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Web Release
05-07-2025
- Health
- Web Release
Lilly's once-weekly insulin efsitora alfa demonstrated A1C reduction and a safety profile consistent with daily insulin in multiple Phase 3 trials
Eli Lilly and Company (NYSE: LLY) today announced detailed results from QWINT-1, QWINT-3, and QWINT-4 Phase 3 clinical trials evaluating the safety and efficacy of investigational once-weekly insulin efsitora alfa (efsitora) in adults with type 2 diabetes who used insulin for the first time, previously used daily basal insulin, and previously used daily basal insulin and mealtime insulin, respectively. In each trial, once-weekly efsitora met the primary endpoint of non-inferior A1C reduction compared to daily basal insulin. The complete results from these studies were presented at the American Diabetes Association (ADA) 85th Scientific Sessions. In QWINT-1, efsitora reduced A1C by 1.31% compared to 1.27% for insulin glargine at week 52 for the efficacy estimand.1,2 In the trial, efsitora was titrated to four fixed doses at four-week intervals, as needed for blood glucose control.3 In QWINT-3, efsitora reduced A1C by 0.86% compared to 0.75% for insulin degludec at week 26 for the efficacy estimand.4 In QWINT-4, efsitora reduced A1C by 1.07% compared to 1.07% for insulin glargine at week 26 for the efficacy estimand.5 In these two trials, efsitora was administered using traditional insulin dosing with adjustments based on each patient's glucose level. 'The novel fixed-dose regimen used in QWINT-1 for once-weekly efsitora, which consisted of only four single-dose titration options, has the potential to facilitate and simplify insulin therapy, reducing the hesitation often associated with starting insulin to treat type 2 diabetes,' said Dr. Julio Rosenstock, senior scientific advisor for Velocity Clinical Research at Medical City Dallas, clinical professor of medicine, University of Texas Southwestern Medical Center, and lead trial investigator for QWINT-1. 'A simpler, once-weekly regimen with efsitora may help people with type 2 diabetes initiate and manage insulin therapy with the goal of improving blood sugar levels. Across all QWINT trials, the results showed that once-weekly efsitora controlled glucose as effectively as the most popular once-daily basal insulins.' QWINT-1 Primary Endpoint QWINT-3 Primary and Key Secondary Endpoints QWINT-4 Primary and Key Secondary Endpoints Efficacy Estimand Treatment-Regimen Estimand6 Primary Endpoint – A1C Reduction (Resulting A1C) at Week 52 Efsitora -1.31% (6.92%) -1.19% (7.05%) Glargine -1.27% (6.96%) -1.16% (7.08%) Efficacy Estimand Treatment-Regimen Estimand Primary Endpoint – A1C Reduction (Resulting A1C) at Week 26 Efsitora -0.86% (6.93%) -0.81% (6.99%) Degludec -0.75% (7.03%) -0.72% (7.08%) Key Secondary Endpoint – Rates of Clinically Significant or Severe Nocturnal Hypoglycemic Events Per Patient-Year of Exposure up to Week 787,8 Efsitora 0.11 Degludec 0.10 Key Secondary Endpoint – Percent Time in Range (70-180 mg/dL) During the 4 Weeks Prior to Week 26 Efsitora 62.8% 61.4% Degludec 61.3% 61.0% Efficacy Estimand Treatment-Regimen Estimand Primary Endpoint – A1C Reduction (Resulting A1C) at Week 26 Efsitora -1.07% (7.12%) -1.01% (7.17%) Glargine -1.07% (7.11%) -1.00% (7.18%) Key Secondary Endpoint – Participants Achieving A1C <7% at Week 26 Without Nocturnal Hypoglycemia Efsitora 39.5% 38.6% Glargine 36.6% 35.9% Key Secondary Endpoint – Rates of Clinically Significant or Severe Nocturnal Hypoglycemic Events Per Patient-Year of Exposure up to Week 26 Efsitora 0.67 Glargine 1.00 'Building on Lilly's legacy of innovation in insulin therapy, once-weekly efsitora may offer a significant advancement for people with type 2 diabetes who need insulin by eliminating over 300 injections per year,' said Jeff Emmick, MD, Ph.D., senior vice president of product development at Lilly. 'These results reinforce the potential for once-weekly efsitora to help reduce the overall burden of insulin therapy through a simplified treatment approach. We look forward to working with regulatory agencies to bring this innovation to patients around the world.' Across the three trials, efsitora demonstrated an overall safety profile similar to two of the most commonly used daily basal insulin therapies for the treatment of type 2 diabetes. In QWINT-1, efsitora resulted in approximately 40% fewer hypoglycemic events compared to insulin glargine, with estimated combined rates of severe or clinically significant hypoglycemic events per patient-year of exposure of 0.50 with efsitora vs. 0.88 with insulin glargine at 52 weeks. In QWINT-3, these rates were 0.84 with efsitora vs. 0.74 with insulin degludec at 78 weeks. In QWINT-4, rates of estimated combined rates of severe or clinically significant hypoglycemic events per patient-year of exposure were 6.6 with efsitora vs. 5.9 with insulin glargine at 26 weeks. Lilly plans to submit efsitora for the treatment of adults with type 2 diabetes to global regulatory agencies by the end of this year. About the QWINT clinical trial program The QWINT Phase 3 global clinical development program for insulin efsitora alfa (efsitora) in diabetes began in 2022 and has enrolled more than 3,000 people living with type 2 diabetes across four global registration studies. QWINT-1 (NCT05662332) was a parallel-design, open-label, treat-to-target, randomized controlled clinical trial comparing the efficacy and safety of efsitora as a once-weekly basal insulin using a fixed dose escalation to daily insulin glargine for 52 weeks in insulin-naïve adults with type 2 diabetes. The trial randomized 795 participants across the U.S., Argentina and Mexico to receive efsitora once weekly or insulin glargine once daily, administered subcutaneously. Participants treated with efsitora received a starting dose of 100 units of insulin, followed by escalation to fixed dosages of 150 units, 250 units and 400 units every 4 weeks, as needed, until achieving a target fasting blood glucose of 80-130 mg/dL. Participants with fasting blood glucose greater than 130 mg/dL on or after 16 weeks were transferred to flexible dosing. The primary objective of the trial was to demonstrate non-inferiority in reducing A1C at week 52 with efsitora compared to daily use of insulin glargine. QWINT-3 (NCT05275400) was a multicenter, randomized, parallel-design, open-label trial comparing the efficacy and safety of efsitora as a once-weekly basal insulin to insulin degludec for 78 weeks after a three-week lead-in followed by a five-week safety follow up period, in adults with type 2 diabetes who are currently treated with basal insulin. The trial randomized 986 participants across the U.S., Argentina, Hungary, Japan, Korea, Poland, Puerto Rico, Slovakia, Spain and Taiwan to receive efsitora once weekly or insulin degludec once daily administered subcutaneously. The primary objective of the study was to demonstrate non-inferiority in reducing A1C at week 26 with efsitora compared to insulin degludec. QWINT-4 (NCT05462756) was a parallel-design, open-label, treat-to-target, randomized controlled clinical trial comparing the efficacy and safety of efsitora as a weekly basal insulin to insulin glargine for 26 weeks in adults with type 2 diabetes who have previously been treated with basal insulin and at least two injections per day of mealtime insulin. The trial randomized 730 participants across the U.S., Argentina, Germany, India, Italy, Mexico, Puerto Rico and Spain to receive efsitora once weekly or insulin glargine once daily, both of which were administered subcutaneously along with insulin lispro. The primary objective of the trial was to demonstrate non-inferiority in reducing A1C at week 26 with efsitora compared to insulin glargine. About insulin efsitora alfa Insulin efsitora alfa (efsitora) is a once-weekly basal insulin, a fusion protein that combines a novel single-chain variant of insulin with a human IgG2 Fc domain. It is specifically designed for once-weekly subcutaneous administration, and with its low peak-to-trough ratio, it has the potential to provide more stable glucose levels (less glucose variability) throughout the week. About Lilly Lilly is a medicine company turning science into healing to make life better for people around the world. We've been pioneering life-changing discoveries for nearly 150 years, and today our medicines help tens of millions of people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges: redefining diabetes care; treating obesity and curtailing its most devastating long-term effects; advancing the fight against Alzheimer's disease; providing solutions to some of the most debilitating immune system disorders; and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we're motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. To learn more, visit and or follow us on Facebook, Instagram, and LinkedIn. P-LLY 1. The efficacy estimand represents the treatment effect on all participants who adhered to the study drug without initiating rescue therapy for persistent severe hyperglycemia. 2. From a baseline of 8.20% for efsitora and 8.28% for insulin glargine. 3. Participants treated with efsitora received a starting dose of 100 units of insulin, followed by escalation to fixed dosages of 150 units, 250 units and 400 units every 4 weeks, as needed, until achieving a target fasting blood glucose of 80-130 mg/dL. Participants with fasting blood glucose greater than 130 mg/dL on or after 16 weeks were transferred to flexible dosing. 4. From a baseline of 7.80% for both efsitora and insulin degludec. 5. From a baseline of 8.18% for both efsitora and insulin glargine. 6. The treatment-regimen estimand represents the estimated average treatment effect regardless of treatment discontinuation or introduction of rescue therapy for persistent severe hyperglycemia. 7. Blood glucose <54 mg/dL. 8. Nocturnal hypoglycemia was defined as any event that occurred at night between midnight and 6 a.m. Cautionary Statement Regarding Forward-Looking Statements This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about insulin efsitora alfa as a potential treatment for people with type 2 diabetes and the timeline for future readouts, presentations, and other milestones relating to insulin efsitora alfa and its clinical trials and reflects Lilly's current beliefs and expectations. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of drug research, development, and commercialization. Among other things, there is no guarantee that future study results will be consistent with study results to date, that insulin efsitora alfa will prove to be a safe and effective treatment for type 2 diabetes, that insulin efsitora alfa will receive regulatory approval, or that Lilly will execute its strategy as expected. For further discussion of these and other risks and uncertainties that could cause actual results to differ from Lilly's expectations, see Lilly's Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this release. Trademarks and Trade Names All trademarks or trade names referred to in this press release are the property of the company, or, to the extent trademarks or trade names belonging to other companies are referenced in this press release, the property of their respective owners. Solely for convenience, the trademarks and trade names in this press release are referred to without the ® and ™ symbols, but such references should not be construed as any indicator that the company or, to the extent applicable, their respective owners will not assert, to the fullest extent under applicable law, the company's or their rights thereto. We do not intend the use or display of other companies' trademarks and trade names to imply a relationship with, or endorsement or sponsorship of us by, any other companies.
Web Release
01-07-2025
- Health
- Web Release
Lilly's oral GLP-1, orforglipron, showed compelling efficacy and a safety profile consistent with injectable GLP-1 medicines, in complete Phase 3 results
Eli Lilly and Company announced detailed results from ACHIEVE-1, a Phase 3 trial evaluating the safety and efficacy of orforglipron compared to placebo in adults with type 2 diabetes and inadequate glycemic control with diet and exercise alone. Orforglipron is the first oral small molecule (non-peptide) glucagon-like peptide-1 (GLP-1) receptor agonist, taken without food and water restrictions, to successfully complete a Phase 3 trial. At 40 weeks, all three doses (3 mg, 12 mg, 36 mg) of orforglipron achieved the primary endpoint of superior A1C reduction. In addition, the 12 mg and 36 mg doses showed clinically meaningful and statistically significant reductions in body weight vs. placebo. In the study, orforglipron had a safety profile similar to the established GLP-1 class, and the most frequently reported adverse events were gastrointestinal-related. The results were presented at the American Diabetes Association (ADA) 85th Scientific Sessions 2025 In the study, orforglipron met the primary endpoint of superior A1C reduction compared to placebo at 40 weeks, lowering A1C by 1.3% to 1.6% from a baseline of 8.0%, for the efficacy estimand.1 In key secondary endpoints, up to 76.2% of participants taking orforglipron achieved the ADA treatment target A1C of <7%, 66.0% achieved an A1C of ?6.5%, and 25.8% achieved <5.7%, defined as a normal A1C value.2,3 Improvements in A1C were observed as early as four weeks and were accompanied by similar reductions in fasting serum glucose. In another key secondary endpoint, participants taking the highest dose of orforglipron lost an average of 16.0 lbs (7.9%). While participants in ACHIEVE-1 did not appear to reach a weight plateau, longer-duration trials, such as the ATTAIN trials, will provide a comprehensive evaluation of the safety and efficacy of orforglipron for the treatment of obesity. 'The ACHIEVE-1 trial demonstrated that orforglipron, a novel oral small-molecule GLP-1, achieved clinically meaningful reductions in A1C and body weight over 40 weeks in adults with type 2 diabetes,' said Dr. Julio Rosenstock, senior scientific advisor for Velocity Clinical Research at Medical City Dallas, and clinical professor of medicine, University of Texas Southwestern Medical Center, and lead trial investigator. 'The early onset of glycemic improvement, observed as soon as four weeks, reinforces the therapeutic potential of orforglipron as an effective, oral GLP-1 therapy for early type 2 diabetes treatment. These findings support further investigation in broader populations and longer-duration studies.' Full Results Orforglipron 3 mg Orforglipron 12 mg Orforglipron 36 mg Placebo Primary Endpoint A1C reduction from baseline of 8.0%i Efficacy estimand 1.3% 1.6% 1.5% 0.1% Treatment-regimen estimand4 1.2% 1.5% 1.5% 0.4% Key Secondary Endpointsii Percent weight reduction from baseline of 90.2 kg (198.9 lbs)i, iii Efficacy estimand 4.7% 6.1% 7.9% 1.6% Treatment-regimen estimand 4.5% 5.8% 7.6% 1.7% Weight reduction from baseline of 90.2 kg (198.9 lbs)i,iii Efficacy estimand 4.4 kg (9.7 lbs) 5.5 kg (12.2 lbs) 7.3 kg (16.0 lbs) 1.3 kg (2.9 lbs) Treatment-regimen estimand 4.2 kg (9.3 lbs) 5.2 kg (11.5 lbs) 7.2 kg (15.8 lbs) 1.5 kg (3.4 lbs) Percent of participants achieving A1C <7%i Efficacy estimand 72.9% 76.2% 74.9% 28.0% Treatment-regimen estimand 68.1% 72.9% 72.7% 33.0% Percent of participants achieving A1C ?6.5%i, ii Efficacy estimand 61.5% 62.3% 66.0% 13.5% Treatment-regimen estimand 56.9% 58.1% 61.9% 14.9% Percent of participants achieving A1C < 5.7 %iii Efficacy estimand 17.7% 25.8% 23.9% 3.8% Treatment-regimen estimand 16.8% 23.9% 21.5% 3.8% Fasting serum glucose reduction from baseline of 147.5 mg/dLi Efficacy estimand 30.6 mg/dL 37.4 mg/dL 37.8 mg/dL 1.1 mg/dL Treatment-regimen estimand 30.7 mg/dL 36.5 mg/dL 34.7 mg/dL 10.8 mg/dL i Superiority test was adjusted for multiplicity. iiData from the full list of key secondary endpoints are available in the publication. iiiPercent of participants achieving A1C < 5.7% across all orforglipron doses and body weight for orforglipron 3 mg were not controlled for Type 1 error. 'This convenient once-daily pill with no restrictions on food and water intake could be an option for millions of people with type 2 diabetes who prefer oral medications over injectables,' said Jeff Emmick, MD, Ph.D., senior vice president of product development at Lilly. 'The positive ACHIEVE-1 results position orforglipron as a potential treatment option with meaningful A1C and weight reduction, and a safety profile similar to injectable GLP-1 therapies. We look forward to the four remaining global readouts from the ACHIEVE program, as well as results of the ATTAIN program in obesity, and working with regulators to bring this once-daily oral GLP-1 to people around the world.' The overall safety profile of orforglipron in ACHIEVE-1 was consistent with the established GLP-1 class. The most common adverse events for participants treated with orforglipron (3 mg, 12 mg and 36 mg, respectively) were diarrhea (19%, 21% and 26%) vs. 9% with placebo, nausea (13%, 18% and 16%) vs. 2% with placebo, dyspepsia (11%, 20% and 15%) vs. 7% with placebo, constipation (8%, 17% and 14%) vs. 4% with placebo, and vomiting (5%, 7% and 14%) vs. 1% with placebo. These gastrointestinal-related adverse events were generally mild-to-moderate in severity, and occurred primarily during dose escalation. Overall treatment discontinuation rates due to adverse events were 6% (3 mg), 4% (12 mg) and 8% (36 mg) for orforglipron vs. 1% with placebo. No hepatic safety signal was observed. Later this year, Lilly expects to share topline results from ACHIEVE-2, evaluating orforglipron compared with dapagliflozin, and ACHIEVE-3, evaluating orforglipron compared to oral semaglutide, both in adults with type 2 diabetes inadequately controlled with metformin. ATTAIN-1 and ATTAIN-2, evaluating orforglipron for weight management, will also be shared in the third quarter of this year. Lilly remains on track to submit orforglipron for weight management to global regulatory agencies by the end of this year and for the treatment of type 2 diabetes in 2026.
Yahoo
23-06-2025
- Health
- Yahoo
Amgen Hammered As 'Tough' Obesity Meeting Reminds It It's Not The Incumbent
Amgen stock dropped Monday after a "tough" American Diabetes Association discussion around its experimental weight-loss drug, MariTide. Dr. Julio Rosenstock, the director of the Dallas Diabetes Research Center at Medical City, reviewed MariTide at the ADA meeting in Chicago. If approved, MariTide would be a monthly shot to reduce weight, rivaling weekly injections from Eli Lilly and Novo Nordisk.
Malaysian Reserve
22-06-2025
- Health
- Malaysian Reserve
Lilly's once-weekly insulin efsitora alfa demonstrated A1C reduction and a safety profile consistent with daily insulin in multiple Phase 3 trials
Results from the fixed-dose QWINT-1 study, along with the QWINT-3 and QWINT-4 studies, reinforce efsitora's potential to simplify insulin management with weekly dosing Lilly plans to submit efsitora for the treatment of adults with type 2 diabetes to global regulatory agencies by the end of this year INDIANAPOLIS, June 22, 2025 /PRNewswire/ — Eli Lilly and Company (NYSE: LLY) today announced detailed results from QWINT-1, QWINT-3, and QWINT-4 Phase 3 clinical trials evaluating the safety and efficacy of investigational once-weekly insulin efsitora alfa (efsitora) in adults with type 2 diabetes who used insulin for the first time, previously used daily basal insulin, and previously used daily basal insulin and mealtime insulin, respectively. In each trial, once-weekly efsitora met the primary endpoint of non-inferior A1C reduction compared to daily basal insulin. The complete results from these studies were presented at the American Diabetes Association (ADA) 85th Scientific Sessions 2025. Simultaneously, results from QWINT-1, a first-of-its-kind fixed-dose study, were published in The New England Journal of Medicine, while results from QWINT-3 and QWINT-4 were published in The Lancet. In QWINT-1, efsitora reduced A1C by 1.31% compared to 1.27% for insulin glargine at week 52 for the efficacy estimand.1,2 In the trial, efsitora was titrated to four fixed doses at four-week intervals, as needed for blood glucose control.3 In QWINT-3, efsitora reduced A1C by 0.86% compared to 0.75% for insulin degludec at week 26 for the efficacy estimand.4 In QWINT-4, efsitora reduced A1C by 1.07% compared to 1.07% for insulin glargine at week 26 for the efficacy estimand.5 In these two trials, efsitora was administered using traditional insulin dosing with adjustments based on each patient's glucose level. 'The novel fixed-dose regimen used in QWINT-1 for once-weekly efsitora, which consisted of only four single-dose titration options, has the potential to facilitate and simplify insulin therapy, reducing the hesitation often associated with starting insulin to treat type 2 diabetes,' said Dr. Julio Rosenstock, senior scientific advisor for Velocity Clinical Research at Medical City Dallas, clinical professor of medicine, University of Texas Southwestern Medical Center, and lead trial investigator for QWINT-1. 'A simpler, once-weekly regimen with efsitora may help people with type 2 diabetes initiate and manage insulin therapy with the goal of improving blood sugar levels. Across all QWINT trials, the results showed that once-weekly efsitora controlled glucose as effectively as the most popular once-daily basal insulins.' QWINT-1 Primary Endpoint Efficacy Estimand Treatment-RegimenEstimand6 Primary Endpoint – A1C Reduction (Resulting A1C) at Week 52 Efsitora -1.31 % (6.92 %) -1.19 % (7.05 %) Glargine -1.27 % (6.96 %) -1.16 % (7.08 %) QWINT-3 Primary and Key Secondary Endpoints Efficacy Estimand Treatment-RegimenEstimand Primary Endpoint – A1C Reduction (Resulting A1C) at Week 26 Efsitora -0.86 % (6.93 %) -0.81 % (6.99 %) Degludec -0.75 % (7.03 %) -0.72 % (7.08 %) Key Secondary Endpoint – Rates of Clinically Significant or Severe Nocturnal Hypoglycemic Events Per Patient-Year of Exposure up to Week 787,8 Efsitora 0.11 Degludec 0.10 Key Secondary Endpoint – Percent Time in Range (70-180 mg/dL) During the FourWeeks Prior to Week 26 Efsitora 62.8 % 61.4 % Degludec 61.3 % 61.0 % QWINT-4 Primary and Key Secondary Endpoints Efficacy Estimand Treatment-Regimen Estimand Primary Endpoint – A1C Reduction (Resulting A1C) at Week 26 Efsitora -1.07 % (7.12 %) -1.01 % (7.17 %) Glargine -1.07 % (7.11 %) -1.00 % (7.18 %) Key Secondary Endpoint – Participants Achieving A1C <7% at Week 26 Without Nocturnal Hypoglycemia Efsitora 39.5 % 38.6 % Glargine 36.6 % 35.9 % Key Secondary Endpoint – Rates of Clinically Significant or Severe NocturnalHypoglycemic Events Per Patient-Year of Exposure up to Week 26 Efsitora 0.67 Glargine 1.00 'Building on Lilly's legacy of innovation in insulin therapy, once-weekly efsitora may offer a significant advancement for people with type 2 diabetes who need insulin by eliminating over 300 injections per year,' said Jeff Emmick, M.D., Ph.D., senior vice president of product development at Lilly. 'These results reinforce the potential for once-weekly efsitora to help reduce the overall burden of insulin therapy through a simplified treatment approach. We look forward to working with regulatory agencies to bring this innovation to patients around the world.' Across the three trials, efsitora demonstrated an overall safety profile similar to two of the most commonly used daily basal insulin therapies for the treatment of type 2 diabetes. In QWINT-1, efsitora resulted in approximately 40% fewer hypoglycemic events compared to insulin glargine, with estimated combined rates of severe or clinically significant hypoglycemic events per patient-year of exposure of 0.50 with efsitora vs. 0.88 with insulin glargine at 52 weeks. In QWINT-3, these rates were 0.84 with efsitora vs. 0.74 with insulin degludec at 78 weeks. In QWINT-4, estimated combined rates of severe or clinically significant hypoglycemic events per patient-year of exposure were 6.6 with efsitora vs. 5.9 with insulin glargine at 26 weeks. Lilly plans to submit efsitora for the treatment of adults with type 2 diabetes to global regulatory agencies by the end of this year. About the QWINT clinical trial programThe QWINT Phase 3 global clinical development program for insulin efsitora alfa (efsitora) in diabetes began in 2022 and has enrolled more than 3,000 people living with type 2 diabetes across four global registration studies. QWINT-1 (NCT05662332) was a parallel-design, open-label, treat-to-target, randomized controlled clinical trial comparing the efficacy and safety of efsitora as a once-weekly basal insulin using a fixed dose escalation to daily insulin glargine for 52 weeks in insulin-naïve adults with type 2 diabetes. The trial randomized 795 participants across the U.S., Argentina and Mexico to receive efsitora once weekly or insulin glargine once daily, administered subcutaneously. Participants treated with efsitora received a starting dose of 100 units of insulin, followed by escalation to fixed dosages of 150 units, 250 units and 400 units every four weeks, as needed, until achieving a target fasting blood glucose of 80-130 mg/dL. Participants with fasting blood glucose greater than 130 mg/dL on or after 16 weeks were transferred to flexible dosing. The primary objective of the trial was to demonstrate non-inferiority in reducing A1C at week 52 with efsitora compared to daily use of insulin glargine. QWINT-3 (NCT05275400) was a multicenter, randomized, parallel-design, open-label trial comparing the efficacy and safety of efsitora as a once-weekly basal insulin to insulin degludec for 78 weeks after a three-week lead-in followed by a five-week safety follow up period, in adults with type 2 diabetes who are currently treated with basal insulin. The trial randomized 986 participants across the U.S., Argentina, Hungary, Japan, Korea, Poland, Puerto Rico, Slovakia, Spain and Taiwan to receive efsitora once weekly or insulin degludec once daily, administered subcutaneously. The primary objective of the study was to demonstrate non-inferiority in reducing A1C at week 26 with efsitora compared to insulin degludec. QWINT-4 (NCT05462756) was a parallel-design, open-label, treat-to-target, randomized controlled clinical trial comparing the efficacy and safety of efsitora as a weekly basal insulin to insulin glargine for 26 weeks in adults with type 2 diabetes who have previously been treated with basal insulin and at least two injections per day of mealtime insulin. The trial randomized 730 participants across the U.S., Argentina, Germany, India, Italy, Mexico, Puerto Rico and Spain to receive efsitora once weekly or insulin glargine once daily, both of which were administered subcutaneously along with insulin lispro. The primary objective of the trial was to demonstrate non-inferiority in reducing A1C at week 26 with efsitora compared to insulin glargine. About insulin efsitora alfaInsulin efsitora alfa (efsitora) is a once-weekly basal insulin, a fusion protein that combines a novel single-chain variant of insulin with a human IgG2 Fc domain. It is specifically designed for once-weekly subcutaneous administration, and with its low peak-to-trough ratio, it has the potential to provide more stable glucose levels (less glucose variability) throughout the week. About Lilly Lilly is a medicine company turning science into healing to make life better for people around the world. We've been pioneering life-changing discoveries for nearly 150 years, and today our medicines help tens of millions of people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges: redefining diabetes care; treating obesity and curtailing its most devastating long-term effects; advancing the fight against Alzheimer's disease; providing solutions to some of the most debilitating immune system disorders; and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we're motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. To learn more, visit and or follow us on Facebook, Instagram, and LinkedIn. P-LLY The efficacy estimand represents the treatment effect on all participants who adhered to the study drug without initiating rescue therapy for persistent severe hyperglycemia. From a baseline of 8.20% for efsitora and 8.28% for insulin glargine. Participants treated with efsitora received a starting dose of 100 units of insulin, followed by escalation to fixed dosages of 150 units, 250 units and 400 units every four weeks, as needed, until achieving a target fasting blood glucose of 80-130 mg/dL. Participants with fasting blood glucose greater than 130 mg/dL on or after 16 weeks were transferred to flexible dosing. From a baseline of 7.80% for both efsitora and insulin degludec. From a baseline of 8.18% for both efsitora and insulin glargine. The treatment-regimen estimand represents the estimated average treatment effect regardless of treatment discontinuation or introduction of rescue therapy for persistent severe hyperglycemia. Blood glucose <54 mg/dL. Nocturnal hypoglycemia was defined as any event that occurred at night between midnight and 6 a.m. Cautionary Statement Regarding Forward-Looking StatementsThis press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about insulin efsitora alfa as a potential treatment for people with type 2 diabetes and the timeline for future readouts, presentations, and other milestones relating to insulin efsitora alfa and its clinical trials and reflects Lilly's current beliefs and expectations. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of drug research, development, and commercialization. Among other things, there is no guarantee that future study results will be consistent with study results to date, that insulin efsitora alfa will prove to be a safe and effective treatment for type 2 diabetes, that insulin efsitora alfa will receive regulatory approval, or that Lilly will execute its strategy as expected. For further discussion of these and other risks and uncertainties that could cause actual results to differ from Lilly's expectations, see Lilly's Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this release. Trademarks and Trade NamesAll trademarks or trade names referred to in this press release are the property of the company, or, to the extent trademarks or trade names belonging to other companies are referenced in this press release, the property of their respective owners. Solely for convenience, the trademarks and trade names in this press release are referred to without the ® and ™ symbols, but such references should not be construed as any indicator that the company or, to the extent applicable, their respective owners will not assert, to the fullest extent under applicable law, the company's or their rights thereto. We do not intend the use or display of other companies' trademarks and trade names to imply a relationship with, or endorsement or sponsorship of us by, any other companies. Refer to: Niki Biro; niki_biro@ 317-358-9074 (Media) Michael Czapar; czapar_michael_c@ 317-617-0983 (Investors)
Medscape
21-06-2025
- Health
- Medscape
Orforglipron Lowers A1c, Weight in Early Type 2 Diabetes
CHICAGO — The investigational non-peptide small-molecule oral GLP-1 agonist orforglipron significantly reduced A1c over 40 weeks in adults with early type 2 diabetes, according to the results of ACHIEVE-1 sponsored by Eli Lilly. In the trial, orforglipron reduced A1c to the 6.5% range and produced clinically meaningful weight loss with a safety profile similar to that of other GLP-1 drugs. ACHIEVE-1 is the first of seven phase 3 studies of the safety and efficacy of the drug in over 6000 patients with type 2 diabetes and obesity, Orforglipron and other similar non-peptide small molecules "have the potential to be widely accepted as a much earlier therapy for type 2 diabetes," Julio Rosenstock, MD, senior scientific advisor for Velocity Clinical Research and clinical professor of medicine at the University of Texas Southwestern Medical Center, Dallas, said at a press briefing here at the American Diabetes Association (ADA) 85th Scientific Sessions. The findings were simultaneously published in the New England Journal of Medicine . Orforglipron is a once-daily non-peptide small molecule that can be taken any time of day without restrictions on meals or water intake. This contrasts with the currently approved oral GLP-1 receptor agonist semaglutide (Rybelsus, Novo Nordisk), a peptide that ideally should be taken while fasting and with no food or water for at least 30 minutes after ingestion to prevent degradation. Lilly is the farthest along in the development of a small-molecule non-peptide GLP-1 agonist, but at least two others are in phase 3 trials, including CX11 (also known as VCT220) from Corxel Pharmaceuticals and HRS-7535 from Jiangsu Hengrui Pharmaceuticals and Kailera Therapeutics. Several more are in phase 2 trials. As a class, the oral non-peptide small-molecule GLP-1 receptor agonists "have the potential to open the access for more people because they're easier to take, they're simpler to produce, and in theory, they should be less expensive. So you can see the potential for these drugs," Rosenstock said. However, Amy E. Rothberg, MD, clinical professor of internal medicine and of nutritional sciences at the University of Michigan, Ann Arbor, told Medscape Medical News that she's concerned because, unlike injectable GLP-1 receptor agonists, "most oral medications are metabolized by the liver. The enzymes that metabolize them may be affected by people's weight. Therefore, if you have obesity, the distribution and the kinetics of the drug may be different than someone who is normal weight. Also, if someone loses weight from having a higher BMI to a lower weight, that may affect the drug distribution and the drug bioavailability." She believes that "the companies need to look at drug exposure before and after weight loss because efficacy and safety could be affected by weight change." First Phase 3 Orforglipron Data Meets Endpoints In ACHEIVE-1, 559 participants with early (duration range, 4.0-5.1 years) type 2 diabetes with A1c levels of 7.0%-9.5% (mean 8.0%) using only diet and exercise and a BMI 23.0 kg/m2 or greater, were randomized equally to receive orforglipron 3 mg, 12 mg, or 36 mg, or placebo once daily for 40 weeks. The primary endpoint, percentage-point change in A1c from baseline to week 40, showed reductions of 1.24, 1.47, 1.48 for the 3-mg, 12-mg, and 36-mg doses, respectively, compared with a 0.41 percentage-point reduction with placebo. All three orforglipron doses produced significant A1c reductions compared with placebo ( P < .001 for all comparisons). At week 40, the mean A1c level ranged from 6.5% to 6.7% with orforglipron, Rosenstock reported. Percentage of body weight losses from baseline to week 40 were 4.5%, 5.8%, and 7.6% for the 3-mg, 12-mg, and 36-mg doses, respectively, versus 1.7% with placebo. The most common adverse events were mild-to-moderate gastrointestinal events, most of which occurred during dose escalation. Gastrointestinal events leading to drug discontinuation occurred in 2.8%, 2.2%, and 5.7% of patients, respectively, for the three orforglipron doses, versus none with placebo. This was similar to what has been observed with other oral and injected GLP-1 agonists, Rosenstock said. "We did not see any surprises. You're going to see the same ranges of nausea and vomiting as with semaglutide and tirzepatide." There were no episodes of severe hypoglycemia. The overall proportions discontinuing permanently due to adverse events ranged from 4% to 8% with orforglipron versus 1% with placebo. "A Remarkable Scientific Achievement" Asked to comment, Simeon Taylor, MD, PhD, professor of medicine and director of the Institutional Research Training Program in Diabetes & Obesity at the University of Maryland School of Medicine, Baltimore, told Medscape Medical News : "This landmark scientific achievement ushers in a new chapter in the development of GLP-1 agonists." Taylor pointed out that "orforglipron's glycemic efficacy is only slightly less than monotherapy with Ozempic" and that it "has somewhat more placebo-subtracted weight loss efficacy in people with type 2 diabetes" than Ozempic. Overall, he said, "It is a remarkable scientific achievement to have developed a first-in-class orally bioavailable organic chemical entity with efficacy comparable to a third-generation injectable peptide drug. It is likely that many people with type 2 diabetes will be attracted to the option of an orally bioavailable drug." The other four ACHIEVE trials, to be reported later in 2025, will examine orforglipron in combination with metformin versus dapagliflozin (ACHIEVE-2), in combination with metformin compared to oral semaglutide (ACHIEVE-3), combined with multiple therapies versus insulin glargine (ACHIEVE-4), and in combination with insulin versus placebo (ACHIEVE-5). Another Lilly phase 3 trial, ATTAIN, is evaluating orforglipron for weight management. Results from ATTAIN-1 and ATTAIN-2 will also be presented later in 2025. "Lilly remains on track to submit orforglipron for weight management to global regulatory agencies by the end of this year and for the treatment of type 2 diabetes in 2026," according to a company statement. Rosenstock has reported receiving research/grant support from, serving on advisory boards for, and/or receiving consulting fees/honoraria from Applied Therapeutics, AstraZeneca, Biomea Fusion, Boehringer Ingelheim, Corcept, Eli Lilly, Hanmi, Merck, Novartis, Novo Nordisk, Oramed, Pfizer, Regeneron, Regor, Roche, Sanofi, Structure Therapeutics, and Terns. Taylor has reported receiving payments from the National Institute of Diabetes and Digestive and Kidney Diseases for an inventor's share of a patent covering metreleptin as a treatment for generalized lipodystrophy. He was employed by Eli Lilly in 2000-2002 and Bristol Myers Squibb in 2002-2013.
