Current Role of Dapagliflozin in Clinical Practice

Dapagliflozin is well studied in type 2 diabetes mellitus and HF and CKD patients with positive results and a good safety profile.

Dapagliflozin was the first drug in a novel class of glucose-lowering agents known as sodium-glucose co-transporter-2 (SGLT2) inhibitors. It was initially approved to manage type 2 diabetes as an adjunct therapy to diet and exercise. Dapagliflozin was also shown to reduce the risk of hospitalization for heart failure in adults with type 2 diabetes. It has recently been approved to reduce the risk of cardiovascular death in adults with heart failure with reduced ejection fraction (NYHA class II-IV). In addition, dapagliflozin is approved by USFDA to reduce the risk of HF in adults with type 2 diabetes and established CVD or multiple CV risk factors.

SGLT2 inhibitors have a novel mechanism of action compared with other medication classes available to treat type 2 diabetes mellitus. Dapagliflozin inhibits SGLT2 in the kidneys, reducing glucose reabsorption in the proximal convoluted tubule and increasing glucose excretion in the urine. They also act independently of pancreatic β cell function. This means as cell function decreases, SGLT2 inhibitors will not lose potency. They also do not inhibit natural insulin or glucose production in episodes of hypoglycemia, reducing the risk of occurrence. The SGLT2 inhibitor’s mechanism of action is complementary to other antidiabetic agents and insulin therapy, resulting in an effective adjunctive therapy option. 

Dapagliflozin has been studied as monotherapy combined with other antidiabetic agents such as metformin, pioglitazone, sulfonylureas, GLP-1 receptor agonists, and insulin therapy. Treatment with dapagliflozin, whether as monotherapy or combination therapy, has produced significant improvements in HbA1c from baseline. The reduction was seen across all subgroups, including gender, age, and BMI. “In a 24-week parallel-group, double-blind, placebo-controlled study, patients with a mean HbA1c of 7–10 % (n = 485), dapagliflozin significantly improved glycemic control with mean HbA1c changes of −0.23, −0.58, −0.77, and −0.89 % with placebo, 2.5, 5, and 10 mg dapagliflozin, respectively” (Ferranninni et al., 2010).

Dapagliflozin is also a well-tolerated medication with few side effects and interactions. Weight reduction is a positive side effect that has been studied with SGLT2 inhibitors. “Initial weight loss may be due to the osmotic diuretic effect of treatment. Nevertheless, sustained weight loss over the subsequent weeks is a consequence of caloric loss due to glycosuria” (Zargar et al., 2021). Additionally, patients treated with SGLT2 inhibitors have shown to have a noticeable reduction in systolic blood pressure. Chronic osmotic diuresis due to glycosuria results in an increase of urine output by 100-400ml per 24 hours. This decrease in the volume of fluid retained has a positive effect on blood pressure. However, due to excess glucose in the urine, patients who take any SGLT2 inhibitor are prone to UTIs. “Numerous placebo-controlled trials have stated that genital and urinary tract infections were more common with dapagliflozin when compared to placebo (genital infection 4.1–5.7 % vs. 0.9 %; UTI 3.6–5.7 % vs. 3.7 %). Similar findings were reported from other SGLT2Is” (Zargar et al., 2021). There are also some concerns about an increased risk of diabetic ketoacidosis. Therefore, the patient’s physician should consider patient history before beginning therapy for patients who have factors predisposing them to diabetic ketoacidosis. Dapagliflozin provides an essential option for managing a broad patient population, regardless of CVD history, due to its promising anti-hyperglycemic, cardioprotective, and possibly renal protective properties and generally favorable tolerability profile.

Practice Pearls:

• Dapagliflozin can be used as monotherapy or adjunct therapy due to its novel mechanism of action.
• SGLT2 inhibitors have positive impacts on blood glucose and BMI, blood pressure, and CV risk.
• Dapagliflozin is well tolerated and has proven effective in all patients regardless of gender, age, BMI, etc.

Ferranninni E, Ramos SJ, Dapagliflozin monotherapy in type 2 diabetic patients with inadequate glycemic control by diet and exercise: a randomized, double-blind, placebo-controlled, phase III trial. Diabetes Care 2010;

Zargar AH, Trailokya AA, Ghag S, Pawar R, Aiwale A, Zalke A. Current Role of Dapagliflozin in Clinical Practice. J Assoc Physicians India. 2021 Sep;69(9):11-12. PMID: 34585897.

Grace Behr, PharmD/MBA Candidate, Creighton University