Long-Term Safety and Efficacy of Empagliflozin, Sitagliptin, and Metformin

Abstract

OBJECTIVETo investigate the long-term safety and efficacy of empagliflozin, a sodium glucose cotransporter 2 inhibitor; sitagliptin; and metformin in patients with type 2 diabetes.RESEARCH DESIGN AND METHODSIn this randomized, open-label, 78-week extension study of two 12-week, blinded, dose-finding studies of empagliflozin (monotherapy and add-on to metformin) with open-label comparators, 272 patients received 10 mg empagliflozin (166 as add-on to metformin), 275 received 25 mg empagliflozin (166 as add-on to metformin), 56 patients received metformin, and 56 patients received sitagliptin as add-on to metformin.RESULTSChanges from baseline in HbA1c at week 90 were −0.34 to −0.63% (−3.7 to −6.9 mmol/mol) with empagliflozin, −0.56% (−6.1 mmol/mol) with metformin, and −0.40% (−4.4 mmol/mol) with sitagliptin. Changes from baseline in weight at week 90 were −2.2 to −4.0 kg with empagliflozin, −1.3 kg with metformin, and −0.4 kg with sitagliptin. Adverse events (AEs) were reported in 63.2–74.1% of patients on empagliflozin and 69.6% on metformin or sitagliptin; most AEs were mild or moderate in intensity. Hypoglycemic events were rare in all treatment groups, and none required assistance. AEs consistent with genital infections were reported in 3.0–5.5% of patients on empagliflozin, 1.8% on metformin, and none on sitagliptin. AEs consistent with urinary tract infections were reported in 3.8–12.7% of patients on empagliflozin, 3.6% on metformin, and 12.5% on sitagliptin.CONCLUSIONSLong-term empagliflozin treatment provided sustained glycemic and weight control and was well tolerated with a low risk of hypoglycemia in patients with type 2 diabetes.

Novel Agents for the Treatment of Type 2 Diabetes

“…By comparison, the efficacy of canagliflozin is modestly reduced in patients with an estimated GFR of 45-60 ml/min/1.73 m 2 and is not approved with an estimated GFR < 45 ml/min/173 m 2 . E mp a g l i f loz i n ( B o eh r i n ge r Ingelheim/Eli Lilly) will be reviewed by the FDA in the first quarter of 2014, and, because of efficacy similar to canagliflozin and dapagliflozin and a paucity of side effects, 80,81 the FDA has waived review by an Endocrine Advisory Committee. Other SGLT-2 inhibitors in phase 2-3 trials include tofogliflozin (Chugai), ipragliflozin (Astellas), luseogliflozin (Taisho), and ertugliflozin (Pfizer/Merck).…”

Metabolic consequences of acute and chronic empagliflozin administration in treatment-naive and metformin pretreated patients with type 2 diabetes

“…For this reason, SGLT2 inhibitors can be used in association with other antihyperglycaemic agents including dipeptidyl peptidase 4 inhibitors, metformin and insulin [14][15][16]. In particular, empagliflozin as add-on to metformin has been shown to improve HbA 1c and fasting plasma glucose levels for up to 78 weeks [17][18][19].…”

Empagliflozin as Add-On to Metformin in Patients With Type 2 Diabetes: A 24-Week, Randomized, Double-Blind, Placebo-Controlled Trial

“…In phase II trials, treatment with empagliflozin as an add-on to metformin therapy was shown to be well-tolerated, with low rates of hypoglycemia, and to lead to significant reductions in HbA 1c and body weight that were maintained over 90 weeks (13,14). Phase III trials have demonstrated the efficacy and tolerability of empagliflozin over 24 weeks when given as monotherapy, as an addon to therapy with metformin plus sulfonylurea, and as an add-on to therapy with pioglitazone (15)(16)(17).…”