Semaglutide, insulin degludec sustain glycaemic control in patients with T2D

Treatment with once-weekly subcutaneous semaglutide and once-daily insulin degludec sustained an HbA_1c level of ≤7.5 percent in individuals with adequately controlled type 2 diabetes (T2D) who were on multiple daily injections of insulin (MDI) regimen, according to the TRANSITION-T2D study presented at ADA 2023.

“Approximately 97.5 percent of participants in the semaglutide group were able to fully replace prandial insulin during the study. Only one participant who stopped semaglutide had to resume prandial insulin,” said Dr Paloma Rodriguez from the Department of Endocrinology at Cleveland Clinic, Ohio, US.

“This transition results in significant reductions in insulin requirements, HbA_1c and body weight, and negates the need for prandial insulin,” she added.

In this single-centre, open-label trial, 60 patients (mean age 68.6 years, 58 percent male) with adequately controlled T2D on MDI were randomized 2:1 to receive subcutaneous semaglutide 1 mg once weekly + insulin degludec once daily (semaglutide group) or to continue MDI with insulin degludec once daily + insulin aspart (MDI group) for 26 weeks. The semaglutide group discontinued prandial insulin on the same day as the first dose of semaglutide was initiated at 0.25 mg weekly, and was then increased monthly, as tolerated. [ADA 2023, abstract 74-LB]

In the intention-to-treat analysis, a higher proportion of patients in the semaglutide group maintained an HbA_1c level of ≤7.5 percent at week 26 than those in the MDI group (90 percent vs 75 percent; odds ratio [OR], 2.6; p=0.18), although this finding did not reach statistical significance.

Mean weight was significantly reduced by 8.6 percent (-8.9 kg) with semaglutide + insulin vs 1.4 percent (1.5 kg) with MDI at week 26 (p<0.001), with 45 percent of semaglutide recipients also achieving a weight loss of >10 percent.

Semaglutide recipients also demonstrated a greater decrease in total daily insulin dose (TDD) at week 26 from baseline than MDI recipients (-37.3 vs 5.2 units[U]/day; p<0.001).

Significant reductions in mean daily basal and prandial insulin doses were also observed in the semaglutide arm over the MDI arm (-7.8 vs 4.1 U/day; p<0.001 and -30 vs 2.1 U/day; p<0.001, respectively).

With regard to treatment satisfaction, DTSQs* and DTSQc** scores did not differ between the semaglutide and MDI groups (p=0.95 and p=0.64, respectively).

There were also no significant differences in the incidence of any adverse events (AEs) and serious AEs between the treatment groups (p>0.99 for both).

“Patients with HbA1c ≤7.5 percent receiving MDI up to 120 U/day can be effectively and safely transitioned to a regimen of [once-weekly subcutaneous] semaglutide 1.0 mg + basal insulin,” Rodriguez noted. “This can be achieved using a simple one-step approach (ie, completely stopping prandial insulin when starting semaglutide) that can be easily implemented in the real-world clinical practice setting.”

“Given these positive results, it seems reasonable to test the transition of prandial insulin to once weekly subcutaneous semaglutide in participants receiving higher doses of MDI (TDD >120 U/day), and/or in patients with uncontrolled T2D (HbA_1c >7.5 percent), especially now that a higher dose of semaglutide (2.0 mg) has been proven safe and effective in patients with T2D,” Rodriguez noted.

*DTSQs: Diabetes Treatment Satisfaction Questionnaire status

**DTSQc: Diabetes Treatment Satisfaction Questionnaire change