Ertugliflozin improves glycaemic outcomes in T2D
The addition of the sodium-glucose cotransporter-2 inhibitor ertugliflozin to metformin improved glycaemic control, body weight, and blood pressure (BP) in patients with inadequately controlled type 2 diabetes (T2D), according to the results of the VERTIS MET* trial presented at ADA 2018.
A total of 621 patients (mean age 56.6 years, 41.1 percent post-menopausal women) with T2D on metformin (≥1,500 mg/day ≥8 weeks) were randomized 1:1:1 to receive ertugliflozin 5 or 15 mg or placebo for 26 weeks. Participants exceeding fasting plasma glucose (FPG) thresholds (11.1 percent, 10.7 percent, and 24.4 percent, respectively) received glimepiride for glycaemic rescue therapy, following which, ertugliflozin recipients continued to receive ertugliflozin, while nonrescued placebo recipients received glimepiride for 78 weeks. [ADA 2018, abstract 1129-P]
At week 104, both ertugliflozin 5 and 15 mg reduced A1C levels (least squares [LS] mean -0.5 percent and -0.8 percent), FPG (LS mean, -17.0 and -26.7 mg/dL), body weight (LS mean, -3.6 vs -3.5 kg), and BP (LS mean, -3.9 and -2.8 mm Hg [systolic] and LS mean, -2.3 and -1.2 mm Hg [diastolic]). The proportion of ertugliflozin 5 and 15 mg recipients achieving A1C <7 percent were 27.1 percent and 36.6 percent, respectively.
Compared with placebo, ertugliflozin 5 and 15 mg reduced symptomatic hypoglycaemia (5.8 percent; p=0.009 and 5.9 percent; p=0.009 vs 13.4 percent). However, the incidence of female genital mycotic infections was significantly higher among ertugliflozin 5 and 15 mg recipients vs those receiving placebo/glimepiride (7.3 percent; p=0.017 and 9.8 percent; p=0.003 vs 0.9 percent).
Nonetheless, the findings suggest that the ertugliflozin-metformin combination was generally well-tolerated and provided effective glycaemic control, noted the researchers.
Adverse ortho, renal outcomes
Adverse orthopaedic and renal outcomes with ertugliflozin were evaluated in a pooled analysis involving 4,859 patients (mean age 57.8 years, 51.8 percent male, mean A1C 8.2 percent) receiving ertugliflozin 5 or 15 mg (n=1,716 and 1,693, respectively) or placebo, glimepiride, or sitagliptin (n=1,450) for up to 2 years. Approximately 12 percent had moderate renal impairment (eGFR <60 mL/min/1.73 m2). [ADA 2018, abstracts 1145-P and 1168-P]
The incidence of adjudication-confirmed fractures was similar across all groups (0.5 percent for ertugliflozin 5 mg, 0.5 percent for ertugliflozin 15 mg, and 0.6 percent for non-ertugliflozin-treated patients).
Serum calcium did not change across all groups at week 26. However, there were small mean increases in serum magnesium (0.13 vs -0.02 mEq/L) and phosphate (0.23 vs 0.04 mg/dL) in both ertugliflozin arms vs the placebo arm.
There was also a low incidence of adverse renal outcomes across all groups (0.6 percent and 0.8 percent for ertugliflozin 5 and 15 mg, respectively, and 0.4 percent for non-ertugliflozin recipients).
Subgroup analyses involving patients with moderate renal impairment found that adverse renal outcomes were more frequent among ertugliflozin vs non-ertugliflozin recipients (3.6 percent and 2.1 percent for ertugliflozin 5 and 15 mg, respectively, vs 1.1 percent).
The findings of the pooled analysis suggest that ertugliflozin does not increase the risk of fractures nor does it lead to clinically significant alterations in bone mineral density or bone biomarkers, said the researchers. Despite the incidence of adverse effects in moderate renal impairment, ertugliflozin generally exhibited a favourable tolerability profile in terms of renal outcomes, they added.