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. 2025 Oct 6.
doi: 10.1007/s13300-025-01799-4. Online ahead of print.

Efficacy and Safety of Once-Weekly Insulin Icodec in Indian Participants with Diabetes: Results from ONWARDS 1, 4, and 6 Studies

Viswanathan Mohan  1 , Jothydev Kesavadev  2 , L Sreenivasa Murthy  3 , Gayathri Anil  4 , Manu Chandrappa  5 , Soumitra Kar  4 , Sunil Mishra  6
Affiliations

Efficacy and Safety of Once-Weekly Insulin Icodec in Indian Participants with Diabetes: Results from ONWARDS 1, 4, and 6 Studies

Viswanathan Mohan et al. Diabetes Ther. .

Abstract

Introduction: These analyses explored the efficacy and safety of once-weekly insulin icodec (icodec) in Indian participants with type 1 or type 2 diabetes (T1D/T2D) from the global ONWARDS 1, 4, and 6 studies.

Methods: This was a subgroup analysis of Indian participants enrolled in the multicentre, randomised, treat-to-target phase 3a studies: ONWARDS 1 (insulin-naïve T2D), ONWARDS 4 (basal-bolus treated T2D), and ONWARDS 6 (basal-bolus treated T1D). Participants were randomised 1:1 to receive once-weekly insulin icodec or once-daily comparator insulin (glargine U100 [ONWARDS 1 and 4] or degludec [ONWARDS 6]). The primary outcome was change in glycated haemoglobin (HbA1c) from baseline to week 52 for ONWARDS 1, week 26 for ONWARDS 4 and 6.

Results: A total of 217 Indian participants were included. The estimated treatment differences (95% confidence interval, CI) in HbA1c change for icodec versus once-daily comparator were 0.04% [- 0.46; 0.54], - 0.04% [- 0.41; 0.32], and 0.08% [- 0.67; 0.82] in ONWARDS 1, 4, and 6 studies, respectively. Time in range was similar between groups in the three studies. Icodec showed numerically lower rates of clinically significant hypoglycaemia compared to glargine U100 in ONWARDS 1 and 4, though a numerically higher rate of hypoglycaemic events was noted in ONWARDS 6 compared with degludec; results were consistent with global populations. Adverse event profiles were similar between groups, and no new safety findings were reported in the Indian subpopulation.

Conclusion: Icodec demonstrated comparable efficacy and safety to once-daily basal insulins in Indian participants with T1D and T2D. These findings support icodec as a viable option for insulin initiation or intensification in Indian clinical practice.

Trial registrations: ONWARDS 1: NCT04460885; ONWARDS 4: NCT04880850; ONWARDS 6: NCT04848480.

Keywords: Basal insulin; Indian subpopulation; Insulin icodec; Once-weekly insulin; Type 1 diabetes; Type 2 diabetes.

Plain language summary

People with diabetes often need insulin to manage their blood sugar levels. Individuals with type 1 diabetes must inject insulin daily because their bodies do not produce insulin. In type 2 diabetes, the body either does not use insulin well or does not produce enough. While other treatments may be used first, many with type 2 diabetes also eventually require insulin injections. Taking daily injections can be difficult, leading to missed doses and suboptimal blood sugar control. Insulin icodec is a new, long-acting insulin taken just once a week. This study examined Indian participants from three global trials that tested icodec in people with type 1 or type 2 diabetes, who were either new to or already on insulin. The study found that Indian participants using icodec had similar improvements in blood sugar as those taking daily insulin. The amount of time their blood sugar stayed within a healthy range was comparable between the groups. In people with type 2 diabetes, icodec caused fewer episodes of low blood sugar (hypoglycaemia), while those with type 1 diabetes had slightly more episodes. These results are similar to the overall global study population. Most side effects were mild or moderate, similar to those observed with daily insulin in other global studies. This suggests that once-weekly insulin icodec could be a convenient and effective option for people with diabetes in India. It may improve treatment adherence and reduce the burden of daily injections, making it easier for people to manage their diabetes.

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Conflict of interest statement

Declarations. Conflict of Interest: Dr. Viswanathan Mohan reports grants and honoraria from Novo Nordisk, Abbott, Medtronic, Sanofi, Servier, Boehringer Ingelheim, Eli Lilly, Johnson & Johnson, Lifescan, Roche, MSD, Novartis, Bayer, USV, Dr. Reddy’s, Sun Pharma, INTAS, Lupin, Glenmark, Zydus, IPCA, Torrent, Cipla, Biocon, Primus, Franco-Indian, Wockhardt, Emcure, Mankind, Fourrts, Apex, GSK, and Alembic. Dr. Jothydev Kesavadev reports honoraria from Novo Nordisk, Abbott, Medtronic, Boehringer Ingelheim and Eli Lilly; has participated in studies sponsored by Novo Nordisk, Eli Lilly, Boehringer Ingelheim, and Sun Pharma and research funding from Roche, and MSD. Dr. L Sreenivasa Murthy reports research grants from Novo Nordisk, Eli Lilly, Servier, Torrent, Sun Pharma, Sanofi India, AstraZeneca. and Bayer; speaker for Eli Lilly, AstraZeneca, J&J, USV, Micro Labs, Torrent Pharma, Sun Pharma, Alkem, Servier, Lupin, Abbott India, Cipla, Mankind Pharma, Eris Pharma, and Intas Pharma. Dr. Sunil Mishra reports honoraria from Sanofi India, Boehringer Ingelheim, Novo Nordisk, Eli Lilly and Cipla. Dr. Gayathri Anil and Soumitra Kar are employees and shareholders of Novo Nordisk Service Centre India Private Ltd., Bengaluru, India. Dr. Manu Chandrappa is an employee of Novo Nordisk Singapore Pharma Pvt. Ltd. and is a shareholder of Novo Nordisk A/S. Ethical Approval: The studies were conducted in accordance with the Declaration of Helsinki, Good Clinical Practice guidelines and International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. Before initiation of the studies, the protocol, consent form, and subject information sheets were reviewed and approved by the appropriate health authorities and an independent ethics committee/institutional review board, in compliance with local regulations. All protocol amendments and subsequent versions were also reviewed and approved, where required, in compliance with local regulations before implementation.

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