Ertugliflozin reduces need for insulin with type 2 diabetes and atherosclerotic CVD
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Adults with type 2 diabetes and atherosclerotic cardiovascular disease were less likely to need insulin and had a lower insulin dose requirement with 5 mg or 15 mg ertugliflozin daily compared with placebo, according to study data.
As Healio previously reported, the VERTIS CV trial randomly assigned adults with type 2 diabetes and atherosclerotic CVD to 5 mg ertugliflozin (Steglatro, Merck), 15 mg ertugliflozin or placebo daily. In a new analysis of findings from VERTIS CV, adults in the two ertugliflozin groups had a decreased risk for needing insulin, a longer time to insulin initiation, and a lower likelihood for having an insulin dose increase of 20% or more if they were using insulin at baseline.
“Insulin is an essential important tool for glycemic control, but the exact timing of its need is imprecise, often varying by patient characteristics, duration of type 2 diabetes, beta-cell reserve and extent of glucose toxicity, among others,” Samuel Dagogo-Jack, MD, FRCP, the A. C. Mullins Endowed Professor, chief of the division of endocrinology, diabetes and metabolism, and director of the clinical research center at the University of Tennessee Health Science Center in Memphis, and an Endocrine Today Editorial Board Member, told Healio. “The VERTIS CV study showed that in some patients who otherwise would have received insulin, an SGLT2 inhibitor, acting via insulin-independent mechanisms, could defer the timing of insulinization while improving glycemic control. Insulin must be prescribed when indicated, but treatment burden should be minimized and adherence optimized, using emerging evidence-based practices.”
VERTIS CV participants had insulin use assessed during the trial. Assessments included the time to initiation of insulin for those not using insulin at baseline and change in baseline insulin dose over time for insulin users. An assessment of time to first 20% or more increase in insulin dose was also conducted. Incidence of hypoglycemic events were collected.
The findings were published in The Journal of Clinical Endocrinology & Metabolism.
Ertugliflozin decreased odds of needing insulin
Of 8,246 participants in the trial, 53% were not using insulin at baseline. Among those using insulin, and about 60% were using a basal-bolus regimen.
Of adults not treated with insulin at baseline, 17.5% of the placebo group initiated insulin compared with 12.8% of the ertugliflozin 5 mg group and 11.6% of the ertugliflozin 15 mg group. Adults receiving ertugliflozin 5 mg (HR = 0.7; 95% CI, 0.58-0.84; P < .001) or ertugliflozin 15 mg (HR = 0.64; 95% CI, 0.53-0.78; P < .001) were less likely to initiate insulin than those assigned placebo.
“Several mechanisms could have contributed to the decrease in insulin initiations observed following treatment with ertugliflozin,” the researchers wrote. “In addition to improvement in glycemic control and amelioration of glucotoxicity, ertugliflozin and other SGLT2 inhibitors are well known to decrease body weight. Furthermore, ertugliflozin treatment has been found to be associated with decreased indices of hepatic steatosis. The resultant improvement in insulin sensitivity following weight loss and reduction in liver fat can be expected to decrease insulin requirements.”
Ertugliflozin use was associated with up to a 245-day delay to reach a 5% incidence of new insulin initiation, up to a 669-day delay to reach a 10% insulin initiation incidence, and up to a 619-day delay to reach a 15% incidence for insulin initiation compared with placebo.
Adults using ertugliflozin need lower insulin doses
Adults using ertugliflozin 5 mg used 4.18 fewer units of insulin per day than those assigned placebo, and the ertugliflozin 15 mg group used a mean 6.9 fewer units of insulin per day compared with the placebo group. Adults using ertugliflozin 5 mg (HR = 0.62; 95% CI, 0.52-0.75; P < .001) or ertugliflozin 15 mg (HR = 0.51; 95% CI, 0.41-0.62; P < .001) were less likely to have an insulin dose increase of 20% or higher than those in the placebo group. A higher proportion in the ertugliflozin 15 mg group (4.1%) discontinued insulin use during the trial compared with the ertugliflozin 5 mg group (2.4%) and the placebo group (2.2%).
Hypoglycemic events did not differ between the ertugliflozin and placebo groups with or without baseline insulin use. Among adults receiving insulin at baseline, there was a lower rate of symptomatic and severe hypoglycemia events and higher rate of asymptomatic hypoglycemia events in the ertugliflozin group compared with placebo.
“Additional insights are needed regarding the mechanisms of our keys observations,” Dagogo-Jack said. “The study design did not enable a detailed evaluation of beta-cell function, possible amelioration of insulin resistance following weight loss and other plausible mechanisms associated with exposure to SGLT2 inhibitors.”
For more information:
Samuel Dagogo-Jack, MD, FRCP, can be reached at sdj@uthsc.edu.
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