Recent insulin update
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insulin efsitora alfa Eli Lilly once weekly FDA 2026 biosimilar insulin updates
Here is a comprehensive update on recent insulin developments as of July 2026:
Recent Insulin Updates (2025-2026)
1. Insulin Icodec (Awiqli) - FDA Approved March 26, 2026
This is the biggest insulin news in recent years. The FDA approved insulin icodec-abae (Awiqli, Novo Nordisk) on March 26, 2026 - the first and only once-weekly basal insulin for adults with type 2 diabetes (T2D).
Key Facts
- Formulation: 700 units/mL subcutaneous injection (U-700), administered via the Awiqli FlexTouch pen
- Dosing: Once weekly, on the same day each week
- Indication: Adjunct to diet and exercise for glycemic control in adults with T2D
- NOT approved in pediatric populations; not yet approved for T1D in the US
ONWARDS Phase 3a Program (Basis of Approval)
4 randomized, active-controlled, treat-to-target trials in ~2,680 adults with uncontrolled T2D:
| Trial | Comparison | Key Result |
|---|---|---|
| ONWARDS 1 | vs. Glargine U100 (insulin-naive) | Superior HbA1c reduction (NEJM 2023) |
| ONWARDS 3 | vs. Degludec (insulin-naive) | Noninferior + superior HbA1c reduction (JAMA 2023) |
| ONWARDS 5 | vs. Daily basal analogs with app-guided dosing | Noninferior HbA1c reduction (Ann Intern Med 2023) |
| ONWARDS 6 | vs. Degludec in T1D (basal-bolus) | Evaluated separately (Lancet 2023) |
HbA1c results (ONWARDS 3): Mean HbA1c fell from 8.6% to 7.0% (icodec) vs. 8.5% to 7.2% (degludec); icodec confirmed superior (ETD -0.2%, p=0.002).
Hypoglycemia - Key Safety Concern
- Combined level 2/3 hypoglycemia rates were statistically higher with icodec vs. degludec from week 0-26 (0.35 vs. 0.12 events/patient-year, p=0.01)
- The prolonged half-life (~1 week) means hypoglycemia can be more prolonged and harder to correct - this is the main clinical trade-off
Other Adverse Effects
Injection site reactions, lipodystrophy, pruritus, rash, peripheral edema, weight gain
Regulatory Status
Already approved in the EU and 13 additional countries. US availability expected in coming months.
2. IcoSema - The Next Step: Icodec + Semaglutide Combination
Building on icodec, Novo Nordisk is developing IcoSema - a once-weekly fixed-ratio combination of icodec + semaglutide (GLP-1 RA). Three phase 3 COMBINE trials have been published (2025):
- COMBINE 1 (vs. icodec alone, Lancet Diab Endocrinol Jul 2025, PMID 40482671): IcoSema superior in HbA1c reduction
- COMBINE 2 (vs. semaglutide alone, Diabetologia Apr 2025, PMID 39820580): IcoSema superior in HbA1c reduction
- COMBINE 3 (vs. MDI, Lancet Diab Endocrinol Jul 2025, PMID 40482670): IcoSema noninferior to multiple daily injections
This positions IcoSema as a potential future single-injection per week replacement for complex insulin regimens.
3. Insulin Efsitora Alfa (Eli Lilly) - Pipeline, Potential Approval H2 2026
Eli Lilly's insulin efsitora alfa is also a once-weekly basal insulin (a fusion protein combining a single-chain insulin variant with a human IgG2 Fc domain). Key differences from icodec:
- Fixed dose regimen (unlike icodec which requires titration)
- Phase 3 QWINT program (QWINT-1, -3, -4) demonstrated noninferior HbA1c reduction vs. daily basal insulins
- Results presented at ADA 85th Scientific Sessions 2025 and published in NEJM
- FDA decision expected as early as H2 2026 - would be direct competition to Awiqli
4. Summary: Once-Weekly Insulin Landscape
| Agent | Developer | Status (July 2026) | Mechanism |
|---|---|---|---|
| Icodec (Awiqli) | Novo Nordisk | FDA approved (Mar 2026) | Long-acting albumin-binding basal analog |
| Efsitora alfa | Eli Lilly | Phase 3 complete, FDA filing | IgG2 Fc-fusion basal insulin |
| IcoSema | Novo Nordisk | Phase 3 complete, filing pending | Icodec + semaglutide combo |
5. Clinical Considerations for Practitioners
- Icodec is for T2D only - not currently approved in children or T1D in the US
- Hypoglycemia risk is higher due to the prolonged pharmacodynamic profile - patient selection matters (avoid in those with hypoglycemia unawareness or erratic schedules)
- Dose conversion: When switching from daily basal insulin, the starting dose and titration algorithm differ from daily insulins
- Cost: Icodec is expected to be priced similarly to Tresiba (
$6,000/year wholesale), significantly more expensive than generic glargine ($1,000/year) - Adherence benefit: Reducing injections from 365 to 52 per year may address therapeutic inertia and improve adherence in appropriate patients
Success rate in Bone marrow transplant in AML patient
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Here is a comprehensive, evidence-based summary of BMT (allogeneic hematopoietic cell transplantation) success rates in AML:
Bone Marrow Transplant (Allo-HCT) Success Rates in AML
Overview
Allogeneic hematopoietic cell transplantation (allo-HCT) is the most effective curative strategy for AML, working primarily through the graft-versus-leukemia (GVL) effect - donor immune cells eliminate residual malignant cells. Success rates vary significantly by several key factors.
Survival Rates by Disease Status at Transplant
This is the single most important determinant of outcome:
| Disease Status at Transplant | Survival |
|---|---|
| First Complete Remission (CR1) | 55-60% long-term disease-free survival |
| Early-stage AML (CR) | 58% 3-year OS |
| Second Remission / First Relapse | 45-50% cure rate |
| Advanced / Active disease (non-CR) | ~29-30% 3-year OS |
| Refractory (no CR after induction) | ~30% with immediate transplantation |
"The best results with allogeneic transplantation are achieved when applied during first remission, with long-term disease-free survival rates averaging 55-60%." - Harrison's Principles of Internal Medicine 22E (2025)
The CIBMTR and National Marrow Donor Program report an overall 65% survival rate for AML patients undergoing stem cell transplantation (City of Hope data), compared to only 24% 5-year survival without transplant.
Survival by ELN Cytogenetic/Molecular Risk Group
Risk stratification (European LeukemiaNet) is central to transplant decisions:
| Risk Group | Transplant Benefit | Notes |
|---|---|---|
| Adverse risk | Strongly recommended in CR1 | Greatest survival benefit from transplant; highest relapse risk without it |
| Intermediate risk | Recommended in CR1 | HR 0.51 vs. no transplant (significant OS benefit) |
| Favorable risk | Not routinely indicated in CR1 | Meta-analyses show no survival advantage over chemo; use MRD to guide |
- In favorable-risk AML (e.g., CBF leukemias with t(8;21), inv(16)), transplant in CR1 offers no advantage over consolidation chemotherapy
- MRD-guided approach: If MRD-positive after consolidation in favorable-risk AML, transplant is indicated; if MRD-negative in intermediate-risk AML, transplant may be deferred
Survival by Donor Type
| Donor | 2-Year OS | Non-Relapse Mortality (NRM) |
|---|---|---|
| Matched Sibling Donor (MSD) | 62.4% | ~17.5% (lowest) |
| Matched Unrelated Donor (MUD) | 43% | ~32.2% |
| Haploidentical Donor | 25.9-77.9%* | ~43.9% (highest) |
*The wide haploidentical range reflects study population differences - a 2025 study showed 77.9% 1-year OS in elderly AML (haplo vs. 62% with chemo), suggesting haplo-HCT is viable when MSD unavailable.
Age and Fitness Considerations
- Transplant can be performed up to age 80, but outcomes decline with age
- Elderly patients (≥55-60 years):
- Reduced-intensity conditioning (RIC) is used instead of myeloablative conditioning (MAC) to reduce toxicity
- RIC in patients ≥70 years paradoxically increases NRM; nonmyeloablative conditioning improves tolerability
- Haploidentical HSCT shows superior outcomes vs. chemotherapy alone in patients ≥55 years (1-year OS 77.9% vs. 62%; relapse rate 16.5% vs. 56.6%)
- A Flu/Mel + Tac/Sir conditioning protocol (City of Hope, 2026) demonstrated a promising 5-year OS and LFS of 55% and 54% respectively in AML
Special Case: Acute Promyelocytic Leukemia (APL)
APL is treated differently - autologous HCT in CR2 actually outperforms allogeneic HCT in APL:
- Autologous HSCT in APL CR2: 82.4% 2-year OS
- Allogeneic HSCT in APL CR2: 64.3% 2-year OS
Key Complications Affecting Success
| Complication | Impact |
|---|---|
| Relapse | ~60% of late deaths post allo-HCT |
| GVHD | ~15% of deaths; also provides GVL benefit |
| Graft rejection | ~10% of deaths |
| Infection | ~15% of deaths (more common than autologous due to prolonged immunosuppression) |
| NRM at Day +100 | 6% with optimal RIC regimens; higher with MAC in older patients |
Summary Table
| Scenario | Expected 5-Year OS/DFS |
|---|---|
| CR1, favorable risk, no transplant | ~65% (chemo alone) |
| CR1, intermediate/adverse risk, MSD transplant | 55-65% |
| CR1, adverse risk, MUD transplant | ~43% |
| CR2 / first relapse transplant | 45-50% |
| Active/refractory disease at transplant | 29-30% |
| No transplant (overall adult AML) | ~24% |
The key principle: transplant in CR1 with the best available donor offers the highest chance of cure, particularly for intermediate and adverse-risk AML. Timing and disease status at transplant are as important as donor choice.
- Harrison's Principles of Internal Medicine 22E (2025), p. 963
- Fishman's Pulmonary Diseases and Disorders, p. 2186
- PMC Systematic Review 2025 - Allo-HSCT in Adult AML
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