Amylin is the second pancreatic hormone (after insulin) that Novo Nordisk and a handful of competitors are now building obesity drugs around. Amylin agonists slow gastric emptying, suppress glucagon secretion, and produce satiety effects that compound the GLP-1 signal.
Lead programs covered on this site: Novo's cagrilintide (long-acting amylin analog) and the CagriSema combination, Lilly's eloralintide, Zealand Pharma's petrelintide, and earlier-stage amylin-receptor agonists from competitors. Amylin biology is increasingly framed as the next add-on layer to GLP-1 therapy after GIP and glucagon.
Stories here cover the REDEFINE readouts, eloralintide and petrelintide trial data, and the combination economics. See #cagrilintide, #cagrisema, and #petrelintide.
Pep2Tango Therapeutics presented preclinical data on PTT-A, a novel long-acting unimolecular peptide tetra-agonist activating the GLP-1, GIP, amylin, and calcitonin receptors simultaneously, in a Medscape 'Moving Beyond GLP-1s' feature drawing from the ADA 2026 session 'Novel Strategies for Obesity Pharmacology' (oral abstracts 85-OR and 299-OR, Diabetes journal supplement). In 21-day chronic studies in diet-induced obese rats, the higher PTT-A dose achieved 19% body weight reduction versus the vehicle, compared to 12% each for tirzepatide and cagrilintide + semaglutide (CagriSema). Body composition analysis showed fat-mass loss without lean-mass loss, distinguishing PTT-A's profile from tirzepatide's documented muscle-loss pattern. PTT-A also showed robust glucose lowering, plasma lipid improvement, insulin sensitization, and liver-fat benefits.
Roche presented ZUPREME-1 Phase 2 data for petrelintide, the once-weekly long-acting amylin analog licensed from Zealand Pharma, at the Monday June 8 investor event. The pitch hinges on tolerability: published topline showed up to 10.7% weight loss at 42 weeks versus 1.7% placebo, with discontinuation 4.8% vs 4.9% placebo and no vomiting at the maximally effective dose. Medical Daily framed the readout as a non-incretin option for the estimated 30-40% of patients who quit GLP-1s for GI side effects. Petrelintide advances to Phase 3 alongside enicepatide.
Genentech confirmed at its Monday investor event that the planned Phase 2 multi-arm fixed-dose combination of petrelintide (amylin analog) and enicepatide (GLP-1/GIP) starts mid-2026. The setup mirrors Novo's CagriSema and Lilly's Mounjaro-plus-amylin work, with Roche aiming for the same dual-mechanism economics that produced REIMAGINE 2's head-to-head win this week. Roche projected $9 billion in peak annual sales for the combined obesity pipeline at its Q1 print.
A Medscape ADA wrap on June 8 framed the post-GLP-1 era taking shape across the meeting: amylin analogs (petrelintide, cagrilintide, eloralintide) targeting GI-intolerance, triagonists (retatrutide), antibody-peptide conjugates (Amgen's maridebart cafraglutide/MariTide), and preclinical acceleration through AI peptide-design platforms. Each angle aims at the population gap that current GLP-1 monotherapy leaves: the patients who quit for tolerability, the ones who plateau, and the ones who need additional metabolic effects beyond appetite.
The 86th ADA Scientific Sessions wrapped Monday June 8 after presenting Phase 3 retatrutide TRIUMPH-1/TRANSCEND-T2D-1, CagriSema REIMAGINE 1/2/3, Foundayo ACHIEVE 1-5, survodutide SYNCHRONIZE-1, petrelintide ZUPREME-1, enicepatide CT388-103, elecoglipron VISTA/SOLSTICE, mazdutide GLORY-2/DREAMS-3, zenagamtide Phase 2, plus the inaugural ADA Standards of Care in Overweight and Obesity. The next inflection points: the July 23-24 PCAC peptide-compounding meeting, August 28 ITM-11 PDUFA in NETs, and the Foundayo T2D filing in Q2.
Novo Nordisk presented Phase 2 data for zenagamtide (formerly amycretin), its unimolecular GLP-1 and amylin receptor agonist, at ADA 2026 in 262 adults with type 2 diabetes randomized across six subcutaneous doses (0.4 to 40 mg) versus placebo. The 40 mg arm cut HbA1c by 1.71 percentage points and reduced body weight by 14.6% at 36 weeks, with nearly 89% of patients reaching HbA1c below 7%. The study met its primary HbA1c endpoint across all doses; Novo plans Phase 3 in H2 2026 and hosted a same-day R&D investor event.
At ADA 2026, Novo Nordisk reported full Phase 3 REIMAGINE 2 data for CagriSema (cagrilintide plus semaglutide fixed-dose combination) in 2,728 adults with type 2 diabetes inadequately controlled on metformin with or without an SGLT2 inhibitor. Over 68 weeks, CagriSema 2.4 mg/2.4 mg produced superior HbA1c reduction of 1.91 percentage points and 14.2% mean weight loss, both better than the semaglutide 2.4 mg, cagrilintide 2.4 mg, and placebo comparator arms. The readout is the first head-to-head Phase 3 win for the dual amylin/GLP-1 combination over its individual components.
Roche will present detailed Phase 2 ZUPREME-1 data for the amylin analog petrelintide as an ADA 2026 late-breaker, with a June 8 investor event. In 493 adults with overweight or obesity (mean BMI 37), once-weekly petrelintide produced up to 10.7% mean weight loss at week 42 versus 1.7% on placebo, with treatment discontinuation of 4.8% versus 4.9% on placebo and no vomiting or GI-related discontinuations at the maximally effective dose. That tolerability is the amylin class's central pitch against the incretins.
Verdiva Bio will present two posters at ADA 2026 on its obesity pipeline: VRB-103, a once-weekly oral amylin-receptor-selective analog, and VRB-104, a unimolecular GLP-1 plus amylin co-agonist. The preclinical data extend the amylin and oral-peptide push from a well-funded newer entrant, as the obesity field broadens beyond incretin monotherapy toward amylin-based and oral approaches.
Ahead of the ADA Scientific Sessions (June 5-8, New Orleans), Novo Nordisk previewed 40 abstracts spanning pivotal Phase 3 CagriSema in the REIMAGINE type 2 diabetes program, new mid-stage data for the amylin/GLP-1 agonist zenagamtide (the molecule previously called amycretin), and IcoSema and semaglutide analyses. Novo said its obesity and diabetes products reached 45.3 million patients by March 2026, with obesity up 58% year over year, and will host an R&D investor event June 7.
Novo Nordisk's AMAZE-12 Phase 3 trial of amycretin — a dual GLP-1 and amylin receptor agonist — began recruiting on May 18, 2026. The trial evaluates amycretin specifically for weight maintenance after initial weight loss, distinguishing it from AMAZE-1 (which measures body weight change over 84 weeks). The amycretin clinical rationale rests on Phase 1 weekly subcutaneous dosing producing 22% weight reduction at 36 weeks and oral formulation producing 13.1% at 12 weeks — both reported in the Lancet earlier in 2026. Amycretin sits within Novo's next-generation pipeline alongside CagriSema (cagrilintide + semaglutide, FDA filing under review with decision expected late 2026) and the orexin-related pipeline acquired via Centessa. The amycretin program is structurally Novo's most direct response to Lilly's retatrutide.
A second body-composition substudy from REDEFINE 1 presented May 14 at ECO 2026 broke out the DXA subgroup by treatment arm. At week 68, CagriSema (cagrilintide 2.4 mg + semaglutide 2.4 mg) produced -23.9% weight reduction in the DXA subgroup, compared with -16.6% on semaglutide 2.4 mg alone, -15.0% on cagrilintide 2.4 mg alone, and -2.8% on placebo. The fat-mass-to-lean-tissue ratios were favorable across all active arms: 66.9% fat-mass contribution on CagriSema, 69.7% on semaglutide, 62.9% on cagrilintide. The cagrilintide monotherapy arm is the first head-to-head body-composition signal for amylin-only therapy at clinically meaningful weight-loss levels — relevant to Zealand and Roche's petrelintide Phase 3 program and the broader amylin-versus-incretin debate.
A prespecified body-composition substudy of REDEFINE 1 presented at ECO 2026 reported that 252 participants on CagriSema 2.4 mg/2.4 mg (semaglutide + cagrilintide) achieved a 35.7% relative reduction in fat mass and a 14.4% reduction in lean soft-tissue mass at week 68 — compared with 5.7% and 4.3% on placebo. The headline 22.7% mean weight reduction in REDEFINE 1 (NEJM publication June 2025) thus broke down with a fat-mass-to-lean-tissue ratio of roughly 2.5:1, a more favorable body-composition profile than the typical 1.5-2:1 ratio reported for GLP-1 monotherapy. The data builds the case for combination amylin-GLP-1 therapy as preferentially fat-selective.
Ascletis Pharma will present multiple poster sessions at ECO 2026 covering programs beyond the already-presented ASC30. ASC47, an adipose-targeting thyroid hormone receptor beta (THRβ) agonist designed for muscle-preserving weight loss, demonstrated up to 111.8% greater relative weight loss when combined with semaglutide vs semaglutide monotherapy in obesity participants. ASC36, a once-monthly next-generation amylin receptor agonist peptide, posted a 32-day average observed half-life — six times longer than Zealand's petrelintide. ASC35, a once-monthly next-generation GLP-1R/GIPR dual agonist peptide, showed a 14-day average observed half-life (six times longer than tirzepatide) and 71% more relative weight loss than tirzepatide in a diet-induced obesity mouse model. Session Thursday May 14, 18:00-19:15 TRT.
Zealand Pharma reported Q1 2026 revenue of DKK 34M against DKK 8M a year earlier and the DKK 17M analyst consensus — a more-than-2× beat on the recognition of Roche's $700M (DKK 4.5B) milestone payment tied to petrelintide's advancement into Phase 3. The board authorized a share buyback of up to DKK 1.3B. Net operating expenses came in at DKK 573M (below the DKK 679M consensus), and the company reaffirmed petrelintide Phase 3 obesity initiation in H2 2026. Petrelintide is the long-acting amylin analog that posted ~10.7% mean weight loss with placebo-like tolerability in ZUPREME-1; the Roche partnership combines it with the GLP-1/GIP enicepatide (CT-388) in a fixed-dose Phase 2 starting mid-2026. Shares rose 8.4% to DKK 344.
Eli Lilly, with the Indiana Biosciences Research Institute, has disclosed an ADA Scientific Sessions Late-Breaking Poster slot (Poster 2839-LB, May 29) for a single peptide molecule that simultaneously activates five receptors: GLP-1, GIP, glucagon, amylin, and calcitonin. Lead investigator Jonathan Douros, PhD, will present rodent data showing weight-loss superiority over retatrutide in Lilly-sponsored animal studies. The compound is distinct from the DiMarchi/Tschöp/Müller GLP-1R/GIPR/PPARα/γ/δ quintuple agonist published in Nature on April 30 — that one is a peptide-drug conjugate combining GLP-1/GIP with the pan-PPAR agonist lanifibranor, while the Lilly + Indiana Biosciences molecule appears to be a single peptide hitting all five receptors directly. Both signal that the obesity-pharmacology ceiling is moving past the triple-agonist generation.
AstraZeneca's ASCEND program is active in Phase 2b, combining AZD9550 (GLP-1 + glucagon dual agonist) with AZD6234 (selective amylin analog) in a two-molecule triple-mechanism strategy aimed at fat-selective weight loss and organ protection. Individual assets are also in Phase 2. The combination reflects the February 2026 $1.2 billion CSPC Pharmaceuticals collaboration that brought both molecules into AstraZeneca's portfolio, alongside elecoglipron (AZD5004 / ECC5004), the small-molecule oral GLP-1 that posted 5.8% weight loss over four weeks in Phase 1b in China. AstraZeneca enters the next-gen obesity race later than Lilly, Novo, Roche, and Boehringer, but the triple-mechanism positioning targets the safety + organ-protection lane that competitors leave open.
Zealand Pharma announced April 29 that it and partner Roche have formally endorsed advancing petrelintide — a long-acting amylin analog suitable for once-weekly subcutaneous administration — into Phase 3 trials for chronic weight management, with initiation planned for H2 2026. The Phase 3 program will evaluate petrelintide as monotherapy and in combination with Roche's GLP-1/GIP receptor dual agonist enicepatide (CT-388). The decision follows positive Phase 2 ZUPREME-1 data showing up to 10.7% weight loss with placebo-like tolerability; petrelintide is now positioned as the lead non-GLP-1 obesity asset behind only Novo's CagriSema.