Chapter 16: SGLT2 Inhibitors And Diabetes!
SGLT2 inhibitors and the reason for hope in the metabolically challenged individuals!
At 3 am, I suddenly woke up and started thinking about heart disease and sudden death in the younger South Asian population. I want to research modern medicines that are making significant progress and can be considered modern miracles. As the world transitions from being undernourished to overnourished, there's a rise in metabolic diseases globally. I believe that impaired glucose might have played a role in my own significant coronary event at a younger age.
Insulin: Discovered in 1921 by Frederick Banting and Charles Best, insulin is essential in treating Diabetes. Penicillin: Discovered in 1928 by Alexander Fleming, penicillin was the first antibiotic that revolutionized treating bacterial infections. Oral contraceptives: Introduced in the 1960s, oral contraceptives have had a profound impact on reproductive rights and women's health. Statins: Developed in the 1980s to lower cholesterol levels and reduce the risk of heart disease. Antiretroviral therapy: Developed in the 1990s, antiretroviral therapy has dramatically improved the prognosis for people with the disease. And now SGLT2 inhibitors in the treatment of Diabetes Mellitus.
The name sounds Greek and Latin for an unscientific eye. But don't worry! I will do my best to explain how to understand this new class of modern miracle drugs. These medications raise awareness of the potential reversal of prediabetes in a world filled with carbohydrate overload. Let's delve into this.
SGLT2 inhibitors were first discovered by a team of researchers at the University of Tokyo led by Dr. Takashi Kashiwagi. In the late 1990s, they investigated glucose transport mechanisms in the kidney and identified sodium-glucose cotransporter 2 (SGLT2) as a potential target for diabetes treatment. This discovery eventually led to developing the first SGLT2 inhibitor drug, Canagliflozin, approved for use in the United States in 2013. So, what are SGLT2 inhibitors?
SGLT2 inhibitors…
SGLT2 or Sodium-glucose cotransporter 2 inhibitors are the newer medications for treating diabetes mellitus. They work acting on the SGLT-2 (Sodium-glucose co-transporter 2 ) proteins expressed in the renal proximal convoluted tubules to reduce the reabsorption of filtered glucose, decrease the renal threshold for glucose (RTG), and promote urinary glucose excretion. SGLT2 inhibitors can promote weight loss and help manage adult patients with type 2 diabetes mellitus (DM) to improve glycemic control and reduce cardiovascular and renal complications.
Additionally, they can lower blood pressure and reduce the risk of cardiovascular events. Examples of SGLT2 inhibitors include Canagliflozin, Dapagliflozin, and Empagliflozin and Ertugliflozin. They are typically taken once daily in pill form. It's important to note that SGLT2 inhibitors are not recommended for people with type 1 diabetes, as they work by targeting the kidneys and require some residual insulin production.
SGLT2 Inhibitors and Proteinuria
CREDENCE trial found that treatment with SGLT2 inhibitors was associated with a significant reduction in the risk of kidney failure and cardiovascular events and a decrease in proteinuria. Similarly, a study published in the Journal of the American Society of Nephrology in 2017 found that treatment with the SGLT2 inhibitor empagliflozin significantly reduced proteinuria in people with type 2 diabetes and kidney disease.
SGLT2 and Prediabetes…
A randomized controlled trial published in the New England Journal of Medicine in 2019 found that treatment with the SGLT2 inhibitor dapagliflozin was associated with a lower incidence of type 2 diabetes among people with prediabetes and cardiovascular risk factors. Another study published in Diabetes Care in 2018 found that treatment with empagliflozin improved glucose tolerance and insulin sensitivity in people with prediabetes and obesity.
SGLT2 Inhibitors and Diabetes…
SGLT2 significantly improved blood sugars lowered HbA1c, and enhanced beta cell function in people with type 2 diabetes. In a 2016 diabetes care study, beta cell function significantly improved in people with type 2 diabetes. Another study, Diabetes, Obesity, and Metabolism, showed substantial improvements in beta cell function and insulin sensitivitycompared to placebo.
SGLT2 inhibitors and Blood Pressure…
SGLT2 affects blood pressure by increasing the removal of blood sugars; with blood sugars, the sodium also gets removed, which in return improves blood pressure. In JASN in 2019, these drugs improved systolic and diastolic blood pressure. In another study, Diabetes, Obesity, and Metabolism in 2019, empagliflozin significantly reduced blood pressure levels and improved blood sugar control, body weight, and other cardiovascular risk factors. A meta-analysis published in the Journal of Hypertension in 2018 looked at the effects of SGLT2 inhibitors on blood pressure in people with type 2 diabetes. The analysis found that treatment with SGLT2 inhibitors was associated with a significant reduction in both systolic and diastolic blood pressure.
SGLT2 inhibitors and heart disease…
EMPA-REG Trial in asians: The trial found that treatment with empagliflozin was associated with a significant reduction in the risk of major adverse cardiovascular events (including heart attacks) in asians compared to placebo. CANVAS and DECLARE-TIMI 58 trials have also demonstrated significant reductions in the risk of major cardiovascular events (including heart attacks) with the use of SGLT2 inhibitors in people with type 2 diabetes and high cardiovascular risk. DAPA-HF trial, which investigated the effects of dapagliflozin in people with heart failure with reduced ejection fraction, a type of heart failure in which the heart does not pump blood effectively. The trial found that treatment with dapagliflozin significantly reduced the risk of cardiovascular death or hospitalization for heart failure compared to placebo. EMPEROR-Reduced investigated the effects of empagliflozin in people with heart failure with reduced ejection fraction. The trial found that treatment with empagliflozin significantly reduced the risk of cardiovascular death or hospitalization for heart failurecompared to placebo.
Side Effects…
As with any medications, SGLT2 inhibitors have side effects; they include an increased risk of Urinary tract infections around 5-6%, Genital yeast infections, Dehydration, Low blood pressure, Increased risk of acidosis, and increased risk of bone fractures. Higher risk of urinary infections due to the action of the medication in the kidneys to pump the sugars through the urine; hence, urinary sugars breed bacteria. Hygiene and staying hydrated are the keys while on these medications.
Conclusion…
This newer medication generation does show significant promise in the coming decade. Our lifestyles are changed forever, as we keep saying AI will take over, just like we see computers take over jobs. However, the inactivity and use of technology only skyrocketed in the coming decades. So is the obesity and metabolic disease. There are more overweight individuals than average weight in any state in this country. Modern medicine is the key, especially SGLT2, which fits correctly in the world of overabundance and overindulgence. As I write this, I slur the smoothie. Now, this drug has been added to the carbohydrate overload antidote regimen. One drug that can lower blood sugars, blood pressure, cholesterol, inflammation, lower heart disease, and reverse prediabetes or repair metabolic pathways.
Suman Manchireddy MD FACP FHM, Internal Medicine, Leesburg, VA.
Email : Sumanm@ReliantMD.com
Disclaimer: This is purely informational and educational purposes only, seek medical advise prior to starting any testing or treatment regimen. The data presented here is researched extensively and has been condensed for a broader audience.