) happens when an absence of insulin causes your blood to change into acidic. The physique’s cells can’t survive below acidic situations. When mixed with dehydration, this course of accelerates into a toxic cocktail that undermines the center, impairs the mind, and may result in demise in days.

In folks with diabetes, an ultra-low-carb weight loss program (fewer than 50 grams per day) is normally secure — till you add one other element that may trigger the manufacturing of ketones to spiral uncontrolled. That’s precisely what SGLT2 inhibitors can do.

On their very own, SGLT2s don’t trigger DKA. As a substitute, they create a really perfect atmosphere for the manufacturing of ketones when mixed with one other ketone-inducing issue, like a low-carb weight loss program, dehydration, acute sickness, pump failures, fasting, or skipping insulin doses.

Simply one in all these extra components can drive your ketone manufacturing into overdrive, sending you into DKA. And in contrast to the DKA that most individuals with diabetes are in all probability aware of, this could even happen when blood sugar ranges stay at a wholesome stage.

“A low-carb weight loss program will increase the chance of DKA as a result of when a affected person consumes a low-carb weight loss program, their complete each day dose (TDD) of insulin is decreased,” explains Kelsey Hutter MS, RD, CDCES, LD/N, who’s additionally lived with kind 1 diabetes (T1D) for 15 years. Although it’s normally thought of wholesome to scale back your insulin necessities, when persons are utilizing a low-carb weight loss program and SGLT2s on the similar time, they’ll find yourself utilizing much less insulin than they actually need, even at wholesome blood sugar ranges.

SGLT2s considerably cut back how a lot glucose your physique absorbs out of your meals by passing the glucose out by way of your urine. On high of all of it, you’re peeing considerably extra, which suggests you’re always on the sting of dehydration. Dehydration additionally contributes to the manufacturing of ketones. Hutter provides that SGLT2s improve your physique’s use of physique fats for gas. This additional contributes to ketone manufacturing. 

SGLT2s & DKA in Kind 2 Diabetes

Whereas DKA isn’t usually related to kind 2 diabetes (T2D), it’s changing into extra widespread — particularly in folks taking SGLT2s.

One explicit examine shares the main points of a 58-year-old man with kind 2 diabetes (T2D) and hypertension. This man was prescribed an SGLT2 inhibitor as a part of his therapy plan. He was not taking insulin.

“[He] was introduced in by ambulance and admitted to the intensive care unit for weak point, lethargy, and altered psychological standing,” explains the examine.

They decided his blood stress was very excessive and he was in extreme DKA. 

The person’s blood work confirmed an A1C of 6.7 p.c however a blood glucose stage of 373 mg/dL on the time of admission. Whereas he’d been taking an SGLT2 remedy for a while, the one change he’d made prior to now month earlier than this episode of DKA was beginning a ketogenic weight loss program. 

“Our case demonstrates an instance during which the usage of SGLT2 inhibitors with adherence to a ketogenic weight loss program and intermittent fasting can result in DKA,” explains the examine. 

The docs additionally concluded that his blood glucose ranges and his pH ranges point out that his blood glucose ranges had been typically tightly managed. This unfortunate man will need to have thought that he was doing every part proper.

“The distinctive presentation of DKA induced by SGLT2 inhibitors makes its prognosis difficult, particularly when all different precipitating components are dominated out. Moreover, upon evaluate of his different [diabetes] drugs, none are related to DKA making them as much less possible the reason for his presentation. On this case, investigating the affected person’s historical past together with his latest change in weight loss program revealed a major offender for his presentation.”

SGLT2s & Kind 1 diabetes

SGLT2 inhibitors are solely FDA-approved for the therapy of kind 2 diabetes, however there has all the time been nice curiosity in utilizing them for kind 1, too. Research counsel that sufferers with T1D can take pleasure in the identical advantages, corresponding to improved glucose ranges, modest weight reduction, and improved long-term kidney well being:

“Medical trials of SGLT2 inhibitors added to intensified insulin remedy in adults with T1D have proven reasonable reductions in A1C, glycemic variability, TDD of insulin, blood stress, and physique weight and elevated time in vary with out improve in hypoglycemia,” explains Hutter.

Nevertheless, being insulin-dependent, folks with T1D face an particularly excessive threat of DKA when taking these drugs. In consequence, SGLT2s are solely not often prescribed off-label to folks with T1D.

“I presently work with two endocrinologists and one superior apply supplier,” explains Hutter. “Certainly one of our endocrinologists will prescribe SGLT2s on a uncommon event to sufferers with T1D.  She’s going to prescribe to sufferers which are overweight and have a excessive TDD of insulin. Our endo does advise in opposition to consuming a low-carb weight loss program and warns them of the DKA dangers.”   

Hutter provides that many endocrinologists will solely prescribe SGLT2s in T1D if a affected person has been recognized with coronary heart illness or kidney illness. 

The rising consensus for T1D is solely that the chance of DKA with SGLT2s is just too dangerous.

“In my skilled opinion, I really feel there’s not sufficient analysis to conclude that kind 1s can safely take SGLT2s,” says Hutter. “It’s nonetheless too quickly to make an evidence-based conclusion on the security of SGLTs and T1D. There are different choices, together with GLP-1s, that will supply extra profit and fewer threat.”  

This threat has additionally prompted well being authorities to proceed cautiously. The FDA and the EMA (European Medical Company) each thought of approving SGLT2s for T1D, and each concluded the chance of DKA was too important. Whereas each additionally acknowledged there are a number of advantages of those drugs for T1Ds, they felt that extra research had been crucial to higher perceive the security dangers. 

Carbohydrate consumption was listed as one in all many components that may contribute to DKA whereas taking an SGLT2. Different components embody excessive alcohol use, illicit medicine, viral or bacterial an infection, vomiting, insulin pump or infusion web site failure. 

“Any affected person with kind 1 diabetes that takes an SGLT2 is in danger for DKA,” explains Hutter. 

Use With Warning

SGLT2 inhibitors supply fantastic advantages for folks with kind 2 diabetes. However these highly effective drugs needs to be approached with information and warning. In case you have kind 1 diabetes, or for those who eat a low-carb or ketogenic weight loss program, the analysis suggests taking an SGLT2 remedy might be harmful.