The following article is part of our coverage of the Endocrine Society’s annual meeting (ENDO 2021) that is being held virtually from March 20-23, 2021. Endocrinology Advisor‘s staff will report on the top research in hormone science and clinical care. Check back for the latest news from ENDO 2021.
Ertugliflozin plus insulin has demonstrated efficacy in reducing body weight, systolic blood pressure, hemoglobin HbA1c (HbA1c), and other metrics among individuals with type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD), according to research recently presented at ENDO 2021, held virtually from March 20 to 23, 2021.
This substudy included 1065 participants with T2DM and ASCVD randomly assigned to ertugliflozin 5 mg once daily (n=348), ertugliflozin 15 mg once daily (n=370), or placebo (n=347). The mean characteristics of all participants were similar: age 64.8 years, T2DM duration of 16.7 years, estimated glomerular filtration rate of 73.7 mL/min/1.73 m, and HbA1c of 8.4%.
Before study initiation, 59.4% were being treated with insulin plus metformin, and 40.6% were receiving insulin alone, with a median insulin dose of 58.0 (20-350) units per day.
The primary endpoint of this study was the 18-week HbA1c change from baseline, with secondary endpoints including body weight, fasting plasma glucose, systolic blood pressure, and the percentage of participants achieving HbA1c <7%. A constrained longitudinal data analysis model was used to assess changes in continuous efficacy endpoints for weeks 0-18.
Those on a stable dose of insulin of at least 20 units per day with or without metformin were treated as a subgroup; further subgroups were designated based on baseline age, race, ethnicity, sex, metformin use, and HbA1c to compare HbA1c reduction.
By week 18, HbA1c reductions were significantly greater for ertugliflozin 5 mg (-0.6%; 95% CI, -0.7 to -0.4) and 15 mg (-0.7%; 95% CI, -0.8 to -0.5) than placebo (P <.001 for both), including for all subgroups. The percentages achieving HbA1c <7% were 20.7% for ertugliflozin 5 mg, 21.1% for 15 mg, and 10.7% for placebo; the treatment groups also achieved significant reductions in body weight, systolic blood pressure, and fasting plasma glucose.
A small decrease in total daily insulin dose was also observed with ertugliflozin 15 mg. Adverse effects were similar across groups. Compared with placebo, ertugliflozin was associated with higher incidences of genital mycotic infections in women (5 mg: 3.4%, P =.05; 15 mg: 3.6%; P =.04; placebo: 0.0%), as well as higher rates of urinary tract infections (3.2-4.1%), severe hypoglycemia (3.5-5.1%), and symptomatic hypoglycemia (26.4-28.5%). Hypovolemia rates were low across treatment groups, with incidences ranging from 1.4% to 2.4%.
The study authors concluded that ertugliflozin plus insulin with or without metformin better reduced HbA1c, body weight, systolic blood pressure, and fasting plasma glucose, and also led to more participants “achieving HbA1c <7.0% vs [placebo] at 18 weeks in [patients] with T2DM and ASCVD” without increased risk for hypoglycemia.
Multiple authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
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Lingvay I, Greenberg MD, Gallo S, Shi H, Liu J, Gantz I. Efficacy and safety of ertugliflozin in patients with type 2 diabetes mellitus and established cardiovascular disease using insulin. Poster presented at: ENDO 2021 virtual conference; March 20-23, 2021. Session P16.