The lancet. Diabetes & endocrinologyMay 6, 2023

Switching from daily to once-weekly insulin in people with type 2 diabetes using daily basal insulin

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 5, 2026

Abstract

HbA1c was reduced to a greater extent with icodec than with degludec after 26 weeks.

Icodec reduced HbA1c from a baseline of 8.17% to 7.20%, while degludec reduced it from 8.10% to 7.42%.
The estimated treatment difference for HbA1c between icodec and degludec was -0.22 percentage points, demonstrating both non-inferiority and superiority of icodec.
Participants treated with icodec experienced an average body weight increase of +1.40 kg, compared to a decrease of -0.30 kg for those on degludec.
Rates of combined level 2 or level 3 hypoglycaemia were low for both treatments, with 0.73 events per patient-year for icodec and 0.27 for degludec.
A higher proportion of participants receiving icodec (61%) experienced any adverse event compared to those receiving degludec (51%), but serious adverse events were similar between groups.

Simplified

BACKGROUND: Insulin icodec (icodec) is a once-weekly basal insulin currently under development. ONWARDS 2 aimed to assess the efficacy and safety of once-weekly icodec versus once-daily insulin degludec (degludec) in basal insulin-treated type 2 diabetes.

METHODS: This 26-week, randomised, open-label, active-controlled, multicentre, treat-to-target phase 3a trial was conducted in 71 sites in nine countries. Eligible participants with type 2 diabetes inadequately controlled on once-daily or twice-daily basal insulin, with or without non-insulin glucose-lowering agents, were randomly assigned (1:1) to once-weekly icodec or once-daily degludec. The primary outcome was change from baseline to week 26 in HbA; the margin used to establish non-inferiority of icodec compared with degludec was 0·3 percentage points. Safety outcomes (hypoglycaemic episodes and adverse events) and patient-reported outcomes were also assessed. The primary outcome was evaluated in all randomly assigned participants; safety outcomes were evaluated descriptively based on all randomly assigned participants who received at least one dose of trial product, with statistical analyses based on all randomly assigned participants. This trial is registered with ClinicalTrials.gov, NCT04770532, and is now complete. 1c

FINDINGS: Between March 5 and July 19, 2021, 635 participants were screened, of whom 109 were ineligible or withdrew, and 526 were randomly assigned to icodec (n=263) or degludec (n=263). From a mean baseline of 8·17% (icodec; 65·8 mmol/mol) and 8·10% (degludec; 65·0 mmol/mol), HbAwas reduced to a greater extent with icodec than degludec (7·20% vs 7·42% [55·2 vs 57·6 mmol/mol], respectively) at week 26. This translates to an estimated treatment difference (ETD) of -0·22 percentage points (95% CI -0·37 to -0·08) or -2·4 mmol/mol (95% CI -4·1 to -0·8), demonstrating non-inferiority (p<0·0001) and superiority (p=0·0028). The estimated mean change from baseline to week 26 in bodyweight was +1·40 kg for icodec and -0·30 kg for degludec (ETD 1·70 [95% CI 0·76 to 2·63]). Overall rates of combined level 2 or level 3 hypoglycaemia were less than one event per patient-year of exposure for both groups (0·73 [icodec] vs 0·27 [degludec]; estimated rate ratio 1·93 [95% CI 0·93 to 4·02]). Overall, 161 (61%) of 262 participants receiving icodec and 134 (51%) of 263 participants receiving degludec experienced an adverse event; 22 (8%) and 16 (6%), respectively, experienced a serious adverse event. One serious adverse event (degludec) was assessed as being possibly related to treatment. No new safety issues were identified in relation to icodec compared with degludec in this trial. 1c

INTERPRETATION: Among adults with basal insulin-treated type 2 diabetes, treatment with once-weekly icodec versus once-daily degludec demonstrated non-inferiority and statistical superiority in HbAreduction after 26 weeks, associated with modest weight gain. Overall rates of hypoglycaemia were low, with numerically but not statistically significantly higher event rates of level 2 or level 3 hypoglycaemia with icodec versus degludec. 1c

FUNDING: Novo Nordisk.

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Competing interests

Declaration of interests AP-T performs research and serves as an advisor on behalf of their employer for Abbott, Dexcom, Eli Lilly, Medtronic, Novo Nordisk, and Sanofi; there have been no direct or indirect transfer of funds. EF serves as an advisor for Boehringer-Ingelheim, Eli Lilly, and Novo Nordisk, and has received lecture fees from Bayer, Bioton, Boehringer-Ingelheim, Eli Lilly, and Servier. TJ, MA, and KS are employees and shareholders of Novo Nordisk. JR has served on advisory panels for Applied Therapeutics, Boehringer Ingelheim, Eli Lilly, Intarcia, Novo Nordisk, Oramed, Hanmi, Sanofi, and Zealand, and has received research support from Applied Therapeutics, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Genentech, Novartis, Intarcia, Merck, Novo Nordisk, Oramed, Pfizer, and Sanofi. HW acted as an advisory board member for Novo Nordisk, as a speaker for Astellas Pharma, AstraZeneca, Eli Lilly Japan, FUJIFILM Pharma, Kissei Pharmaceutical, Kowa Pharmaceutical, Merck Sharp & Dohme, Mitsubishi Tanabe Pharma, Nippon Boehringer Ingelheim, Novartis, Novo Nordisk, Ono Pharmaceutical, Sanofi, Sanwa Kagaku Kenkyusho, Sumitomo Dainippon Pharma, and Takeda Pharmaceutical, and is receiving grants from Astellas Pharma, AstraZeneca, Daiichi Sankyo, Eli Lilly Japan, Johnson & Johnson, Kowa, Kyowa Hakko Kirin, Merck Sharp & Dohme, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Nippon Boehringer Ingelheim, Novartis Pharma, Novo Nordisk Pharma, Ono Pharmaceutical, Pfizer Japan, Sanofi, Sumitomo Dainippon Pharma, Taisho Toyama Pharmaceutical, Takeda Pharmaceutical, and Terumo. MK received honoraria for speaker's bureau or advisory board attendance with Abbott Diabetes Care, AstraZeneca, Bayer AG, Boehinger Ingelheim, Eli Lilly, MSD, Novo Nordisk, and Sanofi, and has also participated in randomised controlled trials funded by AstraZeneca, Eli Lilly, and Novo Nordisk.

PubMed

Switching from daily to once-weekly insulin in people with type 2 diabetes using daily basal insulin

Abstract

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Competing interests

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