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 a once-weekly insulin for diabetes. 

In multiple large trials, efsitora led to similar A1C reductions and safety results compared to daily basal (long-acting) insulin. These findings, together with improved time in range data, point to a promising future for Lilly’s once-weekly insulin. 

"The results 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 of product development at Lilly. 

"With efsitora, we have an opportunity to provide an innovative once-weekly solution that safely achieves and maintains A1C control, reduces the treatment burden of traditional daily injections, and potentially improves adherence for people with diabetes," he said.

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 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. With a once-weekly insulin, it would significantly reduce the number of basal insulin injections to 52 per year.

Now, two insulin companies are pursuing once-weekly injections as a strategy to simplify diabetes management. Novo Nordisk’s insulin icodec is the farthest along in development, having already completed phase 3 clinical trials and been approved in Europe. It has not yet been approved by the U.S. FDA. Lilly’s efsitora is just behind icodec, with recent positive clinical trial data results likely to support U.S. approval for type 2 diabetes sometime in the future.  

What does the research show? 

Five large completed studies that enrolled over 4,000 people with diabetes all yielded positive results when testing efsitora against daily basal insulins. All studies were conducted on people with type 2 diabetes, except QWINT-5, which focused on people with type 1 diabetes. Here are the key findings:

QWINT-1

• The QWINT-1 trial, completed July 2024, was a 52-week long study comparing once-weekly efsitora to once-daily insulin glargine in 795 adults with type 2 diabetes who have not used insulin before. 
• Efsitora was found to reduce A1C levels by 1.31% compared to 1.27% with insulin glargine.
• Efsitora was determined to be similar in safety and tolerability to daily basal insulin. The estimated rates of severe hypoglycemia (low blood sugar) (less than 54 mg/dL) were almost 40% lower with efsitora compared to insulin glargine (0.50 vs. 0.88).

QWINT-2

• The QWINT-2 trial, completed April 2024, was a 52-week long study comparing efsitora to once-daily insulin degludec in 928 adults with type 2 diabetes new to insulin. 
• Efsitora led to a 1.34% reduction in A1C compared to a 1.26% reduction with insulin degludec. 
• Participants taking efsitora spent an additional 45 minutes in range and 37 minutes more in tight range (70-140 mg/dL), without an increased risk of hypoglycemia. 
• Efsitora was found to be safe and tolerable in participants. The estimated rates of severe hypoglycemia were roughly 13% higher with efsitora compared to insulin degludec (0.58 vs. 0.45).

QWINT-3

• The QWINT-3 trial, completed May 2024, was a 78-week long study comparing efsitora to insulin degludec in 986 adults with type 2 diabetes using daily basal insulin. 
• Efsitora was found to reduce A1C levels by 0.86% compared to 0.75% with insulin degludec. 
• Participants taking efsitora spent more time in range compared to insulin degludec (62.8% vs. 61.3%) and more time in tight range (38.3% vs. 36.8%).
• Efsitora was found to be safe and tolerable in participants. The estimated rates of severe hypoglycemia were roughly 10% higher with efsitora compared to insulin degludec (0.84 vs. 0.74).

QWINT-4

• The QWINT-4 trial, completed February 2024, was a 26-week long study comparing efsitora to insulin glargine in 730 adults with type 2 diabetes using daily basal insulin and at least two injections of mealtime insulin per day. 
• Efsitora and insulin glargine were found to be equally effective and led to A1C reductions of 1.07%.
• Efsitora was found to be safe and tolerable in participants. The estimated rates of severe hypoglycemia were roughly 12% higher with efsitora compared to insulin glargine (6.6 vs. 5.9).

QWINT-5

• The QWINT-5 trial, completed May 2024, was a 52-week study comparing efsitora to insulin degludec in 692 adults with type 1 diabetes. 
• Efsitora reduced A1C levels by 0.51% compared to 0.56% with insulin degludec. 
• Severe rates of hypoglycemia were roughly 21% higher with efsitora compared to insulin degludec (14.03 vs. 11.59), with the highest rates occurring in the first 12 weeks of the study before stabilizing.

Dr. Melanie Davies, professor of diabetes medicine at the University of Leicester and director of the NIHR Leicester Biomedical Research Centre, explained that when comparing QWINT-5 to ONWARDS-6 (a large trial that studied Novo’s once-weekly insulin icodec), the starting insulin dose was almost double, which could account for the higher rates of severe hypoglycemia.

“I think the implications for type 1 diabetes are more difficult. We see similar efficacy but we do see issues with safety, particularly around hypoglycemia,” Davies said. “We need to reflect in terms of whether we got this right with the starting dose.”

“So, what do we do?” said Dr. Richard Bergenstal, an endocrinologist, executive director of the International Diabetes Center, and lead investigator of QWINT-5. “I think we work to optimize the starting dose and titration because people with type 1 diabetes really liked this insulin. But we have to figure out the sweet spot to get it just right.”

The bottom line

With these results, efsitora joins Novo Nordisk’s insulin icodec in showing positive safety and efficacy results in late-stage clinical trials for people with type 2 diabetes. While icodec is still battling some approval hurdles in the U.S. (it’s approved in other countries for both type 1 and 2), the positive data shown in the efsitora trials in type 2 diabetes likely means Lilly is next up for U.S. approval after Novo Nordisk.

“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 the 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,” she said. 

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 here: 

• Getting Started with Insulin if You Have Type 2 Diabetes
• 5 Steps for Easier Insulin Injections
• Here’s What the Future of Diabetes Care Might Look Like, According to Experts