Lilly’s Once-Weekly Insulin Delivers Similar A1C Reduction to Daily Basal Insulin

Lilly’s insulin efsitora alfa delivered the latest victory in the quest to develop once-weekly insulin for type 1 and type 2 diabetes. In large trials among people with type 2 diabetes, efsitora led to similar A1C reductions and safety results compared to daily basal insulin. These findings, together with time in range data, point to a promising future for Lilly’s once-weekly insulin. 

Insulin has come a long way over the past century – from the very first insulin produced from pigs to modern ultra-rapid synthetic insulin. Insulin delivery has also changed, with thinner, shorter needles and more discreet insulin pumps. However, for people who use multiple daily injections, the basics haven’t changed: they still must give themselves several injections every single day, 365 days a year. 

Now, two insulin companies are pursuing once-weekly injections as a strategy to simplify diabetes management. Novo Nordisk’s Awiqli (insulin icodec) is the farthest in development, having already completed phase 3 clinical trials, and is likely to be approved by the FDA in the coming months. Lilly’s efsitora is just behind Awiqli and this new clinical trial data will likely support an approval in type 2 diabetes.  

What were the key findings? 

The QWINT-2 trial compared efsitora to the once-daily basal insulin Tresiba (insulin degludec) in adults who were new to insulin. The trial lasted one year and included participants using GLP-1 receptor agonists. The key findings were: 

• Efsitora led to a 1.34% reduction in A1C, compared to a 1.26% reduction with Tresiba. Reductions in A1C were similar for efsitora and Tresiba regardless of GLP-1 use.
• Compared to those taking Tresiba, participants taking efsitora spent an additional 45 minutes in time in range and 37 minutes more in tight range (80 to 140 mg/dL), without an increased risk of hypoglycemia (low blood sugar). 
• The estimated combined rates of severe or clinically significant (< 54 mg/dL) hypoglycemia was 0.58 per year, compared to 0.45 with Tresiba. 

The QWINT-4 trial compared efsitora to the once-daily basal insulin glargine in adults who had previously been treated with multiple daily injections of insulin. Both groups received Humalog (insulin lispro) for their mealtime insulin. This study lasted six months. 

• Overall, Efsitora and insulin glargine both led to A1C reductions of 1.07%, with participants achieving an A1C of about 7.1%. 
• The estimated combined rates of severe or clinically significant (< 54 mg/dL) hypoglycemia was 6.6 per year, compared to 5.9 with insulin glargine. 

In previous clinical trials, efsitora showed lower variation in glucose levels within each day and lower rates of hypoglycemia compared to Tresiba. CGM data from a phase 2 trial showed that both groups receiving efsitora and Tresiba spent over 75% of time in range. 

"The results of QWINT-2 and QWINT-4 are a significant milestone for the diabetes community and demonstrate that efsitora as a weekly insulin provides blood sugar control equivalent to daily basal insulins," said Dr. Jeff Emmick, senior vice president, product development, Lilly. "With efsitora, we have an opportunity to provide an innovative once-weekly solution that safely achieves and maintains A1C control, reduces treatment burden of traditional daily injections and potentially improves adherence for people with diabetes."

The bottom line

With these results, Efsitora joins Novo Nordisk’s Awiqli, with both insulins having shown positive safety and efficacy results in phase 3 studies. Three more studies of efsitora are underway (QWINT-1, QWINT-3, and QWINT-5) and could provide further support for the once-weekly insulin, including in type 1 diabetes. 

“The topline results of Lilly's once weekly insulin are exciting, and means we may potentially have two weekly insulins available in the near future,” said Dr. Diana Isaacs, director of education and training in diabetes technology at Cleveland Clinic. “I expect we will initially use once-weekly insulin for people that struggle to take insulin every day and its use will likely grow since it may be more convenient, reducing the number of injections per week.” 

The data generated from these large-scale global trials can be submitted to the FDA and other regulatory agencies for approval. Indeed, Awiqli is expected to be approved by the FDA in the coming months – stay tuned. 

Ultimately, once-weekly insulin represents a major step forward for people with diabetes given the potential to simplify day-to-day diabetes management. While trials have yet to test once-weekly insulins among children, it’s possible that these novel insulins could be beneficial here too.

Learn more about insulin therapy: 

• Once-Weekly Insulins For Type 1 Diabetes: Latest Research Update
• 5 Steps for Easier Insulin Injections
• Here’s What the Future of Diabetes Care Might Look Like, According to Experts