Effectiveness and Tolerability of Once-Weekly GLP-1 Receptor Agonists in Clinical Practice: A Focus on Switching Between Once-Weekly Molecules in Type 2 Diabetes

Abstract

AimsThis study aims to evaluate the effectiveness and tolerability of once-weekly glucagon-like peptide receptor agonists (OW GLP-1RAs) and to assess the clinical benefits of switching from one GLP-1RA to another (switchers) in a routine clinical setting.Materials and MethodsThis is a retrospective, real-world cohort study, based on electronic medical records utilized in one Italian diabetes clinic. Estimated mean changes in HbA1c and body weight after 6 and 12 months from the first prescription of a long-acting GLP1-RA were evaluated using longitudinal linear mixed models for repeated measures. The effectiveness of the three long-acting GLP1-RAs was compared separately in the GLP1-RA naive and switchers cohorts, after propensity score adjustment.ResultsInitiating a long-acting GLP1-RA was associated with statistically significant improvements in HbA1c (−1%) and body weight (−2.6 kg) after 6 months, and benefits were maintained after 12 months. In GLP1-RA naive cohort, semaglutide showed the largest effect on HbA1c (−1.55%; 95%CI, −1.77;−1.34) and body weight (−3.76 kg; 95%CI, −5.05;−2.47) at 6 months, maintained at 12 months (−1.55%; 95%CI, −1.82;−1.28 and −6.29 kg; 95%CI, −7.94;−4.63). In the switchers’ cohort, statistically significant reductions at 6 months in HbA1c and body weight were documented with semaglutide and dulaglutide only, with semaglutide associated with the most marked reduction (−0.84%; 95%CI, −1.03;−0.65 and −3.43 kg; 95%, −4.67;−2.19). Dropout rates were 9.2%, 28.5%, and 41.7% in semaglutide, dulaglutide, and exenatide groups, respectively.ConclusionsThe effectiveness and tolerability of the OW GLP-1RAs in the real world were documented. Semaglutide was associated with the highest response without impact on safety. Clinical improvements were obtained even in switchers, especially in those switching to semaglutide.

Real world effectiveness of subcutaneous semaglutide in type 2 diabetes: A retrospective, cohort study (Sema-MiDiab01)

“…However, it is important to note that relevant clinical benefits on metabolic parameters and CV risk factors have been achieved also with intermediate dosage. These results are consistent with those of other real-world studies based on cohorts followed in other settings, all documenting effectiveness and safety of OW semaglutide ( 32 , 35 , 40 – 47 ).…”

Once‐weekly semaglutide use in patients with type 2 diabetes: Real‐world data from the SURE Italy observational study

“…Regional, small and retrospective RW observational studies of semaglutide in clinical practice in Italy have shown similar results, 28–32 increasing the body of evidence for the benefits of OW semaglutide treatment in adults with T2D in RW settings. Moreover, as reported by Di Dalmazi et al, semaglutide was associated with greater reductions in HbA1c and weight versus the maximum doses of OW exenatide and dulaglutide that are available in Italy 30 …”

“…6,7 The results of the SURE Italy study are consistent with efficacy and safety data from the SUSTAIN RCTs [13][14][15][16][17][18] and the SURE studies in Canada, 22 Denmark/Sweden, 23 Spain, 24 Switzerland 25 and the UK 26 and pooled analyses of these studies, 27 the latter of which showed that OW semaglutide use in routine clinical practice was associated with clinically relevant improvements in glycaemic control (-0.2-to -2.5%-point) and body weight (-2.5 to -5.6 kg) and was well tolerated in a wide range of adults with T2D. Regional, small and retrospective RW observational studies of semaglutide in clinical practice in Italy have shown similar results, [28][29][30][31][32] increasing the body of evidence for the benefits of OW semaglutide treatment in adults with T2D in RW settings. Moreover, as reported by Di Dalmazi et al, semaglutide was associated with greater reductions in HbA1c and weight versus the maximum doses of OW exenatide and dulaglutide that are available in Italy.…”

“…22 Similar results were observed in previous retrospective, observational RW studies of OW semaglutide in Italy. 28,30 Collectively, these data suggest that switching from another GLP-1RA to OW semaglutide confers additional clinical benefits to patients with T2D.…”

“…Moreover, as reported by Di Dalmazi et al, semaglutide was associated with greater reductions in HbA1c and weight versus the maximum doses of OW exenatide and dulaglutide that are available in Italy. 30 A strength of the SURE Italy study is its inclusion of an RW population of patients with T2D that is more diverse than those typically enrolled in RCTs. Patients with a wide range of baseline characteristics and baseline medications were included.…”