Simple add-on therapy with GLP-1 Agonist albiglutide can reduce insulin use for patients with type 2 diabetes.
Adherence to medications continues to be a setback in the diabetic community. Insulin is considered the mainstay treatment for patients with type 2 diabetes who also have beta-cell failure. Regimens that include both basal and prandial insulin can be complicated to manage. An essential drawback of prandial insulin is increased risk of hypoglycemia events, poor compliance with too complicated insulin regimens, increased weight, and poor glycemic control such as inconsistent pre and postprandial glucose readings.
Albiglutide is in the drug class of glucagon-like peptide, one receptor agonist (GLP-1RA). During this study, the GLP-1 agonist albiglutide was specified as an adjunct treatment in patients with type 2 diabetes who followed a diet and exercised to improve glycemic control. Previous studies show that some GLP-1RAs are similar or better than basal and prandial insulin at decreasing HBA1C. This study investigates the efficacy and safety of swapping prandial insulin with a weekly GLP-1RA in patients with type 2 diabetes who have ineffectively controlled blood glucose levels regardless of an intensive basal plus prandial insulin medication regimen.
Patients with type 2 diabetes deserve less complicated medication regimens to improve glycemic control and to boost adherence. This study was a randomized, open-label, active-control, multicenter, parallel-group, treat-to-target, 26-week study. The two treatment arms were albiglutide plus glargine and lispro plus glargine. The albiglutide initial dose was 30 mg weekly and up titrated to 50 mg during week 4 for the remaining treatment timeframe. There were 402 patients in the albiglutide plus glargine arm and 412 patients in the lispro plus glargine arm. Even though base characteristics were alike in both arms, participants had a higher compliance percentage in the albiglutide plus glargine arm. The change in HbA1C at baseline and 26 weeks was the primary outcome. The secondary outcomes were the number of participants in the albiglutide plus glargine group who did not restart lispro; total, basal, and prandial daily insulin doses at week 26; the number of weekly insulin doses at weeks 4, 10, 18, and 26; the proportion of participants with severe or known characteristic hypoglycemia from randomization to week 26; and variation of body weight from baseline and fasting prandial glucose at week 26. The statistical tests were based on a one-sided significance level of 0.025 and a standard deviation of 1.2%. The researchers assumed a noninferiority margin of 0.3%, a withdrawal rate of 15% that would eventually end in ≥90% power to reject the null hypothesis of inferiority for modification from baseline in HbA1C.
The mean standard deviation of HbA1C at baseline, in the albiglutide plus glargine group and the lispro plus glargine group, weeks 26 to 6.7 it was decreased plus or minus 0.8% (49 ± eight mmol/mol) and 6.6 plus or minus 0.8% (48 ± eight mmol/mol), respectively (least-squares [LS] difference was 0.06% [95% CI −0.05 to 0.17]; noninferiority p-value was< 0.0001). Total daily prandial insulin was reduced by 62 units/day (95% CI −65.9 to −57.8; P < 0.0001) during week 26 in the albiglutide plus glargine arm, the number of weekly injections decreased from 29 to 13 injections per week. The hypoglycemia risk was 57.2% in the albiglutide plus glargine group with significant weight differences (LS mean ± SE −2.0 ± 0.2 vs. +2.4 ± 0.2 kg; P < 0.0001) compared to lispro plus glargine (75.0%). The albiglutide plus glargine arm reported more gastrointestinal adverse events.
This study could have benefited from a higher retention rate in both treatment arms. In the albiglutide plus glargine arm, 54% of patients switched to all prandial insulin without reinstating lispro up to week 26.
- A weekly GLP-1RA has the potential to normalize glycemic control by creating a basic treatment regimen that will also alleviate common undesirable effects associated with insulin.
- This may be the first large randomized control trial using a treat-to-target design that assesses the power of substitution of a weekly GLP-1RA for prandial insulin on glycemic control in patients with type 2 diabetes inadequately controlled with multiple daily insulin therapy.
- Hypoglycemia was a significant drawback in the lispro plus glargine arm.
Rosenstock J, Nino A, Soffer J, et al. Impact of a Weekly Glucagon-Like Peptide 1 Receptor Agonist, Albiglutide, Glycemic Control and on Reducing Prandial Insulin Use in Type 2 Diabetes Inadequately Controlled on Multiple Insulin Therapy: A Randomized Trial. Diabetes Care. 2020;43(10):dc192316. doi:10.2337/dc19-2316
Alexandria Bartley, PharmD. Candidate, Florida Agricultural & Mechanical University, College of Pharmacy and Pharmaceutical Sciences