Table 2.

The key features of SGLT-2 inhibitors and ketogenic diets, along with the potential advantages and disadvantages of their synergism.

	SGLT-2 Inhibitors	Ketogenic Diets
Characteristics	A class of drugs used to treat T2DM by blocking glucose reabsorption in the kidneys, which leads to increased urinary glucose excretion.	A low-carbohydrate, high-fat diet that forces the body to burn fat for energy instead of carbohydrates. This metabolic state is known as ketosis.
Advantages of Synergy	Improved glycemic control → both lower blood glucose levels, and their combined effect can lead to better glycemic control. Weight loss → a ketogenic diet can lead to significant weight loss, and SGLT-2 inhibitors have been shown to reduce body weight and body fat. Cardiovascular benefits → SGLT-2 inhibitors reduce the risk of cardiovascular events in people with type 2 diabetes, and a ketogenic diet may also improve cardiovascular health. Blood pressure reduction→ both have been shown to reduce BP. Lowered inflammation → a ketogenic diet may reduce inflammation in the body, and SGLT-2 inhibitors have been shown to have anti-inflammatory effects. Neuroprotective effects → a ketogenic diet has been shown to have neuroprotective effects, and SGLT-2 inhibitors may also have neuroprotective effects.
Disadvantages of Synergy	Diabetic ketoacidosis → both SGLT-2 inhibitors and a ketogenic diet increase the risk of DKA in people with T1DM Dehydration → SGLT-2 inhibitors increase urinary glucose excretion, which can lead to dehydration, whereas a ketogenic diet can also lead to dehydration if not properly balanced with adequate fluid and electrolyte intake. Electrolyte imbalance → SGLT-2 inhibitors increase the urinary excretion of Na+ and K+, which can lead to electrolyte imbalances. A ketogenic diet can also affect electrolyte balance if not properly balanced with an adequate intake of Na+, K+, and Mg2+. Hypoglycemia → a ketogenic diet can lead to hypoglycemia in people with type 2 diabetes who are taking medications that lower blood glucose levels, such as insulin or sulfonylureas. SGLT-2 inhibitors can also increase the risk of hypoglycemia when used in combination with other glucose-lowering medications. Gastrointestinal symptoms → a ketogenic diet can cause gastrointestinal symptoms such as nausea, vomiting, and diarrhea. SGLT-2 inhibitors can cause gastrointestinal symptoms such as nausea and diarrhea. Genital infections → SGLT-2 inhibitors can increase the risk of genital infections such as yeast infections and UTIs. A ketogenic diet may also increase the risk of yeast infections due to the high-fat content.

Abbreviations: SGLT-2—sodium–glucose cotransporter-2; T2DM—type 2 diabetes mellitus; BP—blood pressure; DKA—diabetic ketoacidosis; T1DM—type 1 diabetes mellitus; Na⁺—sodium cations; K⁺—potassium cations; Mg²⁺—magnesium cations; UTIs—urinary tract infections.