{"id":1892,"date":"2026-06-08T19:32:44","date_gmt":"2026-06-08T19:32:44","guid":{"rendered":"https:\/\/one-peptides.com\/cagrisema-semaglutide-cagrilintide-combination-in-clinical-obesity-research\/"},"modified":"2026-09-29T16:46:18","modified_gmt":"2026-09-29T16:46:18","slug":"cagrisema-semaglutide-cagrilintide-combination-in-clinical-obesity-research","status":"publish","type":"post","link":"https:\/\/one-peptides.com\/de\/cagrisema-semaglutide-cagrilintide-combination-in-clinical-obesity-research\/","title":{"rendered":"CagriSema &#8211; a combination of semaglutide and cagrilintide in clinical trials for obesity"},"content":{"rendered":"<div class=\"op-breadcrumbs\" style=\"margin:0 0 18px;font-size:13px;color:#6b7280;\"><div class=\"aioseo-breadcrumbs\"><span class=\"aioseo-breadcrumb\">\n\t<a href=\"https:\/\/one-peptides.com\/de\/\" title=\"Home\">Home<\/a>\n<\/span><span class=\"aioseo-breadcrumb-separator\">\u00bb<\/span><span class=\"aioseo-breadcrumb\">\n\t<a href=\"https:\/\/one-peptides.com\/de\/category\/metabolism\/\" title=\"Metabolic research\">Metabolic research<\/a>\n<\/span><span class=\"aioseo-breadcrumb-separator\">\u00bb<\/span><span class=\"aioseo-breadcrumb\">\n\tCagriSema \u2013 a combination of semaglutide and cagrilintide in clinical trials for obesity\n<\/span><\/div><\/div>\n<p>The evolution of the pharmacology of obesity treatment in the last decade has been in the sequence of &#8220;adding receptors&#8221; &#8211; from the GLP-1 monoagonist (<a href=\"https:\/\/one-peptides.com\/de\/semaglutide-what-do-we-know-from-clinical-trials\/\">semaglutide<\/a> \u2192 Ozempic, Wegovy), by GLP-1 + GIP agonist (<a href=\"https:\/\/one-peptides.com\/de\/tirzepatide-dual-gip-glp-1-agonist-in-metabolism-research\/\">tirzepatide<\/a> \u2192 Mounjaro, Zepbound), up to the triagonist GLP-1 + GIP + glucagon (<a href=\"https:\/\/one-peptides.com\/de\/retatrutide-triple-agonist-glp-1-gip-glucagon-in-clinical-trials\/\">retatrutide<\/a> in phase III). CagriSema adds to this narrative <strong>a separate signaling pathway &#8211; amylin<\/strong> \u2014 still not through a new molecule, but through <strong>combination of two peptides<\/strong> in one clinical protocol.<\/p>\n<p>The informal shorthand used for retatrutide in online searches is explained in a separate entry: <a href=\"https:\/\/one-peptides.com\/de\/reta-for-weight-loss-diet-what-does-that-mean\/\">the shorthand \u201creta\u201d: terminology explained<\/a>.<\/p>\n<p><strong>CagriSema is a combination of semaglutide (a long-acting GLP-1 analogue) and cagrilintide (a long-acting amylin analogue), developed by Novo Nordisk and currently in phase III clinical trials in the REDEFINE program. The two peptides activate two different satiety signaling pathways simultaneously &#8211; the GLP-1 receptor and the amylin receptor &#8211; which in Phase II clinical trials resulted in higher body weight reduction than with semaglutide monotherapy.<\/strong><\/p>\n<p><em><strong>Regulatory Frame &#8211; A Critical Distinction<\/strong><\/em><\/p>\n<p><em>CagriSema operates in two separate legal statuses:<\/em><\/p>\n<ul>\n<li><em>as <strong>combination of pharmaceutical candidates<\/strong> in phase III clinical trials (REDEFINE Novo Nordisk program), with clinical protocols and full medical supervision<\/em><\/li>\n<\/ul>\n<ul>\n<li><em>as <strong>research reagent (Research Use Only)<\/strong> \u2014 peptides for laboratory research on the GLP-1 + amylin mechanism<\/em><\/li>\n<\/ul>\n<p><em>CagriSema <strong>is not a registered medicine<\/strong> in any major jurisdiction. Semaglutide as <strong>monotherapy<\/strong> is a registered medicine (Ozempic, Wegovy, Rybelsus &#8211; Novo Nordisk). <strong>Cagrilintide as a monotherapy and CagriSema as a combination are not registered.<\/strong> Products marked &#8220;CagriSema&#8221; or &#8220;Sema+Cagri&#8221; in the research peptide catalog operate within the RUO framework &#8211; without protocols for use in humans.<\/em><\/p>\n<h2>What is CagriSema &#8211; a combination of two peptides<\/h2>\n<p>CagriSema is <strong>a combination of two synthetic peptides<\/strong> administered together in one clinical protocol:<\/p>\n<ul>\n<li><strong>Semaglutide<\/strong> \u2014 long-acting GLP-1 analogue (Glucagon-Like Peptide-1) with 31 amino acids, molecular weight ~4113 Da, modified with acylation with C18 fatty acid for binding to albumin and half-life ~7 days<\/li>\n<li><strong>Cagrilintide<\/strong> \u2014 long-acting amylin analogue (Calcitonin Gene-Related Family) designed by Novo Nordisk specifically for combination with semaglutide, modified for a half-life comparable to semaglutide (~7 days)<\/li>\n<\/ul>\n<p>In Novo Nordisk clinical protocols, peptides are administered in one solution, with one subcutaneous injection, once a week. The dose ratio is typically 1:1 (e.g. 2.4 mg semaglutide + 2.4 mg cagrilintide) or in optimized variants. The manufacturer develops the combination as <strong>a combined drug with fixed dose proportions<\/strong> \u2014 that is, a single pharmaceutical preparation containing both peptides in fixed proportions.<\/p>\n<p>The clinical program is run under the name <strong>REDEFINE<\/strong>. In the catalog of research reagents, the same blend of two peptides functions as <a href=\"https:\/\/one-peptides.com\/de\/produkt\/semacagri-pen\/\">Sema+Cagri PEN 2mg+2mg<\/a> \u2014 separate regulatory frame.<\/p>\n<h2>What is cagrilintide &#8211; a long-acting amylin analogue<\/h2>\n<p>Cagrilintide is <strong>a new peptide<\/strong> in the Metabolic Pharmacology Catalog &#8211; not previously described in a separate article in the One Peptides Knowledge Base. It is worth devoting a chapter to it, because understanding the biology of amylin is necessary to explain <strong>why adding cagrilintide to semaglutide makes mechanistic sense<\/strong>.<\/p>\n<h3>Amylin &#8211; endogenous hormone physiology<\/h3>\n<p><strong>Amylin<\/strong> (also known as Islet Amyloid Polypeptide, IAPP) is a peptide consisting of 37 amino acids, produced by pancreatic \u03b2-cells along with insulin. Secreted in response to a meal together with insulin &#8211; in a ratio of approximately 1:100 (one molecule of amylin per 100 molecules of insulin). It performs three main physiological functions:<\/p>\n<ul>\n<li><strong>Slowing down gastric emptying<\/strong> \u2014 prolongs satiety after a meal<\/li>\n<li><strong>Inhibition of post-prandial glucagon secretion<\/strong> \u2014 supports the regulation of glycemia<\/li>\n<li><strong>Central effect on satiety<\/strong> \u2014 signal through the amylin receptor (AMY) within the area postrema<\/li>\n<\/ul>\n<p><strong>Amylin receptor<\/strong> is the assembly of the calcitonin receptor (CTR) with a modulating protein (RAMP &#8211; Receptor Activity Modifying Protein). The three receptor isoforms (AMY1, AMY2, AMY3) differ in RAMP composition and have slightly different tissue distribution. Receptor activation in CNS circuits signals &#8220;satiety&#8221; independently of the GLP-1 axis.<\/p>\n<h3>Cagrilintide &#8211; what was added to amylin<\/h3>\n<p>Endogenous amylin has <strong>very short half-life<\/strong> (~10 minutes) &#8211; which would make it impractical as a weekly medication. Pramlintide (approved by the FDA in 2005 to support insulin therapy in diabetes) has a half-life of only ~50 minutes and requires administration several times daily.<\/p>\n<p>Cagrilintide is <strong>a long-acting amylin analogue<\/strong>, developed by Novo Nordisk with structural modifications extending the half-life to <strong>about 7 days<\/strong> \u2014 comparable to semaglutide. Modifications include:<\/p>\n<ul>\n<li>Fatty chain acylation for binding to serum albumin<\/li>\n<li>Amino acid substitutions stabilizing against proteolysis<\/li>\n<li>Conservation of the amylin receptor recognition domain<\/li>\n<\/ul>\n<p>Thanks to these modifications, cagrilintide can be administered <strong>once a week<\/strong> \u2014 compatible with the semaglutide regimen, which allows for a convenient combination of both peptides in one solution.<\/p>\n<h3>Characterization of cagrilintide<\/h3>\n<table data-border-width=\"1\" style=\"min-width: 50px; border-collapse: collapse; border-spacing: 0px; width: 100%;\">\n<tbody>\n<tr>\n<th style=\"border: 1px solid #d1d5db; padding: 8px 12px;\"><strong>Parameter<\/strong><\/th>\n<th style=\"border: 1px solid #d1d5db; padding: 8px 12px;\"><strong>Value<\/strong><\/th>\n<\/tr>\n<tr>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\">Class<\/td>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\">Long-acting amylin analogue<\/td>\n<\/tr>\n<tr>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\">Producer<\/td>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\">Novell<\/td>\n<\/tr>\n<tr>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\">Number of amino acids<\/td>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\">~37 (amylin analogue)<\/td>\n<\/tr>\n<tr>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\">Molecular mass<\/td>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\">~4,500 Da (estimate)<\/td>\n<\/tr>\n<tr>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\">Structural modifications<\/td>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\">Acylation, stabilizing substitutions<\/td>\n<\/tr>\n<tr>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\">Plasma half-life<\/td>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\">~7 days &#8211; weekly schedule in clinical protocols<\/td>\n<\/tr>\n<tr>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\">Target receptor<\/td>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\">Amylin receptor (AMY) &#8211; CTR + RAMP<\/td>\n<\/tr>\n<tr>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\">Registration status<\/td>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\">No registration as a drug (monotherapy or combination)<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<h2>Mechanism &#8211; two satiety pathways simultaneously<\/h2>\n<p>The hypothesis behind the combination of semaglutide and cagrilintide is simple: <strong>activate two different satiety signaling pathways simultaneously and obtain an additive or synergistic effect<\/strong>, which cannot be achieved in monotherapy. Full physiology of the incretin axis <a href=\"https:\/\/one-peptides.com\/de\/glp-1-gip-glucagon-how-incretins-regulate-metabolism\/\">article about the incretins GLP-1, GIP and glucagon<\/a>.<\/p>\n<h3>Semaglutide &#8211; GLP-1 pathway<\/h3>\n<p>Activation of the GLP-1 receptor modifies:<\/p>\n<ul>\n<li><strong>Pancreatic \u03b2 cells<\/strong> \u2014 increase in glucose-dependent insulin secretion<\/li>\n<li><strong>Pancreatic \u03b1 cells<\/strong> \u2014 inhibition of post-prandial glucagon secretion<\/li>\n<li><strong>Stomach<\/strong> \u2014 slowing down of emptying (prolongation of post-prandial satiety)<\/li>\n<li><strong>Hypothalamus (arcuate nucleus, paraventricular nucleus)<\/strong> \u2014 reduction of appetite, satiety signal in response to peripheral GLP-1 concentration<\/li>\n<\/ul>\n<h3>Cagrilintide &#8211; amylin pathway<\/h3>\n<p>Activation of the amylin receptor modifies:<\/p>\n<ul>\n<li><strong>Stomach<\/strong> \u2014 slowing of emptying (parallel to GLP-1 mechanism)<\/li>\n<li><strong>Pancreatic \u03b1 cells<\/strong> \u2014 inhibition of post-prandial glucagon secretion (complementary to GLP-1)<\/li>\n<li><strong>Area postrema and nucleus of the solitary tract<\/strong> \u2014 satiety signal through <strong>distinct neuroanatomical circuit<\/strong> from GLP-1<\/li>\n<li><strong>Appetite control centers<\/strong> \u2014 modulation of food motivation through pathways independent of the incretin axis<\/li>\n<\/ul>\n<h3>Why a combination can be greater than the sum of its parts<\/h3>\n<p>Main synergy hypothesis: <strong>GLP-1 and amylin signal satiety through distinct neuroanatomical circuits whose activation in monotherapy has a sublimit effect<\/strong>. Satiety in response to the GLP-1 signal is inhibited by counterregulation (e.g., increased expression of Agouti-Related Peptide &#8211; in the arcuate nucleus). The amylin signal can bypass this counterregulation by acting in the area postrema, an anatomically different structure. By combining both signals, the body experiences <strong>stronger subjective feeling of satiety<\/strong> and lower food intake than in monotherapy.<\/p>\n<p>The second hypothesis concerns <strong>stomach emptying<\/strong>. Both peptides slow gastric emptying, but in part through different hormonal and neuronal mechanisms. Combining both may result in a stronger reduction in postprandial glycemia than in monotherapy.<\/p>\n<h2>Status of clinical trials &#8211; REDEFINE program<\/h2>\n<p>CagriSema is one of the high-profile metabolic pharmacology programs of recent years. The clinical program includes early phase II studies (combination of cagrilintide with semaglutide) and advanced phase III studies called <strong>REDEFINE<\/strong>.<\/p>\n<h3>Phase II &#8211; early signals of effectiveness<\/h3>\n<p>In Phase II of the clinical program, Novo Nordisk tested the combination of cagrilintide with semaglutide in patients with obesity (BMI \u226530) and type 2 diabetes. The most frequently cited early data reported <strong>body weight reduction of ~15\u201317% after 32 weeks<\/strong> in the combination group vs ~5\u20136% in the placebo group (Enebo et al. 2021 <em>Lancet<\/em> \u2014 first published Phase 1b\/2a data for this combination).<\/p>\n<h3>Phase III &#8211; REDEFINE program<\/h3>\n<p>Program <strong>REDEFINE<\/strong> includes many phase III studies in various populations:<\/p>\n<ul>\n<li><strong>REDEFINE 1<\/strong> \u2014 obesity without diabetes<\/li>\n<li><strong>REDEFINE 2<\/strong> \u2014 obesity with type 2 diabetes<\/li>\n<li><strong>REDEFINE 3<\/strong> \u2014 direct comparison with treatment standards<\/li>\n<li><strong>REDEFINE 4<\/strong> \u2014 special populations<\/li>\n<\/ul>\n<p>Full results are being published. Lau et al (2021, Lancet) published early phase 2 data for cagrilintide in monotherapy and combination.<\/p>\n<h3>Table: main studies on CagriSema<\/h3>\n<table data-border-width=\"1\" style=\"min-width: 75px; border-collapse: collapse; border-spacing: 0px; width: 100%;\">\n<tbody>\n<tr>\n<th style=\"border: 1px solid #d1d5db; padding: 8px 12px;\"><strong>Test<\/strong><\/th>\n<th style=\"border: 1px solid #d1d5db; padding: 8px 12px;\"><strong>Phase<\/strong><\/th>\n<th style=\"border: 1px solid #d1d5db; padding: 8px 12px;\"><strong>Population<\/strong><\/th>\n<th style=\"border: 1px solid #d1d5db; padding: 8px 12px;\"><strong>Main result<\/strong><\/th>\n<th style=\"border: 1px solid #d1d5db; padding: 8px 12px;\"><strong>Year<\/strong><\/th>\n<\/tr>\n<tr>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\">Enebo et al.<\/td>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\">1b\/2a<\/td>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\">Obesity<\/td>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\">Body weight reduction ~17% (combination) vs ~6% (semaglutide mono) at 20 weeks.<\/td>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\">2021<\/td>\n<\/tr>\n<tr>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\">Lau DCW Lancet<\/td>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\">2<\/td>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\">Obesity<\/td>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\">Dose-finding cagrilintide monotherapy<\/td>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\">2021<\/td>\n<\/tr>\n<tr>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\">REDEFINE 1<\/td>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\">III<\/td>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\">Obesity without diabetes<\/td>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\">Results in the publication phase<\/td>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\">2024+<\/td>\n<\/tr>\n<tr>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\">REDEFINE 2<\/td>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\">III<\/td>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\">Obesity + T2D<\/td>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\">Results in the publication phase<\/td>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\">2024+<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<h2>CagriSema compared to other incretin analogues<\/h2>\n<p>CagriSema&#8217;s position becomes clear in direct comparison with other incretin class molecules. A direct comparison of mono- and tri-agonists can be found in <a href=\"https:\/\/one-peptides.com\/de\/semaglutide-vs-retatrutide-comparison-of-mechanisms-and-clinical-outcomes\/\">comparison of semaglutide and retatrutide<\/a>; full class review in <a href=\"https:\/\/one-peptides.com\/de\/glp-1-peptides-in-metabolic-research\/\">GLP-1 peptide guide<\/a>.<\/p>\n<table data-border-width=\"1\" style=\"min-width: 100px; border-collapse: collapse; border-spacing: 0px; width: 100%;\">\n<tbody>\n<tr>\n<th style=\"border: 1px solid #d1d5db; padding: 8px 12px;\"><strong>Molecule<\/strong><\/th>\n<th style=\"border: 1px solid #d1d5db; padding: 8px 12px;\"><strong>Active receptors<\/strong><\/th>\n<th style=\"border: 1px solid #d1d5db; padding: 8px 12px;\"><strong>Class<\/strong><\/th>\n<th style=\"border: 1px solid #d1d5db; padding: 8px 12px;\"><strong>Registration status<\/strong><\/th>\n<\/tr>\n<tr>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\"><a href=\"https:\/\/one-peptides.com\/de\/produkt\/sema-g-pen-2-mg\/\">Semaglutide<\/a><\/td>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\">GLP-1R<\/td>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\">Monoagonist<\/td>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\">Medicine (Ozempic, Wegovy, Rybelsus &#8211; Novo Nordisk)<\/td>\n<\/tr>\n<tr>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\"><a href=\"https:\/\/one-peptides.com\/de\/produkt\/glp-1gip-5-mg-pen\/\">Tirzepatide<\/a><\/td>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\">GLP-1R + GIPR<\/td>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\">GLP-1R agonist + GIPR<\/td>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\">Medicine (Mounjaro, Zepbound &#8211; Eli Lilly)<\/td>\n<\/tr>\n<tr>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\"><a href=\"https:\/\/one-peptides.com\/de\/produkt\/triple-g-20-mg-pen\/\">Retatrutide<\/a><\/td>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\">GLP-1R + GIPR + GCGR<\/td>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\">Tri-agonist<\/td>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\">Phase III TRIUMPH (no registration)<\/td>\n<\/tr>\n<tr>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\"><strong><a href=\"https:\/\/one-peptides.com\/de\/produkt\/semacagri-pen\/\">CagriSema<\/a><\/strong><\/td>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\"><strong>GLP-1R + amylin receptor<\/strong><\/td>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\"><strong>Combination of two pathways (two peptides)<\/strong><\/td>\n<td style=\"border: 1px solid #d1d5db; padding: 8px 12px;\"><strong>Phase III REDEFINE (no registration)<\/strong><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p>CagriSema <strong>differs in molecular architecture<\/strong> from the others: tirzepatid and retatrutide are <strong>single-molecule peptides<\/strong> activating several receptors simultaneously; CagriSema is <strong>a combination of two separate peptides<\/strong> given together. This is important for researchers evaluating pharmacokinetic and interaction data &#8211; the kinetics of combinations may differ from those of single-molecule dual-agonists.<\/p>\n<h3>CagriSema vs tirzepatide<\/h3>\n<p>The most frequently asked comparison. Both achieve high weight reductions in the clinical phase. Differences:<\/p>\n<ul>\n<li><strong>Mechanism:<\/strong> tirzepatide is a GLP-1+ agonist <strong>GIP<\/strong> (incretin); CagriSema is a GLP-1+ combination <strong>amylin<\/strong> (non-incretin amylin receptor)<\/li>\n<li><strong>Architecture:<\/strong> tirzepatide is <strong>single-molecule peptide<\/strong>; CagriSema is <strong>combination of two peptides<\/strong><\/li>\n<li><strong>Status:<\/strong> tirzepatide is <strong>a registered medicine<\/strong> (Mounjaro, Zepbound); CagriSema remains <strong>in phase III<\/strong><\/li>\n<\/ul>\n<p>A direct comparison between CagriSema and tirzepatide has not yet been published.<\/p>\n<h2>CagriSema \u2013 safety and limitations from clinical trials<\/h2>\n<p>CagriSema&#8217;s safety profile in clinical trials mirrors that of each component individually &#8211; with additional potential for interaction.<\/p>\n<h3>The most frequently reported side effects<\/h3>\n<p>From Phase 1b\/2a (Enebo 2021) and early REDEFINE data:<\/p>\n<ul>\n<li><strong>Gastrointestinal<\/strong> \u2014 nausea predominates (~30\u201340% in some doses), vomiting (~10\u201315%), diarrhea, constipation. Profile typical of the GLP-1 class, with possible enhancement by the action of amylin on gastric emptying<\/li>\n<li><strong>Decreased appetite<\/strong> &#8211; this <strong>desired mechanism<\/strong>, reported as a side effect when it occurs in an intensity that interferes with normal food intake<\/li>\n<li><strong>Low risk of hypoglycemia<\/strong> as monotherapy (both peptides act glucose-dependently); the risk increases when combined with sulfonylureas or insulin<\/li>\n<\/ul>\n<h3>What research has not yet determined<\/h3>\n<ul>\n<li><strong>Long-term cardiovascular profile<\/strong> \u2014 semaglutide has SUSTAIN-6 data showing CV risk reduction; cagrilintide does not have an analogous CV outcome testing program<\/li>\n<li><strong>Pharmacokinetic interactions of two peptides in one solution<\/strong> \u2014 stability of the combination, mutual influence on absorption, distribution profile<\/li>\n<li><strong>Withdrawal profile<\/strong> \u2014 maintaining body weight reduction after completing pharmacotherapy, risk of rebound effect<\/li>\n<li><strong>Special populations<\/strong> \u2014 pregnant or breastfeeding women, patients with severe kidney or liver failure<\/li>\n<\/ul>\n<blockquote>\n<p>\u26a0\ufe0f The security data described above comes from <strong>clinical trials on CagriSema as a combination of pharmaceutical candidates<\/strong> Novo Nordisk. In the context of the RUO research reagent, both peptides are not intended for use in humans &#8211; the clinical protocols of the REDEFINE studies do not translate to the use of laboratory research reagents. For clinical questions regarding molecules, consult your doctor.<\/p>\n<\/blockquote>\n<h2>Frequently asked questions<\/h2>\n<h3>How is CagriSema different from semaglutide?<\/h3>\n<p><a href=\"https:\/\/one-peptides.com\/de\/semaglutide-what-do-we-know-from-clinical-trials\/\">Semaglutide<\/a> Is <strong>GLP-1 receptor monoagonist<\/strong> \u2014 a single molecule activating one signaling pathway. CagriSema is <strong>combination of two peptides<\/strong> (semaglutide + cagrilintide) activating <strong>two different signaling pathways<\/strong> \u2014 GLP-1 and the amylin receptor. Two satiety pathways simultaneously signal the feeling of fullness through <strong>various neuroanatomical circuits<\/strong>, which in clinical trials translated into higher body weight reduction than in semaglutide monotherapy.<\/p>\n<h3>What is cagrilintide?<\/h3>\n<p>Cagrilintide is <strong>long-acting synthetic amylin analogue<\/strong> developed by Novo Nordisk. Amylin is a pancreatic hormone secreted by \u03b2-cells along with insulin in response to a meal; functions to regulate satiety, gastric emptying and postprandial glucagon secretion. Endogenous amylin has a half-life of ~10 minutes &#8211; which is impractical for a weekly drug. Cagrilintide has structural modifications (acylation, amino acid substitutions) extending the half-life to <strong>~7 days<\/strong> \u2014 compatible with semaglutide.<\/p>\n<h3>CagriSema vs tirzepatide \u2013 which is more effective?<\/h3>\n<p>Direct comparison <strong>has not been published yet<\/strong>. <a href=\"https:\/\/one-peptides.com\/de\/tirzepatide-dual-gip-glp-1-agonist-in-metabolism-research\/\">Tirzepatide<\/a> (Mounjaro, Zepbound) is a GLP-1 + GIP agonist in one molecule, registered as a drug. CagriSema is a combination of two peptides (GLP-1 + amylin), in phase III clinical trials. Early results from both programs (SURMOUNT for tirzepatide, REDEFINE for CagriSema) reported strong weight reductions &#8211; full comparative data is an area of active investigation.<\/p>\n<h3>What did the REDEFINE studies show?<\/h3>\n<p>The REDEFINE program includes multiple phase III studies of CagriSema in various populations (obesity without diabetes, obesity with type 2 diabetes, special populations). Full results are being published. Early data (Enebo 2021 <em>Lancet<\/em>, Lau 2021 <em>Lancet<\/em>) suggest a high level of weight loss &#8211; exceeding what was achieved with semaglutide monotherapy.<\/p>\n<h3>Is CagriSema a medicine?<\/h3>\n<p>Currently &#8211; <strong>NO<\/strong>. CagriSema is <strong>combination of pharmaceutical candidates<\/strong> in phase III clinical trials under the supervision of Novo Nordisk. No registration with EMA, FDA or other major jurisdictions. Semaglutide <strong>as monotherapy<\/strong> is a registered medicine (Ozempic, Wegovy, Rybelsus). Cagrilintide as monotherapy <strong>is not<\/strong> registered. CagriSema combination <strong>is not<\/strong> registered.<\/p>\n<\/p>\n<h2>Related content in the knowledge base<\/h2>\n<p>CagriSema expands the narrative of the evolution of incretin analogues with an additional dimension &#8211; <strong>amylin pathway<\/strong>. This is a natural complement to the existing articles: <a href=\"https:\/\/one-peptides.com\/de\/semaglutide-what-do-we-know-from-clinical-trials\/\">semaglutide<\/a> (mono GLP-1), <a href=\"https:\/\/one-peptides.com\/de\/tirzepatide-dual-gip-glp-1-agonist-in-metabolism-research\/\">tirzepatide<\/a> (dual GLP-1\/GIP), <a href=\"https:\/\/one-peptides.com\/de\/retatrutide-triple-agonist-glp-1-gip-glucagon-in-clinical-trials\/\">retatrutide<\/a> (tri GLP-1\/GIP\/glucagon) and <a href=\"https:\/\/one-peptides.com\/de\/glp-1-gip-glucagon-how-incretins-regulate-metabolism\/\">mechanism of the incretin axis<\/a>. For researchers analyzing the pharmacology of obesity, the picture falls into four parallel paths:<\/p>\n<ul>\n<li><strong>Mono-incretin<\/strong> \u2014 semaglutide<\/li>\n<li><strong>Dual-incretin<\/strong> \u2014 tirzepatide<\/li>\n<li><strong>Tri-incretin<\/strong> \u2014 retatrutide<\/li>\n<li><strong>Combination of two pathways (GLP-1 + amylin)<\/strong> \u2014 CagriSema<\/li>\n<li><a href=\"https:\/\/one-peptides.com\/de\/category\/metabolism\/\">metabolism &#038; weight loss category<\/a><\/li>\n<\/ul>\n<p>Adjacent <a href=\"https:\/\/one-peptides.com\/de\/category-product\/peptides\/metabolic-modulators\/\">non-incretin pathways<\/a> include <a href=\"https:\/\/one-peptides.com\/de\/produkt\/tesofensine-500-mcg\/\">tesofensine<\/a> (triple monoamine reuptake inhibitor &#8211; CNS mechanism), <a href=\"https:\/\/one-peptides.com\/de\/produkt\/bam15-25mg\/\">BAM-15<\/a> (mitochondrial uncoupler), <a href=\"https:\/\/one-peptides.com\/de\/produkt\/slu-pp-332-500-mcg\/\">SLU-PP-332<\/a> (ERR panagonist, i.e. \u201cexercise mimetic\u201d) and <a href=\"https:\/\/one-peptides.com\/de\/produkt\/5-amino-1mq-50-mg\/\">5-amino-1MQ<\/a> (NNMT inhibitor). Together, these two groups form a broad map of 21st century metabolic pharmacology.<\/p>\n<h2>Summary<\/h2>\n<p><strong>CagriSema is a combination of semaglutide and cagrilintide<\/strong> \u2014 two peptides activating two different satiety signaling pathways simultaneously (GLP-1 receptor and amylin receptor). Novo Nordisk&#8217;s REDEFINE program includes multiple Phase III studies; full results pending publication. Early data (Enebo 2021 <em>Lancet<\/em>, Lau 2021 <em>Lancet<\/em>) suggest weight reduction at a level exceeding that of semaglutide monotherapy.<\/p>\n<p>Cagrilintide as monotherapy or CagriSema as a combination <strong>are not registered medicines<\/strong> in any major jurisdiction. Semaglutide monotherapy &#8211; yes (Ozempic, Wegovy, Rybelsus).<\/p>\n<p>In the field of research reagents, both peptides function as <strong>Research Use Only reagents<\/strong> \u2014 in the One Peptides catalog available as <a href=\"https:\/\/one-peptides.com\/de\/produkt\/semacagri-pen\/\">Sema+Cagri PEN 2mg+2mg<\/a>. They are not registered medicines, are not dietary supplements and are not intended for use in humans.<\/p>\n<blockquote>\n<p>\u2139\ufe0f <strong>Disclaimer<\/strong><\/p>\n<p>CagriSema (a combination of semaglutide and cagrilintide) in the One Peptides catalog functions only as a set of chemical reagents intended for laboratory tests (Research Use Only). It is not a medicinal product, dietary supplement or food. The information in this article is educational in nature and describes the clinical literature regarding CagriSema as a combination of pharmaceutical candidates in Novo Nordisk&#8217;s Phase III clinical trials &#8211; it does not constitute medical advice, does not encourage the use of peptides in a non-exploratory manner, and does not provide protocols for use for the end purchaser.<\/p>\n<\/blockquote>\n<h2>Bibliography<\/h2>\n<ol>\n<li>Enebo LB, Berthelsen KK, Kankam M et al (2021). <a href=\"https:\/\/doi.org\/10.1016\/s0140-6736(21)00845-x\" rel=\"noopener noreferrer\" target=\"_blank\"><cite>Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2\u00b74 mg for weight management: a randomized, controlled, phase 1b trial<\/cite><\/a><\/li>\n<li>Lau DCW, Erichsen L, Francisco AM et al (2021). <a href=\"https:\/\/doi.org\/10.1016\/s0140-6736(21)01751-7\" rel=\"noopener noreferrer\" target=\"_blank\"><cite>Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomized, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial<\/cite><\/a><\/li>\n<li>Wilding JPH, Batterham RL, Calanna S et al (2021). <a href=\"https:\/\/doi.org\/10.1056\/NEJMoa2032183\" rel=\"noopener noreferrer\" target=\"_blank\"><cite>Once-Weekly Semaglutide in Adults with Overweight or Obesity<\/cite><\/a><\/li>\n<li>Marso SP, Bain SC, Consoli A et al (2016). <a href=\"https:\/\/doi.org\/10.1056\/NEJMoa1607141\" rel=\"noopener noreferrer\" target=\"_blank\"><cite>Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes<\/cite><\/a><\/li>\n<li>Lau J, Bloch P, Sch\u00e4ffer L et al. (2015). <a href=\"https:\/\/doi.org\/10.1021\/acs.jmedchem.5b00726\" rel=\"noopener noreferrer\" target=\"_blank\"><cite>Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide<\/cite><\/a><\/li>\n<li>Fr\u00edas JP, Davies MJ, Rosenstock J et al (2021). <a href=\"https:\/\/doi.org\/10.1056\/NEJMoa2107519\" rel=\"noopener noreferrer\" target=\"_blank\"><cite>Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes<\/cite><\/a><\/li>\n<\/ol>\n<div class=\"author-box\" style=\"border-left: 4px solid #958e09; background: #f9fafb; padding: 16px 20px; margin: 32px 0; border-radius: 4px;\">\n<p style=\"margin: 0 0 8px 0; font-size: 14px; line-height: 1.5;\"><strong>Pharmaceutical Review:<\/strong> <a href=\"https:\/\/one-peptides.com\/de\/team-aneta-kropicka\/\">M.Pharm. Aneta Kropicka<\/a><br \/>\n<em>Pharmaceutical reviewer and sports supplementation expert.<\/em><br \/>\nMaster of Pharmacy with 12 years of professional experience, graduate of the Medical University of Lodz (2014). Reviews One Peptides content against pharmacology, clinical dosages and RUO\/dietary supplement\/drugs regulatory framework.<\/p>\n<p style=\"margin: 0; font-size: 12px; color: #6b7280;\"><small>Publication: <time datetime=\"2026-06-08\">2026-06-08<\/time> \u2022 Last update: <time datetime=\"2026-06-08\">2026-06-08<\/time><\/small><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>The evolution of the pharmacology of obesity treatment in the last decade has been in the sequence of &#8220;adding receptors&#8221; &#8211; from a GLP-1 monoagonist (semaglutide \u2192 Ozempic, Wegovy), through a GLP-1 + GIP agonist (tirzepatide \u2192 Mounjaro, Zepbound), to a GLP-1 + GIP + glucagon triagonist (retatrutide in phase III). CagriSema adds a separate signaling pathway to this narrative \u2013 amylin \u2013 that is still not [\u2026]<\/p>\n","protected":false},"author":31,"featured_media":1825,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":"","_members_access_role":[],"_members_access_error":""},"categories":[152],"tags":[],"class_list":["post-1892","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-metabolism"],"acf":[],"aioseo_notices":[],"aioseo_head":"\n\t\t<!-- All in One SEO Pro 5.0.3 - aioseo.com -->\n\t<meta name=\"description\" content=\"CagriSema combines semaglutide (GLP-1 analogue) and cagrilintide (amylin) in the phase III REDEFINE trials. 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