Dr. Plodkowski is a former chief of endocrinology and Dr. Nguyen was an endocrinologist at the VA Sierra Nevada Health Care System in Reno. Dr. Plodkowski, Dr. McGarvey, and Dr. Huribal are endocrinologists in the Division of Endocrinology, and Dr. McGarvey is also the associate program director of the Endocrinology Fellowship, all at Scripps Clinic in San Diego. Dr. Nguyen is the medical director of Las Vegas Endocrinology and an adjunct associate professor of medicine at Touro University Nevada College of Osteopathic Medicine, both in Nevada, and a clinical associate professor of clinical education at Arizona College of Osteopathic Medicine in Glendale, California. Mr. Reisinger-Kindle and Mr. Kramer are medical students at Touro University Nevada College of Osteopathic Medicine. Dr. Solomon is a senior medical resident at Valley Hospital Medical Center/Touro University.
References
Empaglifilozin
Empagliflozin is the most recently FDA-approved SGLT2 inhibitor (August 2014) for improved glycemic control in T2DM. It has the highest SGLT2 selectivity: > 2,500-fold selectivity for SGLT2 over SGLT1. 13 Empagliflozin regulates blood glucose levels by increased UGE, independent of endogenous insulin secretion. It is associated with modest reductions in body weight, visceral adiposity, and systolic BP.
Empagliflozin is available in 10-mg and 25-mg tablets, with a recommended initial dose of 10 mg daily. 13 Dosing adjustments are not required for geriatric patients or for those patients with hepatic impairment. 14 The use of empagliflozin is contraindicated in patients with eGFR < 45 mL/min/1.73 m 2 or for those whose eGFR declines to < 45 mL/min/1.73 m 2 during therapy. 15,16 Empagliflozin has a pregnancy risk category C. Drug transference during lactation is unknown; therefore, empagliflozin during breast-feeding is not recommended. It is also available in a fixed-dose combination with metformin.
Empagliflozin has been studied alone and in combination therapy with other oral antidiabetic drugs as well as insulin therapy. Metformin, pioglitazone, sitagliptin, and linagliptin have been studied in combination with empagliflozin with sustained glycemic improvement without significantly increased risk of hypoglycemia. 17-21 Empagliflozin/linagliptin combination was recently approved after phase 3 trials demonstrated 62% of patients achieved an A 1c value < 7% on the 25/5-mg dose at 24 weeks. 21 Empagliflozin, coadministered with multiple daily injections of insulin (MDI), has been shown to safely improve glycemic control and reduce total daily insulin requirements without an increased risk of hypoglycemia. 22 Currently, it is not approved for use in patients with T1DM, but phase 3 trials are ongoing.
Pharmacokinetics of empagliflozin among healthy volunteers paralleled those of people with T2DM with rapid absorption. The plasma glucose lowering effect of empagliflozin was evident after the first dose and became more pronounced with treatment duration. The AUC and C max were dose-proportional over a range of empagliflozin doses in a single rising dose study, with maximum UGE of 90.8 g in healthy volunteers reached at the 400-mg dose. 23 The T max was 1.5 to 2.1 hours after dosing, comparable to dapagliflozin. 24 Steady state with once-daily dosing is reached by day 5 with t1/2 range of 10 to 19 hours. 24-27 Plasma levels of empagliflozin declined in a biphasic pattern, with a rapid distribution phase and a slower elimination phase. Total urine volume did not differ significantly in the empagliflozin group compared with placebo.
Healthy subjects treated with placebo or empagliflozin had comparable plasma glucose concentrations. Patients with T2DM demonstrated a decrease in mean daily glucose of -37.0 mg/dL for the 10-mg dose compared with -13.5 mg/dL for placebo. Doses up to 10 mg were found to inhibit renal tubular reabsorption up to 40%, and higher doses inhibit up to 60% of filtered glucose. 22-26 Empagliflozin has been shown to have similar efficacy independent of food. 27 The pharmacodynamic response declines with increasing renal impairment in SGLT2 inhibitors. Empagliflozin has been associated with a decline from UGE of 97.6 g in normal renal function to 18.2 g in severe renal impairment.
