Weight loss, better beta-cell function tied to long-term glycemic control with tirzepatide
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Key takeaways:
- Greater weight loss at 1 year with tirzepatide improved the odds for sustaining an HbA1c of 6.5% or less at 2 years.
- Decreased LDL cholesterol was the only predictor tied to sustained weight loss of 10% or more.
Adults with type 2 diabetes at high risk for cardiovascular events were more likely to sustain an HbA1c of 6.5% or less at 2 years with tirzepatide if they lost more weight and had improved beta-cell function, according to new data.
As Healio previously reported, tirzepatide (Mounjaro/Zepbound, Eli Lilly) conferred greater reductions in HbA1c and body weight at 1 year than insulin glargine for adults with type 2 diabetes and high CV risk. In a post hoc analysis of the SURPASS-4 trial sponsored by Eli Lilly and presented at the European Association for the Study of Diabetes meeting, researchers assessed which factors were associated with odds for sustaining an HbA1c reduction to 6.5% or less or maintaining a 10% or greater weight loss at 2 years.
“The change in weight and better beta-cell function at 52 weeks are the best predictors of durable glucose control,” Steven Kahn, MB, ChB, director of the University of Washington diabetes research center; director of diabetes and professor of medicine in the division of metabolism, endocrinology and nutrition at University of Washington and VA Puget Sound Health Care System, told Healio. “For durable weight control, there is nothing at baseline or a year that is predictive.”
In SURPASS-4, participants were randomly assigned to receive once-weekly 5 mg, 10 mg or 15 mg tirzepatide, or once-daily titrated insulin glargine for 2 years. The primary endpoints of the study were measured at 1 year. Adults who sustained glycemic control with an HbA1c of 6.5% or weight loss with a weight reduction of 10% or more at 1 year with tirzepatide were included in the analysis.
Of adults receiving tirzepatide, sustained glycemic control at 2 years was achieved by 50% in the 5 mg group, 59% in the 10 mg group and 67% in the 15 mg group. Adults were more likely to sustain glycemic control with each 5 kg weight loss achieved at 1 year (OR = 1.25; 95% CI, 1.05-1.49) and with every one standard deviation increase in homeostasis model assessment of beta-cell function at 1 year (OR = 1.34; 95% CI, 1.06-1.69).
Conversely, adults who were using a sulfonylurea at 1 year were less likely to sustain glycemic control at 2 years compared with those not using a sulfonylurea (OR = 0.56; 95% CI, 0.36-0.88).
Of participants assigned tirzepatide, a 10% or greater weight loss was sustained at 2 years by 27% of the 5-mg group, 42% of the 10-mg group and 53% of the 15-mg group. Each 10% decrease in LDL cholesterol from baseline to 1 year was associated with a greater likelihood of sustaining a 10% or greater weight loss at 2 years (OR = 1.05; 95% CI, 1-1.1). No other predictors were associated with sustained weight loss. Kahn said the link between LDL cholesterol and sustained weight loss was surprising to see and there is uncertainty as to whether it is clinically relevant.
Kahn said the CV benefits tirzepatide provides to people with type 2 diabetes and high CV risk means providers should keep patients on the medication, regardless of long-term sustained HbA1c reduction or weight loss.
“Other long-term studies suggest that weight loss may be more durable than glycemia given the progressive loss of beta-cell function that characterizes type 2 diabetes,” Kahn said. “The SURPASS-CVOT study could provide the opportunity to learn more.”
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Kahn SE, et al. P757. Presented at: European Association for the Study of Diabetes Annual Meeting; Sept. 9-13, 2024; Madrid, Spain.
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