Exenatide Once Weekly: Effectiveness, Tolerability, and Discontinuation Predictors in a Real-world Setting

Dalmazi, Giulia Di; Coluzzi, Sara; Baldassarre, Maria Pompea Antonia; Sorbo, Sofia Elena; Dell’Aquila, Stefania; Febo, Fabrizio; Ginestra, Federica; Graziano, Giusi; Rossi, Maria Chiara; Consoli, Agostino; Formoso, Gloria

doi:10.1016/j.clinthera.2020.07.002

Cited by 9 publications

(10 citation statements)

References 39 publications

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“…In patients started on OW exenatide, HbA1c and body weight were reduced from baseline by −0.92% and −0.79% and by −2.78 and −2.94 kg at 6 and 12 months respectively. These data are in line with previous observations (25)(26)(27)(28)(29)(30)(31)(32). The DURATION trials, testing OW exenatide (in several clinical situations including add-on to pioglitazone, sitagliptin, metformin, and insulin glargine), documented reductions in HbA1c of −1.3 to −1.9% points and body weight reductions in the range of −2.0 to −3.7 kg from baseline associated with the use of this molecule (33)(34)(35)(36)(37)(38)(39).…”

Section: Discussionsupporting

confidence: 93%

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

et al. 2022

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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.

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Section: Discussionsupporting

confidence: 93%

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

et al. 2022

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“…This finding provides real‐world evidence that a more stringent glycaemic target should be implemented in patients with a short T2DM duration, in accordance with the individualized glycaemic goals recommended by T2DM management guidelines 21 . This result is in line with the findings from a previous real‐world study 22 and provides evidence supporting the initiation of GLP‐1 RAs at an early stage of T2DM to achieve the maximum benefit in terms of adequate reduction in HbA1c. In addition, a greater reduction in HbA1c was also observed in patients with baseline HbA1c ≥8.5%, which was also identified as a predictor of adequate glycaemic control.…”

Section: Discussionsupporting

confidence: 91%

Safety and effectiveness of dulaglutide in Chinese adults with type 2 diabetes mellitus in a real‐world setting: A prospective, observational post‐marketing study

Guo,

Li,

et al. 2023

Diabetes Obesity Metabolism

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AimTo our knowledge, this is the first real‐world study to investigate the safety and effectiveness of a glucagon‐like peptide‐1 receptor agonist in Chinese patients with type 2 diabetes mellitus (T2DM).Materials and MethodsThis prospective, observational, post‐marketing study conducted at 46 hospitals in China included adults with T2DM prescribed dulaglutide in routine clinical practice. The primary endpoint was the incidence of treatment‐emergent adverse events (TEAEs) and serious AEs in patients who received ≥1 dose of dulaglutide, for up to 24 weeks. Exploratory endpoints included changes in patient‐reported glycated haemoglobin (HbA1c) and body weight. Post hoc analyses and multivariate regression were also performed.ResultsFrom 20 January 2020 to 24 November 2021, 3291 patients received dulaglutide and entered the safety analysis. TEAEs were reported in 1333 (40.5%) patients; the most commonly reported were nausea (n = 193, 5.9%), diarrhoea (n = 183, 5.6%) and decreased appetite (n = 179, 5.4%). serious AEs were reported in 160 (4.9%) patients. TEAEs led to treatment discontinuation in 212 (6.4%) patients. The mean absolute change in HbA1c from baseline to week 24 was −1.65% (p < .001). Greater reductions in HbA1c at week 24 were observed in patients with T2DM duration ≤5 years (p = .002), baseline HbA1c ≥8.5% (p < .001), and without atherosclerotic cardiovascular disease (p = .002). The mean absolute change in body weight from baseline at week 24 was −2.62 kg (p < .001).ConclusionDulaglutide showed a safety profile consistent with previous reports and significantly reduced HbA1c in a real‐world setting. These findings support the clinical use of dulaglutide and inform the individualized treatment of patients with T2DM in China.

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“…Overall, there was no consistent evidence for effect modification by body mass index (BMI), sex, age or kidney function, with studies reporting contrasting, or null, associations for these clinical features 36,37,[41][42][43]47,[51][52][53][54][55][56][57][58][59][60][61] . In comparative analysis, one large observational study found that markers of insulin resistance (including higher HOMA-IR, BMI, fasting triglycerides, and HDL) do not alter GLP1-RA response, but are associated with lesser DPP4-inhibitor response 54 .…”

Section: Glp1-ramentioning

confidence: 99%

“…Studies consistently identified baseline HbA1c as a predictor of greater HbA1c response. For other clinical features, the strongest evidence was that in many observational studies markers of lower insulin secretion (including longer diabetes duration [or proxies such as insulin treatment], lower fasting Cpeptide, lower urine C-peptide-to-creatinine ratio, and positive GAD or IA2 islet autoantibodies) were associated with lesser glycaemic response to GLP1-RA [33][34][35][36][37][38][39][40][41][42][43][44][45][46] . One large prospective study (n=620) observed clinically relevant reductions in HbA1c response with GLP1-RA in individuals with GAD or IA2 autoantibodies (mean HbA1c reduction −5.2 vs. −15.2 mmol/mol without autoantibodies) or C-peptide <0.25 nmol/L (mean HbA1c reduction −2.1 vs. −15.3 mmol/mol with C-peptide >0.25 nmol/L).…”

Section: Glp1-ramentioning

confidence: 99%

Precision medicine in type 2 diabetes: A systematic review of treatment effect heterogeneity for GLP1-receptor agonists and SGLT2-inhibitors

Young

McInnes

Massey

et al. 2023

Preprint

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Background: A precision medicine approach in type 2 diabetes requires identification of clinical and biological features that are reproducibly associated with differences in clinical outcomes with specific anti-hyperglycaemic therapies. Robust evidence of such treatment effect heterogeneity could support more individualized clinical decisions on optimal type 2 diabetes therapy. Methods: We performed a pre-registered systematic review of meta-analysis studies, randomized control trials, and observational studies evaluating clinical and biological features associated with heterogenous treatment effects for SGLT2-inhibitor and GLP1-receptor agonist therapies, considering glycaemic, cardiovascular, and renal outcomes. Results: After screening 5,686 studies, we included 101 studies of SGLT2-inhibitors and 75 studies of GLP1-receptor agonists in the final systematic review. The majority of papers had methodological limitations precluding robust assessment of treatment effect heterogeneity. For glycaemic outcomes, most cohorts were observational, with multiple analyses identifying lower renal function as a predictor of lesser glycaemic response with SGLT2-inhibitors and markers of reduced insulin secretion as predictors of lesser response with GLP1-receptor agonists. For cardiovascular and renal outcomes, the majority of included studies were post-hoc analyses of randomized control trials (including meta-analysis studies) which identified limited clinically relevant treatment effect heterogeneity. Conclusions: Current evidence on treatment effect heterogeneity for SGLT2-inhibitor and GLP1-receptor agonist therapies is limited, likely reflecting the methodological limitations of published studies. Robust and appropriately powered studies are required to understand type 2 diabetes treatment effect heterogeneity and evaluate the potential for precision medicine to inform future clinical care.

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Exenatide Once Weekly: Effectiveness, Tolerability, and Discontinuation Predictors in a Real-world Setting

Cited by 9 publications

References 39 publications

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

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

Safety and effectiveness of dulaglutide in Chinese adults with type 2 diabetes mellitus in a real‐world setting: A prospective, observational post‐marketing study

Precision medicine in type 2 diabetes: A systematic review of treatment effect heterogeneity for GLP1-receptor agonists and SGLT2-inhibitors

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