SGLT2 inhibitors are a family of type 2 diabetes medicines that work in an unusual way: instead of pushing the body to release more insulin, they make the kidneys let go of some excess sugar, which then leaves the body in urine. The surprise that rewrote medical guidelines over the past decade is that their biggest benefits barely show up in the blood sugar number at all. They show up in the heart and the kidneys. Judge these drugs by your HbA1c alone and you are reading the wrong scoreboard.
This article explains what SGLT2 inhibitors are, why the American Diabetes Association recommends them for people with heart failure and kidney disease even where their sugar-lowering effect fades, who needs to be careful with them, and why that caution applies with particular force to anyone on a very low-carb or ketogenic diet. It is educational, and it does not replace your doctor's judgement.
What are SGLT2 inhibitors, and how do they work?
Your kidneys filter blood constantly, and along with water and salts, glucose passes into the early urine. Normally the body takes almost all of that glucose back, using a transporter protein in the kidney called SGLT2. These drugs block that transporter, so some glucose stays in the urine and leaves the body. Cleveland Clinic describes them as helping "your kidneys remove extra glucose through your pee."
The best-known members of the family include:
- Empagliflozin (sold as Jardiance).
- Dapagliflozin (sold as Forxiga, or Farxiga in the US).
- Canagliflozin.
- Ertugliflozin.
Cleveland Clinic notes that these drugs are not a treatment for type 1 diabetes, and that common side effects include peeing more, dizziness and genital yeast infections. We come back to those in detail below.
Why isn't the benefit of SGLT2 inhibitors measured in HbA1c?
Diabetes drugs have traditionally been judged on one number: how far do they lower HbA1c? On that measure, SGLT2 inhibitors look modest. The large outcome trials showed that this measure misses the most important part of their story. That is the idea this whole article turns on: the scoreboard we are used to reading is not where this drug records its biggest wins.
Evidence one: the EMPA-REG OUTCOME trial (2015)
The trial enrolled 7,028 people with type 2 diabetes and established cardiovascular disease and followed them for about 3.1 years. According to the American College of Cardiology's (ACC) summary of the study, published in the New England Journal of Medicine:
HbA1c difference versus placebo at 12 weeks: only about 0.5 to 0.6 percentage points.
Cardiovascular death: 3.7% on empagliflozin versus 5.9% on placebo.
Hospitalization for heart failure: 2.7% versus 4.1%.
Death from any cause: 3.8% versus 5.1%.
A modest drop in blood sugar, set against a striking drop in cardiovascular death. That gap between the two numbers is what made doctors ask: if the sugar barely moved, what protected the heart? Researchers still debate the exact mechanism, but it was the clinical result that changed the guidelines.
Evidence two: DAPA-HF (2019), in people without diabetes
If the benefit ran only through lower blood sugar, people with normal blood sugar should not gain much. Yet DAPA-HF enrolled 4,744 patients with heart failure and reduced pumping strength, and only 42% of them had type 2 diabetes. According to the American Heart Association's trial details, the risk of the main outcome (worsening heart failure or cardiovascular death) fell by almost the same amount in both groups:
Patients with diabetes: hazard ratio 0.75.
Patients without diabetes: hazard ratio 0.73.
In other words, people who had no need for sugar-lowering benefited just as much. The ACC described the reductions as "substantial, clinically important, and consistent in patients with and without type 2 diabetes."
Evidence three: the kidney that no longer lowers sugar, yet still benefits
This is the clearest sign that the benefit does not run through glucose alone. As the kidneys weaken, they filter less glucose, so the drug's effect on blood sugar fades. The American Diabetes Association's guidance on managing kidney disease in diabetes, built on its Standards of Care 2026, states that the "glucose-lowering efficacy of SGLT2i is diminished at lower eGFR." Yet the same document recommends starting the drug if the estimated glomerular filtration rate (eGFR) is 20 or above, and continuing it until dialysis or transplant.
Why give a weakened kidney a drug that no longer lowers sugar much? Because the goal is to protect the kidney itself. In EMPA-KIDNEY, which enrolled 6,609 people with chronic kidney disease, kidney disease progression or cardiovascular death occurred in 13.1% of the empagliflozin group versus 16.9% on placebo, a 28% lower risk, and the benefit held in people with and without diabetes, according to the ACC's summary.
The two tests that decide whether you are a candidate for that protection are the urine albumin-to-creatinine ratio and the eGFR. If you have diabetes and have never been told your results for both, that is worth asking about at your next visit.
What do the guidelines say about SGLT2 inhibitors?
According to the ACC's key points from the American Diabetes Association's 2023 Standards on cardiovascular disease, people with type 2 diabetes and heart failure, whether with reduced or preserved pumping strength, are recommended an SGLT2 inhibitor with proven benefit in reducing worsening heart failure or cardiovascular death. In diabetic kidney disease, one is recommended for people with an eGFR of 20 or above.
What stands out is that these recommendations are tied to the state of the heart and kidneys, not to the HbA1c. In practice, a person whose diabetes is "well controlled" may still be a candidate if they have heart failure or kidney disease. The decision belongs to your doctor, who weighs benefit against risk in your particular case.
What does Saudi data show? The gap is in the diagnosis, not the prescription
In a 2026 study in the journal Pharmaceuticals, Ibrahim Alhomoud and Khalid Alamer reviewed the records of older adults (65 and over) at King Fahad University Hospital in Khobar between 2019 and 2023. Out of 14,146 older outpatients, they found 223 with type 2 diabetes plus documented cardiovascular disease, heart failure or kidney disease, meaning guideline-eligible for these drugs or for GLP-1 medicines.
Among those documented, eligible patients, 83.4% had been prescribed one of the two classes. That is a good rate.
But the authors located the bigger problem upstream of the prescription: in "gaps in the recognition of cardiometabolic comorbidities" and in incomplete documentation. A doctor will not prescribe a heart- or kidney-protecting drug if the heart or kidney disease is not in the file to begin with. They also found lower odds of treatment among older patients, women and unmarried patients.
In fairness, the authors list their limits: one centre, older adults only, two drug classes pooled, and a period likely affected by COVID-19. So we do not present these numbers as a picture of the whole Kingdom. The practical lesson is still clear: having it written in your file that your heart or kidneys are affected may matter more than any sugar reading. Ask your doctor whether you have had a urine albumin test and a kidney-function estimate, and whether anything calls for a heart assessment.
What are the side effects of SGLT2 inhibitors?
A drug that sends sugar into the urine comes with a price, and knowing it is part of using it safely. The main points:
"Euglycemic" ketoacidosis
In 2015 the US Food and Drug Administration (FDA) revised the labels of these drugs after identifying 73 cases of ketoacidosis that needed hospital or emergency care. The key line in its warning: ketoacidosis with these drugs "can occur even if the blood sugar level is not very high." That is why some cases were diagnosed late, because the glucose reading did not look alarming.
The FDA listed risk factors including infection, a low-carbohydrate diet or reduced calorie intake, reducing or stopping insulin, and alcohol use.
Genital and urinary infections
Sugar in the urine is a friendly environment for yeast. A 2025 review in the Cleveland Clinic Journal of Medicine reports that these drugs raise the risk of genital infections "3 to 5 times relative to placebo or active comparators." In EMPA-REG the rates were 6.4% versus 1.8%. The review advises good personal hygiene and adequate fluid intake.
Dehydration and low blood pressure
Because the drug takes water out along with sugar, it can cause dehydration, low blood pressure and dizziness, especially alongside diuretics or blood-pressure medicines, and in summer heat.
Before surgery
Following a 2020 FDA update, doctors should consider stopping canagliflozin, dapagliflozin and empagliflozin at least three days before scheduled surgery, and ertugliflozin at least four days before. Always tell your surgeon and anaesthetist that you take one of these drugs.
Do SGLT2 inhibitors conflict with a keto diet?
This section is written for many of our own readers, and we are writing it plainly even though it concerns the very eating pattern our products serve. The sources list low-carb eating among the ketoacidosis risk factors for these drugs, and they do not agree on how cautious to be:
US FDA: lists a low-carbohydrate diet and reduced calorie intake among the risk factors.
AACE/ACE position statement, as quoted by the canagliflozin manufacturer's medical information service: patients on these drugs "should avoid very-low carbohydrate/ketogenic diets."
Cleveland Clinic review, 2025: treats a ketogenic diet as a higher risk when it is a chronic pattern, and suggests considering continuing the drug with close monitoring rather than stopping it.
The last two differ in strength, and we take the more cautious side, even though it cuts against our own interest: if you take an SGLT2 inhibitor, do not start a strict keto diet or cut carbohydrates sharply on your own. Talk to your doctor first. They may judge that a moderate cut in sugar and white flour suits you, or they may need to adjust your medicines or your monitoring. The same review lists fasting among the triggers for this kind of ketoacidosis, which is also worth discussing with your doctor before any prolonged fast.
When should you get medical help right away?
The FDA advises stopping the drug and seeking medical care immediately if signs of ketoacidosis appear, even if your blood sugar reading is normal or near normal:
- Nausea or repeated vomiting.
- Abdominal pain.
- Unusual tiredness.
- Trouble breathing or fast breathing.
- Extreme thirst or confusion, as Cleveland Clinic also lists.
- Signs of a serious urinary infection: burning, fever, lower-abdominal or back pain, or blood in the urine.
If you can, check ketones in your urine or blood, but do not delay going to the emergency department while you wait for the result.
Who should be careful?
Talk to your doctor before starting or continuing if you:
Follow a keto or very low-carb diet, or plan a long fast.
Take insulin or insulin-releasing tablets: the combination can raise the risk of low blood sugar, and cutting insulin too quickly can raise the risk of ketoacidosis.
Take diuretics or blood-pressure medicines, or work in the heat.
Get frequent urinary or genital infections.
Are going to have surgery or a procedure.
Are pregnant or planning a pregnancy: Cleveland Clinic says you should not take this medication in that case.
Important: This article is for education only. Never start, stop or change the dose of any medicine without speaking to your doctor or pharmacist.
Where do Bakery 8's products fit into this?
Let us be clear: no bread or dessert, from our bakery or anyone else's, protects the heart or kidneys the way these drugs did in the trials. What Bakery 8 (مخبز ثمانية) in Riyadh offers is something different: sugar-free, low-carb alternatives that help people who want less sugar and white flour in their day, as part of a plan agreed with their doctor.
And precisely because our products are low-carb, we wrote the keto section above as plainly as we did. If you take an SGLT2 inhibitor, ask your doctor how much carbohydrate is right for you first. After that, some of our products can be part of a balanced routine:
- Bread: samoli and toast made with almond flour instead of white flour.
- Granola: an alternative to sweetened breakfast cereals.
- Crackers: a snack in place of crisps and sweet biscuits.
Remember too that people with diabetes are more vulnerable to flu complications, and infection is itself a ketoacidosis trigger with these drugs. See our article on the seasonal flu vaccine.
Frequently asked questions about SGLT2 inhibitors
Are SGLT2 inhibitors used in people without diabetes?
Yes, in specific conditions. In DAPA-HF, heart failure patients without diabetes benefited about as much as those with it, and in EMPA-KIDNEY the kidney benefit held in people with and without diabetes. Whether the drug suits you is a medical decision based on your diagnosis and test results, not a way to lower sugar or weight on request.
Why would my doctor prescribe one when my diabetes is controlled?
Because for people with type 2 diabetes, guidelines tie the recommendation to heart failure or kidney disease, not only to the HbA1c. The aim may be protecting the heart or kidneys, a benefit no sugar test measures. Ask your doctor directly why it was prescribed and what it is expected to protect.
What is euglycemic ketoacidosis?
It is a dangerous ketoacidosis that happens while the blood sugar reading is not very high, which is why it can be missed. The FDA has warned about it with these drugs; risk factors include infection, low-carb eating, reduced calorie intake and reduced insulin. Symptoms are nausea, vomiting, abdominal pain, tiredness and trouble breathing, and it needs emergency care.
Can I combine an SGLT2 inhibitor with a keto diet?
The sources disagree. The AACE/ACE statement advises avoiding very-low-carbohydrate diets with these drugs, while a 2025 Cleveland Clinic review suggests continuing with close monitoring for people whose diet is a long-term pattern. The safe position: do not start keto while on the drug without your doctor's approval and follow-up.
When should an SGLT2 inhibitor be paused?
Your doctor decides, but the sources describe common situations: three to four days before scheduled surgery depending on the drug, and during acute illness with vomiting, severe dehydration or inability to eat and drink. If signs of ketoacidosis appear, stop it and go to the emergency department immediately.
The bottom line
SGLT2 inhibitors are a rare case of a drug designed to lower blood sugar whose most important work turned out to happen somewhere else: in the heart and kidneys. So don't judge the drug, or your need for it, by the HbA1c alone. Know the state of your heart and kidneys, make sure it is recorded in your file, learn the danger signs, and don't pair this drug with a strict keto diet without your doctor. When you and your doctor decide to cut back on sugar and white flour, Bakery 8 has sugar-free, low-carb options that make that change easier and more delicious.
References
- Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes (EMPA-REG OUTCOME). N Engl J Med. 2015;373:2117-28. Trial summary: American College of Cardiology.
- McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction (DAPA-HF). N Engl J Med. 2019. Trial details: American Heart Association Professional; American College of Cardiology.
- Herrington WG, Staplin N, Wanner C, et al. Empagliflozin in Patients with Chronic Kidney Disease (EMPA-KIDNEY). N Engl J Med. 2023;388:117-27. Trial summary: American College of Cardiology.
- American Diabetes Association. Management of Chronic Kidney Disease in People with Diabetes (based on Standards of Care in Diabetes—2026).
- ElSayed NA, Aleppo G, Aroda VR, et al. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023. Diabetes Care. 2023;46(Suppl 1). Key points: American College of Cardiology.
- U.S. Food and Drug Administration. FDA Drug Safety Communication: FDA revises labels of SGLT2 inhibitors for diabetes to include warnings about too much acid in the blood and serious urinary tract infections. 2015 (updated 2020 and 2022).
- Kodur N, Sharew B, Lansang MC, Tang WHW. Managing the side effects of sodium-glucose cotransporter-2 inhibitors. Cleveland Clinic Journal of Medicine. 2025;92(8):503-511.
- Cleveland Clinic. SGLT2 Inhibitors. 2025.
- Alhomoud IS, Alamer KA. Real-World Prescribing Patterns of SGLT2 Inhibitors and GLP-1 Receptor Agonists in Older Adults with Type 2 Diabetes and Cardiometabolic Disease. Pharmaceuticals. 2026;19(1):9.
- Janssen Medical Information. Use of INVOKANA in Patients on Special Diets (a manufacturer source, cited only to relay the AACE/ACE statement).
Related keywords: SGLT2 inhibitors, Jardiance, Forxiga, empagliflozin, dapagliflozin, sugar in urine, euglycemic DKA, heart failure and diabetes, kidney disease and diabetes, keto and diabetes medication.