Quick Comparison
| NN1706 | VK2735 | |
|---|---|---|
| Half-Life | Approximately 14-18 hours, supporting once-daily dosing | Approximately 144-168 hours (6-7 days), supporting once-weekly dosing |
| Typical Dosage | Phase 1 trials: stepwise dose escalation from low microgram doses up to multiple milligrams subcutaneous once daily. Optimal dosing for Phase 2/3 still being established. Daily dosing allows tighter dose adjustment than weekly drugs, at the cost of injection burden. | Phase 2 (subcutaneous): doses of 2.5, 5, 10, and 15 mg once weekly with stepwise escalation. The 15 mg arm produced the maximum weight loss of 14.7% at 13 weeks. Oral formulation in Phase 1: 30-100 mg daily, dose escalation ongoing. |
| Administration | Subcutaneous injection (once daily) | Subcutaneous injection (once weekly); oral tablet formulation in earlier development |
| Research Papers | 1 papers | 1 papers |
| Categories |
Mechanism of Action
NN1706
NN1706 is a once-daily GLP-1/GIP/glucagon triple receptor agonist — Novo Nordisk's mechanistic equivalent to Eli Lilly's retatrutide, designed to activate all three pathways simultaneously in a single molecule. Each receptor contributes complementary metabolic effects: GLP-1 agonism centrally suppresses appetite, slows gastric emptying, and stimulates glucose-dependent insulin secretion; GIP agonism augments insulin response and modulates adipose lipid handling; and glucagon receptor agonism in the liver drives fatty acid oxidation, ketogenesis, and hepatic glucose output, while in brown and beige adipose tissue it promotes thermogenesis and increases whole-body energy expenditure.
The key engineering challenge in any glucagon-containing multi-agonist is balancing glucagon's hyperglycemic tendency against the glucose-lowering effect of GLP-1 and GIP. NN1706's receptor potency ratios are tuned so that incretin-driven insulinotropic effects sufficiently offset glucagon-driven glucose production, producing net glycemic improvement alongside enhanced fat oxidation. The glucagon component is what differentiates triple agonists like NN1706 and retatrutide from dual GLP-1/GIP agonists like tirzepatide — the additional energy-expenditure and hepatic-fat-mobilising effects of glucagon are the main reason triple agonists have produced higher weight-loss numbers in early trials.
The pharmacokinetic profile gives NN1706 a half-life of roughly 14-18 hours, matched to once-daily subcutaneous dosing rather than the once-weekly schedule of retatrutide. The trade-off is more injections per week against tighter dose control, smoother plasma concentrations, and faster ability to adjust or pause dosing if side effects emerge. The first human data published in 2026 from Phase 1 trials in rodents, monkeys, and humans showed meaningful weight loss with an acceptable initial tolerability profile, setting up Phase 2 obesity and type 2 diabetes trials.
VK2735
VK2735 is a once-weekly subcutaneous dual GLP-1/GIP receptor agonist with a structure optimised for high potency and a clean tolerability profile. Dual incretin receptor activation produces complementary effects on appetite, glucose handling, and energy expenditure: GLP-1 receptor agonism delivers central appetite suppression through hypothalamic arcuate-nucleus signalling, slows gastric emptying, and triggers glucose-dependent insulin secretion, while GIP receptor activation amplifies the insulin response, supports beta-cell function, and modulates adipose tissue lipid handling.
The molecule's pharmacokinetic profile delivers sustained receptor exposure across a one-week dosing interval, achieved through structural modifications that enable albumin binding and resistance to proteolytic degradation. In the Phase 2 VENTURE trial, the 15 mg dose produced 14.7% mean body weight loss at 13 weeks — the fastest early weight loss observed for any obesity drug, with the loss curve still descending steeply at trial end. This rapid trajectory suggests substantially greater total weight loss would be achievable with longer dosing, and Phase 3 VANQUISH trials launched in 2026 are testing 68-week treatment durations to characterise the full magnitude of effect.
Viking is also developing an oral tablet formulation of VK2735 in parallel, which entered Phase 1 in 2024-2025. If both formulations succeed, Viking would have one of the most flexible GLP-1/GIP product profiles on the market — though as a small biotech company it faces significant manufacturing and commercial scaling challenges relative to Lilly and Novo Nordisk.
Risks & Safety
NN1706
Common
nausea, vomiting, diarrhea, decreased appetite (similar to other GLP-1 class drugs). Daily dosing produces more even side-effect profile vs weekly peaks but requires daily injections.
Serious
pancreatitis, gallstones, slightly elevated heart rate (signal seen with other glucagon-receptor-active drugs).
Rare
thyroid C-cell tumour class warning, severe allergic reactions. Limited human safety data so far.
VK2735
Common
nausea, vomiting, diarrhea, constipation, decreased appetite, injection site reactions. Discontinuation rates in Phase 2 were broadly similar to other GLP-1/GIP dual agonists.
Serious
pancreatitis, gallstones, possible muscle mass loss.
Rare
thyroid C-cell tumour class warning, severe allergic reactions. Long-term safety being established in Phase 3.
Full Profiles
NN1706 →
Novo Nordisk's answer to retatrutide — a once-daily injection that activates all three of the major appetite and metabolism hormones (GLP-1, GIP, and glucagon). The first human data was published in 2026, showing meaningful weight loss in obese subjects and confirming the daily-dosing mechanism is tolerable. Direct competitor to Lilly's once-weekly retatrutide, with the trade-off of more frequent dosing in exchange for potentially smoother side-effect control and easier dose adjustment.
VK2735 →
Viking Therapeutics' once-weekly weight loss injection that, like tirzepatide, hits both the GLP-1 and GIP receptors. In a 13-week Phase 2 trial it produced 14.7% mean body weight loss — the steepest early loss curve recorded for any obesity drug — and Phase 3 VANQUISH trials began in 2026. An oral tablet version is also in earlier development. Viking is one of the only small biotech companies competing directly with Lilly and Novo Nordisk in the GLP-1 space.