Next GLP-1 Drugs After Zepbound: Retatrutide, CagriSema, Amycretin, CT-388, Mazdutide, and Monthly Shots

Retatrutide is the most important next GLP-1 drug after Zepbound because Lilly's Phase 3 TRIUMPH-1 trial reported 28.3% mean body-weight loss at 80 weeks on 12 mg, versus 2.2% with placebo. In a prespecified high-BMI extension, people who continued 12 mg to 104 weeks lost 30.3% on average, equal to 85.0 lb from an average baseline of 268.3 lb.

That does not make retatrutide available. Lilly says retatrutide is investigational and legally available only to clinical-trial participants. It should not be treated as a sourceable, compoundable, or consumer-ready alternative to tirzepatide, Zepbound, semaglutide, or Wegovy.

The next wave is not one drug. CagriSema adds amylin biology to semaglutide. Amycretin, also called zenagamtide in Novo investor materials, combines GLP-1 and amylin receptor agonism in one molecule. CT-388 is a dual GLP-1/GIP agonist. Mazdutide and survodutide add glucagon. Berobenatide is a longer-acting GLP-1 being studied for weekly and monthly dosing. Orforglipron, covered by PeptidePub as Foundayo, is already approved as an oral small-molecule GLP-1 option.

If you need treatment now, compare current clinical options through providers, best online weight-loss programs, Eden, SkinnyRx, Direct Meds, or Medvi. Do not chase research-vial pipeline drugs.

Pipeline Comparison

Retatrutide, Eli Lilly: once-weekly GIP/GLP-1/glucagon triple agonist. Latest status is Phase 3 obesity data. TRIUMPH-1 showed 19.0%, 25.9%, and 28.3% mean weight loss at 80 weeks on 4 mg, 9 mg, and 12 mg, versus 2.2% placebo. Practical status: investigational only.

CagriSema, Novo Nordisk: fixed-dose cagrilintide 2.4 mg plus semaglutide 2.4 mg, once-weekly injection. REDEFINE 1 reported 22.7% mean loss at 68 weeks if patients adhered to treatment, versus 2.3% placebo. Regardless of adherence, loss was 20.4% versus 3.0% placebo. Practical status: not the same as semaglutide alone.

Amycretin or zenagamtide, Novo Nordisk: GLP-1 plus amylin receptor agonism, with subcutaneous and oral programs. Early obesity data showed 24.3% loss at 36 weeks on 60 mg subcutaneous amycretin, versus 1.1% placebo. Novo said the AMAZE Phase 3 obesity program for subcutaneous and oral zenagamtide was expected to start in Q1 2026.

CT-388, also called enicepatide, Roche or Genentech: once-weekly dual GLP-1/GIP agonist. Phase 2 CT388-103 reported 22.5% placebo-adjusted weight loss at 48 weeks on 24 mg, with no plateau. Roche said 54% reached BMI below 30 versus 13% placebo.

Mazdutide, Innovent with Lilly China rights: GLP-1/glucagon dual agonist. GLORY-2 reported 18.55% mean loss at week 60 versus 3.02% placebo in Chinese adults with obesity.

Mazdutide's GLORY-2 details matter because the population was specific: 462 Chinese adults with BMI at least 30 kg/m2, 16% with type 2 diabetes, randomized 2:1 to mazdutide 9 mg or placebo for 60 weeks. Mean baseline weight was 94.0 kg and BMI was 34.3 kg/m2. Among participants without type 2 diabetes, 9 mg mazdutide produced 20.08% mean loss versus 2.81% placebo. At least 20% loss occurred in 44.0% versus 2.6%, and in non-T2D participants it was 48.7% versus 3.1%. In an MRI-PDFF liver-fat subset with baseline liver fat at least 10%, liver fat changed -71.9% versus +5.1% placebo. Adverse-event discontinuation was 2.9% versus 0%.

Survodutide, Boehringer Ingelheim and Zealand Pharma: dual GLP-1/glucagon agonist. SYNCHRONIZE-1 Phase 3 obesity results are promising but estimand-dependent. Company summaries reported about 16.6% to 17% mean loss at 76 weeks and up to about 85% achieving at least 5% loss. Later ADA and NEJM coverage reported about 13% treatment-regimen loss versus about 5% placebo. That makes it worth watching, not an obvious weight-loss leader.

Berobenatide, Pfizer: investigational ultra-long-acting GLP-1 peptide. The story is convenience and adherence. Pfizer described weekly and monthly dosing options, and VESPER-1 Part B reported 15.9% non-placebo-adjusted loss with no plateau at 32 weeks on 2.4 mg weekly berobenatide after escalation from placebo.

Orforglipron, covered by PeptidePub as Foundayo, is different because it is already approved: FDA approved April 1, 2026, once-daily tablet, no injections, no fasting, about 15% body-weight loss at 72 weeks, with ATTAIN-MAINTAIN maintenance evidence.

Why Mechanisms Are Changing After Zepbound

The current ladder is simple. Semaglutide is GLP-1 only. Tirzepatide is GLP-1 plus GIP. Retatrutide is GLP-1 plus GIP plus glucagon. That third receptor is why retatrutide gets so much attention.

Glucagon receptor agonism is being explored because it may affect energy expenditure, liver fat, and plateau biology. That is the logic behind retatrutide, mazdutide, and survodutide. The tradeoff is that more receptors do not automatically mean better real-world use. Glucagon activity may also change tolerability, heart-rate considerations, and which patients are good candidates.

Amylin is the other major pathway. CagriSema uses cagrilintide with semaglutide. Amycretin or zenagamtide combines GLP-1 and amylin receptor agonism in one drug candidate. Amylin can influence satiety and may complement GLP-1 effects, but the best dosing, tolerability, and long-term maintenance picture still need larger trials.

Convenience is a separate race. Oral small molecules and longer-acting peptides are trying to make treatment easier to stay on. Orforglipron is the current oral example on PeptidePub. Berobenatide is the monthly-shot concept to watch, but monthly dosing is not proven as a routine consumer substitute yet.

Do not over-rank these drugs from separate trials. Trial length, baseline BMI, diabetes status, adherence estimand, dose escalation, rescue rules, and dropout handling can move the headline number. Cross-trial comparisons are useful for orientation, not proof that one drug beats another in the same patient.

Retatrutide: The Strongest Late-Stage Signal

TRIUMPH-1 is why retatrutide leads the post-Zepbound pipeline. Lilly enrolled 2,339 adults with obesity or overweight, at least one weight-related comorbidity, and no diabetes. Participants were randomized 1:1:1:1 to retatrutide 4 mg, 9 mg, 12 mg, or placebo. Average baseline weight was 112.7 kg, or 248.5 lb, with BMI 40.0 kg/m2.

At 80 weeks, mean weight loss was 19.0%, or 47.2 lb, on 4 mg; 25.9%, or 64.4 lb, on 9 mg; 28.3%, or 70.3 lb, on 12 mg; and 2.2%, or 5.5 lb, on placebo. The threshold data were also unusually strong. At least 25% loss occurred in 27.8%, 52.9%, 62.5%, and 2.2%. At least 30% loss occurred in 15.3%, 37.9%, 45.3%, and 0.5%. At least 35% loss occurred in 5.9%, 20.8%, 27.2%, and 0.3%, across 4 mg, 9 mg, 12 mg, and placebo.

Lilly also reported that 65.3% of people on 12 mg reached BMI below 30. Among those who started with class 3 obesity, 37.5% reached BMI below 30.

The 104-week extension included 532 participants with baseline BMI at least 35 who completed 80 weeks and tolerated assigned medication. Weight loss at 104 weeks was 27.9%, 29.5%, 30.3%, and 19.2% for 4 mg-to-MTD, 9 mg-to-MTD, 12 mg-to-MTD, and placebo-to-retatrutide MTD.

Retatrutide's safety profile still matters. In Lilly's release, nausea occurred in 28.6%, 38.4%, and 42.4% on 4 mg, 9 mg, and 12 mg, versus 14.8% placebo. Diarrhea occurred in 25.2%, 34.1%, and 32.0%, versus 13.5%. Constipation occurred in 23.8%, 25.9%, and 26.1%, versus 10.9%. Vomiting occurred in 10.6%, 22.8%, and 25.3%, versus 4.8%.

Two less-discussed numbers are worth watching. Dysesthesia occurred in 5.1%, 12.3%, and 12.5%, versus 0.9% placebo. Urinary tract infections occurred in 7.5%, 8.8%, and 8.4%, versus 5.3%. Adverse-event discontinuation was 4.1%, 6.9%, and 11.3%, versus 4.9% placebo.

Other Major Contenders

CagriSema is Novo Nordisk's most direct weekly-injection contender. It combines cagrilintide 2.4 mg and semaglutide 2.4 mg. REDEFINE 1 showed 22.7% mean body-weight reduction at 68 weeks when patients adhered to treatment, versus 2.3% placebo. Regardless of adherence, the number was 20.4% versus 3.0%. Novo also reported that 50.7% of participants with obesity treated with CagriSema reached BMI below 30 from mean baseline BMI 38.

The nuance: this is not just higher-dose semaglutide. It is an amylin-plus-GLP-1 combination, so tolerability, titration, and positioning could differ from both Wegovy and Zepbound. It is also not a clean head-to-head answer against tirzepatide. For that context, see semaglutide vs tirzepatide.

Amycretin, also called zenagamtide in Novo's investor materials, is earlier but important. Novo's June 20, 2025 release described early trials in The Lancet evaluating a GLP-1 and amylin receptor agonist. In a Phase 1b/2a study of 125 adults with overweight or obesity, once-weekly subcutaneous amycretin produced significantly greater weight loss than placebo across doses, with no plateau observed.

Novo's Q4 2025 investor deck said high-dose subcutaneous zenagamtide or amycretin 60 mg produced 24.3% weight loss at 36 weeks versus 1.1% placebo. Lower subcutaneous doses showed 9.7%, 16.2%, and 22.0% loss, with placebo around 1.9% to 2.3% depending on dose cohort and duration. Oral amycretin Phase 1 showed 13.1% loss at 12 weeks versus 1.1% placebo in a very small group with mean baseline weight about 89 kg and n=16.

That is exciting, but it is not the same kind of evidence as a large Phase 3 obesity trial. The sample was small, dose escalation is still being worked out, and early-phase results often look cleaner than real-world treatment.

CT-388 is Roche's dual GLP-1/GIP entrant. The January 27, 2026 Roche release said CT-388 is investigational and once weekly. Phase 2 CT388-103 found 24 mg produced 22.5% placebo-adjusted weight loss at 48 weeks without plateau. Roche also said 54% of participants on 24 mg achieved BMI below 30 versus 13% on placebo, with no new or unexpected safety signals.

The practical read: CT-388 could become a serious dual-agonist competitor, but it still needs broader data, longer follow-up, and regulatory progress before patients can compare it like a prescription option.

What Buyers Should Do Today Instead of Waiting

If you need treatment now, do not try to buy retatrutide, amycretin, mazdutide, survodutide, CT-388, or other investigational peptides online. There is no legitimate consumer market for these drugs. Research-vial products do not have the clinical-trial manufacturing, purity, sterility, dosing, or medical-supervision controls patients need.

The practical choices are current approved or clinically reviewed paths. That can mean FDA-approved brand medicines such as Wegovy or Zepbound when clinically appropriate, Foundayo or orforglipron when available and appropriate, cash-pay telehealth programs, insurance or employer benefit routes, and pharmacy-vetted compounded paths where legally appropriate.

Start with providers if you want to compare current programs. Use best online weight-loss program if you are shopping by support model, clinician review, price, and refill process. Use GLP-1 without insurance if the main issue is cash-pay access. Use best oral GLP-1 options if you want pills instead of injections.

For current shopping options, compare Eden, SkinnyRx, Direct Meds, and Medvi. The goal is not to buy pipeline drugs. The goal is to find a medically supervised option that exists now, fits your health history, and has transparent pricing and follow-up.

For safety context around compounded GLP-1 availability and policy changes, read the compounded GLP-1 telehealth shutdown tracker before trusting any site that claims it can sell the next unreleased drug.

FAQ

What is the next GLP-1 drug after Zepbound? Retatrutide is the most important late-stage candidate because TRIUMPH-1 showed up to 28.3% mean loss at 80 weeks and 30.3% in a 104-week high-BMI extension. It is still investigational and is not legally available as a normal prescription.

When will retatrutide be available? There is no guaranteed consumer availability date. Lilly is running multiple Phase 3 trials, and PeptidePub's retatrutide guide frames potential FDA submission after more Phase 3 data. Today, Lilly says it is legally available only through clinical trials.

Is CagriSema stronger than Zepbound? Do not assume that from cross-trial numbers. CagriSema's REDEFINE 1 result was 22.7% mean loss at 68 weeks with adherence, or 20.4% regardless of adherence. That is in the same broad conversation as tirzepatide trial benchmarks, but this article is not a head-to-head trial.

Are GLP-1 pills going to replace injections? No. Oral options matter, especially orforglipron, covered as Foundayo. Oral semaglutide is also part of the broader oral GLP-1 story. But injections still have stronger or more mature evidence for some drugs and some patients.

Can I buy pipeline GLP-1 drugs online? No legitimate consumer market exists for investigational retatrutide, amycretin, CT-388, mazdutide, survodutide, or berobenatide. Research-vial sellers are not the same as clinical-trial or FDA-reviewed supply chains, and they do not solve purity, sterility, dose, storage, adverse-effect, or medical-supervision risks.

Bottom Line

Retatrutide is the clear headline drug to watch after Zepbound. The reason is specific: 28.3% mean body-weight loss at 80 weeks in TRIUMPH-1 on 12 mg, plus 30.3% mean loss at 104 weeks in a high-BMI extension. Those are stronger late-stage obesity signals than anything else in this handoff.

CagriSema, amycretin or zenagamtide, CT-388, mazdutide, survodutide, and berobenatide still matter because they test different answers: amylin, glucagon, dual agonism, oral convenience, and longer dosing intervals.

If you are buying now, compare current approved or medically supervised options. Do not try to source investigational products online. Start with providers, best online weight-loss program, orforglipron, and retatrutide for the drug-specific availability warning.