Once-Weekly vs Once-Daily Basal Insulin for Treatment of Type 2 Diabetes

Once-Weekly vs Once-Daily Basal Insulin for Treatment of Type 2 Diabetes
Elizabeth Tupper, PharmD, St. Cloud VA

BackgroundCurrent type 2 diabetes treatment guidelines recommend escalation of therapy when individualized glycemic goals are not achieved. Despite known complications of uncontrolled diabetes and recommendations for therapy intensification, clinical inertia exists in the management of type 2 diabetes with the longest delays observed for insulin initiation. Patient and clinician apprehensiveness may be related to discomfort with injections, side effects associated with insulin, and need for adherence to daily basal insulin dosing for optimal glycemic control. Once-weekly insulin may decrease such apprehensiveness, similar to the way literature indicates that treatment with a once-weekly injectable glucagon-like peptide-1 receptor agonist (GLP-1RA) is associated with significantly better treatment adherence and satisfaction compared to once-daily injectable GLP-1RA therapy.

ObjectiveTo compare the glucose-lowering efficacy and the safety profile of once-weekly insulin icodec vs once-daily insulin glargine in patients with type 2 diabetes without previous insulin treatment.

Study DesignTwo hundred forty-seven study participants were randomly assigned to once-weekly subcutaneous icodec plus once-daily placebo or once-daily subcutaneous glargine plus once-weekly placebo in this 26-week, randomized, double-blind, double-dummy, treat-to-target, active-controlled, parallel-group, multinational phase 2 trial. Inclusion criteria included patients aged 18 to 75 years who had not previously received long term insulin treatment, who received diagnosis of diabetes at least 180 days prior to screening, who were receiving stable doses of metformin with or without dipeptidyl peptidase 4 inhibitor (DPP4), and whose A1c was 7-9.5%. Baseline characteristics in both groups were similar, although duration of diabetes was slightly longer in the icodec group. The starting dose of icodec was 70 units once weekly and the starting dose of glargine was 10 units once daily. Doses were adjusted weekly to achieve fasting morning glucose of 70-108 mg/dL. The primary endpoint was change in A1c from baseline to week 26. Secondary endpoints included changes in fasting plasma glucose, body weight, and mean of the nine-point self-monitored glucose profile from baseline to week 26, however, the study was not designed to test the statistical significance of secondary endpoints.The key safety endpoint was the number of adverse effects (hypoglycemia, injection-site reactions) from baseline through the follow-up period. 

Results: The mean A1c in the icodec group decreased from 8.1 ± 0.7% at baseline to an estimated mean of 6.7% at week 26. In the glargine group, A1c decreased from 8.0 ± 0.7% to 6.9%. The estimated mean treatment difference was -0.2 percentage points [95% CI -0.38 - 0.02; P=0.08). The estimated percentage of patients reaching A1c less than 7% was 72% in the icodec group and 68% in the glargine group (estimated OR 1.20 [95% CI 0.98 - 2.13]). The mean self-monitored glucose was lower in the icodec group at all time points. A lower insulin dose and greater time spent within the tight glycemic range (70-140 mg/dL) was found in the icodec group. Changes in fasting plasma glucose and body weight were similar between groups. Approximately 50% of patients in each treatment group had an adverse event. Level one hypoglycemia incidence was 54% in the icodec group and 38% in the glargine group, and the observed rates of level one hypoglycemia during the treatment period were 5.1 and 2.1 events per patient-year of therapy for icodec and glargine, respectively (estimated RR 2.42 [95% CI 1.50 - 3.88]).

ConclusionsOverall, there are similar effects related to A1c lowering, fasting plasma glucose lowering, and rates of hypoglycemia when comparing once-weekly insulin icodec to once-daily insulin glargine. Patients treated with icodec did spend a greater amount of time in the tight glycemic range compared to those treated with once-daily glargine. The mean weekly insulin dose was higher in the glargine group; however, no difference in change in body weight was observed between groups. While no statistical differences were seen, aforementioned findings may hold clinical significance. Future areas of research may involve studies powered to detect statistically significant differences between treatments, compare adherence to weekly vs daily regimens, and assess treatment satisfaction.

Key Point:The once-weekly basal insulin analogue, insulin icodec, provided similar glucose-lowering effects and a similar safety profile to once-daily insulin glargine; however, this study was not powered to detect significant differences between treatments for any end point and further studies are needed to determine significance. 



  1. Rosenstock J, Bajaj HS, Janez A, et al. Once-weekly insulin for type 2 diabetes without previous insulin treatment. N Engl J Med. 2020;383(22):2107-2116.