Agent one: Canagliflozin
Canagliflozin is an effective therapy for type 2 diabetes when used with a nutritious diet and consistent physical activity. Patients who have type 2 diabetes and other cardiovascular complications, such as heart disease or blood vessel disease, take it to lower their risk of experiencing a heart attack, stroke, or death at an earlier age. The kidneys’ capacity to absorb sugar is diminished due to this drug decreasing the sugar in the blood.
Canagliflozin is effective because it inhibits the SGLT-2 transporter. The transporter facilitates glucose reabsorption in the kidney. When it is blocked, glucose is flushed out of the body via the urine, decreasing blood sugar levels. It has also shown promise in managing type 2 diabetes, reducing cholesterol and triglyceride levels more effectively than other medications. Canagliflozin has also demonstrated promise in lowering cholesterol, triglycerides, and LDL cholesterol levels. That is accomplished via several techniques. Simply put, it promotes the movement of bile acids from the liver back into the digestive tract. The liver then decreases its release of bile acids so that they will not build up in circulation and make it tougher to eliminate toxins from the body. That maintains optimal liver function, which may help reduce triglycerides and other indications of liver health. Canagliflozin’s capacity to stimulate weight reduction and reduce blood sugar levels in obese people is an additional aspect that holds promise. It does this by enhancing pancreatic function and boosting glucagon production. Glucagon is a hormone that encourages the use of carbs for energy rather than fat. This results in a decrease in abdominal fat, which, over time, may drastically lower blood sugar levels.
Compared to the placebo, 100 and 300 mg of canagliflozin lower glycated hemoglobin (HbA1c) by 0.6% and 0.8%, respectively. Compared to dipeptidyl peptidase-4 (DPP-4) inhibitors, it appears to be slightly more effective at lowering HbA1c (Karagiannis et al., 2019). It has a positive effect on body weight and blood pressure compared to placebo and the majority of active comparators. However, adverse events associated with osmotic diuresis and infections of the genital tract are more common in patients taking canagliflozin. In the short term, canagliflozin does not raise mortality risk from any cause or cardiovascular complications. According to economic evaluation studies undertaken in various countries, canagliflozin is a cost-effective option in dual- and triple-agent regimens.
Canagliflozin 100 mg was more effective in lowering hemoglobin A1c than dapagliflozin 5 mg and empagliflozin 10 mg, whereas canagliflozin 300 mg was more effective than all controls. In terms of change in HbA1c from baseline, there were no significant differences between canagliflozin 100 mg and empagliflozin 10 and 25 mg; however, fewer patients achieved an HbA1c of 7% with canagliflozin 100 mg (Perkovic et al., 2019). Canagliflozin was superior to dapagliflozin, nateglinide, and saxagliptin and inferior to insulin glargine for lowering HbA1c when added to metformin monotherapy, according to a network meta-analysis using data for both dosages. In a network meta-analysis of trials with patients on background treatment with metformin and sulfonylureas, canagliflozin was discovered to have comparable glycemic efficacy to dapagliflozin, thiazolidinedione, glucagon-like peptide-1 receptor agonists (GLP-1 RA), saxagliptin, vildagliptin, and insulin.
Agent two: Dapagliflozin
Along with dieting, workout, and other medications, dapagliflozin helps individuals with type 2 diabetes regulate their blood sugar levels. Adults with type 2 diabetes and heart and blood vessel disease, or those with many risk factors for developing heart and blood vessel disease, also benefit from taking this to reduce the possibility of requiring hospitalization for heart failure. Additionally, persons with heart failure are provided dapagliflozin in an attempt to reduce the probability that they may develop cardiovascular problems or die from them. Adults with renal disease take this medication to reduce their risk of suffering a deterioration in their health, being hospitalized due to heart failure, and death from cardiovascular causes (Heerspink et al., 2020). Nonetheless, Dapagliflozin is not used to treat type 1 diabetes or diabetic ketoacidosis.
Dapagliflozin has received the most attention among those recommended for the treatment of type 2 diabetes because of its exceptional properties. A diuretic, such as dapagliflozin, limits salt reabsorption, resulting in increased potassium and water excretion through the kidneys and urine. People with hypertension or heart failure who ingest it may have a decrease in blood pressure due to its capacity to retain salt and water. Furthermore, it reduces the absorption of saturated fat. The medication may induce weight loss in obese people, and it has the potential to help promote weight loss when combined with a low-calorie diet.
People who suffer from type 2 diabetes may take advantage of the therapeutic advantages offered by dapagliflozin. By inhibiting SGLT2, the medication, which is known as a sodium-dependent glucose cotransporter two inhibitor, prevents the kidneys from reabsorbing water and hence decreases water reabsorption (Heerspink et al., 2020). That suggests that dapagliflozin may induce an increase in the amount of urine that is produced, a reduction in the amount of sugar in the blood, and an increase in the amount of weight that is lost. Additionally, it may reduce the levels of glucose in the blood, which in turn may diminish the likelihood of long-term complications connected to diabetes, such as damage to the eyes, kidneys, and nerves. Second, it may assist in the reduction of excess body fat. Considering that being overweight is one of the major risk factors for developing type 2 diabetes, this is particularly beneficial for those who are overweight. Dapagliflozin has also been shown to reduce the risk of cardiovascular events such as heart attack and stroke in those who have type 2 diabetes because of the beneficial impact it has on the levels of glucose in the blood.
In summary, Dapagliflozin is an anti-diabetic drug that inhibits SGLT2 in the kidneys leading to reduced glucose absorption by the kidneys. It is a useful treatment that can be used by patients who cannot take metformin or in combination with other diabetic drugs except pioglitazone. Dapagliflozin may be beneficial for those who are overweight or obese, have type 2 diabetes, and have cardiovascular diseases risk factors such as high blood pressure or high uric acid levels. People with moderate or severe renal impairment, or those who are at risk of excessive fluid loss, should not take the medication. On the negative, the medicine increases the risk of infections of the vaginal and lower urinary tracts; nevertheless, these infections are often mild to moderate in severity and respond well to standard antimicrobial treatment.
Heerspink HJL, Stefánsson BV, Correa-Rotter R, et al.; DAPA-CKD Trial Committees and Investigators. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383(15):1436-1446. doi:10.1056/NEJMoa2024816 https://www.nejm.org/doi/pdf/10.1056/NEJMoa2024816
Perkovic V, Jardine MJ, Neal B, et al.; CREDENCE Trial Investigators. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med. 2019;380(24):2295-2306. doi:10.1056/NEJMoa1811744
Karagiannis, T., Bekiari, E., & Tsapas, A. (2017). Canagliflozin in the treatment of type 2 diabetes: an evidence-based review of its place in therapy. Core Evidence, 12, 1.