Drug Update · Endocrinology

FDA Approves Insulin Icodec (Awiqli) for Type 2 Diabetes: 0.22% HbA1c Reduction in ONWARDS 3

July 16, 2026

FDA approval date

2026-03-26

Primary efficacy (ONWARDS 3)

ETD in HbA1c -0.22 percentage points versus insulin degludec U-100 at 26 weeks (95% CI -0.35 to -0.09)

ONWARDS 3 hypoglycemia (week 0-26)

combined level 2 or 3 hypoglycemia 0.35 vs 0.12 events per patient-year exposure (icodec vs degludec); P = .01

Recommended starting dose (insulin‑naïve)

70 units once-weekly

Clinical Perspective

This approval affects clinicians treating adults with type 2 diabetes who are considering initiation of basal insulin or switching from daily basal insulin, since Awiqli provides a once-weekly basal insulin option for adjunctive glycemic control ^[2]^[3]. The source-confirmed trial data show that once-weekly icodec produced greater HbA1c reductions versus once-daily degludec and versus insulin glargine U-100 in randomized trials, and the label provides a recommended 70-unit weekly starting dose in insulin‑naïve patients and detailed switching algorithms for patients on daily basal insulin ^[1]^[3]^[2]. How the observed trial signal of higher combined level 2 or 3 hypoglycemia rates with icodec will translate across broader clinical populations and routine care remains to be defined?

Dr. Amit Desai · Endocrinology

The FDA approved insulin icodec (Awiqli) for use as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus on March 26, 2026, based on phase 3 trial evidence including ONWARDS 3 showing an estimated treatment difference in HbA1c of -0.22 percentage points versus once-daily insulin degludec U-100 at 26 weeks ^[3]^[1]^[2]. The approval is supported by multiple randomized trials comparing once-weekly icodec with once-daily basal insulins, and by prescribing information describing recommended initiation and switching regimens ^[3]^[2].

Clinical Context

Insulin icodec (Awiqli) is a long-acting human insulin analog formulated for once-weekly subcutaneous injection and manufactured by Novo Nordisk, marketed as Awiqli (insulin icodec-abae) ^[2]^[3]. The label states that Awiqli binds reversibly to albumin, creating a circulating depot from which insulin icodec-abae is slowly released to provide a stable glucose-lowering effect over a one-week dosing interval; the mechanism description in the prescribing information attributes its activity to activation of the human insulin receptor with pharmacologic effects comparable to human insulin ^[3]. The product is available in single-patient-use FlexTouch pens delivering doses in 10 unit increments at a concentration of 700 units/mL (U-700) and is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus ^[2]^[3]. Clinicians should consult current prescribing information for full dosing guidance.

Key Findings

The randomized, double-blind ONWARDS 3 trial showed once-weekly insulin icodec reduced HbA1c by 0.22 percentage points versus once-daily insulin degludec U-100 (estimated treatment difference -0.22; 95% CI -0.35 to -0.09) at 26 weeks, supporting superiority for HbA1c change in insulin-naïve adults with type 2 diabetes ^[1]^[3].
In a 52-week randomized, open-label trial (Trial A), once-weekly icodec produced an estimated treatment difference in HbA1c of -0.18 percentage points versus insulin glargine U-100 (95% CI -0.29 to -0.08) at 52 weeks, with a higher proportion achieving HbA1c <7% at trial end in the icodec arm (56.52% vs 44.57%) ^[3].
The Awiqli prescribing information specifies the recommended weekly starting dose in insulin‑naïve patients as 70 units administered subcutaneously once-weekly on the same day each week, and provides detailed switching guidance when converting from daily basal insulin regimens ^[2]^[3]. Clinicians should consult current prescribing information for complete dosing guidance.

Safety & Tolerability

Hypoglycemia: Clinical trials and the label identify hypoglycemia as the most common adverse reaction associated with insulin icodec/Awiqli. In ONWARDS 3, combined level 2 or 3 hypoglycemia rates from week 0 to 26 were 0.35 versus 0.12 events per patient-year exposure for icodec versus degludec (P = .01) and were reported as numerically higher for icodec from week 0 to 31 (0.31 vs 0.15 events per patient-year; P = .11) ^[1]^[2]^[3].
Hypersensitivity reactions (including urticaria and facial/lip swelling) are listed in the prescribing information as adverse reactions ^[2].
Injection site reactions and lipodystrophy are identified in the label and highlights as adverse reactions ^[2].
Other adverse reactions named in the prescribing information include pruritus, rash, edema, and weight gain ^[2].

Study Design

The pivotal ONWARDS 3 trial was a randomized, double-masked, noninferiority, treat-to-target, phase 3a trial conducted from March 2021 to June 2022 at 92 sites in 11 countries in adults with type 2 diabetes inadequately controlled on noninsulin therapies; participants were randomized 1:1 to once-weekly icodec plus once-daily placebo (n = 294) or once-daily degludec plus once-weekly placebo (n = 294) with the primary endpoint of change in HbA1c from baseline to week 26 and a noninferiority margin of 0.3 percentage points ^[1]^[3]. The FDA approval is dated March 26, 2026, per the prescribing information ^[3]^[2].

FAQ

Q1 What is insulin icodec (Awiqli) approved for?

A1 Awiqli (insulin icodec-abae) is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. The approved indication is stated in the prescribing information and highlights of prescribing information for Awiqli.

Q2 How does insulin icodec (Awiqli) work?

A2 According to the prescribing information, insulin icodec binds reversibly to albumin, creating a circulating depot from which the insulin is slowly released; when insulin icodec binds to the human insulin receptor it produces the same pharmacological effects as human insulin, resulting in stimulation of peripheral glucose uptake and inhibition of hepatic glucose production to provide a stable glucose-lowering effect over a one-week dosing interval.

Q3 What is the recommended dose of Awiqli?

A3 The prescribing information specifies a recommended weekly starting dose of 70 units administered subcutaneously once-weekly on the same day each week for insulin‑naïve patients; the Awiqli FlexTouch pen delivers doses in 10 unit increments and can deliver up to 700 units in a single injection, and the label includes detailed switching recommendations when converting patients from daily basal insulin to once-weekly Awiqli. Clinicians should consult current prescribing information for complete dosing guidance.

Q4 What are the most common side effects of Awiqli?

A4 The prescribing information lists adverse reactions commonly associated with Awiqli that include hypoglycemia, hypersensitivity reactions (for example urticaria and swelling of the face and lips), injection site reactions, lipodystrophy, pruritus, rash, edema, and weight gain. In the ONWARDS 3 trial, combined level 2 or 3 hypoglycemia rates were reported as 0.35 versus 0.12 events per patient-year exposure for icodec versus degludec from week 0 to 26 (P = .01), and the label warns of risks of hypoglycemia and medication errors when switching regimens.

Clinicians should consult current prescribing information for complete dosing guidance.

FDA Approves Insulin Icodec (Awiqli) for Type 2 Diabetes: 0.22% HbA1c Reduction in ONWARDS 3

FDA Approves Insulin Icodec (Awiqli) for Type 2 Diabetes: 0.22% HbA1c Reduction in ONWARDS 3

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

Study Design

FAQ

References

Get weekly clinical updates for Endocrinology in your inbox.

Related Clinical Updates

FDA Approves Tirzepatide for Obesity: 20.9% Weight Loss in SURMOUNT-1

REDEFINE 1: CagriSema Achieves 20.4% Weight Loss in Adults

FDA Approves orforglipron for Obesity: 11.2% Weight Loss ATTAIN-1

Verified HCP Portal