Attempts to reduce the burden of this disease by prevention have been universally unsuccessful, due to failure to reverse rising levels of obesity and sedentary lifestyle,1 and pharmacological treatment is often associated with side effects, such as weight gain (sulphonylureas, insulin and thiazolidinediones), hypoglycaemia (sulphonylureas and insulin) and gastrointestinal discomfort (metformin and glucagon-like peptide-1 receptor agonists (GLP-1 RAs).2
Medication adherence and persistence are important in type 2 diabetes management. Higher medication adherence and persistence are associated with better glycaemic control and reduced healthcare resource utilisation. Most studies report an association between higher medication adherence rates and greater glycated haemoglobin (HbA1c) reduction.3
Recently, the GLP-1 RA’s have become attractive options for the treatment of type 2 diabetes due to its ability to reduce HBA1c and weight (presumably due to slow gastric emptying and increased satiety1c) with a low risk of developing hypoglycaemia.4 To date, some GLP-1 RA’s have also shown cardiovascular benefits.4
Four GLP-1 RAs are currently registered in South Africa for use subcutaneously - exenatide (twice daily), liraglutide (daily), semaglutide and dulaglutide (once weekly).
Head-to-head clinical studies have demonstrated that all GLP-1 RA agents are effective therapeutic options in reducing HBA1c and weight.4 In comparative studies, semaglutide was significantly better than other GLP 1 RAs for HBA1c reduction and weight loss in line with findings from previous studies.6 However, adverse events occurred more frequently in patients taking semaglutide.4
New real-world data was recently presented during the American Diabetic Association’s (ADA) 80th scientific sessions. In a retrospective real-world observational study, Mody et al compared six-month adherence, persistence and treatment patterns, among patients, 18 years and older with type 2 diabetes mellitus. Treatment was initiated with once-weekly GLP-1 RAs, dulaglutide vs semaglutide and dulaglutide vs exenatide BCise, using claims from the Healthcore Integrated Research Database (HIRD). Matched cohorts were well balanced for characteristics such as age, gender, adapted Diabetes Complications Severity Index (sDCSI) score and select comorbidities.3
At six months, significantly more dulaglutide users were adherent relative to semaglutide (59.7% vs 42.7%; P <0.0001) or exenatide BCise users (58.1% vs 40.3%; P <0.0001). In addition, dulaglutide users were less likely to discontinue therapy than semaglutide or exenatide BCise (P<0.0001 both) users.3 Better adherence with dulaglutide may be attributable to differences in the adverse event profiles. Previous head-to-head studies have shown that a higher proportion of patients discontinue semaglutide due to adverse events compared with dulaglutide-treated patients in both low (8% vs 5%) and high dose (10% vs 5%) cohorts. Patients’ preference for the dulaglutide injection device and administration may also be associated factors for higher adherence. A previous study has reported that a greater proportion of patients preferred the dulaglutide than the semaglutide device (84.2% vs 12.3%; P <0.0001).3
The ADA recommends the use of GLP-1 RAs among patients with type 2 diabetes who have established atherosclerotic cardiovascular disease, kidney disease and heart failure.7 In patients with type 2 diabetes, a GLP-1 RA is preferred to insulin when possible.7 Given the importance of adherence and its role in glycaemic control, the findings in the above-mentioned real-world study should be considered in patients, especially in those with comorbid disease.3 Patient satisfaction appears highest for dulaglutide, which is a single-use, disposable pen device that requires few steps.4
REFERENCES:
1. Chudleigh RA, Platts J, Bain SC. Comparative Effectiveness of Long-Acting GLP-1 Receptor Agonists in Type 2 Diabetes: A Short Review on the Emerging Data. Diabetes Metab Syndr Obes 2020 Feb 18;13:433-438.
2. Madsbad S. Review of head-to-head comparisons of glucagon-like peptide-1 receptor agonists Diabetes Obes Metab 2016 Apr;18(4):317-32.
3. Mody R, Yu M, Nepal B , Konig M, Grabner M. Adherence and persistence among patients with type 2 diabetes initiating dulaglutide compared with semaglutide and exenatide BCise: 6-month follow-up from US real-world data. Diabetes Obes Metab 2021 Jan;23(1):106-115.
4. Trujillo JM, Nuffer W, Smith BA. GLP-1 receptor agonists: an updated review of head-to-head clinical studies Ther Adv Endocrinol Metab. Ther.2021, Vol. 12: 1–15
5. del Olmo-Garcia MI, Francisco Merino-Torres J, GLP-1 Receptor Agonists and Cardiovascular Disease in Patients with Type 2 Diabetes. J Diabetes Res 2018 Apr 2;2018:4020492
6. Pratley RE, Aroda V, Catarig AM, Lingvay I, Lüdemann J, Emre Yildirim E, Adie Viljoen A. Impact of patient characteristics on efficacy and safety of once weekly semaglutide versus dulaglutide: SUSTAIN 7 post hoc analyses. BMJ Open 10(11):e037883
7. Standards of Medical Care in Diabetes—2021 Abridged or Primary Care Providers. American Diabetes Association.
